Clinical trial NCT04598451
Conditions: Pemphigus Vulgaris Pemphigus Foliaceus
Sponsor: argenx
Start date: 2020-12-01; Completion date: 2023-08-22
Enrollment: 222 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a prospective, multicenter, randomized, double-blinded, placebo-controlled trial to investigate the efficacy, safety, patient outcome measures, tolerability, immunogenicity, PK, and PD of efgartigimod PH20 SC in adult participants aged from 18 years with PV or PF. The trial comprises a screening period of up to 3 weeks, a treatment period of up to 30 weeks, and an 8-week follow-up period for participants who do not enroll into the open-label extension (OLE) trial ARGX-113-1905. The primary objective of the ARGX-113-1904 trial is to demonstrate the efficacy of subcutaneous administration of efgartigimod co-formulated with recombinant human hyaluronidase PH20 (Efgartigimod PH20 SC) compared to placebo in the treatment of participants with Pemphigus Vulgaris (PV). Secondary objectives are to also demonstrate the efficacy of efgartigimod PH20 SC in the treatment of participants with Pemphigus Foliaceus (PF), and to demonstrate early onset of action and a prednisone-sparing effect. After confirmation of eligibility, participants will be randomized in a 2: 1 ratio to receive efgartigimod PH20 SC or placebo

Detailed description:

Arms: arm 1: patients receiving efgartigimod PH20 SC on top of prednisone arm 2: patients receiving placebo on top of prednisone
Interventions: intervention 1: efgartigimod PH20 SC intervention 2: Placebo intervention 3: prednisone
Intervention descriptions: intervention 1: Subcutaneous injection of efgartigimod using rHuPH20 (PH20) as a permeation enhancer intervention 2: Subcutaneous injection of placebo intervention 3: Oral prednisone tablets

Protocol documents:
Prot_000.pdf: 
Clinical Trial Protocol 
Protocol Title: 
A Randomized, Double-Blinded, Placebo-Controlled Trial to 
Investigate the Efficacy, Safety, and Tolerability of Efgartigimod 
PH20 SC in Adult Patients With Pemphigus (Vulgaris or 
Foliaceus) (ADDRESS)
Protocol Number: 
ARGX-113-1904 
Version Number: 
 
 
5.0 (Amendment 4) 
Compound:   
 
 
 
Efgartigimod (ARGX-113) 
Investigational Medicinal 
Efgartigimod PH20 SC (efgartigimod coformulated with 
Product:
recombinant human hyaluronidase PH20 [rHuPH20] for 
subcutaneous [SC] administration) / Placebo (placebo with 
rHuPH20 for SC administration)
Trial Phase:   
 
 
 
3
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)
IND: 
EudraCT: 2020-002915-23 
Date and Version: 
09 Dec 2022, Version 5.0


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Sponsor’s Medical Contact:
, MD, PhD 
 
argenx BV 
 
Industriepark Zwijnaarde 7 
 
B-9052 Zwijnaarde (Ghent) 
 
Belgium  
 
Office Phone: 
  
 
Contract Research Organization: Pharmaceutical Product Development (PPD) Global Ltd 
Granta Park, Great Abington 
Cambridge, CB21 6GQ, United Kingdom   
Phone: +44 1223 374100  
 
Sponsor’s Designee (China only): Zai Lab (Shanghai) 
4/F, No. 1 South Tower 
4560 Jinke Rd.  
Pilot Free Trade Zone (Shanghai)  
P.R. China 
 
Serious Adverse Event Reporting: Parexel International 
 8 Federal Street, Billerica, MA 01821, United States 
 
The following additional numbers are also available for urgent contact: 
24-Hour Urgent Medical 
Helpline Number: 
EMEA/APAC +44 1223 374 240  
North America +1 800 201 8725 
 
 
For drug safety reporting, contact the below email address: 
Safety Mailbox/Fax: 
Email: safety@argenx.com 
Fax: +1 833 874 7325 
Confidentiality Statement 
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. 
 


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Notification: Possible Adaptations of Trial Protocol During the COVID-19 Pandemic
The aim of the ARGX-113-1904 trial is to investigate a new subcutaneous (SC) treatment option 
for patients with pemphigus. This SC treatment consists of efgartigimod coformulated with 
recombinant human hyaluronidase PH20 (rHuPH20) (called efgartigimod PH20 SC) and could 
offer clinically significant benefits to pemphigus patients.
The sponsor (argenx BV) has performed a critical assessment of the use of efgartigimod during 
the COVID-19 pandemic. Following careful evaluation, the risk/benefit profile of efgartigimod 
has not changed in the context of this pandemic. This decision was made based on 
efgartigimod’s mechanism of action, the safety data generated to date, and provisions made in all 
clinical trials with efgartigimod for safety reporting and withholding treatment upon evidence of 
infection. This assessment will be reviewed regularly to consider new information about the 
pandemic and the ongoing, continuous assessment of adverse events reported during argenx BV 
clinical trials. 
During the COVID-19 pandemic, it may not be possible to perform all assessments as planned 
for this trial (see Schedule of Activities [SoA] in Section 1.3). 
In order to provide participants with pemphigus the opportunity to continue the trial during the 
COVID-19 pandemic, an appendix with possible adaptations to the ARGX-113-1904 trial has 
been developed. This appendix describes a minimum number of assessments required to 
guarantee the safety and wellbeing of participants during the trial, to secure the collection of the 
critical parameters for analysis, and the possibility of efgartigimod administration in the 
participant’s home. This appendix is included in Section 10.14 (Appendix 14) of this protocol. 


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SIGNATURE OF SPONSOR
Protocol Title:  
A Randomized, Double-Blinded, Placebo-Controlled Trial to 
Investigate the Efficacy, Safety, and Tolerability of Efgartigimod 
PH20 SC in Adult Patients With Pemphigus (Vulgaris or Foliaceus) 
(ADDRESS)
Protocol Number:  
ARGX-113-1904 
Acronym:  
ADDRESS 
Sponsor Representative:  
 
 
See appended signature page 
 
, MD, PhD 
Chief Medical Officer, argenx BV 
 
Date 


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SIGNATURE OF PRINCIPAL INVESTIGATOR
PROTOCOL TITLE: 
A Randomized, Double-Blinded, Placebo-Controlled Trial to 
Investigate the Efficacy, Safety, and Tolerability of Efgartigimod 
PH20 SC in Adult Patients With Pemphigus (Vulgaris or 
Foliaceus) (ADDRESS) 
PROTOCOL NO: 
 
ARGX-113-1904 
This protocol is a confidential document of argenx BV. I confirm that I have read this protocol, I 
understand it, and I will work according to this protocol. I will also work consistently with the 
ethical principles that have their origin in the Declaration of Helsinki and that are consistent with 
good clinical practices and the applicable laws and regulations. Acceptance of this document 
constitutes my agreement that no unpublished information contained herein will be published or 
disclosed without prior written approval from argenx BV. 
 
Instructions to the investigator: Please SIGN and DATE this signature page. PRINT your 
name, title, and the name of the site in which the trial will be conducted. Return the signed 
original copy to the local representative of your sponsor’s designee or designated CRO. 
I have read this protocol in its entirety and agree to conduct the trial accordingly: 
Signature of Principal
Investigator: 
 
Date:
 
Printed Name: 
 
Principal Investigator Title: 
 
Name/Address of Site:
 
 
 
 
 
 
 


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Protocol Amendment Summary of Changes
DOCUMENT HISTORY 
Document 
Date 
Protocol v5.0 (Amendment 4)
09 Dec 2022
Protocol v4.0 (Amendment 3)
09 Jun 2022
Protocol v3.0 (Amendment 2) 
18 May 2021 
Protocol v2.0 (Amendment 1)
10 Feb 2021
Protocol v1.0
22 Jul 2020
Amendment 4 (09 Dec 2022) 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union. 
Overall Rationale for the Amendment 
The overall rationale for this protocol amendment is to clarify the assessments performed during 
an unscheduled visit. 
The relevant changes implemented in the Germany and China country-specific protocols,
v4.1-Germany and v4.1-China are included also in this protocol amendment. Country-specific 
requirements are described in the applicable sections of the protocol and/or in Section 10.16. 
The main changes from protocol version 4.0 to protocol version 5.0 are summarized in the 
following table. A strikethrough indicates text that was removed, and bold font indicates text that 
was added. Minor editorial changes, including the correction of typographical errors and 
formatting inconsistencies, are not summarized. 
 


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Summary of Changes Between Protocol Version 4.0 and Protocol Version 5.0
Section and name
Description of change
Brief rationale
Section 1.1. Synopsis 
The following text was revised: 
“Approximately 213 participants with PV or PF will be 
randomized as follows: 
Approximately 183 participants with PV will be 
randomized in a 2:1 ratio to receive efgartigimod PH20 
SC or placebo, respectively. The target number of 
Japanese participants with PV is 9 (included in the 
183 participants globally). Among the Japanese 
participants with PV, the randomization ratio will also 
be 2:1 to receive efgartigimod PH20 SC or placebo, 
respectively.  
 Up to approximately 30 participants with PF may be 
randomized in a 2:1 ratio to receive efgartigimod PH20 
SC or placebo, respectively. The target range for the 
number of Japanese participants with PF is 1 to 3 
(included in the 24 30 participants globally). Among 
the Japanese participants with PF, the randomization 
ratio will also be 2:1 to receive efgartigimod PH20 SC 
or placebo, respectively.” 
Revised for accuracy and 
clarity 
Section 8. Trial 
Assessments and 
Procedures 
Other sections impacted 
by this change: 
Section 1.3. Schedule of 
activities  
Section 10.14. Table 10: 
Modified schedule of 
activities during 
COVID-19 pandemic 
Section 10.16.1.1. 
Table 16: Schedule of 
Activities for Trial 
ARGX-113-1904 - China 
Section 10.16.1.4. 
Table 19: Modified 
Schedule of Activities 
During COVID-19 
Pandemic - China 
The assessments to be performed during an unscheduled 
visit in case of new lesions, flare, AEs, or other safety 
reasons have been clarified. 
Modified to provide a clear 
overview of assessments to be 
performed during unscheduled 
visits 


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Summary of Changes Between Protocol Version 4.0 and Protocol Version 5.0
Section and name
Description of change
Brief rationale
Section 1.3. Schedule of 
activities 
Other sections impacted 
by this change: 
Section 10.14. Table 10: 
Modified schedule of 
activities during 
COVID-19 pandemic 
Section 10.16.1.1. 
Table 16: Schedule of 
Activities for Trial 
ARGX-113-1904 - China 
Section 10.16.1.4. 
Table 19: Modified 
Schedule of Activities 
During COVID-19 
Pandemic - China 
In footnote p, the timing of pregnancy tests was further 
specified: “A urine pregnancy test will be performed 
conducted and analyzed locally and during on-site 
visits at least once every 4 weeks (before and after CR) 
and at the time of CR.”
Revised for accuracy 
Section 5.1. Inclusion 
Criteria 
Inclusion criterion 5A.i was revised: 
“Male participants must agree to use an acceptable 
method of contraception (as described in Appendix 5, 
Section 10.5.2.2) and not donate sperm from signing the 
ICF until the endlast dose of the studyIMP.” 
Adjusted to align with the 
current guidance for 
efgartigimod on sperm 
donation 
Section 8. Trial 
Assessments and 
Procedures 
Because the sponsor can review the eligibility of 
participants but the decision to randomize a participant is 
up to the investigator, the following sentence has been 
updated:  
“At screening, all eligibility assessments should be 
performed after obtaining informed consent. All 
screening evaluations must be completed and reviewed, 
and confirmed by the sponsor’s designated CRO and 
medical monitor before enrollment to confirm that 
potential participants meet all eligibility criteria. 
Pseudonymized source documents confirming the 
diagnosis (histology, DIF, and IIF or ELISA) may be 
sent for this eligibility confirmation. The investigator 
will maintain a screening log to record details of all 
participants screened and to confirm eligibility or record 
reasons for screening failure, as applicable.” 
Correction 


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Summary of Changes Between Protocol Version 4.0 and Protocol Version 5.0
Section and name
Description of change
Brief rationale
Section 10.2. Table 7: 
Protocol-Required 
Laboratory Assessments 
Other sections impacted 
by this change:
Section 6.3. Measures to 
Minimize Bias: 
Randomization and 
Blinding 
Section 10.16.1.3. 
Table 17: Protocol-
Required Laboratory 
Assessments – China 
Study sites will no longer be provided with the albumin 
and total protein results in real time. The investigator 
will receive an alert if a participant’s results are outside 
of the normal range. In addition, it has been clarified that 
PK, PD, immunogenicity, albumin, total protein, and 
exploratory research data (where applicable) will also 
remain blinded until database lock. The following 
footnote has therefore been added in Table 7 and 
Table 17:  
“PK, PD, immunogenicity, albumin, and total protein 
data will not be reported to the site. A system will be 
implemented that will alert the investigator of out-of-
range albumin and total protein values, to allow for 
appropriate safety follow-up.”  
 
Caution regarding data 
integrity in double-blinded 
efgartigimod studies 
Section 10.6. 
Administrative Structure 
The legal entity of the laboratory used for the analysis of 
PK and ADA changed from LGC to DDS. 
Administrative update 
Throughout 
Clarifications have been added to specify the aspects of 
the protocol that are globally applicable and those that 
are distinct for China.  
 
Clarification 
 


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TABLE OF CONTENTS
SIGNATURE OF SPONSOR ..........................................................................................................4
SIGNATURE OF PRINCIPAL INVESTIGATOR .........................................................................5
Protocol Amendment Summary of Changes ....................................................................................6
Summary of Changes Between Protocol Version 4.0 and Protocol Version 5.0 .............................7
1.
PROTOCOL SUMMARY ..........................................................................................17
1.1.
Synopsis......................................................................................................................17
1.2.
Schema ........................................................................................................................25
1.3.
Schedule of Activities.................................................................................................26
2.
INTRODUCTION ......................................................................................................33
2.1.
Trial Rationale ............................................................................................................33
2.2.
Background.................................................................................................................35
2.3.
Benefit/Risk Assessment ............................................................................................38
2.3.1. 
Risk Assessment .........................................................................................................38
2.3.2. 
Benefit Assessment .....................................................................................................40
2.3.3. 
Overall Benefit: Risk Conclusion ...............................................................................41
3.
OBJECTIVES AND ENDPOINTS ............................................................................42
4.
TRIAL DESIGN .........................................................................................................44
4.1.
Overall Design ............................................................................................................44
4.2.
Scientific Rationale for Trial Design ..........................................................................46
4.3.
Justification for Dose ..................................................................................................49
4.4.
End of Study Definition..............................................................................................50
5.
TRIAL POPULATION ..............................................................................................51
5.1.
Inclusion Criteria ........................................................................................................51
5.2.
Exclusion Criteria.......................................................................................................52
5.3.
Lifestyle Considerations .............................................................................................54
5.4.
Screen Failures............................................................................................................54
5.5.
Criteria for Temporarily Delaying Randomization ....................................................54
6.
TRIAL INTERVENTION ..........................................................................................55
6.1.
Trial Intervention(s) Administered.............................................................................55
6.2.
Preparation/Handling/Storage/Accountability ............................................................56
6.2.1. 
Preparation..................................................................................................................56


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6.2.2. 
Handling .....................................................................................................................56
6.2.3. 
Storage ........................................................................................................................57
6.2.4. 
Accountability.............................................................................................................57
6.3.
Measures to Minimize Bias: Randomization and Blinding........................................57
6.3.1. 
Emergency Unblinding ...............................................................................................58
6.4.
Trial Intervention Compliance ....................................................................................58
6.4.1. 
Handling Missed Doses of the Investigational Medicinal Product ............................59
6.4.2. 
Protocol Deviations ....................................................................................................59
6.5.
Dose Modification ......................................................................................................59
6.6.
Continued Access to Study Intervention After the End of the Trial...........................59
6.7.
Treatment of Overdose ...............................................................................................60
6.8.
Concomitant Therapy .................................................................................................60
6.8.1. 
Concomitant Pemphigus Therapy...............................................................................60
6.8.2. 
Prohibited Medications and Therapy During the Trial ...............................................64
7.
DISCONTINUATION OF TRIAL INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................65
7.1.
Discontinuation of Trial Intervention.........................................................................65
7.2.
Participant Discontinuation/Withdrawal From the Trial ............................................65
7.3.
Lost to Follow-up .......................................................................................................66
8.
TRIAL ASSESSMENTS AND PROCEDURES .......................................................67
8.1.
Demography ...............................................................................................................69
8.2.
Efficacy Assessments .................................................................................................70
8.3.
Safety Assessments .....................................................................................................70
8.3.1. 
Physical Examinations................................................................................................70
8.3.2. 
Height and Weight......................................................................................................70
8.3.3. 
Vital Signs ..................................................................................................................71
8.3.4. 
Electrocardiography....................................................................................................71
8.3.5. 
Medical and Surgical History.....................................................................................71
8.3.6. 
Clinical Safety Laboratory Assessments ....................................................................72
8.3.6.1. 
Vaccination Antibodies Testing .................................................................................73
8.3.6.2. 
Storage of Blood and Tissue Samples After the Trial ................................................73
8.3.7. 
Infections and Vaccinations........................................................................................73
8.3.8. 
Suicidal Ideation and Behavior Risk Monitoring .......................................................74


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8.3.9. 
Additional Safety Assessment ....................................................................................74
8.4.
Adverse Events and Serious Adverse Events .............................................................75
8.4.1. 
Time Period and Frequency for Collecting AE and SAE Information .......................76
8.4.2. 
Method of Detecting AEs and SAEs ..........................................................................76
8.4.3. 
Follow-up of AEs and SAEs.......................................................................................76
8.4.4. 
Reporting of AEs and SAEs .......................................................................................77
8.4.5. 
Regulatory Reporting Requirements for SAEs...........................................................77
8.4.6. 
Pregnancy ...................................................................................................................78
8.4.7. 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as 
Reportable AEs or SAEs ............................................................................................78
8.4.8. 
Adverse Events of Special Interest .............................................................................78
8.4.9. 
Infusion-related Reactions ..........................................................................................79
8.4.10. 
Injection Site Reactions..............................................................................................80
8.5.
Pharmacokinetics ........................................................................................................80
8.6.
Pharmacodynamics .....................................................................................................80
8.7.
Skin Biopsies ..............................................................................................................80
8.8.
Imaging .......................................................................................................................81
8.9.
Exploratory Research..................................................................................................81
8.9.1. 
IgG Autoantibody Subtype and Specificity Study......................................................81
8.9.2. 
Immunological Profiling .............................................................................................82
8.9.3. 
Genetics ......................................................................................................................82
8.10.
Immunogenicity Assessments ....................................................................................82
8.11.
Medical Resource Utilization and Health Economics ................................................83
8.12.
Quality of Life and Patient-Reported Outcomes ........................................................83
9.
STATISTICAL CONSIDERATIONS .......................................................................84
9.1.
Statistical Methods ......................................................................................................84
9.2.
Statistical Hypotheses .................................................................................................84
9.3.
Sample Size Determination ........................................................................................84
9.4.
Populations for Analyses............................................................................................85
9.5.
Statistical Analyses.....................................................................................................86
9.5.1. 
General Considerations...............................................................................................86
9.5.2. 
Patient Disposition ......................................................................................................86
9.5.3. 
Analysis Sets and Protocol Deviations .......................................................................86


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9.5.4. 
Demographic and Baseline Characteristics, and Concomitant Medication ................87
9.5.5. 
Safety Analyses ..........................................................................................................87
9.5.6. 
Primary Endpoint ........................................................................................................87
9.5.7. 
Key Secondary Endpoints Subject to Alpha Control .................................................88
9.5.8. 
Other Secondary Endpoints ........................................................................................89
9.5.9. 
Other Endpoints ..........................................................................................................90
9.6.
Interim Analyses.........................................................................................................90
9.7.
Data Safety Monitoring Board (DSMB).....................................................................90
10.
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................91
10.1.
Appendix 1: Regulatory, Ethical, and Trial Oversight Considerations ......................91
10.1.1. 
Regulatory and Ethical Considerations ......................................................................91
10.1.2. 
Financial Disclosure ...................................................................................................91
10.1.3. 
Informed Consent Process ..........................................................................................92
10.1.4. 
Data Protection ...........................................................................................................93
10.1.5. 
Committees Structure .................................................................................................93
10.1.5.1. 
Data Safety Monitoring Board ....................................................................................93
10.1.6. 
Dissemination of Clinical Trial Data ..........................................................................93
10.1.7. 
Data Quality Assurance..............................................................................................94
10.1.7.1. 
Data Handling and Record Keeping...........................................................................94
10.1.7.2. 
Quality Assurance Audit .............................................................................................95
10.1.7.3. 
Quality Control ...........................................................................................................95
10.1.8. 
Source Documents ......................................................................................................96
10.1.9. 
Monitoring ..................................................................................................................96
10.1.10. 
Data Management.......................................................................................................97
10.1.11. 
Study and Site Start and Closure ................................................................................98
10.1.12. 
Investigator Obligations..............................................................................................99
10.1.13. 
Protocol Signatures.....................................................................................................99
10.1.14. 
Publication Policy.......................................................................................................99
10.2.
Appendix 2: Laboratory Tests ..................................................................................101
10.2.1. 
Other Screening Tests ...............................................................................................101
10.2.1.1. 
Hepatitis B Virus ......................................................................................................101
10.2.1.2. 
Hepatitis C Virus ......................................................................................................102


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10.2.1.3. 
Human Immunodeficiency Virus .............................................................................102
10.3.
Appendix 3: Washout Requirements Prior to First IMP Administration .................103
10.4.
Appendix 4: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting......................................................................104
10.4.1. 
Definition of AE .......................................................................................................104
10.4.2. 
Definition of SAE .....................................................................................................105
10.4.3. 
Recording and Follow-up of AEs and/or SAEs ........................................................106
10.4.4. 
Reporting of SAEs and AESIs..................................................................................108
10.5.
Appendix 5: Contraceptive and Barrier Guidance and Collection of 
Pregnancy Information .............................................................................................109
10.5.1. 
Definitions: ...............................................................................................................109
10.5.1.1. 
Woman of Childbearing Potential ............................................................................109
10.5.2. 
Contraception Guidance: ..........................................................................................109
10.5.2.1. 
Female Contraception for Women of Childbearing Potential ..................................109
10.5.2.2. 
Male Contraception: .................................................................................................110
10.5.3. 
Collection of Pregnancy Information .......................................................................110
10.6.
Appendix 6: Administrative Structure ......................................................................112
10.7.
Appendix 7: Genetics ...............................................................................................114
10.8.
Appendix 8: Pemphigus Disease Area Index (PDAI) Scoring System ....................115
10.9.
Appendix 9: Karnofsky Performance Score .............................................................116
10.10. 
Appendix 10: EQ-5D-5L Instrument ........................................................................117
10.11. 
Appendix 11: Autoimmune Bullous Disease Quality of Life (ABQOL) 
Questionnaire ............................................................................................................119
10.12. 
Appendix 12: Definition of Terms ...........................................................................122
10.13. 
Appendix 13: Abbreviations .....................................................................................125
10.14. 
Appendix 14: Possible Adaptations of Trial Protocol During COVID-19 
Pandemic ...................................................................................................................129
10.15. 
Appendix 15: Glucocorticoid Toxicity Index (GTI) ................................................142
10.16. 
Appendix 16: Country-Specific Requirements .........................................................151
10.16.1. 
China.........................................................................................................................151
10.16.1.1. Section 1.3. Schedule of Activities - China..............................................................151
10.16.1.2. Section 8.3.6. Clinical Safety Laboratory Assessments – China ..............................157
10.16.1.3. Section 10.2. Appendix 2: Laboratory Tests – Table 7 - China ...............................158


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10.16.1.4. Section 10.14. Possible Adaptations of Trial Protocol During COVID-19 
Pandemic - Table 10 - China ....................................................................................159
10.16.2. 
Germany ...................................................................................................................165
10.16.2.1. Section 1.3: Schedule of Activities – Post-Administration Safety Monitoring 
– Germany ................................................................................................................165
11.
REFERENCES .........................................................................................................166
 


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LIST OF TABLES
Table 1: 
Schedule of Activities for Trial ARGX-113-1904 .....................................................26
Table 2:
Trial Interventions ......................................................................................................55
Table 3: 
Concomitant Prednisone Equivalent Doses (in mg) by Body Weight .......................63
Table 4: 
Assessments to be Performed During an Unscheduled Visit .....................................68
Table 5:
Trial ARGX-113-1701: Summary of Treatment-emergent Adverse Events in 
the Infections and Infestations System Organ Class by Preferred Term – 
Safety Analysis Set .....................................................................................................79
Table 6:
Sample Size Calculation.............................................................................................85
Table 7: 
Protocol-Required Laboratory Assessments.............................................................101
Table 8: 
Interpretation of Hepatitis B Serological Test Results .............................................102
Table 9: 
Interpretation of HIV Test Results in Combination With the Patient’s 
Clinical Condition and CD4 Count ...........................................................................102
Table 10: Modified Schedule of Activities During COVID-19 Pandemic...............................135
Table 11: Approach to Calculating the Baseline GTI 2.0 Score: Toxicities Assigned 
Weighted Scores From C-GTI to Establish a Baseline GTI Score...........................142
Table 12: Approach to Calculating the Changes in GTI 2.0 Score: Weighted Scores 
Assigned to Improvements or Worsenings in the C-GTI .........................................143
Table 13: GTI 2.0 Specific List: 11 Domains (9 of Which Are Shared by the C-GTI) 
and 23 Unique Items .................................................................................................144
Table 14: Severity Categorization of Skin Manifestations by Grade .......................................145
Table 15: Severity Categorization of Neuropsychiatric Manifestations by Grade ...................147
Table 16: Schedule of Activities for Trial ARGX-113-1904 – China ......................................151
Table 17: Protocol-Required Laboratory Assessments - China ................................................158
Table 18: Modified Schedule of Activities During COVID-19 Pandemic - China ..................159
LIST OF FIGURES 
Figure 1: 
Schema Detailing IMP Treatment and Assessments for Trial ARGX-113-
1904 ............................................................................................................................25
Figure 2: 
Impact of COVID-19 Pandemic on argenx BV Clinical Trials ................................131


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1.
PROTOCOL SUMMARY
1.1. 
Synopsis 
Protocol Title: 
A Randomized, Double-Blinded, Placebo-Controlled Trial to Investigate the Efficacy, Safety, 
and Tolerability of Efgartigimod PH20 SC in Adult Patients With Pemphigus (Vulgaris or 
Foliaceus) (ADDRESS)
Short Title:
Not applicable. 
Indication: 
Pemphigus 
Trial Sites/Countries:
This is a global, multicenter trial
Target Population: 
Adult patients with moderate to severe pemphigus vulgaris (PV) or pemphigus foliaceus (PF)
Investigational Medicinal Product (IMP), Dose, and Mode of Administration: 
Efgartigimod PH20 SC will be administered by subcutaneous (SC) injection on day 1 and day 8 
at a dose of 
mg, followed by weekly SC administrations of 1000 mg until complete 
remission on minimal therapy (CRmin).  
Comparator, Dose, and Mode of Administration: 
Participants will also be administered placebo with the same regimen. 
Rationale: 
In the previous trial ARGX-113-1701, a phase 2, open-label, proof-of-concept trial in mild-to-
moderate PV and PF, efgartigimod was found to rapidly decrease the serum levels of pathogenic 
anti-desmoglein (Dsg)-1 antibodies for PV and PF and anti-Dsg-3 antibodies for PV. Decreases 
in these autoantibodies were associated with clinical improvement and reduction in disease 
activity and progression, as shown by results on the Pemphigus Disease Area Index (PDAI) 
scoring system. Efgartigimod was found to have a fast onset of action in that disease control 
(DC), defined as the absence of new lesions and the start of healing of established lesions, was 
achieved in 24 out of 31 participants (77.4%) within 4 weeks. Weekly or biweekly efgartigimod 
administration with an add-on therapy of stable low doses of oral prednisone 
(0.25–0.5 mg/kg/day) resulted in complete clinical remission (CR), defined as the absence of 
new lesions and complete healing of established lesions, in a majority of these participants in 2 
to 13 weeks. 
The mainstays of therapy in PV are systemic corticosteroids and rituximab. Corticosteroids 
rapidly affect PV symptoms (3–4 weeks), but must be administered at high daily doses (eg, oral 
prednisone 1–1.5 mg/kg) to attain effectiveness. At such high doses, the well-known cumulative 
toxicities common to corticosteroid treatment occur frequently; using short courses at the lowest 


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possible dosage, by tapering gradually while keeping the disease in remission, is the therapeutic 
goal. Recently, rituximab has been approved in adults with moderate to severe PV. When 
administered as an adjunctive treatment to a short course of prednisone, rituximab was shown to 
induce a higher rate of remission after 1 or 2 years and a longer duration of remission than 
prednisone alone. However, administration of intravenous (IV) rituximab frequently results in 
infusion-related reactions (IRRs) and adverse events (AEs), which may be of late onset. The late 
onset of action of rituximab is well-documented in the literature: in a meta-analysis reviewing 
30 studies, DC was achieved by a mean of 7 to 8 weeks and CRmin by a mean of 6.5 months.1 
Consequently, an innovative drug is needed for the treatment of PV and PF that has a fast onset 
of action (eg, early DC, CR within weeks), a strong prednisone sparing effect (CR at tapered 
prednisone dose), and a favorable safety profile.  
This trial intends to demonstrate that efgartigimod PH20 SC with an add-on therapy of low doses 
of oral prednisone is a possible treatment modality for PV and PF, the administration of which 
will lead to early disease remission at minimal prednisone dose. The efficacy, safety, patient 
outcome measures, tolerability, immunogenicity, pharmacokinetics (PK), and 
pharmacodynamics (PD) of efgartigimod PH20 SC will be evaluated in participants with PV or 
PF.  
Objectives and Endpoints 
The objectives and endpoints are applicable globally, except for IgG subtypes and exploratory 
objectives/endpoints, which are not assessed in China. 
Objectives 
Endpoints 
Primary 
 
To demonstrate the efficacy of efgartigimod 
PH20 SC compared to placebo in the 
treatment of participants with PV 
 
Proportion of PV participants who achieve 
CRmin within 30 weeks 
Secondary
 
To demonstrate the efficacy of efgartigimod 
PH20 SC in the treatment of participants with 
PV or PF 
Key Secondary Endpoints 
 
Proportion of PV and PF participants who 
achieve CRmin within 30 weeks 
Cumulative prednisone dose over the trial in 
PV participants 
 
Time to CR in PV participants 
 
Time to DC in PV participants 
Other Secondary Endpoints 
 
Proportion of PF participants who achieve 
CRmin within 30 weeks 
 
Cumulative prednisone dose over the trial in 
PV and PF participants 
 
Time to CR in PV and PF participants 
 
Time to DC in PV and PF participants 
 
Rate of treatment failure 


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Objectives 
Endpoints 
 
Rate of flare 
 
PDAI at each visit 
 
To assess the safety of efgartigimod PH20 SC 
in participants with PV or PF 
 
Incidence and severity of treatment-emergent 
adverse events (TEAEs), adverse events of 
special interest (AESIs), and serious adverse 
events (SAEs) by system organ class (SOC) 
and preferred term (PT) 
 
Vital signs, physical examination, 
electrocardiogram (ECG), and clinical 
laboratory safety evaluations 
 
To assess the health impact of glucocorticoid 
(GC) use in participants with PV or PF 
 
Composite Glucocorticoid Toxicity Index 
(C-GTI) comprising the Aggregate 
Improvement Score (AIS) and the Cumulative 
Worsening Score (CWS) 
 
To evaluate the effects of efgartigimod PH20 
SC on quality of life (QoL) in participants 
with PV or PF
 
EuroQol 5-Dimension 5-Level (EQ-5D-5L) 
Scale 
 
Autoimmune Bullous Disease Quality of Life 
(ABQOL) score
 
To evaluate the PK of efgartigimod PH20 SC 
in participants with PV or PF 
 
Efgartigimod serum concentrations 
 
To evaluate the PD of efgartigimod PH20 SC 
in participants with PV or PF 
 
Total IgG and subtype (IgG1, IgG2, IgG3, 
IgG4) serum levels 
 
Anti-Dsg-1 and -3 autoantibodies serum 
levels 
 
To evaluate the immunogenicity of 
efgartigimod PH20 SC in participants with 
PV or PF 
 Incidence and prevalence of anti-drug 
antibodies (ADAs) against efgartigimod 
and antibodies against recombinant 
human hyaluronidase (rHuPH20) 
To evaluate the competency of participants or 
caregivers to self-administer efgartigimod 
PH20 SC 
Number and percentage of participants or 
caregivers completing the self-administration 
training  
 
Number and percentage of participants or 
caregivers determined by the site staff to be 
sufficiently competent to self-administer 
efgartigimod PH20 SC  
 
Number and percentage of participants or 
caregivers that self-administer efgartigimod 
PH20 SC under site staff supervision 
Exploratory  
 
To evaluate the disease-specific genetic 
background and effects of efgartigimod PH20 
 
Anti-Dsg-1 and -3 autoantibody subtypes and 
autoantibody reactivity to Dsg domains and 
other antigens  


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Objectives 
Endpoints 
SC on the serological and immunological 
profiles of participants with PV or PF 
 
Lymphocyte dynamic changes 
 
Serum cytokines profiles 
 
DNA and RNA genetic profiles
 
To evaluate the effects of efgartigimod PH20 
SC on markers of pemphigus pathology in 
skin of participants with PV or PF 
 
Markers of pemphigus pathology in lesional 
and non-lesional skin 
Overall Design 
This is a prospective, multicenter, randomized, double-blinded, placebo-controlled trial to 
investigate the efficacy, safety, patient outcome measures, tolerability, immunogenicity, PK, and 
PD of efgartigimod PH20 SC in adult participants aged from 18 years with PV or PF. Enrolled 
participants are either those who are newly diagnosed or experiencing flare as follows: 
 
treatment. 
 
sed while receiving a first 
course of oral prednisone (or equivalent). According to clinical judgment, the 
participant has shown no significant improvement of PV or PF signs for at least 
2 weeks before baseline and is considered fit to start prednisone treatment at 0.5 
mg/kg daily (qd) at baseline. 
 
therapy ± a conventional immunosuppressant (eg, azathioprine, cyclophosphamide, 
methotrexate, mycophenolate mofetil) or dapsone. Note: conventional 
immunosuppressants and dapsone must be discontinued before baseline. 
 
tapered dose of oral prednisone (or equivalent), provided that prednisone (or 
equivalent) has been given at stable dose ± a conventional immunosuppressant (eg, 
azathioprine, cyclophosphamide, methotrexate, mycophenolate mofetil) or dapsone 
and participants are fit to start prednisone treatment at 0.5 mg/kg qd at baseline. Note: 
conventional immunosuppressants and dapsone must be discontinued before baseline. 
The trial comprises a screening period of up to 3 weeks, a treatment period of up to 30 weeks, 
and an 8-week follow-up period for participants who do not enroll into the open-label extension 
(OLE) trial ARGX-113-1905. 
After confirmation of eligibility, participants will be randomized in a 2:1 ratio to receive 
efgartigimod PH20 SC or placebo, as follows: 
Efgartigimod PH20 SC will be administered by SC injection on day 1 and day 8 at a 
dose of 
mg, followed by weekly administrations of 1000 mg until CRmin is 
observed. Efgartigimod PH20 SC will be administered at on-site visits until CR, with 
a minimum of 6 weekly on-site visits (W1 to W6). After achieving CR, efgartigimod 
PH20 SC will be administered at on-site visits or at home by a nurse until CRmin is 
achieved. 


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 Placebo (vehicle with 2000 U/mL of rHuPH20) SC will be administered using the 
same regimen. 
All participants or their caregivers will be invited to receive training for future self-
administration of efgartigimod PH20 SC in the OLE trial ARGX-113-1905. The caregiver is a 
person of legal age that the participant proposes to perform the administrations. If the 
participants or caregivers have successfully completed self-administration training to the 
satisfaction of authorized staff, then the participants or caregivers may self-administer the next 
injections at the site under supervision of authorized staff.  
CR is defined as the absence of new lesions and complete healing of established lesions (except 
for post-inflammatory hyperpigmentation or erythema from resolving lesions). CRmin is defined 
as the absence of new lesions and complete healing of established lesions while the participant is 
Randomization will be stratified by disease status (experiencing flare and newly diagnosed), 
disease severity (PDAI activity scor
(<77.5 
will comprise a maximum of 30% of the overall trial population.  
All participants, regardless of treatment assignment, will concomitantly receive oral prednisone 
(or equivalent such as prednisolone) at a starting dose of 0.5 mg/kg qd. Except for oral 
prednisone (or equivalent), no other systemic therapies (eg, immunosuppressants, intravenous 
immunoglobulin [IVIg]), immunoadsorption, anti-CD20 biologics) will be permitted during the 
trial.  
Participants will visit the clinic weekly until CR and for a minimum of 6 on-site visits, 
V1(BL)/W1 to W6, to receive investigational medicinal product (IMP) and to be evaluated for 
disease activity and disease outcome. After CR, IMP will be administered weekly at on-site or 
home visits by a nurse until CRmin. At any post-baseline visit before DC is achieved, the 
prednisone dose will be adjusted by incrementing dosage according to clinical judgment, with 
the recommendation to increase by 1 or more steps (refer to Table 3) in case of disease 
progression or insufficient clinical change. To facilitate common judgments among investigators, 
recommendations for assessment of disease progression and insufficient clinical change are:  
 Disease progression: increase of at least 5 in PDAI activity score compared to 
baseline score, observed at any post-baseline visit before DC 
 Insufficient clinical change: absence of DC after 3 to 4 weeks of the participant being 
treated at the starting baseline prednisone (or equivalent) dose or after 3 to 4 weeks of 
any new incremented dose of prednisone 
The recommendations of the prednisone dose escalation are: 
 Stepwise escalation of daily prednisone dose by 1 or more steps according to clinical 
judgment in case of disease progression. 
 Adjustment by incrementing dosage by 1 step in case of insufficient clinical change. 
 Possible further escalation from the previous step by 1 or more steps, according to 
clinical judgment and under the same recommendation as above. 
 Maximum escalation to 1.5 mg/kg qd for 3 weeks. 


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If, after a minimum of 3 weeks of oral prednisone at 1.5 mg/kg qd, DC is not attained, then the 
participant will be considered a treatment failure. 
For participants achieving DC with a daily prednisone dose of 0.5 mg/kg, prednisone will be 
maintained at 0.5 mg/kg qd until CR and 2 weeks thereafter, or until end of consolidation (EoC, 
defined as the time at which no new lesions have developed for a minimum of 2 weeks and 
approximately 80% of lesions have healed) and 4 weeks thereafter, after which tapering will be 
initiated. For participants achieving DC with an escalated prednisone dose (ie, >0.5 mg/kg qd), 
the prednisone dose will be maintained until 2 weeks after achieving DC, then tapering will be 
performed according to the following stepwise procedure: dose reductions by 0.25 mg/kg qd 
(according to Table 3) every 2 weeks until the starting dose is reached (ie, 0.5 mg/kg qd). Then 
the starting dose (0.5 mg/kg qd) will be maintained until a sustained CR is achieved for 2 weeks, 
after which further tapering will be initiated, or prednisone tapering below 0.5 mg/kg qd may be 
initiated in case of sustained EoC for at least 4 weeks. Further tapering will be performed 
thereafter, as long as CR or EoC are sustained. The rules for tapering are shown in Table 3. Each 
new tapered prednisone dose until 20 mg/day must be maintained for 2 weeks. Then, the 
prednisone dose is further tapered by 2.5 mg/day per week. When 10 mg/day is reached, this 
dose level will be maintained until CRmin has been achieved. Prednisone can then be further 
tapered upon clinical judgment by the investigator.  
In case of flare in the period between DC and CRmin, the prednisone dose will be increased. A 
flare is defined by the appearance of 3 or more new lesions in a 4-week period that do not heal 
spontaneously within 1 week, or by the extension of established lesions, in a participant who had 
achieved DC. If the flare occurs after CR and IMP was administered at home by a nurse, the 
participant will resume weekly on-site visits until he/she achieves CR again. Participants who are 
not controlled by a prednisone dose that is 2 dose levels above the dose at which the flare 
between DC and CRmin therapy is observed and that is at least 0.3 mg/kg/day (eg, according to 
Table 3) will be considered treatment failures. At visits when at least 1 new lesion is observed or 
established lesions remain extensive without being defined as a flare, the prednisone dose will be 
maintained or may be increased, according to clinical judgment. If the lesion resolves, then 
tapering of the prednisone dose will be pursued as planned.  
Participants who experience treatment failure, or flare after achieving CRmin, will be allowed to 
roll over into the OLE trial ARGX-113-1905 earlier than W31. Participants who do not roll over 
into the OLE trial ARGX-113-1905 will complete the treatment-free follow-up period. 
Participants experiencing an SAE related to prednisone may also benefit from an early roll over 
to the OLE trial ARGX-113-1905, according to clinical judgment. 
Trial procedures will be performed per the SoA as detailed in Section 1.3.  
Disclosure Statement: ARGX-113-1904 is a double-blinded, randomized, parallel-group trial to 
evaluate efficacy of fixed doses of efgartigimod PH20 SC compared to placebo. 
Number of Participants: 
 Approximately 213 participants with PV or PF will be randomized as 
follows:Approximately 183 participants with PV will be randomized in a 2:1 ratio to 
receive efgartigimod PH20 SC or placebo, respectively. The target number of 
Japanese participants with PV is 9 (included in the 183 participants globally). Among 


Clinical Protocol ARGX-113-1904 v5.0
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the Japanese participants with PV, the randomization ratio will also be 2:1 to receive 
efgartigimod PH20 SC or placebo, respectively. 
Up to approximately 30 participants with PF may be randomized in a 2:1 ratio to 
receive efgartigimod PH20 SC or placebo, respectively. The target range for the 
number of Japanese participants with PF is 1 to 3 (included in the 30 participants 
globally). Among the Japanese participants with PF, the randomization ratio will also 
be 2:1 to receive efgartigimod PH20 SC or placebo, respectively.  
For Japanese participants enrolled in sites in Japan only: A Japanese participant is defined as a 
participant whose parents and 4 grandparents are Japanese, and who has Japanese nationality, 
was born in Japan, has not lived outside of Japan for a total of >10 years, and currently lives in 
Japan.  
Intervention Groups and Duration:
The maximum possible total trial duration for each participant is up to 41 weeks:
 Screening period: up to 3 weeks
 Treatment period: up to 30 weeks from baseline
 Follow-up period: up to 8 weeks after the last dose of IMP for participants who do not 
enroll in the OLE trial 
Data Safety Monitoring Board: Yes 
See Section 10.1.5.1. 
Definitions of Clinical Terms: 
 Complete clinical remission (CR): the absence of new lesions and complete healing 
of established lesions (except for post-inflammatory hyperpigmentation or erythema 
from resolving lesions).  
 Complete remission on minimal therapy (CRmin): the absence of new and 
established lesions completely healed while the participant is receiving prednisone 
 mg/day for at least 2 months (8 weeks). (Note: In this trial, when 10 
mg/day is reached, this dose level must be maintained for 8 weeks until CRmin has 
been achieved) 
 Disease control (DC): the absence of new lesions and the start of healing of 
established lesions. 
 Disease progression: 
any post-baseline visit before DC. 
 End of consolidation (EoC): the time at which no new lesions have developed for a 
minimum of 2 weeks and approximately 80% of lesions have healed. 
 Flare: appearance of 3 or more new lesions in a 4-week period that do not heal 
spontaneously within 1 week, or the extension of established lesions, in a participant 
who had achieved DC. 


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 Insufficient clinical change: the absence of DC after 3 to 4 weeks of the participant 
being treated at the starting baseline dose or after 3 to 4 weeks of any new 
incremented dose of prednisone. 
 Transient and persistent lesions: the appearance of new lesions that do not qualify 
as a flare will be recorded as new transient or new persistent lesions. Transient new 
lesions are defined as new lesions that heal within 1 week. Persistent new lesions are 
defined as new lesions that last more than 1 week. 
 Treatment failure: absence of DC with oral prednisone 1.5 mg/kg/day for a 
minimum of 3 weeks, or flare between DC and CRmin that is not controlled by a 
prednisone dose that is 2 dose levels above the dose at which the flare is observed and 
that is at least 0.3 mg/kg qd (refer to Table 3), or the occurrence of an SAE 
considered related to prednisone by the investigator. 


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1.2. 
Schema 
Figure 1: 
Schema Detailing IMP Treatment and Assessments for Trial ARGX-113-1904  
ABQOL=Autoimmune Bullous Disease Quality of Life; CR=complete clinical remission; CRmin=complete remission on minimal therapy; DC=disease control; 
Efg=efgartigimod PH20 SC; EoC=end of consolidation; EoS=end of study; EQ-5D-5L=EuroQol 5-dimension 5-level; GTI=Glucocorticoid Toxicity Index; 
OLE=open-label extension; PD=pharmacodynamics; PDAI=Pemphigus Disease Area Index; PF=pemphigus foliaceus; PK=pharmacokinetics; PV=pemphigus 
vulgaris; SC=subcutaneous.  
Randomization


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1.3. 
Schedule of Activities  
The schedule of activities is applicable globally, except for China. The China-specific Schedule of Activities is provided in 
Section 10.16.1.1.
Table 1:
Schedule of Activities for Trial ARGX-113-1904 
Trial Period 
Screening 
Treatment 
EoS/
EDa
UNSb 
Follow-up 
V1 (BL) V2 
Observation
al visits 
IMP admin 
only visit 
Observational visits 
Visit Number 
 
 
Weekly on-
site visits 
until CRc 
Weekly home 
or on-site 
visits until 
CRmind 
On-site visits 
every 4 
weeks until 
CRmin 
On-site visits 
every 4 
weeks after 
CRmin until 
W31 
W31 
Follow-
up W34 
 
Follow-
up 
W38e 
 
Trial Day/Week
D-21 to 
D-1 
D1 
(W1) 
D8 
(W2) 
D15 (W3) 
until CR 
CR until 
CRmin 
CR until 
CRmin 
CRmin until 
W31 
W31 
EoS/ED 
+3W 
EoS/E
D +7W 
Visit Window 
±0 days 
±2 daysf
V1 + 7× ±2 daysf 
±2 
daysf
±3 daysf
Assessment/
Procedure 
Informed consentg 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
X 
X 
 
 
 
 
 
 
 
 
 
DIF/histopathologyh
X 
 
 
 
 
 
 
 
 
 
 
Concomitant 
therapies/procedures 
X 
Continuous monitoring 
Karnofsky 
performance score 
X 
 
 
 
 
 
 
 
 
 
 
Demography
X
Height and weighti 
X 
 
 
Xi 
 
Xi 
Xi 
X 
 
 
 


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Trial Period 
Screening 
Treatment 
EoS/
EDa
UNSb 
Follow-up 
V1 (BL)
V2
Observation
al visits 
IMP admin 
only visit 
Observational visits 
Visit Number
Weekly on-
site visits 
until CRc 
Weekly home 
or on-site 
visits until 
CRmind 
On-site visits 
every 4 
weeks until 
CRmin 
On-site visits 
every 4 
weeks after 
CRmin until 
W31 
W31 
Follow-
up W34 
 
Follow-
up 
W38e 
 
Trial Day/Week 
D-21 to 
D-1 
D1 
(W1) 
D8 
(W2) 
D15 (W3) 
until CR 
CR until 
CRmin 
CR until 
CRmin 
CRmin until 
W31 
W31 
EoS/ED 
+3W 
EoS/E
D +7W 
Visit Window
±0 days
±2 daysf
V1 + 7× ±2 daysf
±2 
daysf 
±3 daysf
Physical 
examination and 
vital signsj,k 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
ECGj 
X 
 
 
Xl 
 
Xl 
 
X 
 
 
 
Medical and surgical 
history 
X 
 
 
 
 
 
 
 
 
 
 
Randomizationm 
 
X 
 
 
 
 
 
 
 
 
 
Urinalysisj,n,o
X 
X 
X 
X 
 
X 
X 
X 
Xb 
X 
X 
Urine pregnancy 
testj,p
 
X 
 
Xp
 
X 
X 
X 
Xb
X 
X 
Blood sampling:
Active viral infection 
testq 
X 
 
 
 
 
 
 
 
 
 
 
Serum pregnancy 
testr
X 
 
 
 
 
 
 
 
 
 
 
Clinical chemistry & 
hematologyj,o,s 
X 
X 
X 
X 
 
X 
X 
X 
Xb 
X 
X 


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Trial Period 
Screening 
Treatment 
EoS/
EDa
UNSb 
Follow-up 
V1 (BL)
V2
Observation
al visits 
IMP admin 
only visit 
Observational visits 
Visit Number
Weekly on-
site visits 
until CRc 
Weekly home 
or on-site 
visits until 
CRmind 
On-site visits 
every 4 
weeks until 
CRmin 
On-site visits 
every 4 
weeks after 
CRmin until 
W31 
W31 
Follow-
up W34 
 
Follow-
up 
W38e 
 
Trial Day/Week 
D-21 to 
D-1 
D1 
(W1) 
D8 
(W2) 
D15 (W3) 
until CR 
CR until 
CRmin 
CR until 
CRmin 
CRmin until 
W31 
W31 
EoS/ED 
+3W 
EoS/E
D +7W 
Visit Window
±0 days
±2 daysf
V1 + 7× ±2 daysf
±2 
daysf 
±3 daysf
Anti-Dsg-1 and 
anti-Dsg-3 
antibodiesj,o 
X 
X 
X 
X 
 
X 
X 
X 
Xb 
X 
X 
PKj,o,t
 
X 
Xt
X 
 
X 
X 
X 
Xb,t
X 
X 
Total IgG and IgG 
subtypesj,o,u 
X 
X 
X 
X 
 
X 
X 
X 
Xb
X 
X 
Vaccination 
antibodiesj,o,v 
X 
X 
X 
X 
 
X 
X 
X 
Xb 
X 
X 
Anti-drug 
antibodiesj,w
 
X 
 
X 
(every 2 weeks) 
 
X 
X 
X 
 
X 
X 
IgG autoantibody 
subtypes/specificity 
and cytokinesj,x
 
X 
 
Xx 
 
X 
X 
X 
Xb 
X 
X 
B- and T-cell 
populationsj 
 
X 
 
Xy
 
 
 
X 
 
 
 
RNA transcriptional 
profilej
 
X 
 
Xy 
 
 
 
X 
 
 
 


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Trial Period 
Screening 
Treatment 
EoS/
EDa
UNSb 
Follow-up 
V1 (BL)
V2
Observation
al visits 
IMP admin 
only visit 
Observational visits 
Visit Number
Weekly on-
site visits 
until CRc 
Weekly home 
or on-site 
visits until 
CRmind 
On-site visits 
every 4 
weeks until 
CRmin 
On-site visits 
every 4 
weeks after 
CRmin until 
W31 
W31 
Follow-
up W34 
 
Follow-
up 
W38e 
 
Trial Day/Week 
D-21 to 
D-1 
D1 
(W1) 
D8 
(W2) 
D15 (W3) 
until CR 
CR until 
CRmin 
CR until 
CRmin 
CRmin until 
W31 
W31 
EoS/ED 
+3W 
EoS/E
D +7W 
Visit Window
±0 days
±2 daysf
V1 + 7× ±2 daysf
±2 
daysf 
±3 daysf
HLA/non-HLA 
genotypingj 
 
X 
 
Xz 
 
 
 
 
 
 
 
Substudies: 
 
Skin biopsies (at 
selected sites)j,aa
 
X 
 
Xaa
 
 
 
Xaa
 
 
 
Photography (at 
selected sites)j,bb 
 
X 
Xbb 
Xbb 
 
 
 
 
Xb,bb 
QoL Assessments: 
EQ-5D-5Lj,cc 
X 
Xdd 
 
Xdd 
Xdd 
X 
 
 
 
ABQOLj,cc
 
X 
 
Xdd 
 
Xdd 
Xdd 
X 
 
 
 
GTIj
 
X 
 
Xee
 
Xee
Xee
X 
 
 
 
IMP self-
administration 
trainingff 
 
 
 
X 
 
X 
 
 
 
 
 
IMP administrationgg
X 
(
mg) 
X 
(
mg)
X 
X 
X 
 
 
Xb 
 
 
PDAIj 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 


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Trial Period 
Screening 
Treatment 
EoS/
EDa
UNSb 
Follow-up 
V1 (BL)
V2
Observation
al visits 
IMP admin 
only visit 
Observational visits 
Visit Number
Weekly on-
site visits 
until CRc 
Weekly home 
or on-site 
visits until 
CRmind 
On-site visits 
every 4 
weeks until 
CRmin 
On-site visits 
every 4 
weeks after 
CRmin until 
W31 
W31 
Follow-
up W34 
 
Follow-
up 
W38e 
 
Trial Day/Week 
D-21 to 
D-1 
D1 
(W1) 
D8 
(W2) 
D15 (W3) 
until CR 
CR until 
CRmin 
CR until 
CRmin 
CRmin until 
W31 
W31 
EoS/ED 
+3W 
EoS/E
D +7W 
Visit Window
±0 days
±2 daysf
V1 + 7× ±2 daysf
±2 
daysf 
±3 daysf
Disease assessmenthh 
 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
Prednisone taperii
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
AE monitoring 
Continuous monitoring 
ABQOL=Autoimmune Bullous Disease Quality of Life; admin=administration; BL=baseline; BMI=body mass index; CR=complete clinical remission; 
CRmin=CR on minimal therapy; D=day; DC=disease control; DIF=direct immunofluorescence; Dsg=desmoglein; ECG=electrocardiogram; ED=early 
discontinuation; EoC=end of consolidation; EoS=end of study; FSH=follicle-stimulating hormone; GTI=Glucocorticoid Toxicity Index; HLA=human leukocyte 
antigen; IgG=immunoglobulin G; ICF=informed consent form; IMP=investigational medicinal product; OLE=open-label extension; PDAI=Pemphigus Disease 
Area Index; PK=pharmacokinetics; RBC=red blood cells; UNS=unscheduled visit; WBC=white blood cells; W=week; V=visit 
a All participants will complete EoS/ED, which will be the end of the trial for participants who enroll in the OLE trial ARGX-113-1905. Participants who do not 
enroll in the OLE trial ARGX 113 1905 will complete the follow-up visits at W34 and W38. 
b In case of suspected new lesions as reported by the participants, AEs, flare or other safety reasons, participants should come to the clinic. This may require an 
unscheduled visit. Depending on the reason for the visit, different assessments need to be performed. See Section Section 8 for more information. Participants 
with new lesions or flare after achieving CR should return to weekly on-site visits until CR is achieved again. 
c A minimum of 6 on-site visits, V1(BL)/W1 to W6, are required before switching to home administrations, even if CR is achieved earlier than W6. The W7 visit 
is the first eligible “IMP administration only” visit (refer to column “Weekly home or on-site visits until CRmin”), at home or on-site, if CR is achieved 
between W1 and W6. 
d Home visits are allowed once participants achieve CR, but not before W7. The investigator should call the participant every 2 weeks until CRmin is achieved to 
confirm the participant is still in CR. On-site visits may continue at the investigator’s discretion. 
e W38 (follow-up visit 2) is the end of the trial for participants who do not enroll in the OLE trial ARGX-113-1905. The W38 follow-up visit will only be 
required for those participants who were still receiving IMP at least once from W27 onward. For participants who ended treatment prior to W27, W34 will be 
the end of the trial. 
f Trial visit windows are ±2 days during the treatment period and ±3 days for follow-up visits. 


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g No trial-related assessments can be initiated before the participant has provided a signed ICF. 
h Only required if not available from medical history.
i Height and weight will be measured (and BMI will be calculated accordingly) at screening, at week W15 (or the next on-site visit if W15 does not coincide 
with an on-site visit), and EoS/ED. Weight will also be measured if there has been an obvious change since the last measurement. 
j At visits in which IMP is administered, the assessment or procedure should be completed before dosing. 
k A complete physical examination will be completed at each on-site visit. Vital sign measurements include systolic and diastolic blood pressure, heart rate, and 
body temperature. Supine blood pressure and heart rate will be measured using standard equipment after at least 10 minutes rest. 
l ECG to be taken at W12. If the W12 visit does not coincide with an on-site visit, then the assessment should be performed at the next on-site visit. ECG (heart 
rate, PR, QT, and QRS interval) will be read centrally. QTcF and QTcB will be calculated. 
m Randomization will take place on day 1 after all eligibility checks are confirmed (eg, PDAI) and before other baseline assessments are run, and prior to dosing. 
n Urinalysis will be performed by dipstick method and will include specific gravity, pH, protein, glucose, ketones, blood, bilirubin, urobilinogen, nitrite, 
leukocyte esterase, and microscopic examination (if blood or protein test results are abnormal). 
o Samples will be taken every week from V1(BL)/W1 to W9 and then every 4 weeks and at the visit where CR is observed. Once CR is achieved, samples will 
be taken every 4 weeks at on-site visits until EoS/ED. For participants achieving CR between V1(BL)/W1 and W6, samples will be taken weekly from W1 to 
W6 and then every 4 weeks at on-site visits until EoS/ED. 
p A urine pregnancy test will be conducted and analyzed locally during on-site visits at least once every 4 weeks (before and after CR) and at the time of CR. 
q Viral testing for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), hepatitis B core antibody (anti-HBc), hepatitis B virus (HBV) 
DNA, hepatitis C virus (HCV) antibodies, HCV messenger RNA (mRNA), and human immunodeficiency virus (HIV) antibodies. 
r At screening, a serum pregnancy test must be performed in women of childbearing potential or FSH test to confirm postmenopausal status. 
s Clinical blood laboratory tests will include hematology and blood chemistry at all visits and international normalized ratio (INR) or activated partial 
thromboplastin time (aPTT) at screening only. The hematology profile includes hemoglobin, hematocrit, mean corpuscular volume (MCV), RBC count, platelet 
count, WBC count with differential. The blood chemistry profile includes sodium, potassium, calcium, hemoglobin A1c (HbA1c), creatinine, creatinine 
clearance, blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, gamma-glutamyl transferase (GGT), 
C-reactive protein (CRP), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein 
cholesterol (HDL-C), total cholesterol, triglycerides, uric acid, total protein, and albumin. 
t For PK assessment, blood samples will be taken predose (within 2 hours before the start of IMP administration at visits where IMP is administered). An 
additional PK sample will be taken on D3 and on D11 (±1 day) until samples from 24 participants are obtained. At unscheduled visits blood samples for PK 
will only be taken if IMP is administered. 
u At screening, total IgG will be measured as part of inclusion and exclusion criteria. The pharmacodynamic (PD) biomarkers total IgG and its subtypes (IgG1, 
IgG2, IgG3, and IgG4) will be measured centrally from a blood sample taken predose. 
v An extra sample(s) will be taken for additional research (including vaccination antibodies and other additional research). The actual testing of vaccination 
antibodies depends on (a) whether a vaccination was given to the participant; (b) whether a test is available for the vaccination given to the participant; and (c) 
whether the sample requirements (serum, volume, frozen sample, storage duration) match the serum samples taken and reserved for this. Timepoints for 
analysis will be decided upon occurrence of vaccination during the study. 
w Anti-drug antibodies to efgartigimod (in serum samples) and antibodies against rHuPH20 (in plasma samples) will be tested predose every 2 weeks from 
V1(BL)/W1 to W9 and then every 4 weeks at on-site visits and at the visit where CR is observed. Once CR is achieved, samples will be taken every 4 weeks at 
on-site visits until EoS/ED. For participants achieving CR between V1(BL)/W1 and W6, samples will be taken predose at V1(BL)/W1, W3, W5, the visit 


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where CR is observed, W10, and then every 4 weeks at on-site visits until EoS/ED. Neutralizing antibodies (Nab) will be tested for all confirmed positive ADA 
samples. 
x Blood sampling for IgG autoantibody subtypes and specificity will be taken every 4 weeks (V1[BL]/W1, W5, W9, etc) and at the visit where CR is observed. 
Once CR is achieved, samples will be taken every 4 weeks at on-site visits until EoS/ED. For participants achieving CR between V1(BL)/W1 and W6, samples 
will be taken at V1(BL)/W1, W5, the visit where CR is observed, W10, and then every 4 weeks at on-site visits until EoS/ED. Serum aliquots from all time 
points will be used for IgG subtype and specificity analyses. For cytokines and complementary specificity analyses, aliquots from baseline, after 4 weeks (W5), 
W13 (or the visit at which CR is observed if before W13), and EoS/ED will be used. 
y Samples for B- and T-cell populations and RNA transcriptional profiles will be performed at baseline, after 4 weeks (W5) and at W13 (or the visit at which CR 
is observed if before W13) and at EoS/ED.
z HLA/non-HLA genotyping will be performed at baseline and D15.
aa Two 4 mm skin biopsies, 1 peri-lesional and 1 non-lesional, will be collected solely based on voluntary participation at baseline and after healing of 80% of 
blisters (EoC) or at EoS/ED (in case EoC has not been achieved) for scientific purposes. 
bb Pictures of different anatomical regions may be taken per judgment of the investigator. As a guidance, time points of baseline, DC, CR and flare are indicated. 
Pictures may also be taken at intermediate timepoints. 
ccQuestionnaires are to be completed prior to any other activity.
dd Assessments will be performed at baseline, after 4 weeks (W5), W15, and EoS/ED visits. If the W15 visit does not coincide with an on-site visit, then the 
assessment should be performed at the next on-site visit. 
ee The GTI assessment will be performed only at baseline, W15 and EoS/ED. If W15 does not coincide with an on-site visit, then the assessment should be 
performed at the next on-site visit. 
ff Participants will be trained to self-administer IMP (foreseen in the OLE trial; not in the ARGX-113-1904 trial) during the first 4 visits as of V3 when IMP is 
administered; thereafter, training for self-administration is optional (only if needed). 
gg IMP will be administered until CRmin. To ensure proper safety monitoring, participants should remain at the site for at least 1 hour after the first administration 
and for 15 minutes after subsequent administrations. Participants will be released according to their clinical status. For Germany-specific monitoring 
instructions, refer to Section 10.16.2.1. Participants who experience treatment failure, or flare after achieving CRmin, will be allowed to roll over into the OLE 
trial ARGX-113-1905 earlier than W31. Participants who do not roll over into trial ARGX-113-1905 will complete the treatment-free follow-up period. 
hhDisease assessment parameters include disease control (DC), end of consolidation (EoC), complete clinical remission (CR), complete remission on minimal 
therapy (CRmin), complete remission off therapy (CRoff), flare, and treatment failure. Participants who have achieved CR and have new lesions should come 
to the clinic for a UNS for disease assessment. 
ii Prednisone dose tapering will begin 2 weeks after achieving CR or 4 weeks after sustained EoC (thus, no new lesions have developed for a minimum of 6 
weeks and approximately 80% or more of lesions have healed). 
 
 


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2.
INTRODUCTION
The proposed trial is a prospective, multicenter, randomized, double-blinded, placebo-controlled 
trial to investigate the efficacy, safety, tolerability, immunogenicity, pharmacokinetics (PK), and 
pharmacodynamics (PD) of efgartigimod PH20 SC in adult participants aged from 18 years with 
moderate to severe pemphigus vulgaris (PV) or pemphigus foliaceus (PF). This trial intends to 
demonstrate that efgartigimod PH20 SC with an add-on therapy of low doses of oral prednisone 
is a possible treatment modality for PV and PF, the administration of which will lead to early 
disease remission at minimal prednisone dose. 
In order to allow for a convenient subcutaneous (SC) administration with efgartigimod to 
achieve the targeted exposure and PD effect, efgartigimod will be coformulated with 
recombinant human hyaluronidase PH20 (rHuPH20). This compound is being used in 
coformulations with approved therapeutic antibodies to facilitate SC administration with 
volumes >2 mL. The use of rHuPH20 in combination with other therapeutic proteins typically 
increases the absorption rate of these proteins, albeit to different extents. Increased rate of 
absorption of efgartigimod by rHuPH20 is expected to increase the overall exposure to 
efgartigimod after SC administration allowing administration of a SC dose in an acceptable 
volume and duration of administration that targets an exposure that results in a close to the 
maximal PD effect.  
China- and Germany-specific modifications to the protocol are outlined in Section 10.16 .  
2.1. 
Trial Rationale 
The mainstays of therapy in PV are systemic corticosteroids and rituximab. Corticosteroids also 
rapidly affect PV symptoms (3–4 weeks), but must be administered at high daily doses (eg, oral 
prednisone 1–1.5 mg/kg) to attain effectiveness. At such high doses, the well-known cumulative 
toxicities common to corticosteroid treatment occur frequently, and using short courses at the 
lowest possible dosage by tapering gradually while keeping the disease in remission is the 
therapeutic goal. Recently, rituximab, a monoclonal antibody binding the CD20 antigen on, and 
depleting, B-lymphocytes, has been approved in adults with moderate to severe PV. When 
administered as adjunctive treatment to a short course of prednisone, rituximab was shown to 
induce a higher rate of remission after 1 or 2 years, and a longer duration of remission than 
prednisone alone; however, administration of intravenous (IV) rituximab frequently results in 
infusion-related reactions (IRRs) and adverse events (AEs), which may be of late onset. The late 
onset of action of rituximab is well-documented in the literature: in a meta-analysis reviewing 
30 studies, it was shown that rituximab did not result in an early achievement of disease control 
(DC) (mean time from first infusion: 6–7 weeks1) or CRmin (mean of 6–7 months on minimal 
prednisone therapy, 9 months off-therapy1,2). Furthermore, rituximab therapy carries the risk of 
inducing serious adverse events (SAEs, eg, 33% of infections3). Late onset neutropenia and 
hypogammaglobulinemia and the risk for patients to develop potentially fatal infections (eg, 
Pneumocystis carinii, multifocal leukoencephalopathy, septicemia) require a long-term 
monitoring of the clinical and immunological status of the patients under rituximab.4 
Other therapies for PV are now classified as corticosteroid-sparing agents.5 They include 
immunosuppressants (azathioprine, mycophenolate mofetil, cyclophosphamide), intravenous 


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immunoglobulin (IVIg) and immunoadsorption. Among immunosuppressants, azathioprine and 
mycophenolate mofetil are preferentially used as first-line corticosteroid-sparing agents, whereas 
cyclophosphamide is more considered as a second-line adjuvant treatment.5 Because 
immunosuppressants have a delayed onset of action, they have no significant effect on DC,6 and 
their use as monotherapy is only conceivable in mild and stable cases when a delay in achieving 
DC can be tolerated. The most documented effects of immunosuppressants are a decrease in the 
occurrence of flares, by about 30% compared to prednisone alone,7 and a saving effect on the 
consumption of prednisone. There is evidence that azathioprine has a greater corticosteroid-
sparing effect.8 
Like corticosteroids and rituximab, the side effects of immunosuppressants are of clinical 
concern. They all may result in infections related to their broad immunosuppressive action. 
Azathioprine can cause potentially life-threatening bone marrow suppression, hepatitis, and is 
associated with increased risk of lymphoma. Assessment of methyltransferase activity of each 
individual before beginning azathioprine treatment is recommended, in order to prevent 
overdosage of the drug. The most frequent side effects of mycophenolate mofetil are 
gastrointestinal disturbance and hematologic disorders (lymphocytopenia). It is contraindicated 
in pregnant women and patients with renal insufficiency. Cyclophosphamide has an unfavorable 
safety profile and, for this reason, must be used as a second-line therapeutic option when 
immunosuppressants are indicated. Its main side effects include hemorrhagic cystitis, 
hematologic abnormalities, cancer, and infertility. 
Neonatal crystallized fragment receptor (FcRn) inhibition is the mode of action shared by IVIg 
and efgartigimod. IVIg is today the only therapy other than corticosteroids that has demonstrated 
to improve DC (4–8 weeks), indicating the short onset of action of the drug.9 It has been shown 
to also have a corticosteroid saving effect. Its use as a monotherapy has been reported in a few 
case series.10 Interestingly, IVIg has been tested in combination with rituximab (sequential 
administration of 3 weekly infusions of rituximab and then IVIg at week 4; 6 cycles in 
6 months11). Nine out of 11 patients reached complete remission as early as 8 to 11 weeks. 
Overall, IVIg is relatively safe to use. Its main side effects are hypertension, coagulation 
disorders, aseptic meningitis and renal insufficiency. However, it is an expensive blood-derived 
product that must be used at high dosage (2 g/kg monthly) to achieve its immunomodulatory 
effects. Furthermore, it is not approved for the treatment of PV and other autoimmune bullous 
dermatoses (AIBD). Consequently, the availability of IVIg remains limited, especially in 
countries that have implemented a strict control of its use. 
Immunoadsorption is a procedural treatment that consists of selectively removing the circulating 
immunoglobulin G (IgG) and pathogenic antibodies by extracorporeal adsorption from serum 
with protein A. Plasmapheresis is a less common alternative, involving plasma exchange using 
albumin and fresh frozen plasma. These treatments are only available in a few specialized 
centers, and thus are indicated in cases resistant or intolerant to other adjuvant therapies. When 
immunoadsorption is used, it is typically combined with immunosuppressants to prevent a 
rebound phenomenon, with a post-procedural rise in autoantibodies and transient lesion flare.12 
Otherwise, immunoadsorption treatment results in early DC in a majority of PV patients, ie, 4 to 
8 weeks.13 Its combination with rituximab has also been tried with success.14 Some procedure-
related side effects have been described, including infections at the central catheter site that 
appear to be more frequent in the PV population than in the autoimmune non-PV population.15 


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Non-mainstay adjuvant therapies of PV include methotrexate and ciclosporin as 
immunosuppressants, dapsone, and tetracyclines associated or not with niacinamide. Dapsone at 
high doses frequently induces side effects (hemolysis, hepatitis). Local therapies such as potent 
topical corticosteroids and topical antibiotics are often helpful to amend the mucosal and 
superinfected cutaneous lesions, respectively. 
Patients with PF typically follow the same type of management and monitoring of the clinical 
outcome measures as PV patients, although rituximab has not been labeled in the condition. 
Dapsone as initial treatment has been reported in mild cases, with a satisfactory outcome.16 
There is a need in pemphigus patients for a safer drug with a rapid onset of action and a 
favorable safety profile that would achieve early DC, be corticosteroid sparing, and achieve and 
maintain CR, with or without a low dose of corticosteroids. 
This trial intends to demonstrate that efgartigimod PH20 SC with an add-on therapy of low doses 
of oral prednisone is a possible treatment modality for PV and PF, the administration of which 
will lead to early disease remission at minimal prednisone dose. The efficacy, safety, patient 
outcome measures, tolerability, immunogenicity, PK, and PD of efgartigimod PH20 SC will be 
evaluated in patients with PV or PF. 
2.2. 
Background 
PV and PF (also called superficial pemphigus) are 2 close entities belonging to the heterogenous 
group of autoimmune skin blistering diseases, and clinically characterized by mucosal erosions 
(PV) and cutaneous blisters (PV and PF). PV is caused by IgG autoantibodies against the 
desmosomal proteins, desmoglein-3 (Dsg-3) and/or Dsg-1, on epidermal keratinocytes. Because 
the binding of the antibodies (which are predominantly of the IgG4 subtype and therefore do not 
activate complement) to the extracellular domain of Dsg is sufficient to cause loss of 
keratinocyte adhesion and blister formation, they generate directly the clinical manifestations of 
PV. Dsg-3 is expressed throughout the epidermis of the skin and the mucosa, whereas Dsg-1 
prevails in the superficial layer of the skin and is absent in the mucosa. Accordingly, mucosal PV 
lesions are mostly induced by anti-Dsg-3 antibodies, whereas cutaneous PV lesions are triggered 
by both anti-Dsg-3 and anti-Dsg-1 antibodies. Interestingly, disease activity has been shown to 
be closely correlated with serum levels of antibodies against Dsg-1 and, to a lesser extent, 
Dsg-3.17,18 PF is caused by antibodies against Dsg-1 that is expressed in the superficial layer of 
the epidermis and, therefore, involves the skin only. Two forms have been described: the non-
endemic form, and the endemic form (also called “fogo selvagem”). Fogo selvagem has been 
observed in the Amazonian region, where a non-infectious protein (LJM11) residing in the 
salivary glands of the sand fly (Lutzomyia longipalpis) was suggested to cause a cross-reaction 
with Dsg-1.19 Otherwise, endemic and non-endemic PF share the same clinical, histological and 
immunological findings. Like in PV, anti-Dsg-1 autoantibodies are directly pathogenic.  
Both PV and PF are rare. The incidence of PV is variable, with a higher frequency along the 
Mediterranean border. Its annual incidence ranges from 0.8 per million in Finland to around 1.5 
per million in France, 4 to 5 per million in Italy and up to 8 per million in Greece and even 16 
per million in Israel.20 It is sporadic and affects patients in their middle age, of both sexes. PF is 
even less common in North America and Europe (10%–15% of the pemphigus cases).  


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Both conditions are chronic and intractable, with a life-threatening potential. Clinically, PV 
presents as a mucosal-dominant, mucocutaneous or, less commonly, solely cutaneous type. 
Patients frequently shift from 1 type to another, typically from mucosal type at the beginning of 
the disease to become mucocutaneous later on. Mucocutaneous type tends to be a more severe 
disease, whereas diagnostic delay is common in the mucosal type. Although it may affect a wider 
range of age, its peak frequency ranges between 50 and 60 years of age. Women are slightly 
overrepresented in the PV population, in which the female-predominant thyroid diseases and 
rheumatoid arthritis are associated.21 Typically, lesions begin in the oral mucosa and might then 
extend to other mucosal areas and the skin. Mucosal involvement consists of flaccid blisters that 
rapidly rupture, leaving painful erosions. Mucosal lesions may also affect the pharynx, upper 
larynx, esophagus, nose and eyes, and genitals. They are usually associated with significant 
impairments, including difficulties of eating and swallowing, of having sexual intercourses, etc. 
They frequently lead to weight loss, malnutrition and alteration of QoL. Cutaneous lesions are 
featured by flaccid blisters and erosions that easily ooze and become superinfected (crusty 
lesions). Although any skin area may be involved, lesions predominate in the head, upper trunk 
and groin. They are painful, especially in the folds. At examination, the epidermis can be 
detached when the finger rubs the skin at the periphery of the lesions (Nikolsky sign), which is 
highly indicative of PV diagnosis. 
Diagnosis of PV follows an algorithm of different tools, which should be performed in the 
presence of clinical manifestations suggestive of the disease. They include histology, direct 
immunofluorescence (DIF), and the evidence of autoantibodies against Dsg-3 and/or Dsg-1 in 
serum either through indirect immunofluorescence (IIF) or enzyme-linked immunosorbent assay 
(ELISA) tests. Histopathology shows supra-basal acantholysis (keratinocytes floating in blister 
fluid). Acantholysis is highly suggestive of PV, as it is not seen in other autoimmune blistering 
diseases such as bullous pemphigoid (BP), but the diagnosis should be confirmed by the 
characteristic deposition of IgG and/or complement on the cell surface of keratinocytes by DIF. 
DIF is considered today as the gold standard investigation for diagnosis. However, IIF and/or 
ELISA are necessary to confirm the diagnosis. Commercial ELISA assays are available for 
quantitative measurement of Dsg-1 and Dsg-3 autoantibodies in serum. They potentially offer 
advantages over IIF, such as increased sensitivity (>90%), but are not helpful for excluding other 
self-antigens and AIBDs. Therefore, IIF and ELISA may be considered complementary in the 
diagnostic investigation of PV. Taken together, the international guidelines recommend making 
diagnosis of PV in patients with indicative clinical signs, confirmed by histopathology, positive 
DIF, and positive IIF and/or ELISA.22  
PV is a chronic disease, with no tendency of spontaneous improvement. On the contrary, the 
disease worsens progressively and has a mortality rate 3 times higher than in the general 
population when untreated.23 Under treatment, the disease usually evolves in periods of 
remission and flare. Eventually, it takes many years for achieving a definite cure. As treatments 
are part of the co-morbidity factors that are related to their high rate of serious side effects, the 
mortality is still high and severe infections remain today the main cause of death.5  
Because Dsg-1 is expressed in the superficial portion of the epidermis, PF patients present with 
itchy, scaly and crusted erosions of the cutaneous tissue. Blisters are uncommonly seen, owing to 
their superficial nature and easy rupture. Another clinical variant may be the development of 
squamous and crusty lesions on the face, scalp, chest and inter-scapular areas (“seborrheic 
pemphigus”). In more severe forms, desquamative erythroderma may be observed in almost all 


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of the skin surface. PF diagnosis follows the investigational tools that are used in PV. At 
histology, a cleft in the subcorneal or the superficial granular layer can be seen. DIF shows the 
intercellular deposition of IgG within the epidermis, and the IIF reveals the presence of serum 
autoantibodies against intercellular components of the skin. ELISA tests quantify the positive 
level of anti-Dsg-1 antibodies in serum, whereas the search for anti-Dsg-3 antibodies is negative. 
Like PV, PF does not tend to amend spontaneously. Treatment is always needed, with the aim at 
healing existing lesions and preventing the appearance of new lesions as soon as possible. 
Basic and clinical research has led to a better understanding of the mechanisms of pemphigus 
diseases and novel therapies have been developed. Nonetheless, long diagnostic delay and 
suboptimal treatment are important concerns in pemphigus diseases. As described above, a drug 
with a faster onset of action is needed so that quicker DC can be achieved in combination with 
low starting doses of corticosteroids (eg, prednisone at 0.5 mg/kg per day), and CR can be 
attained and maintained while the patient reaches rapidly minimal corticosteroid dose 
 
The therapeutic management of patients with pemphigus is very challenging. Its primary 
principles are to promptly stop the occurrence of new blisters and then achieve CR and to 
minimize the side effects of systemic corticosteroids. Corticosteroids have indeed a high 
cumulative toxicity in these chronic diseases, which must be mitigated by reducing their amount 
and duration of exposure as much as possible. Secondarily, the objective of the treatments is to 
prevent the development of new lesions either on minimal corticosteroid therapy, or even 
without any treatment. For this purpose, patients must be managed by referral centers, where 
they can be monitored carefully by experienced dermatologists. In many patients, a multi-
disciplinary approach is necessary, including specialists in oral medicine, ophthalmologists and 
gynecologists when mucosal lesions are present. To help the practitioners in the therapeutic 
management of pemphigus patients, consensual definitions of the most important clinical 
endpoints among national and international experts,24 as well as regular guidelines for the 
diagnosis and treatment of these diseases are available.2,10,25,26 In addition, validated scales for 
monitoring disease activity and extension (eg, Pemphigus Disease Area Index [PDAI], 
Autoimmune Bullous Skin Disorder Intensity Score [ABSIS]) have been established.27,28 The 
specific scale Autoimmune Bullous Disease Quality of Life (ABQOL) was developed and 
validated for ascertaining the impact of the disease and its therapies on patient’s daily life.29 
According to the most recent international guideline,22 corticosteroids remain a first-line therapy 
in pemphigus. They are the most rapidly acting treatment known today, ie, DC achieved in about 
3 weeks (no new lesions, established lesions starting to heal) when used at effective dose.30-32 
Oral prednisone is the most commonly used corticosteroid. The starting oral prednisone dose is 
high, ranging from 1–2 mg/kg daily, and may be reduced (0.5–1 mg/kg per day) if combined 
with rituximab or immunosuppressants. If DC is not achieved after 3–4 weeks at the latest, the 
prednisone dose must be increased. In patients with very active disease, an IV bolus of 
corticosteroids (eg, methylprednisolone) may be preferred, especially at treatment initiation.
Tapering of oral prednisone is initiated as soon as DC is achieved or up to the end of 
consolidation (EoC) phase. EoC is defined as the absence of new lesions for at least 2 weeks and 
approximately 80% of established lesions healed. The duration of the consolidation period varies 
greatly between patients, mucosal erosions and extensive cutaneous lesions tending to be late to 
heal. The goal of the EoC phase is to reach CR (no new lesions, all established lesions 


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completely healed) and, at the same time, reach a minimal effective dose of prednisone (10 mg 
per day or less for at least 2 months), or even stop prednisone (off therapy), in order to prevent 
side effects. Unfortunately, this double objective is hard to achieve, and a majority of patients 
flare under a tapered dose of prednisone. In a prospective study, 64% of PV patients with 
prednisone could achieve a first complete remission on minimal dose after 12 months.33 Flare 
occurred frequently, ie, in 45% of the cases within 6 months. Finally, the common course of PV 
is 1 of episodes of flare and transient remission, and it takes several years of prednisone 
treatment before achieving permanent remission. In 1 study, 36% of patients with PV were 
treated with prednisone or equivalent for at least 10 years.34 Meanwhile, the risk of 
corticosteroid-related side effects increased with treatment duration (osteoporosis, diabetes, 
hypertension, Cushing syndrome, cataract, glaucoma, infections, etc).35 Accordingly, most PV 
patients need adjuvant therapies (eg, rituximab, immunosuppressants) to maintain them under 
remission and reduce the cumulative prednisone dose. 
The recent approval of rituximab in PV adults has dramatically changed the mainstay of therapy 
of the disease, and is now approved as a first-line therapy in association with prednisone for 
moderate and severe cases. Rituximab was primarily used in refractory PV patients, who do not 
respond well to other treatments. However, the lack of long-lasting remission and great number 
of SAEs associated with prednisone and immunosuppressants has led researchers to develop 
alternative first-line treatments. Rituximab as second-line and third-line treatment (1–2 g per 
cycle) was shown to a induce long-term remission at a high rate, which could not be achieved by 
any other treatment (75% remission rate in PV after 1 year25). Flare rates after rituximab therapy 
ranged between 25% after 1 year up to 80% in long-term follow-up. Recent evidence has shown 
the efficacy of a first cycle of rituximab (2 g) as first-line treatment followed by new cycles 
(0.5 g) after 12 months and 18 months, in combination with lower doses of prednisone 
(0.5-1 mg/kg per day according to disease severity2). Using this first-line regimen, a higher 
proportion of complete remission after 2 years, ie, 89%, was demonstrated. Flare cases were 
observed to be also lower (24% after 2 years), a majority occurring within 6 to 12 months after 
the first cycle. A strong prednisone sparing effect, ie, by about two-thirds, was demonstrated. 
2.3. 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks of both efgartigimod 
and rHuPH20 may be found in the latest issue of the respective Investigator’s Brochures (IBs). 
2.3.1. 
Risk Assessment 
In clinical studies to date, efgartigimod has been well-tolerated in healthy adult subjects and 
patients with pemphigus, myasthenia gravis (MG), and primary immune thrombocytopenia 
(ITP). The majority of treatment-emergent adverse events (TEAEs) were considered to be mild 
(grade 1) in severity.  
In the phase 2 study ARGX-113-1701 in participants with pemphigus, 5 severe (grade 3) TEAEs 
were reported, 3 of which were assessed as not related to the drug (Syncope, Pneumonia, and 
Tibia fracture) and the remaining 2 TEAEs of Tooth infection and Blood creatine phosphokinase 
(CPK) increased were assessed by the investigator to be possibly related to the IMP. Out of these 
5 severe TEAEs, no action was taken on the drug dose for 3 participants; drug was withdrawn 
from the participant who reported non-related grade 3 Pneumonia; and the dose was interrupted 


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for the participant who reported possibly related blood CPK increase. The most commonly
reported TEAEs were Nasopharyngitis, Diarrhea, and Headache, reported in 4 (11.8%) 
participants each. The most frequently reported treatment-related TEAE was Influenza-like 
illness, which occurred in 3 (8.8%) participants in total.  
In the phase 2 trial ARGX-113-
eported 
and no TEAE led to discontinuation from treatment or from the study. The most common TEAE 
was Headache, reported in 4 of 12 participants (33%) treated with efgartigimod 10 mg/kg and 3 
of 12 participants (25%) who received placebo. Additionally, in a randomized, double-blinded, 
placebo-controlled, phase 3 trial in participants with MG (ARGX-113-1704), 65 (77.4%) 
participants in the efgartigimod group and 70 (84.3%) participants in the placebo group reported 
e severity. TEAEs of grade 3 or 4 severity were 
reported with similar frequencies (efgartigimod: 9 [10.7%] participants; placebo: 8 [9.6%] 
participants). Treatment-emergent SAEs were reported in 4 (4.8%) participants in the 
efgartigimod and 7 (8.4%) participants in the placebo group. No deaths occurred during the 
study. TEAEs that led to discontinuation of IMP were reported in 3 (3.6%) participants in each 
treatment group.
In the phase 2 trial ARGX-113-1603 in participants with ITP, 1 TEAE of Thrombocytopenia 
grade 4 was reported, which was considered unrelated to treatment, but led to treatment 
discontinuation. Injection site haematoma was the most commonly reported TEAE, reported in 3 
of 13 participants (23.1%) in the efgartigimod 5 mg/kg group and in 2 of 13 participants (15.4%) 
in the efgartigimod 10 mg/kg group. Headache was reported in 1 of 13 participants (7.7%) 
treated with efgartigimod 5 mg/kg and 2 of 12 participants (16.7%) who received placebo. 
The only clinically relevant laboratory findings, observed after repeated administration of 
efgartigimod 10 mg/kg, were Decreased monocyte count (reported for 1 participant with MG) 
and abnormal differential white blood cell count in individual healthy subjects after 
administration of a single dose of 25 and 50 mg/kg efgartigimod, which was associated with 
decreased CD8, CD3, CD56, CD4, and CD19 lymphocyte levels. All events were short-lasting 
and resolved within 2 to 4 days. An increase in C-reactive protein was reported in individual 
healthy subjects administered a single dose of 25 and 50 mg/kg efgartigimod. All events resolved 
within 3 to 6 days and were in general not associated with signs of fever or serious infections.
In nonclinical toxicology trials repeated administration of 100 mg/kg (15 infusions, every 2 days) 
efgartigimod was associated with reversible Kupffer cell hypertrophy/hyperplasia in rat, as well 
as hepatic cytoplasmic alterations and degeneration, and diffuse mixed inflammatory cell 
infiltrates (correlating with alanine aminotransferase [ALT] increase) in cynomolgus monkey. 
The former most likely relates to a reaction to the foreign protein in the rodent and the latter 
could be linked to endotoxins that were present in the test article batch used for the study. No 
such observations were made in a 6-month chronic dosing trial where cynomolgus monkeys 
were administered 100 mg/kg efgartigimod IV once a week. In healthy subjects or patients with 
MG or ITP, no clinically significant changes were observed in liver enzyme levels (including 
ALT and aspartate aminotransferase), serum lipids, or electrolytes (including potassium). 
No clinically significant changes in vital signs and/or electrocardiogram (ECG) findings have 
been observed in clinical trials to date.


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Safety for use during pregnancy has not been established. Therefore, efgartigimod should not be 
administered to pregnant or lactating women. However, reproductive toxicity studies in rats and 
rabbits showed that efgartigimod elicited no signs of maternal toxicity or teratogenic effects up 
to the high IV dose of 100 mg/kg/day and did not adversely affect male and female fertility, or 
the reproductive and developmental performance in rats following repeated IV injections at 
100 mg/kg/day.
rHuPH20, used in both the efgartigimod and placebo preparations, is a permeation (diffusion) 
enhancer with a well-characterized nonclinical and clinical safety profile that allows the rapid 
delivery of large volumes of fluid and/or co-administered drugs subcutaneously. In clinical 
studies, the SC administration of rHuPH20 in combination with other substances was well-
tolerated. Most AEs were mild, transient Injection site reactions, including erythema, pain, 
bruising, pruritus, burning, tenderness, edema, induration, irritation, paresthesia, numbness, and 
rash. Moderate Injection site reactions, which have occurred less frequently, include burning, 
erythema, pain, and numbness. Mild-to-moderate Headache was also commonly reported. Many 
AEs in these trials were related to the co-administered drug or have been associated with the 
rapid introduction of a relatively large volume of fluid in the subcutaneous space. rHuPH20 is 
coformulated or coadministered with several products in the US and EU (eg, Herceptin® SC, 
MabThera® SC, HyQvia®, and Darzalex Faspro™).  
In the phase 1 trial ARGX-113-1901, overall, single-dose SC administration of 750 mg, 
1250 mg, 1750 mg, or 10 mg/kg efgartigimod co-mixed with 2000 U/mL rHuPH20 was 
well-tolerated by all subjects. No deaths, SAEs, or TEAEs leading to discontinuation were 
reported. The most frequently reported TEAEs were Injection site reactions, most of which were 
considered related to the IMP. A total of 27 TEAEs reported in 20 (60.6%) subjects were 
considered by the investigator to be related to the IMP. All related TEAEs were reported as mild 
in severity, except for 1 related TEAE (Injection site erythema) that was reported as moderate in 
severity. Dose-related effects were observed. All subjects recovered from their TEAEs by the 
end of the study, except for 1 subject who experienced a TEAE of Dizziness. There were no 
clinically relevant findings with respect to clinical laboratory, vital signs, ECGs, or full-body 
physical examination. Targeted physical examination showed that a total of 19 subjects (57.6%) 
had 1 or more abnormalities at the injection site (including erythema, bruising, pain, 
discoloration, pruritus, swelling, and Hematoma), which were reported as TEAEs. The 
percentage of subjects with 1 or more abnormalities at the injection site appeared to increase 
with increasing SC doses of efgartigimod co-mixed with rHuPH20. 
2.3.2. 
Benefit Assessment 
Efgartigimod has been shown to effectively reduce IgG antibodies and improve clinical 
outcomes in several clinical trials, including healthy subjects, participants with pemphigus, MG, 
and ITP. 
In the phase 2 trial ARGX-113-1701 in participants with pemphigus, the efficacy of efgartigimod 
was supported by PD effects (effects on IgG, anti-Dsg-1 and -3 autoantibodies) and the effects 
on the clinical activity (PDAI) and clinical outcomes of the disease (DC and CR). The drug had a 
fast onset of action by sharply reducing the serum levels of autoantibodies. Autoantibody 
reduction was correlated with a rapid decrease of the disease activity (PDAI), and was associated 
with an early achievement of DC and CR. Participants were able to achieve DC with or without 


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concomitant prednisone, whereas CR was achieved in combination with low prednisone dose. 
Flare was prevented when efgartigimod was given at weekly intervals, before and after DC or 
CR.  
In December 2021, the FDA approved efgartigimod for the treatment of generalized myasthenia 
gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody 
seropositive. In the phase 2 trial (ARGX-113-1602) of participants with gMG, 4 weekly IV 
infusions of 10 mg/kg efgartigimod led to statistically significant improvements in clinical scales 
and were well-tolerated.36 Additionally, in a randomized, double-blinded, placebo-controlled, 
phase 3 trial in participants with gMG (ARGX-113-1704), the primary endpoint of the 
percentage of acetylcholine receptor–antibody (AChR-Ab) seropositive participants who after 
the first tr
 points on the Myasthenia Gravis Activities of Daily 
Living (MG-
-point reduction observed no later than 1 week after the last IMP infusion was met. 
Participants who met this criterion were considered MG-ADL responders. In the AChR-Ab 
seropositive population, there was a statistically significantly higher proportion of MG-ADL 
responders in the efgartigimod group (67.7%) than in the placebo group (29.7%) (p<0.001; 
logistic regression, 2-sided exact p-value) in cycle 1.  
In the phase 2 trial (ARGX-113-1603) in participants with ITP, efgartigimod resulted in a rapid 
and marked reduction of IgG antibodies (maximum mean reduction of 65%) and of all IgG 
subtypes.37 Additionally, efgartigimod was associated with an increase in platelet counts in more 
participants than occurred in the placebo group, with greater numerical separation from placebo 
as the platelet count threshold stringency was increased. Additional post hoc analyses further 
supported these observations, showing a longer duration of clinically meaningful effect and 
statistically significantly more active-
9/L 
for more than 10 cumulative days compared to the placebo group. 
Efgartigimod is under investigation in an ongoing phase 2 trial (ARGX-113-1802) in participants 
with chronic inflammatory demyelinating polyneuropathy (CIDP) using efgartigimod PH20 SC, 
which uses the same formulation used in the current trial in pemphigus participants.
2.3.3.
Overall Benefit: Risk Conclusion
Taking into account the efficacy and safety data collected up to date, the benefit-risk assessment 
supports further testing of efgartigimod PH20 SC in pemphigus. 
 
 


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3.
OBJECTIVES AND ENDPOINTS
The objectives and endpoints are applicable globally, except for IgG subtypes and exploratory 
objectives/endpoints which are not assessed in China. 
Objectives 
Endpoints 
Primary 
 
To demonstrate the efficacy of efgartigimod 
PH20 SC compared to placebo in the 
treatment of participants with PV 
 
Proportion of PV participants who achieve 
CRmin within 30 weeks 
Secondary
 
To demonstrate the efficacy of efgartigimod 
PH20 SC in the treatment of participants 
with PV or PF
Key Secondary Endpoints 
 
Proportion of PV and PF participants who 
achieve CRmin within 30 weeks 
 
Cumulative prednisone dose over the trial in 
PV participants 
 
Time to CR in PV participants 
 
Time to DC in PV participants 
Other Secondary Endpoints 
 
Proportion of PF participants who achieve 
CRmin within 30 weeks 
 
Cumulative prednisone dose over the trial in 
PV and PF participants 
 
Time to CR in PV and PF participants 
 
Time to DC in PV and PF participants 
 
Rate of treatment failure 
 
Rate of flare 
 
PDAI at each visit 
 
To assess the safety of efgartigimod PH20 
SC in participants with PV or PF
 
Incidence and severity of TEAEs, adverse 
events of special interest (AESIs), and SAEs 
by system organ class (SOC) and preferred 
term (PT) 
 
Vital signs, physical examination, ECG, and 
clinical laboratory safety evaluations 
 
To assess the health impact of 
glucocorticoid (GC) use in participants with 
PV or PF 
 
Composite Glucocorticoid Toxicity Index 
(C-GTI) comprising the Aggregate 
Improvement Score (AIS) and the 
Cumulative Worsening Score (CWS) 
 
To evaluate the effects of efgartigimod 
PH20 SC on quality of life (QoL) in 
participants with PV or PF 
 
EuroQol 5-Dimension 5-Level (EQ-5D-5L) 
Scale 
 
ABQOL score 
 
To evaluate the PK of efgartigimod PH20 
SC in participants with PV or PF 
 
Efgartigimod serum concentrations 


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To evaluate the PD of efgartigimod PH20 
SC in participants with PV or PF 
 
Total IgG and subtype (IgG1, IgG2, IgG3, 
IgG4) serum levels 
 
Anti-Dsg-1 and -3 autoantibodies serum 
levels 
 
To evaluate the immunogenicity of 
efgartigimod PH20 SC in participants with 
PV or PF 
 
Incidence and prevalence of anti-drug 
antibodies (ADAs) against efgartigimod and 
antibodies against recombinant human 
hyaluronidase (rHuPH20) 
 To evaluate the competency of 
participants or caregivers to self-
administer efgartigimod PH20 SC 
Number and percentage of participants or 
caregivers completing the self-
administration training  
 
Number and percentage of participants or 
caregivers determined by the site staff to be 
sufficiently competent to self-administer 
efgartigimod PH20 SC  
 
Number and percentage of participants or 
caregivers that self-administer efgartigimod 
PH20 SC under site staff supervision 
Exploratory  
 
To evaluate the disease-specific genetic 
background and effects of efgartigimod 
PH20 SC on the serological and 
immunological profiles of participants with 
PV or PF 
 
Anti-Dsg-1 and -3 autoantibody subtypes 
and autoantibody reactivity to Dsg domains 
and other antigens  
 
Lymphocyte dynamic changes 
 
Serum cytokines profiles 
 
DNA and RNA genetic profiles
 
To evaluate the effects of efgartigimod 
PH20 SC on markers of pemphigus 
pathology in skin of participants with PV or 
PF 
 
Markers of pemphigus pathology in lesional 
and non-lesional skin 


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4.
TRIAL DESIGN
4.1. 
Overall Design 
This is a prospective, multicenter, randomized, double-blinded, placebo-controlled trial to 
investigate the efficacy, safety, patient outcome measures, tolerability, immunogenicity, PK, and 
PD of efgartigimod PH20 SC in adult participants aged from 18 years with PV or PF. See 
Section 1.2 for a diagram of the trial design. Enrolled participants are those who are either newly 
diagnosed or experiencing flare as follows: 
 
treatment. 
 Moderate to severe (PDAI activity scor
course of oral prednisone (or equivalent). According to clinical judgment, the 
participant has shown no significant improvement of PV or PF signs for at least 
2 weeks before baseline and is considered fit to start prednisone treatment at 
0.5 mg/kg daily (qd) at baseline. 
 
therapy ± a conventional immunosuppressant (eg, azathioprine, cyclophosphamide, 
methotrexate, mycophenolate mofetil) or dapsone. Note: conventional 
immunosuppressants and dapsone must be discontinued before baseline. 
 
tapered dose of oral prednisone (or equivalent), provided that prednisone (or 
equivalent) has been given at stable dose ± a conventional immunosuppressant (eg, 
azathioprine, cyclophosphamide, methotrexate, mycophenolate mofetil) or dapsone 
and participants are fit to start prednisone treatment at 0.5 mg/kg qd at baseline. Note: 
conventional immunosuppressants and dapsone must be discontinued before baseline. 
The trial comprises a screening period of up to 3 weeks, a treatment period of up to 30 weeks, 
and an 8-week follow-up period for participants who do not enroll into the OLE trial 
ARGX 113-1905. 
After confirmation of eligibility, participants will be randomized in a 2:1 ratio to receive 
efgartigimod PH20 SC or placebo, as follows: 
Efgartigimod PH20 SC will be administered by SC injection on day 1 and day 8 at a 
dose of 
mg, followed by weekly SC administrations of 1000 mg until CRmin is 
observed. Efgartigimod PH20 SC will be administered at on-site visits until CR. After 
achieving CR, efgartigimod PH20 SC will be administered at on-site visits or at home 
by a nurse until CRmin is achieved. 
 Placebo (vehicle with 2000 U/mL of rHuPH20) SC will be administered using the 
same regimen. 


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All participants or their caregivers will be invited to receive training for future 
self-administration of IMP in the OLE trial ARGX-113-1905. The caregiver is a person of legal 
age that the participant proposes to perform the administrations. If the participants or caregivers 
have successfully completed self-administration training to the satisfaction of authorized staff, 
then the participants or caregivers may self-administer the next injections at the site under 
supervision of authorized staff. 
CR is defined as the absence of new lesions and complete healing of established lesions (except 
for post-inflammatory hyperpigmentation or erythema from resolving lesions). CR on minimal 
therapy (CRmin) is defined as the absence of new lesions and complete healing of established 
2 months (8 weeks). In non-Japanese participants, randomization will be stratified by disease 
status (experiencing flare and newly diagnosed), disease severity (PDAI activity score <30 and 
with 
population.  
All participants, regardless of treatment assignment, will concomitantly receive oral prednisone 
(or equivalent such as prednisolone) at 0.5 mg/kg qd starting dose. Except for oral prednisone (or 
equivalent), no other systemic therapies (eg, immunosuppressants, IVIg, immunoadsorption, 
anti-CD20 biologics) will be permitted during the trial.  
Participants will visit the clinic weekly until CR and for a minimum of 6 weeks to receive IMP 
and be evaluated for disease activity and disease outcome. After CR, IMP will be administered 
weekly at on-site or at home visits by a nurse until CRmin. At any post-baseline visit before DC 
is achieved, the prednisone dose will be adjusted by incrementing dosage according to clinical 
judgment, with the recommendation to increase by 1 or more steps (refer to Table 3) in case of 
disease progression or insufficient clinical change. To facilitate common judgments among 
investigators, recommendations for assessment of disease progression and insufficient clinical 
change are:  
 Disease progression: increase of at least 5 in PDAI activity score compared to 
baseline score, observed at any post-baseline visit before DC. 
 Insufficient clinical change: absence of DC after 3 to 4 weeks of the participant being 
treated at the starting baseline prednisone (or equivalent) dose or after 3 to 4 weeks of 
any new incremented dose of prednisone. 
The recommendations of the prednisone dose escalation are: 
 Stepwise escalation of prednisone dose by 1 or more steps according to clinical 
judgment in case of disease progression. 
 Adjustment by incrementing dosage by 1 step in case of insufficient clinical change.
 Possible further escalation from the previous step by 1 or more steps, according to 
clinical judgment and under the same recommendation as above. 
 Maximum escalation to 1.5 mg/kg qd for 3 weeks. 
If, after a minimum of 3 weeks of oral prednisone at 1.5 mg/kg qd, DC is not attained, then the 
participant will be considered a treatment failure. 


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For participants achieving DC with a daily prednisone dose of 0.5 mg/kg, prednisone will be 
maintained at 0.5 mg/kg qd until CR and 2 weeks thereafter, or until EoC (defined as the time at 
which no new lesions have developed for a minimum of 2 weeks and approximately 80% of 
lesions have healed) and 4 weeks thereafter, after which tapering will be initiated. For 
participants achieving DC with an escalated prednisone dose (ie, >0.5 mg/kg qd), the prednisone 
dose will be maintained until 2 weeks after achieving DC, then tapering will be performed 
according to the following stepwise procedure: dose reductions by 0.25 mg/kg qd (according to 
Table 3) every 2 weeks until the starting dose is reached (ie, 0.5 mg/kg qd). Then the starting 
dose (0.5 mg/kg qd) will be maintained until a sustained CR is achieved for 2 weeks, after which 
further tapering will be initiated, or prednisone tapering below 0.5 mg/kg qd may be initiated in 
case of sustained EoC for at least 4 weeks. Further tapering will be performed thereafter, as long 
as CR or EoC are sustained. The rules for tapering are shown in Table 3. Each new tapered 
prednisone dose until 20 mg/day must be maintained for 2 weeks. Then, the prednisone dose is 
further tapered by 2.5 mg/day per week. When 10 mg/day is reached, this dose level will be 
maintained until CRmin has been achieved. Prednisone can then be further tapered upon clinical 
judgment by the investigator.  
In case of flare in the period between DC and CRmin, the prednisone dose will be increased. A 
flare is defined by the appearance of 3 or more new lesions in a 4-week period that do not heal 
spontaneously within 1 week, or by the extension of established lesions in a participant who had 
achieved DC. If the flare occurs after CR and IMP was administered at home by a nurse, the 
participant will resume weekly on-site visits until he/she achieves CR again. Participants who are 
not controlled by a prednisone dose that is 2 dose levels above the dose at which the flare 
between DC and CRmin is observed and that is at least 0.3 mg/kg/day (eg, according to Table 3) 
will be considered treatment failures. At visits when at least 1 new lesion is observed or 
established lesions remain extensive without being defined as a flare, the prednisone dose will be 
maintained or may be increased, according to clinical judgment. If the lesion resolves, tapering 
of the prednisone dose will be pursued as planned.  
Participants who experience treatment failure, or flare after achieving CRmin, will be allowed to 
roll over into the OLE trial ARGX-113-1905 earlier than W31. Participants who do not roll over 
into the OLE trial ARGX-113-1905 will complete the treatment-free follow-up period. 
Participants experiencing an SAE related to prednisone may also benefit from an early roll over 
to the OLE trial, according to clinical judgment. 
Trial procedures will be performed per the SoA as detailed in Section 1.3.  
4.2. 
Scientific Rationale for Trial Design 
Concomitant therapy of oral prednisone at a starting dose level of 0.5 mg/kg per day: The 
active treatment (efgartigimod PH20 SC) will be used in association with oral prednisone (or 
prednisolone as prednisone equivalent) at the starting dose of 0.5 mg/kg per day, because results 
of the phase 2 study ARGX-113-1701 showed that CR was achieved best in combination with 
prednisone at doses ranging from 0.25 to 0.5 mg/kg per day. Taking into account that the 
proposed trial plans to include participants of higher disease severity (moderate to severe, instead 
of mild-to-moderate in phase 2), a concomitant prednisone dose of 0.5 mg/kg per day has been 
chosen as a starting dose, with an active stepwise tapering schedule initiated when CR is 
achieved (Section 6.8.1).  


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Prednisone dose escalation for achieving DC: Disease activity varies among pemphigus 
participants. In addition, oral prednisone doses as part of standard of care ranges from 1.0–1.5 
mg/kg per day. Rapid dose adjustment by incremental doses of prednisone is therefore allowed 
to achieve DC (Section 6.8.1). This approach is taken to allow for timely DC and therefore 
avoiding participants with uncontrolled disease symptoms dropping out of the trial early.   
Dose escalation guidance is based on disease progression or insufficient clinical change before 
DC happens or flare. Whereas flare is well-defined by guidelines (appearance of 3 or more new 
lesions a month that do not heal within 1 week, or extension of established lesions), disease 
progression and insufficient clinical change are not defined by consensus. Accordingly, the trial 
protocol specifies that the assessment of these conditions will be based on clinical judgment. In 
order to facilitate some common judgments between investigators, recommendations for 
assessment of disease progression and insufficient clinical change are:   
 For disease progression, an increase in the active PDAI activity score of at least 5 
compared to baseline or the preceding visit, as observed at any post-baseline visit 
before DC  
 For insufficient clinical change, the absence of DC for 3 to 4 weeks after baseline or 
after a new incremented dose of prednisone.   
Treatment failure: Prednisone dose escalation in the trial will happen in a stepwise approach 
(from 0.5 to 0.75, 1, 1.25 and 1.5 mg/kg per day), investigators being able to increase the dose by 
1 or more steps according to the severity of the disease progression. The prednisone dose of 
1.5 mg/kg per day for 3 weeks without DC defines treatment failure, in accordance with the 
guidelines.24 In such circumstances, participants will be considered as nonresponders and will be 
invited to roll over prematurely into the OLE (trial ARGX-113-1905). Additionally, flare 
between DC and CRmin that is not controlled by a prednisone dose that is 2 dose levels above 
the dose at which the flare is observed and that is of at least 0.3 mg/kg qd (refer to Table 3) or 
the occurrence of an SAE considered related to prednisone by the investigator will be defined as 
treatment failure. 
Prednisone tapering: Two weeks after DC is achieved after an escalated prednisone dose above 
0.5 mg/kg qd, prednisone tapering will begin (Section 6.8.1). Prednisone tapering is a procedure 
that is applied by all practitioners, in order to minimize the side effects of corticosteroids while 
preventing a flare of the disease. In this trial:  
 Two-week intervals between tapering are defined with a step down of 0.25 mg/kg 
from 1.5 to 0.5 mg/kg per day (eg, from 1.5 to 1.25 mg/kg per day, then to 1 mg/kg 
and 0.75 mg/kg per day; refer to Table 3). The dosage of prednisone at which CR is 
achieved (which cannot be lower than the starting dose 0.5 mg/kg per day) will be 
maintained for 2 weeks after CR for observing a sustained CR, or prednisone tapering 
may be initiated or continued in case of sustained EoC (defined by the time at which 
no new lesions have developed for a minimum of 2 weeks and approximately 80% of 
lesions have healed) for at least 4 weeks.  
When CR is observed on daily prednisone of no lower than 0.5 mg/kg for 2 weeks, or 
when sustained EoC is observed, tapering may be initiated (see Section 6.8.1). Each 
new tapered prednisone dose until 20 mg/day must be maintained for 2 weeks. Then, 


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the prednisone dose is further tapered by 2.5 mg/day per week. When 10 mg/day is 
reached, this dose level will be maintained until CRmin has been achieved.  
When CRmin is achieved, prednisone can be tapered further upon clinical judgment, 
with the recommendation of a prednisone decrease by 2.5 mg/day every 4 weeks. 
When transient lesions appear, prednisone tapering will be temporarily delayed, or prednisone 
may be increased according to clinical judgment. Dose escalation will be performed when flare 
occurs. Taken together, the trial aims to be as close as possible to the real-world clinical practice 
regarding the prednisone regimen policy, while it allows studying the potential of prednisone 
sparing when associated with efgartigimod PH20 SC treatment.  
Definitions of clinical outcomes: Consensual definitions of the most important clinical 
outcomes have been established through international guidelines24, and are now accepted by the 
vast majority of clinicians taking care of participants with PV and PF. They include in particular 
DC (no new lesions and established lesions beginning to heal), which corresponds to the 
beginning of the healing, and CR (no new lesions and established lesions completely healed), 
which is the end of the healing. The international guidelines recommend assessing CR in the 
light of the concomitant therapy status by corticosteroids, eg, achievement of CR associated with 
 this is more clinically 
meaningful than CR itself. Rollover to the OLE trial will occur at W31 or earlier in case of 
treatment failure or flare after CRmin.  
Flare is defined in international guidelines as the appearance of 3 or more new lesions in a 4 
week period that do not heal spontaneously within 1 week, or the extension of established lesions 
in a participant who had achieved DC. The appearance of new lesions that do not qualify as flare 
will be recorded as new transient or new persistent lesions. Transient new lesions are defined as 
new lesions that heal within 1 week. Persistent new lesions are defined as new lesions that last 
more than 1 week. As nonspecific lesions frequently occur in participants with pemphigus, it will 
be the duty of the investigators to confirm the nature of new pemphigus lesions through a 
physical examination during the visits. A historical report of new lesions by participants will not 
be evidence of a diagnosis of transient lesions or flare of pemphigus unless deemed indicative of 
pemphigus by the investigator. 
Proportion of participants who achieve CRmin within 30 weeks as primary endpoint and 
treatment duration of 30 weeks: A trial duration of 30 weeks was selected based on results 
from the phase 2 trial ARGX-113-1701 in participants with pemphigus for encompassing the 
observation of the primary endpoint of CRmin in the majority of participants belonging to the 
active group. The time point at which CRmin is anticipated to be achieved for most participants 
varies between 24 and 30 weeks in participants under active treatment and depends on the body 
weight of the participants. Accounting for this variation between participants, all participants 
having achieved CRmin within the 30 weeks of the trial will be considered in the primary 
endpoint as responsive to treatment.
Tailored regimen of efgartigimod PH20 SC and rollover to the OLE: The trial comprises a 
screening period of up to 3 weeks, a treatment period until CRmin of up to 30 weeks, and an 
8-week follow-up period for participants who do not enroll into the OLE trial ARGX-113-1905. 
A tailored efgartigimod PH20 SC regimen is proposed due to its rapid effect and the variability 
of disease activity between participants. Participants will be administered the efgartigimod PH20 


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SC with concomitant low dose prednisone regimen subcutaneously until CRmin is achieved. 
Then, efgartigimod PH20 SC administration will be stopped, whereas the concomitant treatment 
by prednisone will be pursued with the option for further tapering to achieve CR off therapy 
(CRoff).   
4.3. 
Justification for Dose 
SC administration is highly preferred over an IV formulation for pemphigus patients in view of 
the expected need for prolonged weekly administration. Therefore, efgartigimod with rHuPH20 
will be administered SC each week for a maximum of 30 weeks in this trial. To achieve a fast PD 
effect and clinical response a dose of 
 mg will be administered in the first 2 weeks, followed 
by weekly doses of 1000 mg to maintain the PD effect and related clinical response. 
Active pemphigus is seen by most clinicians as a disease that requires urgent control. Signs of 
activity include the extension of the lesions (eg, mucosal lesions becoming mucocutaneous in 
PV) and the sharp increase in anti-Dsg serum levels. In such circumstances, respiratory 
infections related to lesions of the mouth or throat as well as skin infections are frequent. 
Infections are today the first cause of mortality in pemphigus. The exposure to non-targeted 
immunosuppressive therapies such as high doses of corticosteroids and immunosuppressants is a 
co-morbidity factor.5 
Trial ARGX-113-1701 showed that IV administration of efgartigimod resulted in a rapid DC 
with or without associated prednisone, as well as CR associated with low to intermediate 
prednisone doses (0.25 to 0.5 mg/kg per day).  
In view of the severity of the disease a fast onset of action is desirable. Therefore, the proposed 
dose regimen for this trial starts with a dose that achieves close to maximal IgG reduction within 
2 weeks with a goal to reduce the time to a clinically relevant improvement. Subsequently, a 
lower weekly dose is expected to maintain improvement in this patient population. 
As pathogenic IgGs are key to the pathophysiology of pemphigus, the selected doses and dose 
regimen target a nearly maximal PD effect (ie, reduction of pathogenic IgGs). Considering the 
chronic nature of pemphigus, where patients are typically treated chronically for years with 
corticosteroids or immunosuppressants, the dosing regimen of a weekly regimen, reflects the 
need for chronic treatment to keep suppressing pathogenic IgGs. 
Results of the phase 1 trial in healthy subjects, the phase 2 studies in participants with MG, ITP, 
and pemphigus, and PK/PD modeling analysis, indicate that a dose of 10 mg/kg efgartigimod, 
administered weekly (q7d) through IV infusion achieved close to maximal IgG reduction, 
resulted in a reduction of pathogenic autoantibodies, and was associated with clinical efficacy in 
participants with MG, ITP, and pemphigus. Furthermore, this dose was considered safe and 
well-tolerated in all populations. The PK and PD profile of efgartigimod appeared to be similar 
in all investigated populations so far. Therefore, a flat SC dose resulting in a similar PD effect as 
achieved with 10 mg/kg weekly IV administration is targeted as a maintenance dose for 
participants with pemphigus.
PK and PD data from trial ARGX-113-1901, which investigated different efgartigimod PH20 SC 
doses, were used for a population PK/PD analysis to find an efgartigimod PH20 SC dose that 
results in a similar PD effect compared to efgartigimod 10 mg/kg IV. Simulations were 
performed to include parameter uncertainty. Outcome measures investigating comparable effects 


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on IgG levels as the 10 mg/kg IV dosed weekly, include area under effect-time curve days 22 to 
29, maximal IgG reduction between day 22 and 29, and trough IgG reduction at day 29. 
To maximize the probability of clinical improvement, both the median values and the 90% CI 
ranges of the PD outcome parameters were considered in the dose selection. A SC dose was 
selected for which the predicted median value on each of the 3 outcome parameters has at least 
reached the median value of the IV dosing, and for which the lower limits of the 90% CI are 
predicted to fall within the lower limits of the IgG reduction of 10 mg/kg IV dosing. A dose of 
1000 mg efgartigimod PH20 SC meets all these requirements. 
Based on these simulations, a weekly dose of 1000 mg efgartigimod PH20 SC is selected as the 
maintenance dose for this trial. The predicted IgG reduction with weekly efgartigimod PH20 SC 
1000 mg doses is comparable to that of efgartigimod IV 10 mg/kg. 
Based on the chronic dosing data from nonclinical studies, it is anticipated that this chronic 
dosing regimen in pemphigus is safe. A chronic dosing regimen of weekly IV infusions of 
10 mg/kg efgartigimod, or a SC equivalent as proposed for pemphigus, is anticipated to be safe 
as indicated by a 6-month study in cynomolgus monkey. In this study, animals were dosed with 
weekly efgartigimod infusions of up to 100 mg/kg. The no-observed-adverse-effect level 
(NOAEL) was set at the highest administered dose of 100 mg/kg. Both the Cmax and exposure 
data at the NOAEL observed in the nonclinical toxicity studies have been considered to provide 
sufficient exposure multiples to support the proposed dosing regimen for this trial. Furthermore, 
a bridging toxicity study of efgartigimod co-administered with rHuPH20 has been performed. In 
this 12-week bridging SC repeat-dose study, cynomolgus monkeys were treated with 
efgartigimod SC ± rHuPH20. As efgartigimod SC was well-tolerated, without toxicologically 
relevant systemic adverse findings up to the highest dose tested, a NOAEL above 100 mg/kg 
±2000 U/mL rHuPH20 (the highest tested dose) was established. No efgartigimod-related 
toxicity via SC injection was noted for behavior, external appearance, condition of feces, body 
weight, or food and water consumption, and there were no overt signs of toxicity or mortality or 
any influence on the myeloid:erythroid ratio in bone marrow. 
In view of the severity of the disease, a fast onset of action is desirable. Therefore, the dose 
regimen for the phase 3 trial starts with a dose that achieves close to maximal IgG reduction 
within 2 weeks, after which the PD effect is maintained with a lower weekly dose.  
PK/PD modeling indicated that 2 weekly doses of 
mg efgartigimod PH20 SC result within 
2 weeks in total IgG reduction close to maximal IgG reduction comparable to maximal IgG 
reductions achieved at steady state with 1000 mg efgartigimod PH20 SC. 
A maintenance dose of 1000 mg efgartigimod has been selected for this trial to be administered 
as weekly SC administrations coformulated with rHuPH20 until CRmin.  
4.4. 
End of Study Definition 
The end of the study is defined as the date of the last visit of the last participant in the study. 
A participant is considered to have completed the study if he/she has completed all periods of the 
study including the end of study (EoS)/early discontinuation (ED) visit and any follow-up visits, 
if applicable, depending on whether the participant rolls over to ARGX-113-1905 or continues 
the treatment-free follow-up period in ARGX-113-1904.  


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5.
TRIAL POPULATION
Protocol deviations to recruitment and enrollment criteria, also known as protocol waivers or 
exemptions, are not permitted. 
Participants who do not meet all the inclusion criteria or who meet any of the exclusion criteria 
will not be eligible to receive any trial medication. 
The criteria for screening and enrollment are to be followed explicitly. If it is noted that a 
participant who does not meet 1 or more of the inclusion criteria and/or meets 1 or more of the 
exclusion criteria was inadvertently enrolled and dosed, the sponsor’s designated contract 
research organization (CRO) medical monitor/sponsor’s designee and the sponsor’s medical 
director must be contacted immediately. The decision to discontinue a participant from the trial 
will be taken on a case-by-case basis, where safety and benefit/risk assessment will be 
considered.
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the trial only if all of the following criteria apply:
1. Ability to understand the requirements of the trial, to provide written informed consent 
(including consent for the use and disclosure of research-related health information), 
willingness and ability to comply with the trial protocol procedures (including required 
trial visits). 
2. The participant is male or female, and aged from 18 years at the time of signing the 
informed consent form (ICF).
3. The participant has a clinical diagnosis of PV (mucosal, cutaneous, mucocutaneous) or 
PF that has been confirmed by cutaneous histology, positive DIF, and positive IIF and/or 
ELISA.  
4. The participant meets 1 of the following profiles: 
i. 
on 10.8) at baseline 
 
ii. 
of oral prednisone (or equivalent). According to clinical judgment, the participant has 
shown no significant improvement of PV or PF signs for at least 2 weeks before 
baseline and is considered fit to start prednisone treatment at 0.5 mg/kg qd at 
baseline. 
iii. 
since disease 
onset, and off prednisone therapy ± a conventional immunosuppressant (eg, 
azathioprine, cyclophosphamide, methotrexate, mycophenolate mofetil) or dapsone. 
Note: conventional immunosuppressants and dapsone must be discontinued before 
baseline. 
iiii. 
onset, and receiving a tapered dose of oral prednisone (or equivalent), provided that 
prednisone has been given at stable dose ± a conventional immunosuppressant (eg, 
azathioprine, cyclophosphamide, methotrexate, mycophenolate mofetil) or dapsone 
for at least 2 weeks and participants are fit to start prednisone treatment at 0.5 mg/kg 


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qd at baseline. Note: conventional immunosuppressants and dapsone must be 
discontinued before baseline. 
5A.Contraceptive use by men and women should be consistent with local regulations 
regarding the methods of contraception for those participating clinical trials and:  
i. Male participants: 
Male participants must agree to use acceptable method of contraception (as 
described in Appendix 5, Section 10.5.2.2) from signing the ICF until the last 
dose of IMP. 
ii. Female participants: 
 Women of childbearing potential (defined in Appendix 5, Section 10.5.1) must: 
 have a negative serum pregnancy test at screening and negative urine 
pregnancy test at baseline before the IMP can be administered. 
 agree to use a highly effective or acceptable contraception method (as 
described in Appendix 5, Section 10.5.2.2), which should be maintained at 
minimum until after the last dose of IMP. 
6. For Japanese participants enrolled in sites in Japan only: A Japanese participant is 
defined as a participant whose parents and 4 grandparents are Japanese, and who has 
Japanese nationality, was born in Japan, has not lived outside of Japan for a total of 
>10 years, and currently lives in Japan.  
5.2. 
Exclusion Criteria  
Participants are excluded from the trial if any of the following criteria apply: 
1. Participant has a confirmed diagnosis of paraneoplastic pemphigus, drug-induced 
pemphigus, pemphigus vegetans, pemphigus erythematosus, or any other non-PV/non-PF 
autoimmune blistering disease.
2. Participants with mild disease severity as defined by PDAI activity score <15 at baseline.
3. Participants who show a significant improvement of PV or PF in the period from 
screening to baseline according to clinical judgment (eg, the participant has achieved DC 
or a substantial reduction in PDAI activity score during screening period).
4. The participant has been administered therapy(ies) other than oral prednisone, 
conventional immunosuppressants (eg, azathioprine, cyclophosphamide, methotrexate, 
mycophenolate mofetil) or dapsone within 2 months before the baseline visit and that can 
affect clinical disease activity. For example, excluded medications are intravenous 
methylprednisolone, sulfasalazine, tetracyclines, nicotinamide at doses above the 
recommended daily allowance (RDA)/dietary reference intake (DRI), plasmapheresis/ 
plasma exchange, immunoadsorption, and IVIg. Note: conventional immunosuppressants 
and dapsone must be discontinued before baseline. Nicotinamide doses at or below 
RDA/DRI from oral supplements is allowed.
5. Use of any monoclonal antibody (including rituximab or another anti-CD20 biologic) 
within 6 months before the baseline visit. 


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6. Known hypersensitivity to any of the components of the administered treatments.
7. The participant has a known contraindication to oral prednisone. 
8. The participant has a history of refractory disease, as defined by a failure to respond to 
first-line and second-line therapies. 
9. Participants who have a history of malignancy unless deemed cured by adequate 
tration. 
Participants with any of the following cancers can be included at any time, provided they 
are adequately treated prior to their participation in the study: 
i. Basal cell or squamous cell skin cancer 
ii. Carcinoma in situ of the cervix 
iii. Carcinoma in situ of the breast  
iiii. Incidental histological finding of prostate cancer (TNM stage T1a or T1b) 
10. Participants with clinical evidence of other significant serious disease or participants who 
recently underwent or have planned a major surgery during the period of the trial, or any 
other condition in the opinion of the investigator, that could confound the results of the 
trial or put the participant at undue risk. 
11. Pregnant and lactating women and those intending to become pregnant during the trial. 
12. Current or history (ie, within 12 months of screening) of alcohol, drug, or medication 
abuse. 
13. Any other known autoimmune disease that, in the opinion of the investigator, would 
interfere with an accurate assessment of clinical symptoms of PV or PF or put the 
participant at undue risk.  
14. The participant has a Karnofsky performance score <60% (see Section 10.9). 
15. Vaccination with live/attenuated viral vaccines within 28 days prior to randomization 
(see Section 8.3.7).  
16. The participant has clinically significant uncontrolled active or chronic bacterial, viral, or 
fungal infection. 
17. Positive serum test at screening for an active viral infection with any of the following 
conditions (refer to Section 10.2.1): 
i. Hepatitis B Virus (HBV) that is indicative of an acute or chronic infection, unless 
associated with a negative HBV DNA test. 
(https://www.cdc.gov/hepatitis/HBV/PDFs/SerologicChartv8.pdf; refer to Table 8). 
ii. Hepatitis C Virus (HCV) based on HCV antibody assay (unless associated with a 
negative HCV mRNA test; refer to Section 10.2.1.2). 
iii. HIV based on test results that are associated with an AIDS-defining condition or a 
CD4 count 200 cells/mm3 (refer to Table 9). 
18. The participant has total IgG <6 g/L at screening. 


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19. The participant has previously participated in a trial with efgartigimod and has received 
at least 1 administration of IMP. 
20. Use of an investigational drug within 3 months or 5 half-lives of the drug (whichever is 
longer) prior to first IMP administration. 
21. For Chinese participants enrolled in China only: Use of complementary therapies, 
including traditional Chinese medications, herbs, or procedures (eg, acupuncture) within 
4 weeks prior to randomization, that can potentially interfere with the efficacy 
assessments and the safety of the participant, as assessed by the investigator. 
5.3. 
Lifestyle Considerations 
No lifestyle restrictions are required.
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical trial but are 
not subsequently randomly assigned to trial intervention. A minimal set of screen failure 
information is required to ensure transparent reporting of screen failure participants to meet the 
Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes demography, 
screen failure details, eligibility criteria, and any SAE. 
Participants may be rescreened (ie, redoing the full assessments), per the SoA (Section 1.3) or 
retested once (ie, redoing 1 assessment) after the sponsor’s written approval.
Examples of conditions under which retesting may be considered include the following:  
 Participants who have clinical laboratory test values meeting 1 or more exclusion 
criteria that are not in line with the medical history and clinical evaluation of the 
participant, may be retested to confirm the value of the tests, if still allowed within 
the screening period. If not feasible, the participant should be rescreened. 
Participants may be rescreened once under the following conditions:
 Participants who required treatment for an acute illness that resolved (eg, a urinary 
tract infection) or had stabilization of a chronic medical problem (eg, uncontrolled 
hypertension). 
 Participants who are not on a stable dose of a concomitant medication prior to 
randomization as per inclusion and exclusion criteria may be rescreened once the 
stable dose criterion is met. 
The decision to rescreen participants may be optional based on clinical state of the participant 
and the decision to rescreen will solely be made per the sponsor’s discretion on a case-by-case 
basis. For the purpose of rescreening, a new ICF should be completed. 
5.5. 
Criteria for Temporarily Delaying Randomization 
Refer to Section 5.4. 


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6.
TRIAL INTERVENTION
Trial intervention is defined as any investigational intervention(s), marketed product(s), or 
placebo intended to be administered to a trial participant according to the trial protocol.  
6.1. 
Trial Intervention(s) Administered 
A list of trial interventions is presented in Table 2. Fixed doses of SC IMP will be administered 
on body sites spared of any cutaneous pemphigus lesions, the abdomen being used as preferred 
site. If the abdomen is affected by lesions, optional sites (thighs and the arms) may be chosen. 
The placebo solution for injection will contain the same excipients as the efgartigimod PH20 SC 
solution for injection but without the active ingredient efgartigimod. Masked vials will be 
provided to preserve the study blind (see Section 6.2.1). Refer to the Pharmacy Manual and 
preparation guide for further details. Additionally, participants will receive oral prednisone (or 
equivalent such as prednisolone) as concomitant therapy (see Section 6.8.1).  
Table 2: 
Trial Interventions 
Intervention 
Efgartigimod PH20 SC 
Placebo 
Prednisone (or Equivalent) 
Type 
Biologic 
Other: placebo
Non-IMP 
Dose formulation
Efgartigimod 165 mg/mL 
or 180 mg/mL + 
2000 U/mLrHuPH20 
solution for SC injection to 
be dosed at a fixed dose of 
1000 mg per injection 
Vehicle + 
2000 U/mL 
rHuPH20 for SC 
administration 
Prednisone/prednisolone 
tablets for oral 
administration  
Unit dose 
strength(s) 
165 mg/mL or 180 mg/mL 
Placebo 
Prednisone 5 mg, 10 mg, 
20 mg, 50 mg 
Prednisolone 5 mg 
Dosage level(s) 
in separate sites on day 1 
and day 8 followed by 
weekly 1000 mg 
administrations until 
CRmin 
SC administrations 
in separate sites on 
day 1 and day 8 
followed by weekly 
single 
administrations until 
CRmin
Refer to Section 6.8.1 
Route of 
administration 
Abdominal SC injection(s); 
preferred sitea 
Abdominal SC 
injection(s); 
preferred sitea 
Oral administration 
Use 
Investigational drug
Placebo for 
investigational drug 
Non-IMP or concomitant 
therapy 
IMP  
IMP  
IMP  
Non-IMP 
Sourcing 
Provided by the sponsor to 
the trial site 
Provided by the 
sponsor to the trial 
site
Provided by the sponsor to 
the trial site, or sourced 
locally 


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Intervention 
Efgartigimod PH20 SC 
Placebo 
Prednisone (or Equivalent) 
Packaging and 
Labeling 
The IMP will be provided 
in glass vials. Each glass 
vial will be labeled as 
required per country 
requirement 
The IMP will be 
provided in glass 
vials. Each glass vial 
will be labeled as 
required per country 
requirement 
Non-IMP will be provided in 
the commercial package and 
labeled as required per 
country requirements, or as 
magistral preparation upon 
prescription by the 
investigator
CRmin=complete remission on minimal therapy; IMP=investigational medicinal product; SC=subcutaneous(ly) 
a IMP will be administered on body sites spared of any cutaneous pemphigus lesions, the abdomen being used as 
preferred site. If the abdomen is affected by lesions, optional sites (thighs or arms) may be chosen. 
Efgartigimod PH20 SC will be provided in a vial at a concentration of 165 mg/mL or 
180 mg/mL (new concentration) for efgartigimod and 2000 U/mL for rHuPH20. Each dose of 
efgartigimod PH20 SC will include 1000 mg efgartigimod. Note that there will be a transition 
period during which both formulations (165 mg/mL and 180 mg/mL) will be used. After this 
transition period, all participants will receive the efgartigimod PH20 SC formulation with 
efgartigimod at the higher concentration of 180 mg/mL. The formulation with a higher 
concentration of efgartigimod (180 mg/mL) reduces the dosing volume for each SC injection.
Placebo will be vehicle (with 2000 U/mL of rHuPH20) provided in a vial as a ready to use SC 
formulation. For both efgartigimod PH20 SC formulations (with efgartigimod at a concentration 
of 165 mg/mL or 180 mg/mL), a corresponding placebo is available containing placebo drug 
product at the same volume and in the same vial as the active drug product.  
6.2. 
Preparation/Handling/Storage/Accountability 
6.2.1. 
Preparation 
Refer to the Pharmacy Manual for information about IMP preparation, including the volume of 
efgartigimod PH20 SC or placebo to be administered. 
Efgartigimod PH20 SC will be provided as a sterile, clear to opalescent, colorless to yellowish 
solution for SC injection. 
Placebo will be provided as a sterile, colorless, clear solution for injection in glass vials with the 
same formulation as the efgartigimod PH20 SC solution for injection, but without the active
ingredient efgartigimod. Vials for both IMP and placebo will be covered with a blinding shell. 
The trained and authorized staff will use an amber colored syringe for preparation and 
administration of IMP. The administration will be performed by the site staff who prepared the 
syringe. 
Efgartigimod PH20 SC and placebo will be manufactured in accordance with Good 
Manufacturing Practice regulations. 
6.2.2.
Handling
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all IMP received and any discrepancies are reported and resolved 
before use of the IMP. 


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Only participants enrolled in the trial may receive IMP. IMP administration must be performed 
by authorized and trained site staff or by an adequately trained and supervised participant or 
caregiver.  
6.2.3. 
Storage 
Efgartigimod PH20 SC and placebo will be supplied to the pharmacy or substitute at the 
investigational site by and under the responsibility of the sponsor’s designated IMP supply 
vendor. The IMP supply vendor will also provide the investigator with the certificate of analysis, 
certificate of conformity, and European Union qualified person release documents (if 
applicable).
The IMP must be stored refrigerated (2°C to 8°C or 35°F to 46°F) in its secondary packaging, 
should not be exposed to freezing temperatures, should not be shaken, and should be protected 
from direct sunlight during storage at the clinical site. 
The investigator (or his/her designee) is responsible for the correct and safe storage of the IMP 
assigned to the clinical site, in a locked, secure storage facility with access limited to those 
individuals authorized to dispense the IMP and maintained within the appropriate temperature 
ranges. 
Further guidance and information for the final disposition of unused IMP are provided in the 
Pharmacy Manual. 
For home administrations, the participant is responsible for the correct storage of the IMP at 
home. Participants will receive a guide on transport, storage and temperature monitoring of the 
IMP. 
6.2.4. 
Accountability 
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for IMP accountability, reconciliation, and record maintenance (ie, receipt, 
reconciliation, and final disposition records). 
Detailed instructions on accountability of the IMP will be included in the Pharmacy Manual. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
Once the participant has provided informed consent, the site will enroll the participant and a 
screening number will be allocated through the interactive response technology (IRT). 
The results of all screening procedures have to be available prior to baseline (day 1) to determine 
the eligibility for entering the trial. Randomization should be performed as soon as the 
participants meet the appropriate criteria to begin treatment. 
Participants will be randomized in a 2:1 ratio to receive efgartigimod PH20 SC or placebo. 
As this is a randomized, double-blinded trial, access to the IMP treatment assigned will be 
limited. No trial team members from the investigating staff, the sponsor (except the sponsor’s 
clinical trial supplies team), and the sponsor’s designated CRO/sponsor’s designee (except the 
specialty laboratories responsible for PK, PD, and immunogenicity [ie, ADA] analysis), will 
have access to the information related to IMP treatment assigned until after database lock.  


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The following data will remain blinded until database lock:
PK
 PD 
 Immunogenicity 
 Albumin and total protein 
 Exploratory research  
An independent unblinded data safety monitoring board (DSMB), including an independent 
statistician, may review all unblinded safety data as specified in Section 10.1.5.
6.3.1. 
Emergency Unblinding 
The process of breaking the blind will be handled through the IRT.
Participant safety is of utmost importance. If a safety issue is deemed a medical emergency by an 
investigator and timing is critical, then the investigator is permitted to use the IRT directly to 
unblind an IMP assignment code in order to ensure the medical emergency is properly managed 
and participant safety is maintained. If the issue is not deemed an emergency and timing permits, 
then the investigator is encouraged to first discuss the need to break a blind with the medical 
monitor at the sponsor’s designated CRO/sponsor’s designee or the sponsor’s medical expert in 
order to preserve the integrity of study data. 
If the blind is broken by the investigator, then it may be broken only for the participant 
concerned, and the IMP treatment assignment should not be revealed to the trial team members 
from the sponsor, nor from the sponsor’s designated CRO/sponsor’s designee, pharmacy 
personnel, or other site staff. 
Once unblinded, the participant should be discontinued from the trial. When the participant is 
withdrawn from the trial, the participant will be followed for 8 weeks for ongoing safety 
monitoring.  
Pertinent information regarding the circumstances of unblinding of a participant’s IMP treatment 
code must be documented in the participant’s source documents and electronic case report form 
(eCRF) without breaking the blind.
The sponsor and monitor at the sponsor’s designated CRO/sponsor’s designee must be notified 
immediately if a participant and/or investigator is unblinded during the course of the trial.
6.4. 
Trial Intervention Compliance 
The participants are dosed by qualified approved personnel. They will receive IMP directly from 
the investigator or designee, under medical supervision. Participants or their caregivers will be 
invited to receive training in self-administration or caregiver-supported administration 
respectively, and will be permitted to perform administration of the IMP on-site under 
supervision from the authorized staff. The date and time of each dose administered at the site 
will be recorded in the source documents and recorded in the eCRF.  
The investigator should promote treatment compliance by stating that compliance is necessary 
for the participant’s safety and the validity of the trial. The prescribed dose, timing, and mode of 


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administration cannot be changed. All dates, start and end time of IMP administration, and any 
deviations from the intended regimen must be recorded in the eCRF. 
A sponsor’s designated monitor will review the pharmacy records at each site including the drug 
accountability and dispensing records on which the pharmacist or designated person should 
record all IMP released for participant use. The sponsor’s designated monitor will compare the 
dispensing record and vials with the individual participant’s identifiers, kit number, and visit 
schedule to confirm that the participant received the correct treatment and dose, and that the 
dosing schedule is correct. 
Errors that are identified will be communicated to the site personnel to ensure that the errors are 
not repeated. The sponsor’s designated monitor’s report will include details of any missed doses, 
medication errors (see Section 6.7), treatment or scheduling errors, and the associated 
explanations. It will be evaluated if these dosing errors will be reported as protocol deviations in 
the clinical database. All supplies and pharmacy documentation must be made available 
throughout the trial for the sponsor’s designated monitor to review. 
6.4.1. 
Handling Missed Doses of the Investigational Medicinal Product 
All efforts will be made to ensure that the participant receives all administrations of IMP within 
the allowed visit windows. 
If a dose of IMP is missed or cannot be administered within the window of ±2 days of the 
planned administration day, this should be communicated to the medical monitor. The next dose 
should be planned as scheduled in the SoA (refer to Section 1.3). 
6.4.2. 
Protocol Deviations 
The investigator should not implement any deviation from, or changes to the approved protocol 
without agreement of the sponsor, and prior to review and documented approval of an 
amendment from the Institutional Review Board/Independent Ethics Committee (IRB/IEC) and 
regulatory authority as per local regulation, except where necessary to eliminate an immediate 
hazard to trial participants, or when the change involves only logistical or administrative aspects 
of the trial (eg, change of telephone numbers, etc). The investigator (or designee) should 
document and explain any deviation from the approved protocol. 
6.5. 
Dose Modification 
Not applicable. 
6.6. 
Continued Access to Study Intervention After the End of the Trial 
Efgartigimod PH20 SC or placebo SC will be administered subcutaneously until CRmin. 
Participants at the EoS visit or ED visit in trial ARGX-113-1904 will be given the option to 
enroll into the OLE trial ARGX-113-1905 after confirmation of eligibility, while retaining the 
blinding of trial ARGX-113-1904. For each participant, the date of the baseline visit in the OLE 
trial ARGX-113-1905 will be the same as the date of the EoS visit in trial ARGX-113-1904. 
There is no need to schedule an additional visit for a roll over visit. At baseline of the OLE 
study, participants will be treated according to their clinical status at entry of the OLE trial 
ARGX-113-1905, as defined in the trial protocol. 


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Week 34 (follow-up visit 1) or week 38 (follow-up visit 2) is the EoS for participants who do not 
enroll in the OLE trial ARGX-113-1905. The week 38 follow-up visit will only be required for 
those participants who were still receiving IMP at least 1 visit between week 26 and EoS/ED. 
For participants who ended treatment prior to week 26, week 34 will be the EoS visit.
If a participant withdraws/discontinues early and does not roll over to the OLE trial 
(ARGX-113-1905), usual treatment will be administered, if required, in accordance with the trial 
site’s standard of care and generally accepted medical practice depending on the participant’s 
individual needs. Depending on the clinical status of the participant and the clinical judgment 
from the investigator, completion of the treatment-free follow-up period may be performed. 
6.7.
Treatment of Overdose 
For this trial, a variation of more than 10% of the amount of efgartigimod will be considered an 
overdose. 
An overdose is defined as a deliberate or accidental administration of IMP to a participant, at a 
dose greater than that assigned to that participant per the trial protocol. 
In the event of an overdose, the investigator should: 
 Contact the medical monitor immediately. 
 Closely monitor the participant for any AE/SAE and laboratory abnormalities.
 Document the quantity of the excess dose as well as the duration of the overdose in 
the eCRF. 
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical evaluation of the participant. 
6.8. 
Concomitant Therapy 
All concomitant medications and procedures, whether allowed or not, must be recorded in the 
eCRF (including the name, indication for use, dose/schedule, start and stop dates). 
6.8.1. 
Concomitant Pemphigus Therapy
All participants, regardless of treatment assignment, will concomitantly receive oral prednisone 
(or equivalent such as prednisolone) at 0.5 mg/kg qd as a starting dose. Except for oral 
prednisone (or equivalent), no other systemic therapies (eg, immunosuppressants, IVIg, 
immunoadsorption, anti-CD20 biologics) will be permitted during the trial. 
At any post-baseline visit before DC is achieved, the prednisone dose will be adjusted by 
incrementing dosage according to clinical judgment, with the recommendation to increase by 1 
or more steps (refer to Table 3) in case of disease progression or insufficient clinical change. To 
facilitate common judgments among investigators, recommendations for assessment of disease 
progression and insufficient clinical change are:  
 Disease progression: increase of at least 5 in PDAI activity score compared to 
baseline score, observed at any post-baseline visit before DC.


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 Insufficient clinical change: absence of DC after 3 to 4 weeks of the participant being 
treated at the starting baseline prednisone (or equivalent) dose or after 3 to 4 weeks of 
any new incremented dose of prednisone. 
The recommendations of the prednisone dose escalation are: 
 Stepwise escalation of daily prednisone dose by 1 or more steps according to clinical 
judgment in case of disease progression. 
 Adjustment by incrementing dosage by 1 step according to clinical judgment in case 
of insufficient clinical change. 
 Possible further escalation from the previous step by 1 or more steps, according to 
clinical judgment and under the same recommendation as above. 
 Maximum escalation to 1.5 mg/kg qd for 3 weeks. 
If, after a minimum of 3 weeks of oral prednisone at 1.5 mg/kg qd, DC is not attained, then the 
participant will be considered a treatment failure. 
For participants achieving DC with a daily prednisone dose of 0.5 mg/kg, prednisone will be 
maintained at 0.5 mg/kg qd until CR and 2 weeks thereafter, or until EoC (defined as the time at 
which no new lesions have developed for a minimum of 2 weeks and approximately 80% of 
lesions have healed) and 4 weeks thereafter, after which tapering will be initiated. For 
participants achieving DC with an escalated prednisone dose (ie, >0.5 mg/kg qd), the prednisone 
dose will be maintained until 2 weeks after achieving DC, then tapering will be performed 
according to the following stepwise procedure: dose reductions by 0.25 mg/kg qd (according to 
Table 3) every 2 weeks until the starting dose is reached (ie, 0.5 mg/kg qd). Then the starting 
dose (0.5 mg/kg qd) will be maintained until a sustained CR is achieved for 2 weeks, after which 
further tapering will be initiated, or prednisone tapering below 0.5 mg/kg qd may be initiated in 
case of sustained EoC for at least 4 weeks. Further tapering will be performed thereafter, as long 
as CR or EoC are sustained. The rules for tapering are shown in Table 3. Each new tapered 
prednisone dose until 20 mg/day must be maintained for 2 weeks. Then, the prednisone dose is 
further tapered by 2.5 mg/day per week. When 10 mg/day is reached, this dose level will be 
maintained until CRmin has been achieved. Prednisone can then be further tapered upon clinical 
judgment by the investigator. 
In case of flare in the period between DC and CRmin, the prednisone dose will be increased. A 
flare is defined by the appearance of 3 or more new lesions in a 4-week period that do not heal 
spontaneously within 1 week, or by the extension of established lesions in a participant who had 
achieved DC. If the flare occurs after CR and IMP was administered at home by a nurse, the 
participant will resume weekly on-site visits until he/she achieves CR again. Participants who are 
not controlled by a prednisone dose that is 2 dose levels above the dose at which the flare 
between DC and CRmin is observed and that is at least 0.3 mg/kg/day (according to Table 3) will 
be considered treatment failures. At visits when at least 1 new lesion is observed or established 
lesions remain extensive without being defined as a flare, the prednisone dose will be maintained 
or may be increased, according to clinical judgment. If the lesion resolves, tapering of the 
prednisone dose will be pursued as planned. 
The investigator should not implement any deviation from the concomitant oral prednisone (or 
equivalent) regimen, except for immediate safety concerns of the participants. After taking 


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appropriate action to ensure the safety of the participants, such concerns should be documented 
and communicated to the CRO’s medical monitor and the sponsor. 
Additionally, the following treatments may be used during the trial:  
 Skin-directed topical corticosteroids  
 Skin-directed topical antibiotics, antiseptics and moisturizers  
Buccal and mucosa-directed corticosteroids, antiseptics and anesthetics 
Analgesics 
Usual supportive treatments associated with intake of oral corticosteroids (eg, 
vitamin D, calcium, KCl, bisphosphonates) are intended to be used according to 
standard of care and current guidelines 
 Non-live/non-attenuated vaccinations, and seasonal vaccinations (eg, influenza)


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Table 3: 
Concomitant Prednisone Equivalent Doses (in mg) by Body Weight 
Daily 
Prednisone 
Dose 
Participant Body Weight (±2.5 kg)a 
Tapering 
Frequency 
50 kg 
(47.5 – 
52.4) 
55 kg 
(52.5 – 
57.4) 
60 kg 
(57.5 – 
62.4)
65 kg 
(62.5 – 
67.4) 
70 kg 
(67.5 – 
72.4) 
75 kg 
(72.5 – 
77.4) 
80 kg 
(77.5 – 
82.4) 
85 kg 
(82.5 – 
87.4) 
90 kg 
(87.5 – 
92.4)
95 kg
(92.5 – 
97.4)
100 kg 
(97.5 – 
102.5) 
1.5 mg/kg 
75 mg 
80 mg 
90 mg 
95 mg 
105 mg 
110 mg 
120 mg 
125 mg 
135 mg 
140 mg 
150 mg 
Tapering 
every 2 
weeks 
1.25 mg/kg
60 mg
70 mg
75 mg
80 mg
85 mg
95 mg
100 mg
105 mg
110 mg
120 mg
125 mg
1 mg/kg 
50 mg 
55 mg 
60 mg 
65 mg 
70 mg 
75 mg 
80 mg 
85 mg 
90 mg 
95 mg 
100 mg 
0.75 mg/kg 
35 mg 
40 mg 
45 mg 
50 mg 
50 mg 
55 mg 
60 mg 
65 mg
65 mg 
70 mg 
75 mg 
0.5 mg/kg 
25 mg 
25 mg 
30 mg 
30 mg 
35 mg 
35 mg 
40 mg 
40 mg 
45 mg 
45 mg 
50 mg 
0.3 mg/kg or 
20 mg
20 mg
20 mg
20 mg
20 mg
20 mg
20 mg
25 mg
25 mg
25 mg
30 mg
30 mg
0.2 mg/kg or 
20 mg
Skip 
Skip 
Skip 
Skip 
Skip 
Skip 
20 mg 
20 mg 
20 mg 
20 mg 
20 mg 
Below 20 mg/day 
17.5 mg/day 
17.5 mg 
17.5 mg 
17.5 mg
17.5 mg 
17.5 mg 
17.5 mg 
17.5 mg 
17.5 mg 
17.5 mg 
17.5 mg 
17.5 mg 
Tapering 
every 
week 
15 mg/day 
15 mg 
15 mg 
15 mg 
15 mg 
15 mg 
15 mg 
15 mg 
15 mg
15 mg 
15 mg 
15 mg 
12.5 mg/day 
12.5 mg 
12.5 mg 
12.5 mg
12.5 mg 
12.5 mg 
12.5 mg 
12.5 mg 
12.5 mg 
12.5 mg 
12.5 mg 
12.5 mg 
10 mg/day
10 mg
10 mg
10 mg
10 mg
10 mg
10 mg
10 mg
10 mg
10 mg
10 mg
10 mg
a Body weight should be rounded to the nearest whole number. For body weights not covered by the table (ie, <47.5 kg and >102.5 kg), the prednisone 
equivalent doses can be based on the indicated daily prednisone dose per kg body weight. The proposed doses should be confirmed by the medical monitor. 
 


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6.8.2. 
Prohibited Medications and Therapy During the Trial 
The following medications or treatments are not permitted during the trial: 
 Any monoclonal antibody (including rituximab or another anti-CD20 biologic)  
 Intravenous methylprednisolone and any other corticosteroid by the parenteral route 
 Sulfasalazine 
 Tetracyclines 
Nicotinamide at doses above the RDA/DRI
Nicotinamide doses at or below RDA/DRI from oral supplements are allowed
Plasmapheresis/plasma exchange 
Immunoadsorption 
 IVIg  
 Vaccination with live/attenuated vaccines (eg, measles, mumps, rubella, rotavirus, 
smallpox, chickenpox, yellow fever) 
 Conventional immunosuppressants (eg, azathioprine, cyclophosphamide, 
methotrexate, mycophenolate mofetil) or dapsone from baseline 
 Other investigational drug 
 For Chinese participants enrolled in China only: Complementary therapies, including 
traditional Chinese medicines, herbs, or procedures (eg, acupuncture) that can 
potentially interfere with the efficacy assessments and the safety of the participant, as 
assessed by the investigator 
 


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7.
DISCONTINUATION OF TRIAL INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of Trial Intervention 
In rare instances, it may be necessary for a participant to permanently discontinue trial 
intervention. If study intervention is permanently discontinued, the participant will enter the 
treatment-free follow-up period or be invited to roll over into the OLE trial ARGX-113-1905. 
See the SoA for data to be collected at the time of discontinuation of study intervention and 
follow-up and for any further evaluations that need to be completed (refer to Section 1.3). 
7.2.
Participant Discontinuation/Withdrawal From the Trial
A participant may withdraw from the trial at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons. This is expected to be uncommon. 
At the time of withdrawal from the trial, if possible, an ED visit (equivalent to EoS visit) should 
be conducted, as shown in the SoA (refer to Section 1.3). Refer to the SoA for data to be 
collected at the time of trial discontinuation and follow-up and for any further evaluations that 
need to be completed. The participant will be offered to enter the treatment-free follow-up 
period. A comment must be added to the source records to note if the participant accepts or 
rejects to perform the EoS visit and/or the follow-up period. 
If the participant withdraws consent, the sponsor may retain and continue to use any data 
collected before such a withdrawal of consent. 
If a participant withdraws from the trial, he or she may request destruction of any samples taken 
and not tested, and the investigator must notify the sponsor immediately and document this in the 
site trial records. 
Reasons for ED from the trial include: 
 It is in the participant’s best interest – discussion with the medical monitor of the 
CRO/sponsor’s designee and the sponsor’s medical director is encouraged prior to 
discontinuation 
 The participant experiences a severe AE or SAE, or a clinically significant change in 
a laboratory test, if the investigator deems discontinuation appropriate 
 The participant became pregnant, which requires follow-up until delivery of the baby 
 The participant has active PV or PF disease as judged by the investigator, notably 
despite prednisone escalation 
Physician decision 
Unblinding occurred
If allergic angioedema or other serious hypersensitivity reactions such as anaphylaxis 
or anaphylactoid reactions occurs. Administration of IMP should be discontinued 
immediately, and appropriate therapy initiated. 


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7.3.
Lost to Follow-up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the trial site. 
The following actions must be taken if a participant fails to return to the clinic for a required trial 
visit: 
 The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the trial. 
 Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (if 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 should be documented in the 
participant’s medical record. 
 Should the participant continue to be unreachable, he/she will be considered to have 
been lost to follow-up.  
Discontinuation of specific sites or of the trial as a whole are described in Section 10.1. 


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8.
TRIAL ASSESSMENTS AND PROCEDURES
Trial procedures and their timing are summarized in the SoA (refer to Section 1.3). Adherence to 
the trial requirements, including those specified in the SoA, is essential and required for trial 
conduct. 
When a protocol-required procedure cannot be performed, the investigator will document the 
reason, and any corrective and preventive actions that he/she has taken to ensure that the normal 
processes are adhered to in source documents. The trial team should be informed of these 
incidents in a timely manner. This will be considered a protocol deviation and will be recorded 
accordingly.
Screening 
At screening, all eligibility assessments should be performed after obtaining informed consent. 
All screening evaluations must be completed and reviewed before enrollment to confirm that 
potential participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable. 
The first day of the screening period is the day of the screening visit (the date of first screening 
visit is defined by the date of first screening procedure after signing the ICF).
Treatment Period
Each participant should attend each trial visit on the designated days. There is a permissible visit 
window of ±2 days during the treatment period. 
From signing of the ICF until the last trial-related activity, all AEs that occur and all concomitant 
medications that are taken and procedures performed, whether allowed or not, during the trial are 
to be recorded on the appropriate screens in the eCRF.
Immediate safety concerns should be discussed first with the CRO’s medical monitor/sponsor’s 
designee and then with the sponsor immediately upon occurrence or awareness to determine if 
the participant should continue or discontinue IMP. Additionally, an independent unblinded 
DSMB may review all unblinded safety data on a regular basis as specified in Section 10.1.5.
A minimum of 6 on-site visits, V1(BL)/W1 to W6, is required before switching to home 
administrations, even if CR is achieved earlier than W6. Home visits are allowed once 
participants achieve CR, but not before the W7 visit. The investigator should call the participant
at least every 2 weeks until CRmin is achieved to confirm the participant is still in CR. On-site 
visits may continue at the investigator’s discretion.
During the IMP treatment period, all assessments and procedures have to be performed before 
the start of the IMP administration, except for the continuous assessment of AEs (see 
Section 8.4), and the recording of concomitant therapy and procedures (see Section 8.3.5).
At all visits, the efficacy and QoL assessments should be performed first, prior to any other trial-
specific procedure with the only exception of obtaining informed consent at screening. The 
EQ-5D-5L and ABQOL should be performed prior to all other efficacy assessments 
(Section 8.2).


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End of Study (EoS)/Early Discontinuation (ED)
All participants will complete W31/ED, which will be EoS for participants who enroll in the 
OLE trial ARGX-113-1905. 
Unscheduled Visits 
In case of suspected new lesions as reported by the participant, AEs, flare, or other safety 
reasons, participants should come to the clinic. This may require an unscheduled visit or can 
coincide with a planned observational or IMP-only visit. At this visit, assessments need to be 
performed as follows: 
- 
Assessments as specified in Table 4 below:  
Note: In case of new lesions or flare, the assessments indicated with footnote “b” in 
Table 4 should be performed only once at the visit where the new lesions or the flare is 
confirmed. These should not be repeated at subsequent visits (even if more new lesions 
develop at these subsequent visits or the flare is sustained) unless the subsequent visits 
coincide with planned observational or IMP-only visits and the assessments are to be 
performed during those visits per the SoA . 
- 
Assessments specified for the planned observational or IMP-only visit per the SoA 
(Section 1.3), if applicable. 
In case the participant was in CR when the new lesions/flare was observed: the planned weekly 
IMP-only or observational visits should be performed on-site (home visits are not allowed) for 
disease assessment and PDAI until CR is reached again. 
In case the participant was in CRmin or CRoff at the time of the new lesions: the participant 
should return for weekly on-site visits for disease assessment and PDAI until CR is reached 
again. This will require unscheduled visits or can coincide with planned observational visits. In 
case flare is confirmed in participants who had achieved CRmin, participants will be allowed to 
roll over into the OLE trial ARGX-113-1905 earlier than week 31. 
Table 4: 
Assessments to be Performed During an Unscheduled Visit 
Assessmenta
UNS  any reason other 
than new lesion(s) or flare 
UNS – new lesion(s) 
UNS – flare 
Physical 
examination & 
vital signs 
X 
Xb 
Xb 
PDAI 
X 
X 
X 
Disease 
assessment 
X 
X 
X 
Urinalysis 
X 
 
 
Urine pregnancy 
X 
 
 
Blood sample for 
PK 
Only if IMP is 
administered 
Only if IMP is 
administered 
Only if IMP is 
administered 


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Assessmenta
UNS  any reason other 
than new lesion(s) or flare 
UNS – new lesion(s) 
UNS – flare 
Clinical chemistry 
& hematology 
At the discretion of the 
investigator 
At the discretion of the 
investigator 
At the discretion of the 
investigator 
Anti-Dsg-1 and 
anti-Dsg-3 
antibodies 
 
 
Xb
Vaccination 
antibodiesc 
 
 
Xb 
Total IgG (no IgG 
subtypes) 
X 
 
 
IgG autoantibody 
subtypes and 
cytokinesc
 
 
Xb 
Photographyc 
(substudy 
conducted at 
selected sites) 
At the discretion of the 
investigator 
At the discretion of the 
investigator 
At the discretion of the 
investigator 
IMP 
administration 
Only if the UNS coincides 
with a planned IMP-only 
visit 
Only if the UNS 
coincides with a 
planned IMP-only visit 
Only if the UNS 
coincides with a planned 
IMP-only visit 
Prednisone taper 
X 
X 
X 
AE monitoring 
X 
X 
X 
Concomitant 
therapies 
X 
X 
X 
IgG=immunoglobulin gamma; IMP=investigational medicinal product; PDAI=Pemphigus Disease Area Index; 
UNS=unscheduled visit 
a These assessments can coincide with a planned observational or IMP-only visit. 
b These assessments should be performed once (only during the visit where the new lesion(s) or flare is confirmed. 
They should not be repeated at subsequent visits (even if more new lesions develop at these subsequent visits or 
the flare is sustained) unless the subsequent visits coincide with planned observational or IMP-only visits and the 
assessment is to be performed during those visits per the SoA. 
c These assessments will not be performed in China. 
Treatment-free Follow-up Period 
Participants who reach week 31, discontinue early, or participants under treatment failure, and 
who do not roll over to the OLE trial, will enter the treatment-free follow-up period. There is a 
permissible visit window of ±3 days during the follow-up period. 
8.1. 
Demography 
Demographic characteristics comprise age, year of birth, gender, race, and ethnicity (per local 
regulations). Only if requested as per local regulations, no source data verification will be 
performed on race and ethnicity.


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8.2.
Efficacy Assessments
The efficacy of the IMP will be assessed at on-site visits by the investigator, assessing the 
following: PDAI, DC, EoC, CR, CRmin, CRoff, and flare. The investigator will record the daily 
prednisone dose since the last visit, and treatment failures at on-site visits. For home visits, the 
investigator should call the participant at least every 2 weeks until CRmin is achieved to confirm 
the participant is still in CR.
The clinical activity of pemphigus will be assessed using the PDAI (see Section 10.8), which has 
been developed by the International Pemphigus Committee.24,27 It is an evaluation tool able to 
capture the extent of the disease on the skin and mucosa. It is a validated system, which was 
found to be reproducible, reliable in the inter-rater assessment, and correlates with the global 
physician impression of extent. It is more sensitive than another developed scale, called ABSIS, 
especially in the pemphigus population with mild-to-moderate intensity. The PDAI has a 
possible score ranging from 0 to 263. Participants of mild severity distribute between PDAI 
activity scores of 1 to 15, those with moderate severity range from 15 to 44, and participants with 
 
8.3. 
Safety Assessments 
The planned time points for all safety assessments are provided in the SoA (refer to Section 1.3).
8.3.1. 
Physical Examinations 
Physical examinations will be performed at the time points indicated in the SoA (refer to 
Section 1.3). 
A physical examination will include, at a minimum, an assessment of general appearance, skin, 
head and neck (including ears, eyes, nose and throat), lymph nodes, thyroid, 
musculoskeletal/extremities, abdomen, breast, and cardiovascular, respiratory, neurological, and 
genital/rectal systems. Any signs related to the natural history of pemphigus are not to be 
reported as physical abnormalities. 
Investigators should pay special attention to clinical signs related to previous serious illnesses.
Abnormalities in physical examination at screening will be reported as medical history in the 
eCRF. At all other trial visits, new clinically significant abnormal or worsened pre-existing 
conditions will be reported as an AE. 
8.3.2. 
Height and Weight 
Height and weight will be measured at screening, and body mass index (BMI) will be calculated 
accordingly. Weight will be measured again at week 15 (or the first on-site visit thereafter if 
week 15 does not coincide with an on-site visit), and EoS/ED. Weight will also be measured if 
there has been an obvious change since the last measurement. For the assessment of height and 
weight, participants will be required to remove their shoes and wear light indoor clothing. 


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8.3.3. 
Vital Signs 
The assessment of vital signs (supine blood pressure, heart rate, and body temperature) will be 
performed at the time points indicated in the SoA (refer to Section 1.3) and should be completed 
predose at visits when IMP is administered. 
Supine blood pressure and heart rate will be measured using standard equipment after at least 
10 minutes rest.
It is recommended that the method used to measure body temperature (eg, orally, tympanic, 
rectal, axillary, skin, temporal) at screening is maintained throughout the trial for each 
participant. 
Abnormalities in vital signs at screening will be reported as medical history in the eCRF. At all 
other trial visits, new clinically significant abnormal or worsened pre-existing vital sign 
abnormalities will be reported as an AE. 
8.3.4. 
Electrocardiography
Electrocardiography (ECG) will be performed at the time points indicated in the SoA (refer to 
Section 1.3) and should be completed predose at visits when IMP is administered. 
ECGs will be acquired according to instructions provided by a centralized ECG reading facility 
where the ECGs will be centrally assessed. At a minimum, interval data (PR, QT, QTcF 
[Fridericia corrected QT interval], and QRS intervals), ventricular rate, and overall interpretation 
will be recorded for each ECG. Data will be transferred electronically for inclusion in the 
database.   
Abnormalities in ECG at screening will be reported as medical history in the eCRF. At all other 
trial visits, new clinically significant abnormal or worsened pre-existing ECG abnormalities will 
be reported as AEs.
8.3.5. 
Medical and Surgical History 
All significant findings, surgeries, and pre-existing conditions present at screening must be 
reported on the relevant medical history/current medical conditions page of the eCRF, including 
start and end dates, if known. 
Information should be provided on medical and surgical history and concomitant medical 
conditions specifying those ongoing at screening. 
Details collected as a part of the medical history must include, but are not limited to, all previous 
treatment/therapy taken for pemphigus, including start and end dates, if known. 
All available vaccination history will be recorded as part of the participant’s prior medication for 
vaccinations received in the past, or concomitant medication for vaccinations received during the 
trial as described in the SoA (Section 1.3). Any vaccination information the participant, his/her 
caregiver, or his/her legally authorized representative can remember should be recorded in the 
eCRF (with the brand name of the vaccine and date of vaccination, if possible).  
For vaccines where multiple doses or boosters are received, only the last 1 must be recorded in 
the eCRF (with the brand name of the vaccine and the date of vaccine administration entered, if 
known). 


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8.3.6. 
Clinical Safety Laboratory Assessments 
This section is applicable globally, except for China. For China-specific instructions, refer to 
Section 10.16.1.2.
Blood and urine samples for determination of clinical chemistry, hematology, coagulation, 
urinalysis, and serology (ie, viral testing) will be collected and analyzed at a central lab as 
indicated in the SoA (refer to Section 1.3) and Section 10.2. The urine sample for the pregnancy 
test will be analyzed locally. 
Participants may be rescreened (ie, redoing the full assessments as per SoA in Section 1.3) or 
retested once (ie, repeating 1 test, see Section 5.4) if still within the screening period. 
On days that IMP is administered, blood for laboratory assessments should be collected before 
dosing. 
Additional safety samples may be collected if clinically indicated, at the discretion of the 
investigator. 
The estimated total maximum blood volume needed for a participant during the trial (when 
completing the trial) is approximately 910 mL for the entire duration of the trial. 
For all female participants of childbearing potential, a serum pregnancy test will be performed 
centrally at screening (on the samples taken for clinical laboratory tests), and a urine pregnancy 
test will be conducted and analyzed locally at the site visits specified in the SoA (Section 1.3). A 
follicle-stimulating hormone (FSH) test will be run to confirm postmenopausal status and 
exclude that a woman is of childbearing potential; see Section 10.5. 
Clinical laboratory tests will be reviewed for results of potential clinical significance at all time 
points throughout the trial. The investigator will evaluate any change in laboratory values. If the 
investigator determines a laboratory abnormality to be clinically significant, it will be considered 
as a laboratory AE, however, if the abnormal laboratory value is consistent with a current 
diagnosis, then it may be documented accordingly without being reported as an AE. 
The details of sampling, handling, storage, and transportation of the samples will be described in 
the Laboratory Manual. 
Refer to Section 10.6 for the addresses of the laboratories used for sample analyses.
All laboratory tests with values considered clinically significantly abnormal during participation 
in the trial should be recorded as an AE and repeated until the values return to normal or baseline 
or are no longer considered clinically significant by the investigator or medical monitor. 
 If such values do not return to normal/baseline within a period of time judged 
reasonable by the investigator, then the etiology should be identified and the sponsor 
notified. 
 All protocol-required laboratory assessments, as defined in Section 10.2, must be 
conducted in accordance with the Laboratory Manual and the SoA (Section 1.3).  
 If laboratory values from non-protocol specified laboratory assessments performed at 
the institution’s local laboratory require a change in participant management or are 
considered clinically significant by the investigator (eg, SAE or AE or dose 
modification), then the event must be recorded in the eCRF.  


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8.3.6.1. 
Vaccination Antibodies Testing 
Vaccination antibodies testing will not be performed in China. 
Sites participating in the vaccination antibody testing will collect all available vaccination history 
from participants. Serum samples collected at screening and further visits according the SoA 
(Section 1.3) may be used to analyze vaccination antibodies and any response to vaccines 
received during the trial. Data from testing of vaccination antibodies will be described in a 
separate report. 
8.3.6.2. 
Storage of Blood and Tissue Samples After the Trial 
This section is applicable globally, except for China. For China-specific instructions, refer to 
Section 10.16.1.2.1.
Any samples remaining after the laboratory analyses as defined in the protocol have been 
completed may be stored for up to 15 years after the end of the trial, 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 pemphigus, unless this would not be allowed according to local 
regulations or the participant would not have agreed. 
In addition, blood and tissue samples may be used to validate methods to measure efgartigimod, 
antibodies, and biomarkers, as well as used for vaccination antibody testing and any other 
additional research interests. 
8.3.7. 
Infections and Vaccinations 
Pemphigus patients are prone to develop infections. They include infections of the bronchi 
(bronchitis) and the lung (pneumonia), resulting from the mucosal pemphigus lesions of the 
upper respiratory tract, infections of the mouth and ear-nose-throat (ENT) system, 
superinfections of the skin, and infections of the genital and urinary tract. Concomitant and 
historical treatments by non-targeted therapies (corticosteroids, immunosuppressants) or targeted 
therapies (rituximab) are co-morbidity factors able to trigger or aggravate these infections.  
In this trial, some measures able to mitigate the occurrence of infections are required, and other 
precautionary measures optimizing the prevention of infections are recommended. For these 
reasons, the following actions are excluded for trial entry (refer to Section 5.2): 
 the administration of live/attenuated vaccines (eg, measles, mumps, rubella, rotavirus, 
smallpox, chickenpox, yellow fever) within the 4-week period prior to baseline visit 
(exclusion criterion 15) or during the trial. 
 participants with an active or uncontrolled bacterial, viral, or fungal infection at 
screening (exclusion criterion 16). 
 Participants that tested positive for an active viral infection at screening with HBV 
type B or type C, and HIV (exclusion criterion 17). 
 participants with hypogammaglobulinemia, ie, total IgG <6 g/L (exclusion 
criterion 18).
The following measures prior to and during the study are highly recommended: 


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 To initiate or renew administration of non-live, inactivated, polysaccharide or 
recombinant vaccines (eg, tetanus, hepatitis A, hepatitis B, shingles) in participants 
susceptible to enter the trial, at least 4 weeks before baseline visit.  
 To vaccinate participants that are especially prone to or with an history of respiratory 
infections against Pneumococcus or Streptococcus pneumoniae. 
 To vaccinate pemphigus participants with seasonal vaccines (eg, influenza virus), 
especially those susceptible to enter the trial in the winter months. 
 To screen for possible infections (eg, respiratory, skin, mouth, eyes, nose and throat, 
genitals) and, if appropriate, initiate antibiotic treatment before baseline visit. 
 To provide participants suffering from recurrent episodes of herpes simplex or herpes 
zoster with antiviral treatment throughout the trial treatment.
Any other preventive measure that may be considered for the safety of the participants can also 
be discussed on a case-by-case basis with the medical monitor of the CRO/sponsor’s designee 
and, subsequently, the sponsor’s medical monitor, before the participant enters the trial. 
All available vaccination history and any vaccination received during the study should be 
recorded in the eCRF with the brand name of the vaccine and the date of vaccine administration. 
8.3.8. 
Suicidal Ideation and Behavior Risk Monitoring 
Not applicable. 
8.3.9. 
Additional Safety Assessment 
As an additional assessment of the impact of glucocorticoid morbidity, the GTI will be used. It is 
a complementary scoring system to the overall report of AEs that are judged as related to 
glucocorticoids by investigators during interventional studies. It also enables the monitoring of 
long-term tolerability of glucocorticoids during their prolonged use during clinical practice.  
The original version of the GTI (GTI 1.0) has been developed as a prospective tool to assess the 
impact of glucocorticoid morbidity.38 Its optimal use is in prospective, randomized, controlled-
clinical trials in which glucocorticoids are administered chronically, but the GTI has also been 
employed in real-world applications. In this trial, the GTI 2.0 will be used.39 In this new version, 
the weights derived in the initial GTI validation study are used to generate 2 scores from the 
composite GTI, ie, the CWS and the AIS. These scores and their rationales are briefly outlined 
below. For the sake of simplicity, we use the term “GTI” below to refer to the GTI 2.0 
instrument that will be used in this trial.
The GTI is composed of 2 components: 
 The Composite GTI (C-GTI), which serves as a primary instrument intended to 
capture common glucocorticoid toxicities (ie, toxicities that are likely due to 
glucocorticoid exposure and sensitive to cumulative doses over the period of 
6 months to 3 years). The C-GTI has 9 functional domains (specifically: BMI, 
glucose control, blood pressure, lipid metabolism, bone mineral density, muscle 
strength, skin toxicity, neuropsychiatric effects and infection). Each of the domains 
contains 3 to 4 weighted items that correspond to varying degrees of glucocorticoid 


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toxicity within their respective domain. Among the 9 GTI domains, bone mineral 
density is excluded if the GTI will be measured at intervals shorter than 1 year, 
because bone densitometry is not sufficiently reliable in measuring changes at shorter 
intervals. Therefore, in the context of the ARGX-113-1904 trial with a maximum 
duration of 30 weeks, the index is truncated by removing the “bone mineral density” 
domain. Development of the GTI beyond the original validation work has suggested 2 
approaches to analysis. These approaches provide complementary information about 
the ability of an investigational agent to reduce GC toxicity and also optimize the 
granularity with which the GTI captures the GC toxicity. The CWS is designed to 
assess cumulative GC toxicity, regardless of whether the toxicity has lasting effects or 
is transient. New toxicities that occur are added, but toxicities that appear to resolve 
on follow-up are not removed. Thus, the CWS serves as a lasting record of GC 
toxicity observed, and can only increase or remain the same over time. In the case of 
the presence of some GC toxicity at baseline, the AIS can be used to establish that a 
new therapy is effective at diminishing any baseline GC toxicity over time. With the 
AIS, toxicities can be removed if improvement occurs and added if worsening occurs. 
If toxicities present at baseline or occurring during the trial resolve over the course of 
follow-up, then that improvement is reflected in a negative score for that item during 
the interval. Both the CWS and the AIS are calculated for each interval, and then the 
interval scores are summed. 
 The complementary GTI Specific List (GTI-SL) captures well-known glucocorticoid-
related side effects. It is not weighted, and provides additional information in the 
domains most affected by glucocorticoid use during an individual’s treatment course.
It comprises 11 domains (including 9 shared in common with the C-GTI) and 
23 items. In this study, the item “major decrease in bone mineral density” will be 
excluded as bone matter density will not be assessed, and 22 items will be used.
The GTI with its 2 components (C-GTI and GTI-SL) are located in Section 10.15 (Appendix 15). 
8.4. 
Adverse Events and Serious Adverse Events 
Definitions of AE and SAE are provided in Section 10.4 as well as guidelines for assessing 
causality and relationship to IMP. 
AEs may be reported by the participant (or, when appropriate, by a caregiver, surrogate, or the 
participant's legally authorized representative). 
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up AEs that are serious, considered related to the trial intervention or trial procedures, or that 
caused the participant to discontinue IMP and/or the trial (see Section 7). 
An unexpected AE is any adverse drug event that is not listed in the reference safety information 
in the current IB or is not listed at the specificity or intensity that has been observed. 
Suspected adverse reaction means any AE for which there is a reasonable possibility that the 
drug caused the AE. 


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Each AE is to be evaluated for duration, severity (using the Common Terminology Criteria for 
Adverse Events [CTCAE Version 5.0]), seriousness, and causal relationship to the IMP or trial 
procedures. The action taken with the investigational drug and the outcome of the event must 
also be recorded. 
8.4.1. 
Time Period and Frequency for Collecting AE and SAE Information 
All AEs and SAEs will be collected from the signing of the ICF until the last follow-up visit 
(Section 1.3). 
All SAEs and AESIs will be recorded and reported to the sponsor or designee immediately and 
under no circumstance should this exceed 24 hours, as indicated in Section 10.4. The investigator 
will submit any updated SAE data to the sponsor within 24 hours of it being available. 
Investigators are not obligated to actively seek AE or SAE after conclusion of the trial 
participation. However, if the investigator learns of any SAE, including a death due to any cause, 
at any time after a participant has been discharged from the trial, and the investigator considers 
the event to be reasonably related to the trial intervention, trial participation, or corticosteroid 
(non-IMP) use, then the investigator must promptly notify the sponsor. 
8.4.2. 
Method of Detecting AEs and SAEs 
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Section 10.4. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences. 
8.4.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts.  
Any AEs observed from signing the ICF until End-of-Treatment, the last follow-up visit, until 
the participant is lost to follow-up, or until the participant withdraws consent (as defined in 
Section 7.3) must be followed until resolution. Resolution means that the participant has returned 
to a baseline state of health or the investigator does not expect any further improvement or 
worsening of the AE. 
Every effort should be made to follow all (S)AEs considered to be related to the IMP or trial 
procedures until an outcome can be reported. If the participant is lost to follow-up, all AEs will 
be categorized based on the investigator’s last assessment. 
As long as the participant is still in the trial, resolution of SAEs (with dates) should be 
documented on the AE page of the eCRF and in the participant’s medical record to facilitate 
source data verification. If, after follow-up, return to the baseline status or stabilization cannot be 
established, an explanation should be recorded on the SAE form. 
All pregnancies reported during the trial should be followed until pregnancy outcome. See 
Section 10.5. 


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For SAEs, AESIs (see Section 8.4.8), non-serious AEs, and pregnancies, the sponsor’s designee 
may follow-up by telephone, fax, electronic mail, and/or a monitoring visit to obtain additional 
case details and outcome information (eg, from hospital discharge summaries, consultant reports, 
or autopsy reports) in order to perform an independent medical assessment of the reported case. 
Further information on follow-up procedures is provided in Section 10.4. 
8.4.4. 
Reporting of AEs and SAEs 
All AEs that occur during the trial, from signing of the ICF until End-of-Treatment or the last 
follow-up visit, are to be recorded on the appropriate AE pages (either “serious” or 
“non-serious”) of the eCRF. The investigator should complete all the details requested, including 
date of onset, time of onset, stop date (when applicable), stop time (when applicable), severity, 
action taken, outcome, and relationship to IMP, to corticosteroid (non-IMP) use, and to trial 
procedures. Each event should be recorded separately in the eCRF. 
Any SAE, including death due to any cause, which occurs during this trial after the signing of the 
ICF, whether or not related to the IMP, must be reported immediately (within 24 hours of the 
trial site’s knowledge of the event). Further information on follow-up procedures is provided in 
Section 8.4.3 and Section 10.4. 
The report will contain as much available information concerning the SAE as possible, to enable 
the sponsor (or an authorized representative) to file a report, which satisfies regulatory reporting 
requirements. These timelines apply to initial reports of SAEs and to all follow-up reports. 
Criteria for documenting the relationship to IMP as well as severity, outcome, and action taken 
will be the same as those previously described. 
All SAEs that are spontaneously reported within 30 days after the last trial visit are to be 
collected and reported in the safety database, and all efforts should be made to follow-up until 
resolution. 
Additional follow-up information should be completed and entered on a paper SAE report form 
and sent by fax/email to the sponsor’s designated CRO/sponsor’s designee. 
8.4.5. 
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 toward the safety of participants and the safety of a study 
intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, IRB/ IEC, and investigators.
An investigator who receives an investigator safety report describing an SAE or other specific 
safety information (eg, summary or listing of SAEs) from the sponsor will review and then file it 
along with the IB and will notify the IRB/IEC, if appropriate according to local requirements.
The sponsor (or its designee) will be responsible for reporting suspected unexpected serious 
adverse reactions (SUSARs) to the relevant regulatory authorities and IEC/IRB, as per applicable 


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regulatory requirements. The sponsor (or its designee) will also be responsible to forward 
SUSAR reports to all investigators involved in the study, who will be required to report these 
SUSARs to their respective IECs/IRBs, as per their local regulatory requirements.
8.4.6. 
Pregnancy 
If a pregnancy is reported, then the investigator will record pregnancy information on the 
appropriate form and submit it to the sponsor within 24 hours of learning of the pregnancy of a 
female participant or female partner of male participant (after obtaining the necessary signed ICF 
from the female partner; see Section 10.5). 
While pregnancy itself is not considered to be 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 as such. 
The participant/pregnant female partner 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 the information will be forwarded to the sponsor. 
Any post-study pregnancy-related SAE considered reasonably related to the study intervention 
by the investigator will be reported to the sponsor as described in Section 8.4.5. While the 
investigator is not obligated to actively seek this information in former study 
participants/pregnant female partner, the investigator may learn of an SAE through spontaneous 
reporting. 
Any female participant who becomes pregnant while participating in the study will discontinue 
study intervention or be withdrawn from the study. 
8.4.7. 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as 
Reportable AEs or SAEs 
Not applicable. 
8.4.8. 
Adverse Events of Special Interest  
An AESI (serious or non-serious, related or not related) is an event of scientific and medical 
concern specific to the sponsor’s product or program (eg, an underlying condition being 
investigated, a mechanism of action/potential immunosuppression). Further characterizing 
information will be collected in the eCRF. This event could be expected due to the natural 
progression of the underlying disease, disorder, or condition of the participant(s) and the 
participant’s predisposing risk factor profile including concomitant medications. 
Efgartigimod treatment induces reductions in IgG levels, and there is a potential risk for 
infections associated with low IgG levels. Moreover, due to the nature of underlying disease, 
Pemphigus patients are more prone to infections; therefore, infections are considered as AESI in 
this trial (see Section 8.3.7).  
The characteristics of infections in the phase 2 trial ARGX-113-1701 with efgartigimod in 
pemphigus patients are summarized in Table 5. A total of 32 TEAEs related to infections were 
reported in 21 (61.8%) patients; among them, 7 events in 5 (14.7%) patients were assessed as 


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probably or possibly related to efgartigimod, and the remaining 25 events were assessed as not or 
unlikely related to efgartigimod.  
Table 5: Trial ARGX-113-1701: Summary of Treatment-emergent Adverse Events in the 
Infections and Infestations System Organ Class by Preferred Term – Safety 
Analysis Set 
Efgartigimod
(10 mg/kg IV) 
(N=19) 
n (%) e
Efgartigimod
(25 mg/kg IV) 
(N=15) 
n (%) e
Overall 
(N=34) 
n (%) e
Subjects with at least 1 TEAE
Infections and infestations 
Rhinitis 
Urinary tract infection 
Bronchitis 
Gastroenteritis 
Nasopharyngitis 
Upper respiratory tract infection 
Oral herpes 
Pustule 
Bacteriuria 
Candida infection 
Conjunctivitis 
Folliculitis 
Impetigo 
Pneumonia 
Pulpitis dental 
Respiratory tract infection 
Sialoadenitis 
Skin infection 
Tonsillitis 
Tooth infection 
16 (84.2) 60
11 (57.9) 15  
0 
1 (5.3) 2 
2 (10.5) 2 
1 (5.3) 1 
0 
0 
1 (5.3) 1 
1 (5.3) 2 
1 (5.3) 1 
0 
1 (5.3) 1 
0 
1 (5.3) 1 
1 (5.3) 1 
0 
1 (5.3) 1 
1 (5.3) 1 
0 
1 (5.3) 1 
0 
13 (86.7) 61
10 (66.7) 17 
2 (13.3) 3 
2 (13.3) 2 
0 
1 (6.7) 1 
4 (26.7) 4 
1 (6.7) 1 
0 
0 
0 
1 (6.7) 1 
0 
1 (6.7) 1 
1 (6.7) 1 
0 
1 (6.7) 1 
0 
0 
1 (6.7) 1 
0 
1 (6.7) 1 
29 (85.3) 121
21 (61.8) 32 
2 (5.9) 3 
3 (8.8) 4 
2 (5.9) 2 
2 (5.9) 2 
4 (11.8) 4 
1 (2.9) 1 
1 (2.9) 1 
1 (2.9) 2 
1 (2.9) 1 
1 (2.9) 1 
1 (2.9) 1 
1 (2.9) 1 
2 (5.9) 2 
1 (2.9) 1 
1 (2.9) 1 
1 (2.9) 1 
1 (2.9) 1 
1 (2.9) 1 
1 (2.9) 1 
1 (2.9) 1 
Source: ARGX-113-1701 CTR Table 14.3.1.2 all available data; Listing 16.2.7.1 
e=number of events; IV=intravenous(ly); n=number of subjects; MedDRA=Medical Dictionary for Regulatory 
Activities; PT=preferred term; SOC=system organ class; TEAE=Treatment-emergent adverse events, 
Notes: Percentages are based on the number of patients in the safety analysis set. Adverse event terms are coded by 
SOC and PT using MedDRA version 23.1. 
No causal factor related to the mechanism of action of efgartigimod (eg, severe 
hypogammaglobulinemia) could be identified. However, it is important to mention that the trial 
does not include a comparative arm (ie, placebo control) to better assess the relationship to the 
drug; thus, the contribution of a drug that reduces serum IgG levels cannot be excluded.  
8.4.9. 
Infusion-related Reactions 
IRRs are defined as AEs within the standardized Medical Dictionary for Regulatory Activities 
(MedDRA) queries for hypersensitivity, anaphylactic reaction, and extravasation (excluding 
implant); all broad search applied; and all AEs that occurred within 48 hours of an infusion.  


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In the phase 2 trial ARGX-113-1701 in pemphigus, efgartigimod IV infusions have resulted in 
only 1 case of grade 1 urticaria, which was assessed as an IRR.   
8.4.10. 
Injection Site Reactions
Efgartigimod co-mixed with rHuPH20 in single-dose SC administrations was well-tolerated in 
healthy subjects with frequently reported mild Injection site reactions, including erythema, pain, 
bruising, pruritus, burning, tenderness, edema, induration, irritation, paresthesia, numbness, and 
rash. Injection site reactions observed after SC administration in this study will be reported as an 
AE. 
8.5. 
Pharmacokinetics 
Blood samples for PK will be collected from each participant as presented in the SoA 
(Section 1.3). Sampling will be done predose on IMP administration visits (within 2 hours before 
IMP). 
An additional PK sample will be taken on day 3 and on day 11 (±1 day) until samples from 
24 participants are obtained.
Concentrations of efgartigimod will be determined using a validated assay. 
The actual date and time of collection of the blood sample will be recorded in the requisition 
form. If no sample was taken, the reason will be recorded in the relevant section of the eCRF.  
8.6. 
Pharmacodynamics 
This section is applicable globally, except for China, where IgG subtypes will not be determined.  
At screening, total IgG will be measured as part of inclusion and exclusion criteria, but they will 
not be part of PD evaluation parameters at this time point.  
Blood samples for the determination of the PD markers (total IgG, IgG subtypes [IgG1, IgG2, 
IgG3, and IgG4]) and anti-Dsg-1 and anti-Dsg-3 autoantibodies will be collected as indicated in 
the SoA (Section 1.3). Sampling will be done predose on IMP administration visits. 
These PD markers will be determined using validated assays. IgG subtype analyses may be 
limited to a representative portion of study participants.
The actual date and time of collection of the blood sample will be recorded in the requisition 
form. If no sample was taken, the reason will be recorded in the relevant section of the eCRF.
8.7. 
Skin Biopsies 
A substudy to evaluate markers of pemphigus pathology in skin biopsies will be conducted at 
selected sites. Not all countries participating in the study, including China, will include sites that 
perform the substudy. 
At participating sites, two 4-mm skin biopsies, 1 peri-lesional and 1 non-lesional, will be 
collected solely based on voluntary participation and giving informed consent, at 2 time points: 
at baseline and after healing of 80% of blisters (EoC) or at End-of-Treatment if 80% of healing is 
not achieved, to scientifically address the disease dynamics in response to experimental therapy 
with efgartigimod plus corticosteroids or corticosteroids only.  


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Collected biopsy samples will be immediately fixed in 10% neutral buffered formalin, at room 
temperature, and after 24 hours transferred in ethanol for shipment to a central laboratory for 
processing and analysis. 
The following markers are planned to be measured in these samples: 
 Total IgG and subtypes IgG1, IgG2, IgG3, and IgG4  
 Inflammatory cytokines: IL-1, IL-2, IL-4, IL-6, TNF- , and IFN-   
 Cellular infiltrates: CD45+ leukocytes, CD3+ T cells, CD4+ T helper cells, CD8+ 
cytotoxic T cells, CD20+ B cells, CD138+ plasma cells, neutrophils  
 Desmoglein and FcRn expression level 
Skin biopsies for this exploratory substudy will be collected as indicated in the SoA 
(Section 1.3). To maintain the study blind, samples will be recoded before analysis. 
8.8. 
Imaging 
For illustrative purposes, pictures of different anatomical regions may be taken at selected sites 
at the discretion of the investigator. The imaging substudy will be performed at selected sites and 
will not be performed in China.
As a guidance for participating sites, time points of baseline, DC, CR and flare are indicated. 
Pictures may also be taken at intermediate timepoints. 
Photography is generally accepted as routine practice for documenting dermatological conditions 
in medical practice. Photographs will be taken at baseline and at subsequent visits to document 
response and progression. Participants will be requested to provide consent for any use that will 
be made of the image and for sharing anonymized pictures with the sponsor. 
8.9. 
Exploratory Research 
The subsections below are applicable globally, except for China, where no exploratory research 
will be conducted.
8.9.1. 
IgG Autoantibody Subtype and Specificity Study 
Pemphigus is an autoimmune blistering disease caused by IgG autoantibodies against adhesion 
proteins. These autoantibodies are characteristically directed against Dsg-1 and Dsg-3, and 
predominantly of the IgG4 subtype.40 Despite this, serum concentrations of anti-Dsg 
autoantibodies do not always correlate with the disease activity, the anti-Dsg-1/3 autoantibody 
profile does not always match the clinical phenotype of skin and mucosal involvement when 
taking into account the relative expression patterns of Dsg-1 and Dsg-3 in skin and mucosa, and 
there is evidence of synergy of anti-Dsg and non-Dsg antibodies in pemphigus.40-42 
Efgartigimod, an FcRn inhibitor that gives a targeted reduction of IgG antibodies of all 
subtypes43 has been evaluated in the treatment of participants with MG,36 ITP,37 and pemphigus 
(trial ARGX-113-1701). 


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The objective of the IgG autoantibody subtype and specificity research in this trial is to link 
serological profiles (ie, beyond the overall IgG reactivity toward Dsg-1 and/or -3 whole 
extracellular domains) with clinical observations. 
Blood samples for this exploratory research will be collected as indicated in the SoA 
(Section 1.3). To maintain the study blind, samples will be recoded before analysis. 
8.9.2. 
Immunological Profiling
Immunological profiling aims to comprehensively evaluate the impact of efgartigimod on 
immune parameters to confirm the drug mode of action, illuminate previously unappreciated 
pathways and targets impacted by therapy, and define molecular and cellular biomarkers 
associated with treatment response. Specific analysis will include evaluation of:
 Anti-non-Dsg specific autoantibodies
 Pro-inflammatory cytokines
 T- and B-cell populations
Blood samples will be collected as indicated in the SoA (Section 1.3). 
8.9.3. 
Genetics 
The genetics study aims to understand how specific human leukocyte antigen (HLA) and 
non-HLA genes affect dynamic changes in T- and B-cell receptor repertoires and changes in 
RNA transcriptional profiles of genes linked to disease activity. Participation is optional and 
participants who do not wish to partake in the genetic research may still join in the trial. 
A blood sample for DNA isolation will be collected from participants who have consented to 
participate in the genetic analysis component of the study (Section 8.9.2).  
In the event of DNA extraction failure, a replacement genetic blood sample may be requested 
from the participant. A signed ICF will be required to obtain a replacement sample unless it was 
included in the original consent. 
Blood samples for RNA extraction will be collected at baseline, after 4 weeks (W5), W13 (or the 
visit at which CR is observed if before W13), and at EoS/ED. 
See Section 10.7 for information regarding genetic research. Details on processes for collection 
and shipment of these samples can be found in the Laboratory Manual. 
8.10. 
Immunogenicity Assessments 
Blood samples to assess immunogenicity of efgartigimod and rHuPH20 will be collected as 
indicated in the SoA (Section 1.3). Sampling will be done predose on IMP administration visits. 
All samples will be analyzed first in a validated screening assay, followed by an assessment of 
specificity of the measured ADA response in screening positive samples in a confirmation assay. 
Finally, in samples scoring positive in both screening and confirmatory assays, a titration of the 
ADA response will be performed. Neutralizing antibodies (Nab) will be tested for all confirmed 
positive ADA samples. 


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The actual date and time of collection of the blood sample will be recorded in the requisition 
form. If no sample was taken, the reason will be recorded in the relevant section of the eCRF. 
8.11. 
Medical Resource Utilization and Health Economics 
See Section 8.12. 
8.12. 
Quality of Life and Patient-Reported Outcomes 
The participant will complete the patient-reported outcome (EQ-5D-5L) and the QoL 
questionnaire (ABQOL) as indicated in the SoA (Section 1.3).  
EQ-5D-5L: EQ-5D (5-level version) is a standardized measure of health status developed by the 
EuroQoL Group in order to provide a simple, generic measure of health for clinical and 
economic appraisal (see Section 10.10). The descriptive system comprises 5 dimensions 
(mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each dimension now 
has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme 
problems. The respondent is asked to indicate his/her health state by ticking (or placing a cross) 
in the box against the most appropriate statement in each of the 5 dimensions. This decision 
results in a 1-digit number expressing the level selected for that dimension. The digits for 5 
dimensions can be combined in a 5-digit number expressing the level selected for that 
dimension. A unique health state is defined by combining 1 level from each of the 5 dimensions. 
A total of 3125 possible health states is defined in this way. Each state is referred to in terms of a 
5-digit code. For example, state 11111 indicates no problems on any of the 5 dimensions, while 
state 12345 indicates no problems with mobility, slight problems with washing or dressing, 
moderate problems with doing usual activities, severe pain or discomfort and extreme anxiety or 
depression. 
ABQOL: The ABQOL scale was developed and validated for ascertaining the impact of 
pemphigus and its therapies on patient’s daily life (see Section 10.11).29  


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9.
STATISTICAL CONSIDERATIONS
The statistical analyses will be performed by the sponsor’s designated CRO using statistical 
analysis systems SAS® (SAS Institute, Cary, NC, US) version 9.4 or higher, and the software 
package R, if applicable. The standard operating procedures (SOPs) and work instructions of the 
sponsor’s designated CRO will be used as the default methodology if not otherwise specified. 
A detailed and comprehensive Statistical Analysis Plan (SAP) will be written and signed-off 
prior to final analysis database lock. Minor changes to the statistical methods set out in this 
protocol do not require a protocol amendment but will be documented (as changes from the 
protocol) in the SAP and in the trial report(s). The below paragraphs contain the main general 
features of the statistical analysis. More details will be provided as needed in the SAP. 
9.1. 
Statistical Methods 
In general, data collected will be listed, together with derived variables. Graphical displays will 
show safety and efficacy variables over time. Descriptive statistical methods will be used to 
analyze safety and efficacy data. Summaries will generally be provided by treatment assignment 
and overall. 
Summaries for continuous measures will include the number of observations (n), mean, SE, 
median, minimum and maximum. For categorical variables, summaries will include sample size, 
frequencies, and percentages. 
9.2. 
Statistical Hypotheses 
The statistical hypothesis is derived from the primary trial objective as stated in Section 3. 
 Null hypothesis: There is no difference between efgartigimod PH20 SC and placebo 
in the proportion of participants with PV having achieved CRmin within 30 weeks. 
 Alternative hypothesis: There is a difference between efgartigimod PH20 SC and 
placebo in the proportion of participants with PV having achieved CRmin within 
30 weeks.
9.3. 
Sample Size Determination 
The sample size calculation is based on the following assumptions: 
 Endpoint: proportion of PV participants having achieved CRmin within 30 weeks 
 Percentages for sample size calculation 
 Efgartigimod: 40% to 50% 
 Placebo: 1% to 20% 
 Power: 90% 
 Significance level: 5% (two-sided) 
The sample size calculation was performed using PASS 2019 software (NCSS Statistical 
Software, Kaysville, Utah). The assumption is made that the responses from each group follow a 
binomial distribution.  


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Table 6 presents the number of participants needed in the placebo group; with a randomization 
ratio of 2:1 the efgartigimod group should have twice the number of participants. 
Table 6: 
Sample Size Calculation
Efgartigimod
40%
45%
50%
Placebo 
1%
16
14
12
5%
22
19
16
10%
34
27
22
15%
52
39
30
20%
87
59
42
Assuming a clinically relevant difference of 30% and an expectation to achieve CRmin in 50% 
of PV participants, a total of 126 participants randomized to either the efgartigimod arm or the 
placebo arm in a 2:1 ratio (84 participants in the efgartigimod arm and 42 participants in the 
placebo arm) will yield more than 90% power in a 2-sided test at the 5% significance level. The 
target number of Japanese participants with PV is 9.  
A representative number of participants with PF (up to approximately 24 participants or 16% of 
the total target population) may participate in the trial, although they are not included in the 
sample size calculation. The target range for the number of Japanese participants with PF is 1 to 
3 (included in the 24 participants globally). Thus, a total of 150 participants can be randomized 
in an allocation ratio of 2:1.
As a result of regulatory interactions, this amendment includes an additional analysis: absence of 
new or established lesions while a participant is off IMP and is receiving minimal therapy for at 
least 2 months (8 weeks).  
For this additional analysis, the assumed response rates are 34% and 11% for efgartigimod and 
placebo, respectively. With 183 participants with PV, this will result in 95% power in a 2-sided 
test at the 5% significance level, assuming that the geopolitical situation in Ukraine and impacted 
areas might result in a 5% power loss.  
In addition, the representative number of participants with PF may increase (up to approximately 
30 participants or 14% of the total target population) to compensate for participants whose data 
are at risk due to the geopolitical situation.  
9.4. 
Populations for Analyses 
The following populations are defined:
Population 
Description 
Modified intent-to-treat 
(mITT) 
All randomized participants (PV and PF participants) who received at least 1 
dose or part of a dose of IMP. Two subsets are identified: PV participants 
and PV+PF participants. Participants will be analyzed according to their 
randomized treatment. 
Per protocol (PP) 
All participants in the mITT population for whom no major protocol 
deviations were reported 


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Population 
Description 
Safety (SAF) 
All randomized participants (PV and PF participants) who received at least 1 
dose or part of a dose of IMP. Participants will be analyzed according to the 
treatment actually received. 
Pharmacokinetic
All participants in the SAF population for whom at least 1 serum PK 
concentration is available 
Pharmacodynamic 
All participants in the SAF population for whom at least 1 serum PD 
concentration is available 
9.5. 
Statistical Analyses 
The SAP will be finalized prior to database lock and it will include a more technical and detailed 
description of the statistical analyses described in this section. This section is a summary of the 
planned statistical analyses of the most important endpoints including primary and key secondary 
endpoints. 
9.5.1. 
General Considerations 
The primary efficacy analysis will be performed on the mITT population subset of PV 
participants. All efficacy key secondary and other secondary analyses will be performed on the 
PV+PF participants population, unless otherwise specified. The safety analyses will also be 
performed on the SAF population (PV+PF participants).
The baseline value will be the last assessment prior to the first administration of efgartigimod 
PH20 SC treatment.  
All trial visits will be recalculated based on actual dates and will be referred to as “analysis 
visits” which will be used in the statistical analyses. The rules for calculating the analysis visits 
will be documented in the SAP. Rules for imputing partial dates or missing dates will also be 
documented in the SAP. 
9.5.2. 
Patient Disposition 
Patient disposition will be summarized in a table. It will include the number of participants 
screened, enrolled or randomized, received IMP treatment, completed the trial, as well as the 
number of early discontinuations from IMP treatment and trial, with reasons for discontinuation 
from IMP or trial. Summaries will be provided overall and by treatment group, for the overall 
trial period, by treatment period and, by follow-up period.
9.5.3. 
Analysis Sets and Protocol Deviations 
The number of participants for each analysis set, as described in Section 9.4, will be presented in 
a table and listing. 
Major protocol deviations, by treatment group and trial stage, will be summarized in a table and 
presented in a listing. 


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9.5.4. 
Demographic and Baseline Characteristics, and Concomitant Medication 
Participant demographic and baseline characteristic data, including prior and concomitant 
therapies will be summarized using standard summary statistics (see Section 9.1) and listed. 
9.5.5. 
Safety Analyses 
Exposure to IMP and cumulative prednisone statistics will be summarized by treatment group, 
separately. 
Summaries of TEAEs and other safety parameters will be provided by treatment group. 
Summary statistics will be presented for all other safety endpoints including vital signs, physical 
examinations, laboratory values and ECGs. 
AEs will be classified using the latest version of the MedDRA classification system. Adverse 
events and AESIs will be listed corresponding to SOC and MedDRA PT. Multiple occurrences 
of a single PT in a participant will be counted only once at the maximum severity/grade. Any 
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. 
9.5.6. 
Primary Endpoint
The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for 
Human Use [ICH] E9 (R1) provides further information on estimands and sensitivity analyses in 
clinical trials; ICH E9 (R1) came into effect on 30 Jul 2020 and follows below.  
Definition of the Estimand for the Primary Endpoint 
 Population: adult participants with moderate to severe PV newly diagnosed or experiencing 
flare, on add-on therapy of low doses of oral prednisone, and that are further defined by the 
inclusion (Section 5.1) and exclusion (Section 5.2) criteria. 
 Variable: proportion of PV participants who achieve CRmin within 30 weeks
 Main intercurrent events (ICEs): 
1. Intercurrent medications before CRmin 
a. Immunosuppressants or dapsone at therapeutic doses for at least 4 weeks 
b. 
 
c. Immunoadsorption or plasma exchange
d. Rituximab or other anti-CD20 biologics 
e. IV corticosteroids >200 mg cumulatively within 2 weeks
2. Discontinuation of IMP before CRmin due to lack of efficacy 
 Population-level summary: the strata-adjusted difference in the proportion of responders
(95% CI) between efgartigimod PH20 SC in combination with add-on therapy of low doses 
of oral prednisone and placebo in combination with add-on therapy of low doses of oral 
prednisone. 


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Handling of Main ICEs
A composite strategy approach will be taken to address both main ICEs. This implies that 
participants that take intercurrent medications before CRmin as specified previously, as well as 
participants that discontinue IMP before CRmin due to lack of efficacy, will be considered 
nonresponders for the primary endpoint analysis. 
Estimation of Treatment Effect and Statistical Inference 
The proportion of participants with PV having achieved CRmin within 30 weeks will be tested 
by means of a stratified Cochran-Mantel-Haenszel (CMH) test using the mITT population. The 
model will be stratified by disease status, disease severity, and body weight at randomization. 
The strata-adjusted difference of proportions will be presented with its 95% CI and 2-sided 
p value. In addition, the odds ratio and its 95% CI will be provided. 
Handling of Missing Data 
Missing data for reason of 1 of the main ICEs will be handled as described above.  
If, for the primary endpoint, CR assessment is missing, the participant will be considered a 
nonresponder. Further details on other imputation techniques for missing CR values will be 
provided in the SAP.  
Details on handling other missing data will also be provided in the SAP. 
Supplementary Analyses 
To facilitate interpretation of the estimated treatment effect in the primary analysis, 
supplementary analyses will be conducted on the supportive estimands where the main ICEs are 
handled differently (eg, by using the hypothetical or treatment policy strategy instead of a 
composite strategy). Moreover, a supplementary landmark analysis will be performed at week 30 
using the same CMH test. Details will be provided in the SAP. 
The proportion of participants with PV who have achieved CRmin and sustain CR while not 
receiving IMP and while receiving minimal prednisone 
(8 weeks) will be analyzed within the scope of the integrated summary of efficacy with 
combined data from trial ARGX-113-1904 and the open-label follow-on trial ARGX-113-1905.  
9.5.7. 
Key Secondary Endpoints Subject to Alpha Control 
The first key secondary endpoint, defined by the proportion of PV+PF participants that have 
achieved CRmin within 30 weeks, will be tested using a stratified CMH test with stratification 
variables similar as for the primary endpoint, using the mITT population. As this first key 
secondary endpoint is similar to the primary endpoint, the same approach for handling the main 
ICEs, as suggested for the primary analysis, will be applied. 
The second key secondary endpoint, cumulative prednisone dose over the trial duration, will be 
analyzed in the form of a normalized cumulative prednisone dose (NCPD), normalizing by 
weight and by number of days in study and will be denoted as NCPD. The NCPD endpoint will 
be analyzed using the mITT population in PV participants. The following formula will be 
adopted to calculate NCPD for each participant. 
NCPD = 
 
 
 
 
 
 
 
 
 
(
 
 
 
 
 
)  (
 
 
 
)  


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For the NCPD endpoint, the analysis of variance (ANOVA) model will be used to compare both 
treatment groups. The model will include treatment and the stratification variables will be 
considered as factors.  
For the third and fourth key secondary endpoint, respectively time to CR and time to DC, both 
treatment groups will be compared using the Fleming-Harrington weighted log-rank statistic FH 
(1,0).44 This analysis will be performed using the mITT population (PV participants). For both 
endpoints, survival curves will be estimated using the Kaplan-Meier time to event method. 
Details on how to deal with the main ICEs for the second, third, and fourth key secondary 
endpoints will be provided in the SAP. 
The primary endpoint will be tested at a 5% 2-sided alpha level and will act as a gatekeeper for 
testing the secondary endpoints. Subject to meeting significance for the primary endpoint, 
secondary endpoints will be tested at the 5% 2-sided significance level in a strict hierarchical 
order as follows: 
1. Comparison of the proportion of PV+PF participants having achieved CRmin within 
30 weeks between efgartigimod PH20 SC and placebo 
2. Comparison of the NCPD in PV participants between efgartigimod PH20 SC and placebo 
3. Comparison of time to CR in PV participants between efgartigimod PH20 SC and 
placebo 
4. Comparison of time to DC in PV participants between efgartigimod PH20 SC and 
placebo 
Supplementary analyses for the key secondary endpoints will be conducted. Subgroup analyses 
for the primary and/or key secondary endpoints may also be conducted. Details will be provided 
in the SAP. 
9.5.8. 
Other Secondary Endpoints 
The time to event and cumulative prednisone dose endpoints that are part of the other secondary 
efficacy endpoints will be analyzed in the mITT population (PV+PF participants) in line with the 
methodologies outlined above for the key secondary efficacy endpoints.  
The remaining binary endpoints will be analyzed in the mITT population using the same 
methodology as for the primary endpoint (stratified CMH test). 
The magnitude of the effect of efgartigimod PH20 SC compared to placebo in the PF 
subpopulation will be evaluated using the posterior distribution of the treatment effect 
(difference between efgartigimod PH20 SC and placebo) obtained in a Bayesian analysis. This 
Bayesian analysis will incorporate historical data for the placebo in an informative maximum a 
posteriori probability estimate prior with robustness modifier.45 Details of this analysis will be 
included in the SAP.  
Analysis of the continuous endpoints GTI-CWS and GTI-AIS (as components of the C-GTI) at 
week 15 and the EoS/ED visit will be analyzed in the mITT using the ANOVA model to 
compare both treatment groups (see Section 9.5.7). The complementary GTI-SL will be analyzed 
descriptively. More details on additional analyses (eg, correlation between GTI-CWS and GTI-
AIS and cumulative or average daily prednisone dose) will be specified in the SAP. 


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Summary statistics and/or summary plots will be presented for all other endpoints, including PK, 
PD, immunogenicity, QoL, and self-administration training. More details for the analysis of the 
endpoints will be described in the SAP. 
9.5.9. 
Other Endpoints 
Results from the exploratory research will be described in a separate report. 
9.6. 
Interim Analyses  
Not applicable.
9.7. 
Data Safety Monitoring Board (DSMB) 
Refer to Section 10.1.5.  


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10.
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, Ethical, and Trial Oversight Considerations 
10.1.1.
Regulatory and Ethical Considerations
This trial will be conducted in accordance with the protocol and with the following:
 Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
 Applicable International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH) Good Clinical Practice (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 trial is initiated.  
Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the trial design, except for changes necessary to eliminate an immediate hazard 
to trial participants. 
Protocols and any substantial amendments to the protocol will require health authority approval 
prior to initiation except for changes necessary to eliminate an immediate hazard to study 
participants. 
The investigator will be responsible for the following: 
 Providing written summaries of the status of the trial to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established 
by the IRB/IEC 
 Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
 Providing oversight of the conduct of the trial at the site and adherence to 
requirements of 21 Code of Federal Regulations (CFR), ICH guidelines, the IRB/IEC, 
European regulation 536/2014 for clinical studies (if applicable), and all other 
applicable local regulations. 
10.1.2.
Financial Disclosure 
The sponsor will fund the trial as outlined in the clinical trial agreement. 
The sponsor will obtain adequate global/local insurance for the trial participants including the 
trial participants for the required duration of time. 
The sponsor maintains an insurance coverage for this trial in accordance with the laws and 
regulations of the countries in which the trial is performed. Liability and insurance provisions for 


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this trial are specified in the investigator’s contract. The terms and conditions will apply as 
specified in the policy document.
10.1.3. 
Informed Consent Process 
Prior to signing the ICF, the trial participants will be instructed not to participate in any other 
clinical trial that involves an intervention or collection of data until the completion of the current 
trial. 
Any participant who provides informed consent will be assigned a unique participant ID via the 
IRT system. 
The investigator or his/her representative will explain the following to the participant and answer 
all questions regarding the trial: the nature of the trial, its purpose, the procedures involved, the 
expected duration, any potential discomfort, potential alternative procedure(s) or course(s) of 
treatment available, and the extent of maintaining confidentiality of the participant's records. 
Participants must be informed that their participation is voluntary, that they may withdraw from 
the trial at any time, and that withdrawal of consent will not affect their subsequent medical 
treatment or relationship with the treating physician. 
Participants will be required to sign a statement of informed consent, after receipt of detailed 
information on the trial, that meets the requirements of 21 CFR 50, local regulations, ICH 
guidelines, Health Insurance Portability and Accountability Act (HIPAA) requirements, where 
applicable, and the IRB/IEC or trial center. 
The ICF will be used to explain the potential risks and benefits of trial participation to the 
participant in simple terms before the participant is screened. 
A separate ICF will be issued in case of pregnancy of a female partner of a male participant.
The ICF contains a statement that the consent is freely given. 
All participant information and ICFs must be available in the local and vernacular languages 
required at the site and include participant information sheets/brochures that outline the trial 
procedures. All ICF(s) must be signed and dated by the participant. 
Confirmation of a participant's informed consent must also be documented in the participant's 
medical record prior to any trial-related procedure under this protocol, including screening tests 
and assessments. The authorized person obtaining the informed consent must also sign the ICF. 
The investigator is responsible for ensuring that the informed consent is obtained from each 
participant and for obtaining the appropriate signatures and dates on the ICF prior to the 
performance of any protocol procedures and prior to the administration of IMP. 
Participants must be re-consented to the most current version of the ICF(s) during their 
participation in the trial. 
A signed and dated copy of the ICF(s) must be provided to the participant. 
Participants may be rescreened (ie, redoing the full assessments as per SoA, Section 1.3) or 
retested once (ie, redoing 1 test) if still within the screening period. See Section 5.4. 


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10.1.4. 
Data Protection 
Participants will be assigned a unique identifier by the sponsor. Any participant records or 
datasets that are 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 his/her personal trial-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant who will be required to give consent for their data to be used as 
described in the informed consent. 
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
Photography is generally accepted as routine practice for documenting dermatological conditions 
in medical practice. Photographs will be taken at baseline and at subsequent visits to document 
response and progression. Participants will be requested to provide consent for any use that will 
be made of the image and for sharing anonymized pictures with the sponsor. 
The ICF will incorporate (or, in some cases, be accompanied by a separate document 
incorporating) wording that complies with relevant data protection and privacy legislation.
10.1.5. 
Committees Structure 
10.1.5.1. Data Safety Monitoring Board 
The sponsor will appoint an independent DSMB consisting of an independent group of clinical 
experts who are not involved in the trial management. They will be supplemented by an 
independent statistician. The objective of the DSMB will be to review all unblinded safety data 
(including the overall number of participants treated up to that point, rates, and participant-level 
details) and the evaluation of IgG. The planning and frequency of the meetings will be detailed 
in a DSMB charter. In addition, ad hoc meetings can be requested at any time during the trial by 
either the sponsor or the DSMB. The DSMB will advise the sponsor regarding continuation, 
modification, or termination of the trial after every meeting.
Additionally, the composition, objectives, role, and responsibilities of the independent DSMB 
will be described in the DSMB charter, agreed with the DSMB members and the sponsor. The 
DSMB charter will also define and document the content of the safety summaries and general 
procedures (including communications). 
10.1.6. 
Dissemination of Clinical Trial Data 
The sponsor or designee, and auditor may access participant records for the purpose of 
monitoring this trial, auditing, and managing progress details. The investigator must be fully 
aware that the sponsor or designee and auditor can inspect documents to verify the accuracy and 
completeness of a participant’s chart and eCRF records. Such information must be kept 
confidential in locked facilities that allow for this. The investigator will prepare and maintain 
adequate and accurate source documents to record all observations and other pertinent data for 
each participant enrolled into the trial.


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The investigator is responsible for maintaining source documents. These will be made available 
for verification by the sponsor’s designated monitor at each monitoring visit. The investigator 
must submit an eCRF for each participant, regardless of duration of participation or 
administration of IMP (ie, an eCRF has to be submitted for screen failures as well). All 
supportive documentation submitted with the eCRF, such as laboratory or hospital records, 
should be clearly identified with the trial and participant number. Any personal information, 
including participant name, should be removed or rendered illegible to preserve data privacy. 
10.1.7. 
Data Quality Assurance 
All participant data relating to the trial will be recorded on electronic CRF unless transmitted to 
the sponsor or designee electronically (eg, laboratory data). The investigator is responsible for 
verifying that data entries are accurate and correct by physically or electronically signing the 
CRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. Only if requested as per local regulations, no source data 
verification will be performed on race and ethnicity. 
The investigator must permit trial-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents.  
Monitoring details describing strategy (eg, risk-based initiatives in operations and quality such as 
Risk Management and Mitigation Strategies and Analytical Risk-Based Monitoring), methods, 
responsibilities and requirements, including handling of noncompliance issues and monitoring 
techniques (central, remote, or on-site monitoring) are provided in the monitoring plan. 
The sponsor or designee is responsible for the data management of this trial including quality 
checking of the data.  
The sponsor assumes accountability for actions delegated to other individuals (eg, 
CROs/sponsor’s designee). 
Trial monitors will perform ongoing source data verification to confirm that data entered into the 
CRF 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 trial is being conducted 
in accordance with the currently approved protocol and any other trial agreements, ICH GCP, 
and all applicable regulatory requirements.  
10.1.7.1. Data Handling and Record Keeping 
It is the investigator’s responsibility to maintain essential trial documents (records and 
documents pertaining to the conduct of this trial and the distribution of IMP, including regulatory 
documents, eCRFs, signed participant ICFs, laboratory test results, IMP inventory records, 
source documents, relevant correspondence, AE reports, and all other supporting documentation) 
as required by the applicable national regulatory requirements. The trial site should plan on 
retaining such documents for approximately 25 years after trial completion. The trial site should 
retain such documents until at least 2 years after the last approval of a marketing application in 
an ICH region and until there are no pending or contemplated marketing applications in an ICH 
region, or at least 2 years after the formal discontinuation of clinical development of the IMP. 
The sponsor will notify the principal investigator of these events. 


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These documents should be retained for a longer period if required by the applicable regulatory 
requirements or the hospital, institution, or private practice in which the trial is being conducted. 
Participant identification codes (ie, participant names and corresponding trial numbers) will be 
retained for this same period of time. These documents may be transferred to another responsible 
party, acceptable to the sponsor, who agrees to abide by the retention policies. The investigator is 
required to notify the sponsor (or an authorized representative) in writing prior to changing the 
location or status of any essential clinical trial documents. The investigator must contact the 
sponsor prior to disposing of any trial records. 
No records should be disposed without the written approval of the sponsor, argenx BV. 
For studies conducted outside the US under an US investigational new drug (IND), the principal 
investigator must comply with US Food and Drug Administration IND regulations and with 
those of the relevant national and local health authorities. 
10.1.7.2. Quality Assurance Audit 
Trial processes, trial sites (including, but not limited to site visits, central laboratories, vendors), 
the trial database, and trial documentation may be subject to quality assurance audit during the 
course of the trial by the sponsor or sponsor’s designee, CRO, or other vendor, on behalf of 
sponsor. In addition, inspections may be conducted by regulatory bodies at their discretion. Such 
audits/inspections can occur at any time during or after completion of the trial. 
10.1.7.3. Quality Control 
Quality control will be applied to each stage of trial-related activities. 
The following steps will be taken to ensure the accuracy, consistency, completeness, and 
reliability of the data: 
 Investigator meetings 
 Central laboratories for clinical laboratory parameters 
 Site initiation visit 
 Routine site monitoring 
 Ongoing site communication and training 
 Ongoing oversight by sponsor’s designated monitors of safety parameters and 
adherence to selection criteria 
 Eligibility review by sponsor’s designated CRO and medical monitors/sponsor’s 
designee 
 Data management quality control checks 
 Continuous data acquisition and cleaning 
 Quality control check of the clinical trial report (CTR) 
 To avoid interobserver variability, every effort should be made to ensure that the 
same individual who made the initial baseline determinations completes all efficacy 
and safety evaluations. 


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In addition, periodic audits can be performed as specified in Section 10.1.7.2.
When audits or inspections are conducted, access must be authorized for all trial-related 
documents including medical history and concomitant medication documentation to the 
authorized sponsor’s representatives and regulatory authorities. 
10.1.8. 
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 trial. Also, current medical 
records must be available. 
The definition of what constitutes source data can be found in the source data agreement, defined 
per site and agreed upon between the CRO/sponsor’s designee and the investigator. 
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the CRF 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. 
10.1.9. 
Monitoring 
The sponsor has engaged the services of a CRO to perform all clinical study monitoring 
functions within this clinical study outside of China. In China, the sponsor has engaged a 
designee. The sponsor’s designated monitors will work in accordance with their applicable 
SOPs. 
Monitoring visits must be conducted according to the applicable ICH GCP guidelines to verify 
that, among others, the: 
 Data are authentic, accurate, and complete 
 Safety and rights of participants are being protected 
 The study is conducted in accordance with the currently approved protocol, any other 
study agreements, and all applicable regulatory requirements. 
The investigator and the head of the medical institution (where applicable) agree to allow the 
sponsor’s designated monitor direct access to all relevant documents. 
The investigator must ensure provision of reasonable time, space, and qualified personnel for 
monitoring visits. 
The sponsor’s designated monitor will perform an eCRF review, source document verification 
(wherever allowed as per local regulations), and source document review. 


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The source documentation agreement form describes the source data for the different data in the 
eCRF. This document should be completed and signed by the sponsor’s designated monitor and 
investigator, and should be filed in the investigator’s study file. Any data item for which the 
eCRF will serve as the source must be identified, agreed, and documented in the source 
documentation agreement form.
Upon completion or premature discontinuation from the study, the sponsor’s designated monitor 
will conduct site closure activities with the investigator and site staff as appropriate, in 
accordance with applicable regulations, ICH GCP guidelines, and CRO/sponsor’s 
designee/sponsor procedures. 
10.1.10. 
Data Management 
Data generated within this clinical study will be processed according to the SOPs of the data 
management and biostatistics departments of the sponsor’s designated CRO/sponsor’s designee.
Case report forms are provided for each participant in electronic format (ie, eCRF). Data will be 
transcribed by the study site staff from the source documents onto the eCRF, as per local 
regulations. Data must be entered in English. Guidelines for eCRF completion, including the 
collection of the investigator’s e-signature, will be provided by the CRO/sponsor’s designee. 
Appropriate training and security measures will be completed by the investigator and all 
designated site staff prior to the study being initiated, and any data being entered into the system 
for any study participant at the site. 
The eCRF is essentially considered a data entry form and should not constitute the original (or 
source) medical records unless otherwise specified. Only if requested as per local regulations, no 
data collection or source data verification will be performed on race and ethnicity. Source 
documents are all documents used by the investigator or hospital that relate to the participant’s 
medical history, that verify the existence of the participant, the inclusion and exclusion criteria, 
and all records covering the participant’s participation in the study. They can include laboratory 
notes, ECG results, memoranda, pharmacy dispensing records, participant files, etc. The eCRFs 
should be completed by the investigator or a qualified designee from the site as soon as the data 
are available. 
As a matter of regulation, the investigator is responsible for the accuracy and authenticity of all 
clinical data entered onto eCRFs. Prior to database lock, each completed eCRF must be reviewed 
for accuracy by the investigator, corrected as necessary, and then approved. The investigator’s e-
signature serves to attest that the information contained in the eCRFs has been reviewed by the 
investigator and is true and accurate. The investigator will be required to electronically sign off 
the eCRF. 
The data will be verified for completeness, missing data, inconsistencies, and for necessary 
medical clarifications. Queries arising from these checks will be flagged to the study site, and the 
study site staff will correct data, confirm, or clarify data as appropriate. The CRO/sponsor’s 
designee will provide the details of the review process in a data management plan and a 
monitoring plan. Any change, including the issuing of queries, will be fully audit-trailed by the 
electronic data capture system, meaning the name of the person, time, and date stamp are 
captured, as well as the reason for change. 


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Data will also be provided by third party vendors, such as the results generated by the central 
laboratories, ECG reader, etc. These data will need to be reconciled with the data recorded in the 
eCRF before it can be merged with the eCRF data into the clinical database. The CRO/sponsor’s 
designee will provide a data management plan detailing this reconciliation. 
AEs, concomitant diseases, and medical history terms will be assigned to a lowest level term and 
a PT, and will be classified by high level term, high level group term, and primary SOC 
according to the MedDRA thesaurus. 
Prior and concomitant medications, including concomitant pemphigus therapy, will be classified 
according to active drug substance using the WHO drug dictionary (WHODD). The generic 
name, the preferred name, and the WHO name will be assigned using the WHODD thesaurus.
The anatomical therapeutic chemical classes will be assigned to the prior and concomitant 
medications and procedures. Prior and concomitant procedures will be coded according to the 
MedDRA thesaurus.
10.1.11. 
Study and Site Start and Closure 
The study start date is the date on which the clinical study will be open for recruitment of 
participants, upon availability of mandatory approvals. 
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 may 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 may include but are not limited to: 
 Safety concerns as recommended by the DSMB 
 Inability to achieve the recruitment target within a reasonable time 
 Determination that no further benefits are expected from the study (in the sponsor’s 
judgment)
 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
 Discontinuation of further study medication development
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, any CRO(s) used in the study, and the 
sponsor’s designee of the study, of the reason for termination or suspension, as specified by the 
applicable regulatory requirements. The investigator shall promptly inform the participant and 
should assure appropriate participant therapy and/or follow-up. 
The study can also be terminated by the regulatory authority for any reason or at a site level by 
the IRB/IEC. The sponsor may close individual study sites prematurely for reasons such as poor 
protocol compliance or unsatisfactory recruitment of participants. 


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10.1.12. 
Investigator Obligations 
This study will be conducted by qualified investigators under the sponsorship of argenx BV (the 
sponsor). 
The name and telephone/fax numbers of the sponsor’s designated monitor and other contact 
personnel at the sponsor and the sponsor’s designee are listed in the investigator study file 
provided to each site. 
The investigator is responsible for ensuring that all study site personnel, including sub 
investigators, adhere to all applicable regulations and guidelines, including local laws and 
regulations, regarding the study, both during and after study completion. The investigator is 
responsible for informing the IRB/IEC of the progress of the study and for obtaining annual 
IRB/IEC renewal. The investigator is responsible for informing the IRB/IEC of completion of 
the study and will provide the IRB/IEC with a summary of the results of the study. 
The investigator will comply with the protocol that has been approved/given favorable opinion 
by the IRB/IEC, according to ICH GCP and applicable regulatory requirements. The investigator 
is ultimately responsible for the conduct of all aspects of the study at the study site and verifies 
by signature the integrity of all data transmitted to the sponsor. The term “investigator” as used 
in this protocol as well as in other study documents, refers to the investigator or site staff that the 
investigator has designated to perform certain duties. Sub investigators or other designated site 
staff are eligible to sign for the investigator, except where the investigator’s signature is 
specifically required. 
10.1.13. 
Protocol Signatures 
After reading the protocol, each principal investigator will sign the protocol signature page and 
send a copy of the signed page to the sponsor or representative. By signing the protocol, the 
investigator confirms in writing that he/she has read, understands, and will strictly adhere to the 
study protocol, and will conduct the study in accordance with ICH tripartite guidelines for GCP 
and applicable regulatory requirements. The study will not be able to start at any site where the 
principal investigator has not signed the protocol. 
10.1.14. 
Publication Policy 
All information regarding efgartigimod supplied by the sponsor to the investigator and all data 
generated as a result of this study, are considered confidential and remain the sole property of the 
sponsor. The results of the study will be reported in a CTR. 
The CTR written in accordance with the ICH E3 guideline, will be submitted in accordance with 
local regulations. 
Any manuscript, abstract or other publication, presentation of results, or information arising in 
connection with the study must be prepared in conjunction with the sponsor after the study has 
been analyzed and reported and must be submitted to the sponsor for review and comment prior 
to submission for publication or presentation. Study participant identifiers will not be used in the 
publication of results. 
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 


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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 in line with International Committee of 
Medical Journal Editors criteria authorship requirements, based on scientific input and 
recruitment efforts.
The sponsor will register and/or disclose the existence of and the results of clinical studies as 
required by law. 


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10.2.
Appendix 2: Laboratory Tests
Table 7 is applicable globally, except for China. An overview of the protocol-required laboratory 
assessments performed in China is provided in Section 10.16.1.3, Table 17.  
Table 7: 
Protocol-Required Laboratory Assessments 
Hematology 
Hemoglobin, hematocrit, MCV, RBC count, platelet count, WBC count with 
differential 
Clinical chemistry 
Sodium, potassium, calcium, HbA1c, creatinine, creatinine clearance, BUN, 
ALT, AST, total bilirubin, GGT, LDL-C, CRP, ALP, LDH, HDL-C, total 
cholesterol, triglycerides, uric acid, total proteina, and albumina 
Coagulation 
 INR or aPTT  
Urinalysis
Specific gravity, pH, protein, glucose, ketones, blood, bilirubin, urobilinogen, 
nitrite, leukocyte esterase, and microscopic examination (if blood or protein test 
results are abnormal) 
Serology 
HIV antibodies (1 and 2), HBsAg, anti-HBs; anti-HBc, HBV DNA, HCV 
antibodies, HCV mRNA 
Other 
Serum ß-HCG, FSH test 
Pharmacokineticsa 
Serum levels of efgartigimod 
Pharmacodynamic 
markersa 
Serum levels of total IgG and IgG subtypes (IgG1, IgG2, IgG3, and IgG4) and 
anti-Dsg-1 and anti-Dsg-3 autoantibodies  
Immunogenicitya 
Serum levels of ADA to efgartigimod and plasma levels of antibodies against 
rHuPH20 
Local evaluations 
Urine pregnancy test 
ß-HCG= ß subunit of  human chorionic gonadotrophin; ADA= antidrug antibodies; ALP= alkaline phosphatase; 
ALT= alanine aminotransferase; anti-Dsg-1=anti-desmoglein-1; anti-Dsg-3=anti-desmoglein-3; 
anti-HBs=antibodies to the surface antigens of the hepatitis B virus; anti-HBc= antibodies to the surface core 
antigens of the hepatitis B virus; aPTT= activated partial thromboplastin time; AST=aspartate aminotransferase; 
BUN=blood urea nitrogen; CRP=C-reactive protein; DNA= deoxyribonucleic acid; FSH=follicle-stimulating 
hormone GGT=gamma-glutamyl transferase; HbA1c= hemoglobin A1c; HBV=hepatitis B virus; HBsAg=hepatitis 
B surface antigen; HCV=hepatitis C virus; HDL-C=high-density lipoprotein cholesterol; HIV= human 
immunodeficiency viruses; IgG=immunoglobulin G; INR=international normalized ratio; LDH= lactate 
dehydrogenase; LDL-C=low-density lipoprotein cholesterol MCV=mean corpuscular volume; mRNA= messenger 
RNA; RBC= red blood cell; rHuPH20=recombinant human hyaluronidase; RNA=ribonucleic acid; WBC=white 
blood cell 
a PK, PD, immunogenicity, albumin, and total protein data will not be reported to the site. A system will be 
implemented that will alert the investigator of out-of-range albumin and total protein values, to allow for 
appropriate safety follow-up.  
10.2.1. 
Other Screening Tests 
10.2.1.1. Hepatitis B Virus 
Patients with an active acute or chronic hepatitis B viral (HBV) infection at screening cannot be 
enrolled in the trial. 
The following combinations of serologic markers will be used to identify an active HBV 
infection (https://www.cdc.gov/hepatitis/HBV/PDFs/SerologicChartv8.pdf): 


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Table 8:
Interpretation of Hepatitis B Serological Test Results
Test Result 
Interpretation 
HBsAg
Anti-HBc
Anti-HBs
Positive 
Positive 
Negative 
The patient cannot be enrolled in the trial because the test 
results indicate an active HBV infection.  
Negative 
Positive 
Negative 
The patient cannot be enrolled in the trial because the test 
results indicate a low-level chronic HBV infection with 
impaired liver function.a 
anti-HBc=total hepatitis B core antibody; anti-HBs=hepatitis B surface antibody; HBsAg=hepatitis B surface 
antigen; HBV=hepatitis virus 
a This decision will be made by a medical doctor with sufficient experience in hepatology or infectious disease. 
Additional tests (eg, HBV viral load) may be required to determine the status of the participant. 
10.2.1.2. Hepatitis C Virus 
Patients with an active acute or chronic hepatitis C viral infection at screening cannot be enrolled 
in the trial. Patients with positive serology for hepatitis C virus antibody should not be enrolled 
unless associated with a negative HCV mRNA test.
10.2.1.3. Human Immunodeficiency Virus 
Patients who are HIV positive and do not have an AIDS-defining condition or a CD4 count 
>200 cells/mm3 at screening can be enrolled in the trial (see Table 9). Patients who are HIV 
positive and have an AIDS-
3 at screening 
cannot be enrolled in the trial. The following are considered AIDS-defining conditions: 
 Cytomegalovirus retinitis with loss of vision
 Pneumocystis jiroveci pneumonia
 Chronic intestinal cryptosporidiosis 
 HIV-related encephalopathy 
 Mycobacterium tuberculosis (pulmonary or extrapulmonary) 
 Invasive cervical cancer 
Table 9: 
Interpretation of HIV Test Results in Combination With the Patient’s 
Clinical Condition and CD4 Count
HIV Test Result 
Clinical Condition or CD4 Count 
Interpretation 
Positive 
AIDS-defining condition is present or 
 cells/mm3 
The patient cannot be enrolled in the 
trial because test results and clinical 
condition or CD4 count confirm the 
diagnosis of AIDS.   
AIDS=acquired immune deficiency syndrome; HIV=human immunodeficiency virus 
 


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10.3.
Appendix 3: Washout Requirements Prior to First IMP 
Administration 
Drug/Intervention/Event 
Prohibited Period (from Last Dose of Agent) 
Any monoclonal antibody (including rituximab or 
another anti-CD20 biologic) 
6 months 
Intravenous methylprednisolone, sulfasalazine, 
tetracyclines, nicotinamidea, plasmapheresis/plasma 
exchange, immunoadsorption, and IVIg 
2 months 
Live/attenuated viral vaccines
28 days
Any investigational drug
3 months or 5 half-lives of the drug (whichever 
is longer) 
Conventional immunosuppressants (eg, azathioprine, 
cyclophosphamide, methotrexate, mycophenolate 
mofetil) or dapsone 
Allowed until baseline 
For Chinese participants enrolled in China only: 
Complementary therapies, including traditional 
Chinese medicines, herbs, or procedures (eg, 
acupuncture) that can potentially interfere with the 
efficacy assessments and the safety of the participant, 
as assessed by the investigator 
4 weeks 
DRI=dietary reference intake; IVIg=immunoglobulins given intravenously; RDA=recommended daily allowance 
a Only nicotinamide above the RDA/DRI must fulfill the washout requirements. Nicotinamide doses at or below the 
RDA/DRI are allowed and do not required washout. 


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10.4.
Appendix 4: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
10.4.1. 
Definition of AE 
AE Definition 
 
An AE is any untoward medical occurrence in a clinical study participant, temporally 
associated with the use of study intervention, whether or not considered related to the study 
intervention. 
 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the 
use of study intervention. 
Definition of Unsolicited and Solicited AE 
 
An unsolicited adverse event is an adverse event that was not solicited using a Participant 
Diary and that is communicated by a participant who has signed the informed consent. 
Unsolicited AEs include serious and non-serious AEs. 
 
Potential unsolicited AEs may be medically attended (ie, symptoms or illnesses requiring a 
hospitalization, or emergency room visit, or visit to/by a health care provider). The 
participants will be instructed to contact the site as soon as possible to report medically 
attended event(s), as well as any events that, though not medically attended, are of 
participant’s concern. Detailed information about reported unsolicited AEs will be collected 
by qualified site personnel and documented in the participant’s records. 
 
Unsolicited AEs that are not medically attended nor perceived as a concern by participants 
will be collected during interview with the participants and by review of available medical 
records at the next visit. 
 
Solicited AEs are predefined local at the injection site and systemic events for which the 
participant is specifically questioned, and which are noted by the participant in their diary. 
Events to be Collected as AEs 
 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other 
safety assessments (eg, ECG, radiological scans, vital signs measurements), including those 
that worsen from baseline, considered clinically significant in the medical and scientific 
judgment of the investigator (ie, not related to progression of underlying disease). 
 
Exacerbation of a chronic or intermittent pre-existing condition including either an increase in 
frequency and/or intensity of the condition. 
 
New conditions detected or diagnosed after study intervention administration even though it 
may have been present before the start of the study. 
 
Signs, symptoms, or the clinical sequelae of a suspected intervention- intervention interaction. 
 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study intervention 
or a concomitant medication. Overdose per se will not be reported as an AE/SAE unless it is 
an intentional overdose taken with possible suicidal/self-harming intent. Such overdoses 
should be reported regardless of sequelae. 


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Events to be Collected as AEs 
 
“Lack of efficacy” or “failure of expected pharmacological action” per se will not be reported 
as an AE or SAE. Such instances will be captured in the efficacy assessments. However, the 
signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will be reported as 
AE or SAE if they fulfill the definition of an AE or SAE. 
Events NOT to be Collected as AEs
 
Any clinically significant abnormal laboratory findings or other abnormal safety assessments 
which are associated with the underlying disease, unless judged by the investigator to be more 
severe than expected for the participant’s condition. 
 
The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
condition. 
 
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to the 
procedure is the AE. 
 
Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital). 
 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen. 
10.4.2. 
Definition of SAE
A SAE is defined as any untoward medical occurrence that, at any dose: 
1. Results in death 
2. Is life-threatening 
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, which 
hypothetically might have caused death, if it were more severe. 
3. Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been admitted (usually involving at 
least an overnight stay) at the hospital or emergency ward for observation and/or treatment that 
would not have been appropriate in the physician’s office or outpatient setting. Complications 
that occur during hospitalization are AEs. If a complication prolongs hospitalization or fulfills 
any other seriousness criteria, the event will be considered as serious. When in doubt as to 
whether “hospitalization” occurred or was necessary, the AE should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline will not collected as an AE. 
4. Results in persistent or significant disability/incapacity 
The term disability means a substantial disruption of a person’s ability to conduct normal life 
functions. 
This definition is not intended to include experiences of relatively minor medical significance 
such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma 


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A SAE is defined as any untoward medical occurrence that, at any dose: 
(eg, sprained ankle) which may interfere with or prevent everyday life functions but do not 
constitute a substantial disruption.
5. Is a congenital anomaly/birth defect
6.
Other situations:
Medical or scientific judgment should be exercised by the investigator in deciding whether SAE 
reporting is appropriate in other situations such as significant medical events that may jeopardize 
the participant or may require medical or surgical intervention to prevent 1 of the other outcomes 
listed in the above definition. These events should usually be considered serious. 
Examples of such events include invasive or malignant cancers, intensive treatment for allergic 
bronchospasm, blood dyscrasias, convulsions or development of intervention dependency or 
intervention abuse. 
10.4.3. 
Recording and Follow-up of AEs and/or SAEs 
AE and SAE Recording 
When an AE/SAE occurs, it is the responsibility of the investigator to review all documentation 
(eg, hospital progress notes, laboratory reports, and diagnostics reports) related to the event. 
The investigator will then record all relevant AE/SAE information. 
It is not acceptable for the investigator to send photocopies of the participant’s medical records in 
lieu of completion of the required form. 
There may be instances when copies of medical records for certain cases are requested. In this 
case, all participant identifiers, with the exception of the participant number, will be redacted on 
the copies of the medical records before submission. 
The investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information. Whenever possible, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE/SAE. 
Assessment of Severity 
The investigator will make an assessment of intensity for each AE and SAE reported during the 
study. 
All AEs observed will be graded using the National Cancer Institute (NCI) Common 
Terminology Criteria for Adverse Events (CTCAE) version 5.0. The NCI CTCAE is a descriptive 
terminology, which can be utilized for AE reporting. A grading (severity) scale is provided for 
each AE term.  
The grade refers to the severity of the AE. If a particular AE’s severity is not specifically graded 
by the guidance document, the investigator is to use the general NCI CTCAE definitions of grade 
1 through grade 5 following his or her best medical judgment. The CTCAE displays grades 1 
through 5 with unique clinical descriptions of severity for each AE based on the following 
general guideline: 
Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate 
instrumental activities of daily living. 


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Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living.
Grade 4: Life-threatening consequences; urgent intervention indicated. 
Grade 5: Death related to AE. 
Note: a semi-colon indicates ‘or’ within the description of the grades. 
An AE that is assessed as severe should not be confused with an SAE. Severe is a category 
utilized for rating the intensity of an event; both AEs and SAEs can be assessed as severe. An 
event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as described in 
the definition of an SAE, NOT when it is rated as severe. 
Assessment of Causality 
The investigator is obligated to assess the relationship between study intervention and each 
occurrence of each AE/SAE, under 1 of the following categories. 
 
Not related: Events can be classified as “not related” if there is not a reasonable possibility 
that the IMP caused the AE. 
 
Unlikely related: An “unlikely” relationship suggests that only a remote connection exists 
between the IMP and the reported AE. Other conditions, including chronic illness, 
progression or expression of the disease state, or reaction to concomitant medication, appear 
to explain the reported AE. 
 
Possibly related: A “possible” relationship suggests that the association of the AE with the 
IMP is unknown; however, the AE is not reasonably supported by other conditions. 
 
Probably related: A “probable” relationship suggests that a reasonable temporal sequence of 
the AE with drug administration exists and, in the Investigator’s clinical judgment, it is likely 
that a causal relationship exists between the drug administration and the AE, and other 
conditions (concurrent illness, progression or expression of disease state, or concomitant 
medication reactions) do not appear to explain the AE. 
 
Related: A “related” relationship suggests that the AE follows a reasonable temporal 
sequence from administration of IMP, it follows a known or expected response pattern to the 
IMP, and it cannot reasonably be explained by known characteristics of patient’s clinical 
state. 
A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
The investigator will use clinical judgment to determine the relationship. 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, as 
well as the temporal relationship of the event to study intervention administration will be 
considered and investigated. 
The investigator will also consult the IB and/or Product Information, for marketed products, in 
his/her assessment. 
For each AE/SAE, the investigator must document in the medical notes that he/she has reviewed 
the AE/SAE and has provided an assessment of causality. 
There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report. However, it is very important that the investigator 
always make an assessment of causality for every event before the initial transmission of the SAE 
data. 


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Assessment of Causality 
The investigator may change his/her opinion of causality in light of follow-up information and 
send an SAE follow-up report with the updated causality assessment.
The causality assessment is 1 of the criteria used when determining regulatory reporting 
requirements. 
For final reporting purposes, the relationship will be converted into “Binary Determination,” per 
CIOMS. Unrelated and Unlikely Related will be merged into “Unrelated” and Related, Possibly 
Related, and Probably Related will be merged into “Related.” 
Follow-up of AEs and SAEs 
The investigator is obligated to perform or arrange for the conduct of supplemental measurements 
and/or evaluations as medically indicated or as requested to elucidate the nature and/or causality 
of the AE or SAE as fully as possible. This may include additional laboratory tests or 
investigations, histopathological examinations, or consultation with other health care 
professionals. 
If a participant dies during participation in the study or during a recognized follow-up period, the 
investigator will provide a copy of any post-mortem findings including histopathology.  
New or updated information will be recorded in the originally submitted documents. 
The investigator will submit any updated SAE data within 24 hours of receipt of the information.
10.4.4. 
Reporting of SAEs and AESIs
SAE and AESI Reporting 
 All SAEs and AESIs will be recorded on the AE form of the eCRF. SAEs will also be recorded 
on the paper SAE report form. 
 The investigator or designated site staff will ensure all entered data are consistent. 
 An email alert for the SAE and AESI reports on the eCRF will automatically be sent to the 
sponsor/designee’s safety mailbox via the electronic data capturing (eDC) system. 
 The paper SAE report form will be faxed or emailed to the sponsor/designee (see Serious 
Adverse Event Reporting on page 2 of this protocol). 


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10.5.
Appendix 5: Contraceptive and Barrier Guidance and Collection of 
Pregnancy Information 
10.5.1. 
Definitions:
10.5.1.1. Woman of Childbearing Potential
A woman is considered to be of childbearing potential 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. A historical pretreatment FSH measurement of >40 IU/L is accepted as 
proof of a postmenopausal state for women on hormone replacement therapy.
b. Surgically sterilized: Women who have had a documented permanent sterilization 
procedure (ie, hysterectomy, bilateral salpingectomy, or bilateral oophorectomy). 
10.5.2. 
Contraception Guidance:
10.5.2.1. Female Contraception for Women of Childbearing Potential
Women of childbearing potential must use a highly effective or acceptable contraception 
method, which should be maintained at minimum until after the last dose of IMP. 
The same type of hormonal contraception must have been received for at least 1 month before 
starting the study. 
Highly effective methods of contraception are: 
1. Combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulation 
a. Oral 
b. Intravaginal 
c. Transdermal 
2. Progestogen-only hormonal contraception associated with inhibition of ovulation 
a. Oral 
b. Injectable 
c. Implantable 
3. Intrauterine device (IUD) 
4. Intrauterine hormone-releasing system (IUS) 
5. Bilateral tubal occlusion 
6. Vasectomized partner 
7. Sexual abstinence 


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Acceptable methods of contraception are:
1. Progestogen-only hormonal contraception in which inhibition of ovulation is not the 
primary mode of action 
a. Oral 
b. Injectable 
c. Implantable 
2. Male or female condom with or without spermicide
3. Cap, diaphragm, or sponge with spermicide
10.5.2.2. Male Contraception: 
An acceptable method of contraception is a condom. 
10.5.3. 
Collection of Pregnancy Information 
Male Participants With Partners Who Become Pregnant 
 Male participants will be instructed through the ICF to immediately inform the 
investigator if their partner becomes pregnant during the trial. 
 The investigator will attempt to collect pregnancy information on any male 
participant’s female partner who becomes pregnant while the male participant is in 
this trial. 
 After obtaining the necessary signed informed consent from the pregnant female 
partner directly, the investigator will record pregnancy information on the appropriate 
form and submit it to the sponsor within 24 hours of learning of the partner’s 
pregnancy and submitted via email or fax (see the Safety Mailbox/Fax details on 
page 2 of this protocol). 
 The female partner will also be followed to determine the outcome of the pregnancy. 
Information on the status of the mother and child will be forwarded to the sponsor. 
Generally, the follow-up will be no longer than 6 to 8 weeks following the estimated 
delivery date. Any termination of the pregnancy will be reported regardless of fetal 
status (presence or absence of anomalies) or indication for the procedure. 
 An investigator, who is contacted by the male participant or his pregnant partner, may 
provide information on the risks of the pregnancy and the possible effects on the 
fetus, to support an informed decision in cooperation with the physician and/or 
obstetrician. 
Female Participants Who Become Pregnant 
 A serum pregnancy test will be performed at screening. A urine pregnancy test will 
be conducted and analyzed locally at the visits detailed in the SoA (Section 1.3). 
 The investigator will collect pregnancy information on any female participant who 
becomes pregnant during the period of administration of IMP. The initial information 
will be recorded on the appropriate form and submitted to the sponsor and/or 


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sponsor’s designee within 24 hours of learning of a participant’s pregnancy. The 
following actions will be performed: 
The participant should immediately be discontinued from treatment.
The participant should have the ED assessments and enter the follow-up period.
All assessments for ED (see Section 7) must be performed unless contraindicated 
by pregnancy (harmful to fetus) or unless the participant withdraws informed 
consent. 
 The participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow-up information on the participant and the neonate and 
the information will be forwarded to the sponsor. Generally, follow-up will not be 
required for longer than 6 to 8 weeks beyond the estimated delivery date. Any 
termination of pregnancy will be reported, regardless of fetal status (presence or 
absence of anomalies) or indication for the procedure. 
 While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be 
reported as an AE or SAE. A spontaneous abortion (occurring at <22 weeks 
gestational age) or still birth (occurring at >22 weeks gestational age) is always 
considered to be an SAE and will be reported as such. Any posttrial pregnancy-
related SAE considered reasonably related to the IMP by the investigator will be 
reported to the sponsor as described in Section 8.4.5. While the investigator is not 
obligated to actively seek this information in former trial participants, he or she may 
learn of an SAE through spontaneous reporting. 
 The investigator must update the participant with information currently known about 
potential risks and available treatment alternatives. 
 If required by local regulations, the female participant will be requested to sign a 
separate pregnancy ICF. 
 Full details will be recorded on a paper pregnancy report form and submitted via 
email or fax (see the Safety Mailbox/Fax details on page 2 of this protocol), and 
reporting details will be specified in the trial manual. The investigator will update the 
pregnancy report form with additional information as soon as the outcome of the 
pregnancy is known.
If the outcome of the pregnancy is an SAE, then this must be additionally reported as 
an SAE on the appropriate SAE report form.
 


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10.6.
Appendix 6: Administrative Structure 
The vendors listed below are applicable globally, except for China, where only SGS Life 
Sciences and Clario are used. 
Central Laboratories
Cerba Research NV 
Industriepark Zwijnaarde 3 
B-9052 Gent 
Belgium
Analysis of Pharmacokinetics (PK) and Antidrug Antibodies (ADA)
DDS (formerly known as LGC) 
Newmarket Road 
Fordham 
Cambridgeshire 
CB7 5WWW 
United Kingdom
Total IgG and IgG Subtypes
PPD Central Lab 
PPD Laboratories – US 
2 Tesseneer Drive  
Highland Heights, KY 41076  
USA 
Antibodies and Neutralizing Antibodies Against rHuPH20
Labcorp Bioanalytical Services LLC 
8211 SciCor Drive, Suite B 
Indianapolis, IN 46214 
USA 
Long-term Storage of Samples 
Azenta Life Sciences 
BioStorage Technologies GmbH 
Im Leuschnerpark 1B 
64347 Griesheim  
Germany 
Central ECG Reading 
Clario 
1818 Market Street, Suite 2600
Philadelphia, PA 19103 
USA 
Trial Monitoring/Medical Monitoring 
Pharmaceutical Product Development (PPD) Global Ltd 
Granta Park, Great Abington 
Cambridge, CB21 6GQ, United Kingdom   
Phone: +44 1223 374100  
Data Management and Biostatistics, and Coordination of Data Safety Monitoring Board 
SGS Life Sciences (SGS LS), a division of SGS Belgium NV
Generaal de Wittelaan 19A b5 
B-2800 Mechelen 
Belgium 


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Urinalysis and Peripheral Blood Mononuclear Cell (PBMC) Processing – India only
IQVIA RDS (India) Private Limited
301-A-2, Leela Business Park 
M.V. Road, Andheri (East) 
Mumbai- 400059 
India
 


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10.7.
Appendix 7: Genetics
The instructions outlined in this section are applicable globally, except for China, where no 
genetic research will be conducted. 
Use/Analysis of DNA 
Genetic variation may impact a participant’s response to study intervention, susceptibility to, and 
severity and progression of disease. Variable response to study intervention may be due to 
genetic determinants that impact intervention absorption, distribution, metabolism, and 
excretion; mechanism of action of the intervention; disease etiology; and/or molecular subtype of 
the disease being treated. Therefore, where local regulations and IRB/IEC allow, a blood sample 
will be collected for DNA analysis from consenting participants. 
DNA samples will be used for research related to efgartigimod or pemphigus and related 
diseases. They may also be used to develop tests/assays including diagnostic tests related to 
efgartigimod and pemphigus. Genetic research may consist of the analysis of 1 or more 
candidate genes or the analysis of genetic markers throughout the genome (as appropriate). 
The samples may be analyzed as part of a multi-study assessment of genetic factors involved in 
the response to efgartigimod PH20 SC or study interventions of this class to understand study 
disease or related conditions. 
The results of genetic analyses may be reported in the clinical study report or in a separate study 
summary. 
The sponsor will store the DNA samples in a secure storage space with adequate measures to 
protect confidentiality. 
The samples will be retained while research on efgartigimod continues but no longer than 
15 years or other period as per local requirements. 
 
 


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10.8.
Appendix 8: Pemphigus Disease Area Index (PDAI) Scoring System
Copyright © 2007 University of Pennsylvania; All Rights Reserved


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10.9.
Appendix 9: Karnofsky Performance Score


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10.10.
Appendix 10: EQ-5D-5L Instrument


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10.11.
Appendix 11: Autoimmune Bullous Disease Quality of Life (ABQOL) 
Questionnaire


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10.12.
Appendix 12: Definition of Terms
Blinding: 
A procedure in which 1 or more parties to the trial are kept unaware of the treatment assignment 
in order to reduce the risk of biased trial outcomes. The level of blinding is maintained 
throughout the conduct of the trial, and only when the data are cleaned to an acceptable level of 
quality will appropriate personnel be unblinded or when required in case of an AE or SAE. In a 
double-blinded trial, the participant, the investigator, site staff, and sponsor staff who are 
involved in the treatment or clinical evaluation of the participants and the review or analysis of 
data are all unaware of the treatment assignment. 
Complete clinical remission (CR):  
The absence of new lesions and complete healing of established lesions (except for 
post-inflammatory hyperpigmentation or erythema from resolving lesions). 
Complete remission on minimal therapy (CRmin):  
The absence of new and established lesions completely healed while the participant is receiving 
(Note: In this trial, when 
10 mg/day is reached, this dose level must be maintained for 8 weeks until CRmin has been 
achieved.) 
Council for International Organizations of Medical Sciences (CIOMS): 
The CIOMS is an international, non-governmental, non-profit organization established jointly by 
the WHO and United Nations Educational, Scientific and Cultural Organization in 1949. They 
provide a set of ethical principles regarding human experimentations, including International 
Reporting of Adverse Drug Reactions (ADRs) and International Reporting of Periodic Drug 
Safety Update Summaries. 
The CIOMS form provides a standardized format for the reporting of suspected adverse reactions 
to any particular medicinal product and is the accepted and widely used format for reporting 
suspected ADRs/suspected unexpected serious adverse reaction (SUSARs) in clinical trials. 
Contract Research Organization (CRO): 
A person, or a group of persons (commercial, academic, or other), who, as an independent 
contractor with argenx BV, assume(s) 1 or more obligations of argenx BV, eg, development of a 
protocol, selection and/or monitoring of investigators, evaluation of reports, preparation of 
materials to be submitted to regulatory authorities. 
Database lock: 
An action taken to prevent further changes to a trial database. A database is locked after review, 
query resolution, data cleaning and determination that it is ready for analysis. 
Data Safety Monitoring Board (DSMB): 
Independent group of experts that advises and whose responsibilities are to periodically review 
and evaluate the accumulated trial data for participant safety, trial conduct and progress and, 


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when appropriate, efficacy, and to make recommendations to the sponsor concerning the 
continuation, modification or termination of the trial. 
Disease control (DC):  
The absence of new lesions and the start of healing of established lesions.
Disease progression:  
d at any post-baseline visit before DC. 
Eligible: 
Qualified for randomization into the trial based upon strict adherence to inclusion/exclusion 
criteria. 
End of consolidation (EoC):  
The time at which no new lesions have developed for a minimum of 2 weeks and approximately 
80% of lesions have healed . 
Flare:  
Appearance of 3 or more new lesions in a 4-week period that do not heal spontaneously within 
1 week or the extension of established lesions, in a participant who had achieved DC. 
Good Clinical Practice (GCP): 
A standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and 
reporting of clinical trials that provides assurance that the data and reported results are credible 
and accurate, and that the rights, integrity, and confidentiality of trial participants are protected 
(ICH E6 [R2]). 
Institutional Review Board/Independent Ethics Committee: 
An independent body (a review board or a committee, institutional, regional, national, or 
supranational), constituted of medical professionals and non-medical members, whose 
responsibility it is to ensure the protection of the rights, safety and wellbeing of human subjects 
involved in a trial and to provide public assurance of that protection, by, among other things, 
reviewing and approving / providing favorable opinion on, the trial protocol, the suitability of the 
investigator(s), facilities, and the methods and material to be used in obtaining and documenting 
informed consent of the trial subjects. 
Informed consent/ Informed Consent Form (ICF): 
A process by which a clinical investigation participant voluntarily confirms his or her 
willingness to participate in a particular clinical trial, after having been informed of all aspects of 
the trial that are relevant to the participant’s decision to participate. Informed consent is 
documented by means of a dated and signed ICF. 
Insufficient clinical change:  
The absence of DC after 3–4 weeks of the participant being treated at the starting baseline dose 
or after 3–4 weeks of any new incremented dose of prednisone. 


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International Council for Harmonisation (ICH):
The ICH is a project that brings together the regulatory authorities of Europe, Japan, and the US, 
and experts from the pharmaceutical industry in the 3 regions to discuss scientific and technical 
aspects of pharmaceutical product registration. 
Investigational Medicinal Product (IMP):
A pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a 
clinical trial, including a product with a marketing authorization when used in a way different 
from the approved form, or when used for an unapproved indication, or when used to gain 
further information about an approved use. 
Japanese participant: 
A participant whose parents and 4 grandparents are Japanese, and who has Japanese nationality, 
was born in Japan, has not lived outside of Japan for a total of >10 years, and currently lives in 
Japan.  
Protocol amendment: 
A written description of a change(s) to or formal clarification of a protocol. 
Randomization: 
Process of random attribution of treatment to subjects in order to reduce bias of selection. 
Transient and persistent lesions: 
The appearance of new lesions that do not qualify as flare will be recorded as new transient or 
new persistent lesions. Transient new lesions are defined as new lesions that heal within 1 week. 
Persistent new lesions are defined as new lesions that last more than 1 week. 
Treatment: 
Term used throughout the clinical trial to denote a set of investigational product(s) or marketed 
product(s) or placebo intended to be administered to a trial participant. 
Treatment failure:  
Absence of DC with oral prednisone 1.5 mg/kg/day for a minimum of 3 weeks, or flare between 
DC and CRmin that is not controlled by a prednisone dose that is 2 dose levels above the dose at 
which the flare is observed and that is of at least 0.3 mg/kg qd (according to Table 3), or the 
occurrence of an SAE considered related to prednisone by the investigator. 


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10.13.
Appendix 13: Abbreviations
ABQOL
Autoimmune Bullous Disease Quality of Life 
ABSIS 
Autoimmune Bullous Skin Disorder Intensity Score 
AChR-Ab 
acetylcholine receptor–antibody 
ADA 
anti-drug antibodies 
ADR 
adverse drug reaction 
AE 
adverse event 
AESI
adverse event of special interest
AIBD 
autoimmune bullous dermatoses 
AIDS 
acquired immunodeficiency syndrome
AIS
aggregate improvement score
ALP 
ALT 
alkaline phosphatase 
alanine aminotransferase 
ANOVA
analysis of variance 
aPTT 
activated partial thromboplastin time 
AST
aspartate aminotransferase
anti-HBc 
total hepatitis B core antibody 
anti-HBs
hepatitis B surface antibody 
BMI
body mass index 
BP 
bullous pemphigoid 
BSA 
body surface area
BUN
blood urea nitrogen 
CFR
Code of Federal Regulations 
C-GTI 
Composite Glucocorticoid Toxicity Index 
CI
confidence interval
CIDP
chronic inflammatory demyelinating polyneuropathy
CIOMS 
Council for International Organizations of Medical Sciences
CMH
CONSORT 
Cochran-Mantel-Haenszel 
Consolidated Standards of Reporting Trials 
CPK 
creatine phosphokinase 
CR 
complete clinical remission 
CRmin
complete remission on minimal therapy 
CRF
case report form 
CRO 
contract research organization 
CRoff 
complete remission off therapy 
CRP 
C-reactive protein


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CTCAE
common terminology criteria for adverse events
CTR
clinical trial report
CWS
cumulative worsening score
DC 
disease control 
DIF
direct immunofluorescence
DNA 
deoxyribonucleic acid 
DRI 
dietary reference intake 
Dsg 
desmoglein 
DSMB
data safety monitoring board
ECG
electrocardiogram 
ED 
early discontinuation
eCRF 
electronic case report form
ELISA 
enzyme-linked immunosorbent assay
ENT 
ear-nose-throat 
EoC
end of consolidation
EoS 
end of study 
EQ-5D-5L 
EuroQol 5-Dimension 5-Level Scale 
EU 
European Union 
FcRn 
neonatal crystallized fragment receptor 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GGT 
gamma-glutamyl transferase 
GTI 
Glucocorticoid Toxicity Index 
GTI-SL
Glucocorticoid Toxicity Index Specific List
HbA1c
hemoglobin A1c 
HBsAg
hepatitis B surface antigen 
HBV 
hepatitis B virus
HCV 
hepatitis C virus
HDL-C 
high-density lipoprotein cholesterol
HIV 
human immunodeficiency virus 
HLA 
human leukocyte antigen
IB
Investigator’s Brochure 
ICE 
intercurrent event 
ICF 
informed consent form
ICH
International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use 


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IEC
Independent Ethics Committee 
Ig
immunoglobulin
IgG
immunoglobulin G
IIF 
indirect immunofluorescence 
IMP
investigational medicinal product 
IND 
investigational new drug 
INR
international normalized ratio 
IRB 
Institutional Review Board 
IRR
infusion-related reaction
IRT
interactive response technology
ITP 
immune thrombocytopenia
IUD 
intrauterine device 
IUS 
intrauterine hormone-releasing system 
IV 
intravenous 
IVIg
immunoglobulins given intravenously 
LDH 
lactate dehydrogenase 
LDL-C 
low-density lipoprotein cholesterol
MedDRA 
Medical Dictionary for Regulatory Activities
MG 
myasthenia gravis 
MG-ADL
Myasthenia Gravis Activities of Daily Living 
mITT
modified intent-to-treat 
mRNA 
messenger RNA 
NCI 
National Cancer Institute 
NCPD
normalized cumulative prednisone dose
Nab 
neutralizing antibody 
NOAEL
no-observed-adverse-effect level 
OLE 
open-label extension 
PD 
pharmacodynamic 
PDAI 
Pemphigus Disease Area Index 
PF
pemphigus foliaceus
PK
pharmacokinetics 
PP
per protocol 
PPE 
personal protective equipment 
PT 
preferred term 
PV
pemphigus vulgaris 
qd
daily 


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QoL 
quality of life
rHuPH20
recombinant human hyaluronidase PH20
RDA
recommended daily allowance
RNA 
ribonucleic acid
SAE
serious adverse event 
SAP 
statistical analysis plan 
SC 
subcutaneous 
SoA 
schedule of activities 
SOC
SUSAR 
system organ class
suspected unexpected serious adverse reaction 
TEAE 
treatment-emergent adverse event 
US 
United States 
WHO 
World Health Organization 
WHO-DD 
World Health Organization Drug Dictionary 


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10.14.
Appendix 14: Possible Adaptations of Trial Protocol During 
COVID-19 Pandemic 
Introduction 
The aim of the ARGX-113-1904 trial is to investigate a new SC treatment option for patients 
with pemphigus. This SC treatment consists of efgartigimod coformulated with recombinant 
human hyaluronidase PH20 (rHuPH20) (called efgartigimod PH20 SC) and could offer clinically 
significant benefits to pemphigus patients. 
The sponsor (argenx BV) has performed a critical assessment of the use of efgartigimod during 
the COVID-19 pandemic. Based on the risk-benefit assessment, the clinical trial 
ARGX-113-1904 can be conducted; however, because of the pandemic, argenx BV 
acknowledges that considerable difficulties for participating centers to meet all previously 
planned assessments might occur (see the SoA in Section 1.3). Therefore, an Appendix with 
possible adaptations to this trial has been developed. This Appendix describes a minimum 
number of assessments required to guarantee the safety and wellbeing of the participants during 
the trial and to secure the collection of the critical parameters for analysis. It remains at the 
investigator’s discretion to assess if it is in the best interest of the participant to 
participate/continue in the trial.  
Note that a “home visit” as described in this Appendix could also be a visit at an alternative 
convenient location. 
Note that the home nurse, who will go to the participant in case of a home visit, could also be 
another qualified person to perform all tasks (eg, a physician). In addition, a home nurse can be 
qualified personnel from an alternative convenient location if the trial visit cannot be performed 
at the trial site. 
During the COVID-19 pandemic, the 2 main goals of the study are the participant’s safety and 
the participant’s data collection. 
For participants with no suspected signs of COVID-19 or have tested negative:  
The administration of efgartigimod PH20 SC may continue, while the safety of the participants 
should be preserved. For participants who have no suspected signs of COVID-19 disease or are 
tested negative, there is no evidence that efgartigimod PH20 SC must be discontinued. In these 
participants, it is therefore recommended to make an individual benefit/risk assessment, which 
includes the participant’s age, the co-morbidities (eg, obesity, respiratory and cardiovascular 
diseases, diabetes), the treatment history (eg, corticosteroids, immunosuppressants, and 
rituximab) and the disease activity. The environmental conditions of containment for each 
participant are also to be considered. Based on this benefit/risk assessment, administration of 
efgartigimod PH20 SC may be pursued, postponed or discontinued. 
Data collection:
It is important to continue collecting critical clinical trial data, for example, through telephone 
communication when trial site visits cannot be performed. The assessments deemed suitable for 
regular telephone consultation are questions on AEs, disease outcomes (DC, CR, flare) and 
compliance for prednisone intake and its dose. Prednisone dose must be adapted according to the 
study protocol.


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POSSIBLE ADAPTATIONS TO ARGX-113-1904 TRIAL PROTOCOL DURING 
COVID-19 PANDEMIC 
Implementation of this Appendix
 Implementation for all sites includes social distancing, personal protective equipment 
(PPE), and a telephone call before each trial visit for checking of COVID-19 
symptoms. 
 The adaptations to the visits and procedures described in this Appendix that are 
acceptable alternatives to the main protocol procedures should only be implemented 
in exceptional cases and after approval of the sponsor and/or CRO. Approval will be 
granted based on the possibility of the participant to go to the site and per local and/or 
hospital regulations. 
The Appendix is intended for countries and/or sites in geographical areas where COVID-19 has 
affected trial sites’ workload, severe movement restrictions have been imposed, or when there is 
a risk to participants/trial staff if attending trial sites for trial visits. The initial duration of the 
implementation of this Appendix will be agreed and can be extended based on the local epidemic 
status.
When a (home) visit is performed under this COVID-19 Appendix, it should be documented as a 
COVID-19 (home) visit in the eCRF for the applicable visit. 
Testing for COVID-19 
Additional testing for COVID-19 beyond that mandated by relevant local authorities is not 
required at the start of the study. However, argenx BV recommends participants who develop 
symptoms of COVID-19 during the trial to be tested. 
Protecting Home Nurse and Site Staff From COVID-19 
The home nurse and site staff as well as qualified personnel from an alternative convenient 
location. Staff should apply appropriate social distancing and use personal protection equipment 
according to the local hospital and governmental regulations/recommendations; see also below.
Participants With COVID-19 (Either a Positive Test or With Symptoms [Suspicion of 
COVID-19 Infection]) 
Participants with a COVID-19 infection should not enter the trial. In case a participant develops 
a COVID-19 infection during trial participation, the following applies. 
The instructions to manage an infection that are in the main protocol are also applicable in case 
of an infection with COVID-19 (ie, it will be considered an AESI similar to all infections). 
Treatment should be interrupted until the participant is considered recovered from COVID-19 
(according to the local recommendations). 
During the pandemic, the trial site staff should contact participants prior to each visit to inquire 
about COVID-19 symptoms and exposure using the flow charts below and make a decision on 
proceeding or postponing the visit according to the following flow charts. 
The following symptoms should be specifically addressed during that phone call: fever, cough, 
sneezing, loss of taste/smell, difficulties breathing/chest tightness. 


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The impact of the COVID-19 pandemic on argenx BV clinical trials is outlined in Figure 2.
Figure 2:
Impact of COVID-19 Pandemic on argenx BV Clinical Trials
Does the patient
COVID-19 symptoms1 ?
Day before site/home 
: 
site calls patient
YES
Discontinue IMP
administration
Cancel 
Recommend
COVID-19 Test1
STEPS TO FOLLOW
Report as AE
EVALUATION AND POSSIBLE DECISIONS
1
2
Resume IMP admin.
and 
Discont. IMP admin. until
resolution. Safety follow-up2
3
Discontinue from trial 
POSITIVE
UNAVAILABLE
NEGATIVE
No specific
COVID-19 action
required
Follow country
and site COVID-19 
recommendations
COVID-19 SPECIFIC SITUATIONS
COVID-19 OUTBREAK: IMPACT ON ARGENX STUDIES – PATIENTS ALREADY IN THE STUDY
NO
Patient has been in 
contact with COVID-19 
infected patient in the
14 days ?
YES
NO
Visit (site/home) takes place 
as per protocol taking into account
country/site recommendations
Follow country/site-specific
recommendations
2In COVID-
patients, 
IMP 
, 
1
facilitate
of COVID-19 test (PCR): 


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Participants with symptoms of COVID-19 infection will be treated for this infection as guided by 
the local health care system. Participants will be monitored by the trial site by telephone contact. 
In case the participant will have to be in self-isolation for a longer period than 2 weeks, it will be 
discussed on a case-by-case basis with the sponsor and/or with the CRO whether the participant
can remain in the trial.
Once a participant has recovered, the participant can continue the trial and receive trial 
medication, provided that the participant has not received/is not receiving prohibited medication 
(see Section 6.8.2). 
Critical Parameters to Be Collected During the Trial 
Please note that, if feasible, all assessments, including those that are not critical (ie, indicated as 
assessments that are not mandatory in the SoA in Section 1.3) should be performed. 
The critical parameters that must be collected during the trial are summarized in the following 
table: 
Eligibility 
 
ICF 
 
Demographics 
 
Disease and medical history 
 
Physical examination and study assessments 
 
Other parameters to confirm eligibility 
Efficacy 
 
Disease assessment (DC, CR, EoC, flare) 
 
Monitoring of prednisone dosage 
Safety 
 
AEs 
 
Safety labs 
IMP 
 
Administration  
 
Accountability 
During the COVID-19 pandemic, the collection of these critical parameters is specified in the 
SoA in Table 10. 
 The evaluation of eligibility for the trial will be as described in the main protocol. The 
screening visit must be performed at the trial site (see below). 
For the evaluation of efficacy, safety, and for the IMP administration and 
accountability, certain modifications compared to the main protocol are allowed in 
this protocol compared to the main protocol (see below). 
Mandatory Site Visits and Allowed Home Visits
In order to collect the critical parameters of the trial, certain visits have to be performed at the 
site (screening, baseline, and EoS/ED) and other visits can be at home (“home” as described in 
this Appendix could also be a visit at an alternative convenient location). 
 Screening Visit 
The screening visit of the trial needs to be performed at the trial site. If it is not possible to go to 
the trial site due to the COVID-19 situation, the participant cannot start screening and has to wait 
until the situation changes and the participant is able to go to the trial site. Note that 


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transportation to the trial site can be facilitated if the situation due to the COVID-19 pandemic 
allows this. 
Baseline Visit 
The baseline visit has to be performed at the trial site. If it is not possible to go to the trial site for 
these baseline visits due to the COVID-19 situation, the sponsor or CRO have to be contacted as 
soon as possible to discuss viable options.  
 Other Trial Visits 
During the COVID-19 pandemic, study visits after the screening and baseline visits will be done 
at home, including blood and urine collection. A home nurse will travel to the participant’s home 
to conduct this visit (or the participant will go to an alternative convenient location). The 
investigator will talk to the participant via an audio or video interview to elicit AE, concomitant 
medications, and general wellbeing of the participant. The investigator will also perform efficacy 
assessments using an audio or video interview with the participant. The assessments via an audio 
or video interview will be conducted before the home nurse administers the trial medication. The 
division of tasks between the investigator and home nurse are indicated in the following scheme.
In the exceptional case that a home nurse cannot be identified or cannot travel to the participant’s 
home, vital sign measurements and blood and urine collection will not be performed, and IMP 
may be administered through self- or caregiver administration, provided that the participant 
or caregiver has completed the training and has been deemed competent. IMP administration by 
the patient or caregiver can be supported by a video connection. Such an exception will require 
concurrent sponsor and investigator approval on a case-by-case basis. 
 EoS/ED 
The EoS/ED visit of the trial needs to be performed at the trial site. If it is not possible to go to 
the trial site for this visit due to the COVID-19 pandemic, the sponsor or CRO have to be 
contacted as soon as possible to discuss viable options. 
 
Scheme for Home Visitsa 
Critical Assessments
Performed by 
Method of Assessment
 ICF (not initial ICF at screening, explained to participant) 
Investigator 
Audio or video interview 
 Disease assessment (DC, CR, EoC, flare) 
 Adverse events 
 Concomitant medication (including prednisone dosage) 
 Vital signs 
 IMP administration 
 Blood sampling (weekly until week 6, then every 4 
weeks until EoS/ED) 
 Urine collection 
Home nurse 
In person at participant’s 
homea 
a. Note that a “home visit” could also be a visit at an alternative convenient location. 
 
 


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Efficacy Assessments
The critical efficacy assessments of the trial are: 
- 
Disease assessment (DC, CR, EoC, flare) 
- 
Monitoring of prednisone dosage 
Safety Assessments 
Adverse event
During home visits, a telephone/video interview will be conducted by the treating physician or 
designee about possible AEs. Any suspected COVID-19 infection relevant signs or symptoms 
(including an abnormal laboratory findings) will be reported as an AE, with clear distinction 
whether it is a confirmed test positive COVID-19 infection or suspected infection if not tested.
 Vital signs 
During home visits, vital signs (heart rate, body temperature, and blood pressure) will be 
measured by the home nurse at the beginning of the home visit and the results will be 
communicated to the treating physician. If pyrexia is detected, the home nurse should call the 
trial site immediately and await further instructions from the treating physician. 
 Blood and urine sampling 
During home visits, blood samples will be collected for clinical chemistry, hematology, anti-
Dsg-1 and anti-Dsg-3 antibodies, PK, total IgG and IgG subtypes (IgG subtypes are not 
determined in China), and ADA weekly until week 6 and then every 4 weeks until EoS/ED. 
Additionally, urine samples will be collected for urinalysis and urine pregnancy testing.
 Electrocardiogram (ECG) 
At screening (which is performed at the site), ECGs are required. A local ECG machine from the 
site can be used in case equipment from the central ECG laboratory does not arrive at the site. A 
test transfer to the central ECG laboratory (eResearchTechnology [ERT]) with an anonymized 
test ECG is required. Requirement for the test ECG and test transfer are described in the user 
guide (“site upload tool quick guide”) from ERT. Except for screening, an ECG is not considered 
as critical data at other visits and will not be done in case of a home visit. 
Concomitant Medication 
At the time of the home visit, the site treating physician will telephone/video interview the 
participant about concomitant medications, especially prednisone dosage. It will be documented 
whether concomitant medication is taken for a confirmed test positive COVID-19 infection or 
suspected infection (if not tested). 
IMP Administration 
IMP can be administered at home by trained and authorized personnel (eg, home nurse). 
Trial Endpoint
The criteria for the trial endpoint for a participant as described in the main protocol also apply to 
this Appendix. 


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Table 10: 
Modified Schedule of Activities During COVID-19 Pandemic 
A China-specific version of the modified schedule of activities during COVID-19 pandemic is provided in Section 10.16.1.4. 
In the SoA of the ARGX-113-1904 trial (see below), the mandatory assessments are indicated in red (X). The assessments that need to 
be performed only if feasible during the COVID-19 pandemic are indicated in black (X). At site visits, all assessments have to be 
performed (critical [X] and non-critical [X], if operationally feasible). 
 
Trial Period 
Screening 
Treatment 
EoS/
EDa
UNSb
Follow-up 
V1 
(BL) 
V2 
Observation
al visits 
IMP admin 
only visit 
Observational visits 
Visit Number
Weekly on-
site visits 
until CRc 
Weekly 
home or on-
site visits 
until 
CRmind 
On-site visits 
every 4 
weeks until 
CRmin 
On-site 
visits every 
4 weeks 
after 
CRmin 
until W31 
W31 
Follow-
up W34 
Follow
-up 
W38e 
Trial Day/Week 
D-21 
to D-1 
D1 
(W1) 
D8 
(W2) 
D15 (W3) 
until CR 
CR until 
CRmin 
CR until 
CRmin 
CRmin 
until W31 
W31 
EoS/ED 
+3W 
EoS/E
D +7W 
Visit Window 
±0 days 
±2 
daysf 
V1 + 7× ±2 daysf 
±2 
daysf 
±3 daysf 
Assessment/ 
Procedure 
 
Informed consentg 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
X 
X 
 
 
 
 
 
 
 
 
 
DIF/histopathologyh 
X 
 
 
 
 
 
 
 
 
 
 
Concomitant 
therapies/procedures 
X 
Continuous monitoring 
Karnofsky 
performance score 
X 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 


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Trial Period 
Screening 
Treatment 
EoS/
EDa 
UNSb
Follow-up 
V1 
(BL) 
V2 
Observation
al visits 
IMP admin 
only visit 
Observational visits 
Visit Number 
 
 
Weekly on-
site visits 
until CRc 
Weekly 
home or on-
site visits 
until 
CRmind 
On-site visits 
every 4 
weeks until 
CRmin 
On-site 
visits every 
4 weeks 
after 
CRmin 
until W31 
W31 
Follow-
up W34 
Follow
-up 
W38e 
Trial Day/Week
D-21 
to D-1 
D1 
(W1) 
D8 
(W2) 
D15 (W3) 
until CR 
CR until 
CRmin 
CR until 
CRmin 
CRmin 
until W31 
W31 
EoS/ED 
+3W 
EoS/E
D +7W 
Visit Window 
±0 days 
±2 
daysf
V1 + 7× ±2 daysf 
±2 
daysf
±3 daysf 
Height and weighti 
X 
 
 
Xi 
 
Xi 
Xi 
X 
 
 
 
Physical 
examination and 
vital signsj,k 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
ECGj 
X 
 
 
Xl 
 
Xl 
 
X 
 
 
 
Medical and 
surgical history 
X 
 
 
 
 
 
 
 
 
 
 
Randomizationm 
 
X 
 
 
 
 
 
 
 
 
 
Urinalysisj,n,o 
X 
X 
X 
X 
 
X 
X 
X 
Xb
X 
X 
Urine pregnancy 
testj,p 
 
X 
 
Xp 
 
X 
X 
X 
Xb
X 
X 
Blood sampling: 
 
Active viral 
infection testq 
X 
 
 
 
 
 
 
 
 
 
 
Serum pregnancy 
testr 
X 
 
 
 
 
 
 
 
 
 
 


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Trial Period 
Screening 
Treatment 
EoS/
EDa 
UNSb
Follow-up 
V1 
(BL) 
V2 
Observation
al visits 
IMP admin 
only visit 
Observational visits 
Visit Number 
 
 
Weekly on-
site visits 
until CRc 
Weekly 
home or on-
site visits 
until 
CRmind 
On-site visits 
every 4 
weeks until 
CRmin 
On-site 
visits every 
4 weeks 
after 
CRmin 
until W31 
W31 
Follow-
up W34 
Follow
-up 
W38e 
Trial Day/Week
D-21 
to D-1 
D1 
(W1) 
D8 
(W2) 
D15 (W3) 
until CR 
CR until 
CRmin 
CR until 
CRmin 
CRmin 
until W31 
W31 
EoS/ED 
+3W 
EoS/E
D +7W 
Visit Window 
±0 days 
±2 
daysf
V1 + 7× ±2 daysf 
±2 
daysf
±3 daysf 
Clinical chemistry 
& hematologyj,o,s 
X 
X 
X 
X 
 
X 
X 
X 
Xb
X 
X 
Anti-Dsg-1 and 
anti-Dsg-3 
antibodiesj,o 
X 
X 
X 
X 
 
X 
X 
X 
Xb
X 
X 
PKj,o,t
 
X 
Xt
X 
 
X 
X 
X 
Xb,t
X 
X 
Total IgG and IgG 
subtypesj,o,u
X 
X 
X 
X 
 
X 
X 
X 
Xb
X 
X 
Vaccination 
antibodiesj,o,v
X 
X 
X 
X 
 
X 
X 
X 
Xb
X 
X 
Anti-drug 
antibodiesj,w 
 
X 
 
X 
(every 2 weeks)
 
X 
X 
X 
 
X 
X 
IgG autoantibody 
subtypes/specificity 
and cytokinesj,x
 
X 
 
Xx 
 
X 
X 
X 
Xb
X 
X 
B- and T-cell 
populationsj
 
X 
 
Xy 
 
 
 
X 
 
 
 


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Trial Period 
Screening 
Treatment 
EoS/
EDa 
UNSb
Follow-up 
V1 
(BL) 
V2 
Observation
al visits 
IMP admin 
only visit 
Observational visits 
Visit Number 
 
 
Weekly on-
site visits 
until CRc 
Weekly 
home or on-
site visits 
until 
CRmind 
On-site visits 
every 4 
weeks until 
CRmin 
On-site 
visits every 
4 weeks 
after 
CRmin 
until W31 
W31 
Follow-
up W34 
Follow
-up 
W38e 
Trial Day/Week
D-21 
to D-1 
D1 
(W1) 
D8 
(W2) 
D15 (W3) 
until CR 
CR until 
CRmin 
CR until 
CRmin 
CRmin 
until W31 
W31 
EoS/ED 
+3W 
EoS/E
D +7W 
Visit Window 
±0 days 
±2 
daysf
V1 + 7× ±2 daysf 
±2 
daysf
±3 daysf 
RNA transcriptional 
profilej 
 
X 
 
Xy 
 
 
 
X 
 
 
 
HLA/non-HLA 
genotypingj 
 
X 
 
Xz 
 
 
 
 
 
 
 
Substudies: 
 
Skin biopsies (at 
selected sites)j,aa 
 
X 
 
Xaa 
 
 
 
Xaa 
 
 
 
Photography (at 
selected sites)j,bb 
 
X 
Xbb 
Xbb 
 
 
 
 
Xb,bb 
 
 
QoL Assessments: 
 
EQ-5D-5Lj,cc
 
X 
 
Xdd
 
Xdd
Xdd
X 
 
 
 
ABQOLj,cc 
X
Xdd
 
Xdd
Xdd
X 
 
 
 
GTIj 
 
X 
 
Xee 
 
Xee 
Xee 
X 
 
 
 
IMP self-
administration 
trainingff
 
 
 
X 
 
X 
 
 
 
 
 


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Trial Period 
Screening 
Treatment 
EoS/
EDa 
UNSb
Follow-up 
V1 
(BL) 
V2 
Observation
al visits 
IMP admin 
only visit 
Observational visits 
Visit Number 
 
 
Weekly on-
site visits 
until CRc 
Weekly 
home or on-
site visits 
until 
CRmind 
On-site visits 
every 4 
weeks until 
CRmin 
On-site 
visits every 
4 weeks 
after 
CRmin 
until W31 
W31 
Follow-
up W34 
Follow
-up 
W38e 
Trial Day/Week
D-21 
to D-1 
D1 
(W1) 
D8 
(W2) 
D15 (W3) 
until CR 
CR until 
CRmin 
CR until 
CRmin 
CRmin 
until W31 
W31 
EoS/ED 
+3W 
EoS/E
D +7W 
Visit Window 
±0 days 
±2 
daysf
V1 + 7× ±2 daysf 
±2 
daysf
±3 daysf 
IMP 
administrationgg 
 
X 
 
X 
 
X 
X 
X 
 
 
Xb
 
 
PDAIj 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
Disease 
assessmenthh 
 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
Prednisone taperii
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
AE monitoring
Continuous monitoring
ABQOL=Autoimmune Bullous Disease Quality of Life; BL=baseline; BMI=body mass index; CR=complete clinical remission; CRmin=CR on minimal therapy; 
D=day; DC=disease control; DIF=direct immunofluorescence; Dsg=desmoglein; ECG=electrocardiogram; ED=early discontinuation; EoC=end of consolidation; 
EoS=end of study; EQ-5D-5L=EuroQol 5-dimension 5-level; FSH=follicle-stimulating hormone; GTI=Glucocorticoid Toxicity Index; HLA=human leukocyte 
antigen; IgG=immunoglobulin G; IMP=investigational medicinal product; OLE=open-label extension; PDAI=Pemphigus Disease Area Index; 
PK=pharmacokinetics; RBC=red blood cells; WBC=white blood cells; W=week; V=visit 
a All participants will complete EoS/ED, which will be the end of the trial for participants who enroll in the OLE trial ARGX-113-1905. Participants who do not 
enroll in the OLE trial ARGX 113 1905 will complete the follow-up visits at W34 and W38. 
b In case of suspected new lesions as reported by the participants, AEs, flare or other safety reasons, participants should come to the clinic. This may require an 
unscheduled visit. Depending on the reason for the visit, different assessments need to be performed. See Section 8 for more information. Participants with new 
lesions or flare after achieving CR should return to weekly on-site visits until CR is achieved again. 
c A minimum of 6 on-site visits, V1(BL)/W1 to W6, are required before switching to home administrations, even if CR is achieved earlier than W6. The W7 visit 
is the first eligible “IMP administration only” visit (refer to column “Weekly home or on-site visits until CRmin”), at home or on-site, if CR is achieved 
between W1 and W6. 


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d Home visits are allowed once participants achieve CR, but not before W7. The investigator should call the participant every 2 weeks until CRmin is achieved to 
confirm the participant is still in CR. On-site visits may continue at the investigator’s discretion. 
e W38 (follow-up visit 2) is the end of the trial for participants who do not enroll in the OLE trial ARGX-113-1905. The W38 follow-up visit will only be 
required for those participants who were still receiving IMP at least once from W27 onward. For participants who ended treatment prior to W27, W34 will be 
the end of the trial. 
f Trial visit windows are ±2 days during the treatment period and ±3 days for follow-up visits. 
g No trial-related assessments can be initiated before the participant has provided as signed ICF. 
h Only required if not available from medical history. 
i Height and weight will be measured (and BMI will be calculated accordingly) at screening, at week W15 (or the next on-site visit if W15 does not coincide 
with an on-site visit), and EoS/ED. Weight will also be measured if there has been an obvious change since the last measurement. 
j At visits in which IMP is administered, the assessment or procedure should be completed before dosing. 
k A complete physical examination will be completed at each on-site visit. Vital sign measurements include systolic and diastolic blood pressure, heart rate, and 
body temperature. Supine blood pressure and heart rate will be measured using standard equipment after at least 10 minutes rest. 
l ECG to be taken at W12. If the W12 visit does not coincide with an on-site visit, then the assessment should be performed at the next on-site visit. ECG (heart 
rate, PR, QT, and QRS interval) will be read centrally. QTcF and QTcB will be calculated. 
m Randomization will take place on day 1 after all eligibility checks are confirmed (eg, PDAI) and before other baseline assessments are run, and prior to dosing. 
n Urinalysis will be performed by dipstick method and will include specific gravity, pH, protein, glucose, ketones, blood, bilirubin, urobilinogen, nitrite, 
leukocyte esterase, and microscopic examination (if blood or protein test results are abnormal). 
o Samples will be taken every week from V1(BL)/W1 to W9 and then every 4 weeks and at the visit where CR is observed. Once CR is achieved, samples will 
be taken every 4 weeks at on-site visits until EoS/ED. For participants achieving CR between V1(BL)/W1 and W6, samples will be taken weekly from W1 to 
W6 and then every 4 weeks at on-site visits until EoS/ED. 
p A urine pregnancy test will be conducted and analyzed locally during on-site visits at least once every 4 weeks (before and after CR) and at the time of CR. 
q Viral testing for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), hepatitis B core antibody (anti-HBc), hepatitis B virus (HBV) 
DNA, hepatitis C virus (HCV) antibodies, HCV messenger RNA (mRNA), and human immunodeficiency virus (HIV) antibodies. 
r At screening, a serum pregnancy test must be performed in women of childbearing potential or FSH test to confirm postmenopausal status. 
s Clinical blood laboratory tests will include hematology and blood chemistry at all visits and international normalized ratio (INR) or activated partial 
thromboplastin time (aPTT) at screening only. The hematology profile includes hemoglobin, hematocrit, mean corpuscular volume (MCV), RBC count, platelet 
count, WBC count with differential. The blood chemistry profile includes sodium, potassium, calcium, hemoglobin A1c (HbA1c), creatinine, creatinine 
clearance, blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, gamma-glutamyl transferase (GGT), 
C-reactive protein (CRP), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein 
cholesterol (HDL-C), total cholesterol, triglycerides, uric acid, total protein, and albumin. 
t For PK assessment, blood samples will be taken predose (within 2 hours before the start of IMP administration at visits where IMP is administered). An 
additional PK sample will be taken on D3 and on D11 (±1 day) until samples from 24 participants are obtained. At unscheduled visits blood samples for PK 
will only be taken if IMP is administered. 
u At screening, total IgG will be measured as part of inclusion and exclusion criteria. The pharmacodynamic (PD) biomarkers total IgG and its subtypes (IgG1, 
IgG2, IgG3, and IgG4) will be measured centrally from a blood sample taken predose. 
v An extra sample(s) will be taken for additional research (including vaccination antibodies and other additional research). The actual testing of vaccination 
antibodies depends on (a) whether a vaccination was given to the participant; (b) whether a test is available for the vaccination given to the participant; and (c) 


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whether the sample requirements (serum, volume, frozen sample, storage duration) match the serum samples taken and reserved for this. Timepoints for 
analysis will be decided upon occurrence of vaccination during the study. 
w Anti-drug antibodies to efgartigimod (in serum samples) and antibodies against rHuPH20 (in plasma samples) will be tested predose every 2 weeks from 
V1(BL)/W1 to W9 and then every 4 weeks at on-site visits and at the visit where CR is observed. Once CR is achieved, samples will be taken every 4 weeks at 
on-site visits until EoS/ED. For participants achieving CR between V1(BL)/W1 and W6, samples will be taken predose at V1(BL)/W1, W3, W5, the visit 
where CR is observed, W10, and then every 4 weeks at on-site visits until EoS/ED. Neutralizing antibodies (NAb) will be tested for all confirmed positive 
ADA samples. 
x Blood sampling for IgG autoantibody subtypes and specificity will be taken every 4 weeks (V1[BL]/W1, W5, W9, etc) and at the visit where CR is observed. 
Once CR is achieved, samples will be taken every 4 weeks at on-site visits until EoS/ED. For participants achieving CR between V1(BL)/W1 and W6, samples 
will be taken at V1(BL)/W1, W5, the visit where CR is observed, W10, and then every 4 weeks at on-site visits until EoS/ED. Serum aliquots from all time 
points will be used for IgG subtype and specificity analyses. For cytokines and complementary specificity analyses, aliquots from baseline, after 4 weeks (W5), 
W13 (or the visit at which CR is observed if before W13), and EoS/ED will be used. 
y Samples for B- and T-cell populations and RNA transcriptional profiles will be performed at baseline, after 4 weeks (W5) and at W13 (or the visit at which CR 
is observed if before W13) and at EoS/ED.
z HLA/non-HLA genotyping will only be performed at baseline and D15. 
aaTwo 4 mm skin biopsies, 1 peri-lesional and 1 non-lesional, will be collected solely based on voluntary participation at baseline and after healing of 80% of 
blisters (EoC) or at EoS/ED (in case EoC has not been achieved) for scientific purposes. 
bb Pictures of different anatomical regions may be taken at the discretion of the investigator. As a guidance, time points of baseline, DC, CR and flare are 
indicated. Pictures may also be taken at intermediate timepoints. 
cc Questionnaires are to be completed prior to any other activity. 
ddAssessments will be performed at baseline, after 4 weeks (W5), W15, and EoS/ED visits. If the W15 visit does not coincide with an on-site visit, then the 
assessment should be performed at the next on-site visit. 
ee The GTI assessment will be performed only at baseline, W15 and EoS/ED. If W15 does not coincide with an on-site visit, then the assessment should be 
performed at the next on-site visit. 
ff Participants will be trained to self-administer IMP (foreseen in the OLE trial; not in the ARGX-113-1904 trial) during the first 4 visits as of V3 when IMP is 
administered; thereafter, training for self-administration is optional (only if needed). 
gg IMP will be administered until CRmin. To ensure proper safety monitoring, participants should remain at the site for at least 1 hour after the first administration 
and for 15 minutes after subsequent administrations. Participants will be released according to their clinical status. For Germany-specific monitoring 
instructions, refer to Section 10.16.2.1. Participants who experience treatment failure, or flare after achieving CRmin, will be allowed to roll over into the OLE 
trial ARGX-113-1905 earlier than W31. Participants who do not roll over into trial ARGX-113-1905 will complete the treatment-free follow-up period. 
hh Disease assessment parameters include disease control (DC), end of consolidation (EoC), complete clinical remission (CR), complete remission on minimal 
therapy (CRmin), complete remission off therapy (CRoff), flare, and treatment failure. Participants who have achieved CR and have new lesions should come 
to the clinic for a UNS for disease assessment. 
ii Prednisone dose tapering will begin 2 weeks after achieving CR or 4 weeks after sustained EoC (thus, no new lesions have developed for a minimum of 6 
weeks and approximately 80% or more of lesions have healed). 


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10.15.
Appendix 15: Glucocorticoid Toxicity Index (GTI)
Table 11: 
Approach to Calculating the Baseline GTI 2.0 Score: Toxicities Assigned 
Weighted Scores From C-GTI to Establish a Baseline GTI Score 


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Table 12: 
Approach to Calculating the Changes in GTI 2.0 Score: Weighted Scores 
Assigned to Improvements or Worsenings in the C-GTI 


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Table 13: 
GTI 2.0 Specific List: 11 Domains (9 of Which Are Shared by the C-GTI) 
and 23 Unique Items 


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GTI Supporting Information: Definitions
Glucocorticoid-induced myopathy definitions: 
Glucocorticoid myopathy is defined as mild symmetrical weakness of the proximal 
muscles and/or neck flexors associated with steroid therapy and NOT due to any 
other apparent cause. Muscle enzymes are typically within normal limits. 
 Minor/Mild and moderate severity myopathy are defined by a muscle strength of 
grade 4 on the standard Medical Research Council Rating scale.
A 4 means weaker than normal but greater than antigravity strength against 
resistance. 
“Minor” or “Mild” is mild weakness (Grade 4) that does NOT functionally limit 
the patient. 
 “Moderate” is mild weakness (Grade 4) that does impose functional limitations on 
the patient enough to interfere with normal daily activities. 
Note that a person may have muscle weakness consistent with glucocorticoid-
induced myopathy that is detectable on physical examination but the person is not 
aware of it or have any corresponding functional limitation. This would be 
classified as minor or mild. 
 Severe glucocorticoid-induced myopathy, defined as a weakness of grade 3 or less 
(no more than antigravity strength and unable to overcome any resistance or any 
degree weaker), is included in the Specific List. People who are severely weak may 
have difficulty rising from a chair without assistance or other major functional 
limitations but the formal categorization should be based on the degree of weakness 
on strength testing. 
Severity of glucocorticoid toxicity to the skin:
Manifestations to be considered:
Acneiform rash
 Easy bruising 
 Hirsutism 
 Atrophy/striae 
Erosions/tears/ulcerations
Table 14: 
Severity Categorization of Skin Manifestations by Grade 
Minor/Mild 
Moderate 
Severe (Specific Domain) 
Acneiform rash (Grades 1-2) 
Acneiform rash (Grade 3) 
Acneiform rash (Grade 4) 
Easy bruising (Grade 1) 
Easy bruising (Grade 2) 
 
Hirsutism (Grade 1) 
Hirsutism (Grade 2) 
 
Atrophy/Striae (Grade 1) 
Atrophy/Striae (Grade 2) 
Atrophy/Striae (Grade 3) 


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Minor/Mild 
Moderate 
Severe (Specific Domain) 
Erosions/Tears/Ulcerations 
(Grade 1) 
Erosions/Tears/Ulcerations (Grade 
2) 
Erosions/Tears/Ulcerations (Grade 
3) 
Skin definitions from the National Cancer Institute CTCAE: 
 Acneiform rash
Grade 1: papules and/or pustules covering <10% body surface area (BSA), which 
may or may not be associated with symptoms of pruritus or tenderness 
Grade 2: papules and/or pustules covering 10% to 30% BSA, which may or may 
not be associated with symptoms of pruritus or tenderness; associated with 
psychosocial impact; limiting instrumental ADL; papules and/or pustules 
covering > 30% BSA with or without mild symptoms
Grade 3: papules and/or pustules covering >30% BSA with moderate or severe 
symptoms; limiting self-care ADL; associated with local superinfection with oral 
antibiotics indicated 
 Grade 4: life-threatening consequences; papules and/or pustules covering any 
percent of BSA, which may or may not be associated with symptoms of pruritus 
or tenderness and are associated with extensive superinfection with IV antibiotics 
indicated
 Easy bruising 
 Grade 1: localized or in a dependent area 
 Grade 2: generalized 
 Hirsutism: In women, an increase in length, thickness, or density of hair in a male 
distribution
 Grade 1: hirsutism that the patient is able to camouflage by periodic shaving, 
bleaching, or removal of hair
Grade 2: hirsutism that requires daily shaving or consistent destructive means of 
hair removal to camouflage; associated with psychological impact
Atrophy/striae
Grade 1: covering <10% BSA; OR associated with telangiectasias or changes in 
skin color
Grade 2: covering 10% to 30% BSA; OR associated with striae or adnexal 
structure loss
Grade 3: covering >30% BSA; OR associated with ulceration
Erosions/tears/ulcerations
Grade 1: combined area of ulcers <1 cm; nonblanchable erythema of intact skin 
associated with warmth or erythema


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Grade 2: combined area of ulcers 1-2 cm; partial thickness skin loss involving 
skin or subcutaneous fat 
Grade 3: combined area of ulcers >2 cm; full-thickness skin loss involving 
damage to or necrosis of subcutaneous tissue that may extend down to the fascia 
Severity of neuropsychiatric glucocorticoid toxicity: 
 Manifestations to be considered
Insomnia 
Mania 
Cognitive impairment
Depression 
Table 15: 
Severity Categorization of Neuropsychiatric Manifestations by Grade
Minor/Mild 
Moderate 
Severe (Specific Domain) 
Insomnia – (Grade 1) 
Insomnia – (Grade 2) 
 
Mania (Grade 1) 
Mania (Grade 2) 
Mania (Grade 3) 
Cognitive impairment (Grade 1) 
Cognitive impairment (Grade 2) 
Cognitive impairment (Grade 3) 
Depression (Grade 1) 
Depression (Grade 2) 
Depression (Grade 3) 
Definitions of Severity within the Neuropsychiatric Domain 
 Insomnia: dissatisfaction with sleep quality and difficulty initiating or maintaining 
sleep or early morning awakening 
Grade 1: mild difficulty falling asleep, staying asleep or waking up early 
Grade 2: Moderate difficulty falling asleep, staying asleep or waking up early 
(typically associated with some degree of functional impairment) 
 Mania 
Grade 1: mild manic symptoms (eg, elevated mood, rapid thoughts, rapid speech, 
decreased need for sleep). Grade 1 mania is typically associated with a slightly or 
occasionally elevated or irritable mood, often accompanied by 1 of the following 
symptoms: mild or occasional inflated self-esteem, decreased need for sleep, 
increased talkativeness, feeling that thoughts are faster than usual, distractibility, 
increased activity or agitation, and impulsive actions. 
Grade 2: moderate manic symptoms (eg, relationship and work difficulties; poor 
hygiene). Grade 2 mania is typically associated with a slightly or occasionally 
elevated (or irritable) mood, often accompanied by 2 to 3 of the following 
symptoms: mild or occasional inflated self-esteem, decreased need for sleep, 
increased talkativeness, feeling that thoughts are faster than usual, distractibility, 
increased activity or agitation, and impulsive actions. 


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Grade 3: severe manic symptoms (eg, hypomania; major sexual or financial 
indiscretions); hospitalization not indicated; new onset. Grade 3 mania is typically 
associated with a slightly or occasionally elevated (or irritable) mood, often 
accompanied by 4 or more of the following symptoms: mild or occasional inflated 
self-esteem, decreased need for sleep, increased talkativeness, feeling that 
thoughts are faster than usual, distractibility, increased activity or agitation, and 
impulsive actions. 
 Cognitive impairment
 Grade 1: mild cognitive disability; not interfering with work/school/life 
performance; specialized educational services/devices not indicated. Grade 1 
cognitive dysfunction is noted by the patient but is not apparent to the examiner.  
Grade 2: moderate cognitive disability; interfering with work/school/life 
performance but capable of independent living; specialized resources on part time 
basis indicated. Grade 3: severe cognitive disability; significant impairment of 
work/school/life performance. This may correspond to a glucocorticoid-induced 
delirium. 
 Depression 
 Grade 1: mild depressive symptoms. Grade 1 depression is often associated with 
mild, occasional symptoms of up to 2 of the following: loss of interest, low 
energy, guilt, poor concentration, insomnia, restlessness, or change in appetite. 
 Grade 2: moderate depressive symptoms; limiting instrumental activities of daily 
living. Grade 2 depression is often associated with frequent or moderate feelings 
of being down or depressed and/or up to 4 of the following: loss of interest, low 
energy, guilt, poor concentration, insomnia, restlessness, or change in appetite. 
 Grade 3: severe depressive symptoms; limiting self-care ADL; hospitalization not 
indicated. Grade 3 depression is often associated with a constant feeling of being 
down or depressed and/or 5 or more symptoms of loss of interest, low energy, 
guilt, poor concentration, insomnia, restlessness, change in appetite, or suicidal 
thoughts. 
Infection Definitions 
 No or no significant infection: no grade 3, grade 4, or grade 5 infection, and no minor 
Candida infection and no localized zoster (see grade 2 specific infection) as defined 
below. Grade 1 infections and grade 2 infections other than the specific infections are 
recorded on this form as no infection or no significant infection. Grade 2 specific 
infection/Minor Candida or localized zoster: oral or vaginal candidiasis or zoster 
infections without post-herpetic neuralgia or eye involvement (Both of these 
infections correspond to grade 2 CTCAE infections). Grade 3 infection: any infection 
requiring intravenous antibiotic, antifungal, or antiviral intervention or hospitalization 
indicated OR radiologic or operative intervention indicated OR herpes zoster 
complicated by post-herpetic neuralgia or eye involvement.   


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 Grade 4 infection: life-threatening consequences (eg, septic shock, hypotension, 
acidosis, necrosis); urgent intervention indicated. 
 Grade 5: death from infection.  
Definitions for the Specific List 
 Hypertensive emergency: the blood pressure has reached levels that are damaging 
organs. 
Hypertensive emergencies generally occur at blood pressure levels exceeding 
180 mm Hg systolic OR 120 mm Hg diastolic, but can occur at even lower levels 
in patients whose blood pressure has not been elevated 
Complications can include stroke, loss of consciousness, memory loss, 
myocardial infarction, hypertensive retinopathy or nephropathy, aortic dissection, 
angina, and pulmonary edema
 Posterior reversible leukoencephalopathy syndrome (PRES): a clinical radiological 
entity. Clinical features may include headaches, altered mental status, seizures, and 
visual loss depending on the affected neuroanatomy. 
Characteristic magnetic resonance imaging (MRI) findings include vasogenic 
edema involving the white matter that predominantly affects the posterior 
occipital and parietal lobes of the brain, although other brain regions may also be 
affected. Confirmation by MRI is required as is exclusion of the other potential 
causes (including hypertensive emergency). 
 Severe glucocorticoid myopathy: Grade 3 or worse myopathic weakness or 
respiratory myopathic weakness attributable to glucocorticoid myopathy. 
 Central serous retinopathy: a fluid detachment of macula layers from their supporting 
tissue 
 Requires formal ophthalmology examination, typically accompanied by optical 
coherence tomography and/or fluorescein angiography for diagnostic 
confirmation 
 Diabetic nephropathy: Macroalbuminuria; ie, a urinary albumin excretion > 300 mg 
in a 24-hour collection or a urinary protein: creatinine ratio >300mg/g.
 Diabetic neuropathy: any of 4 types of peripheral neuropathy occurring in the setting 
of diabetes mellitus as follows:
A distal sensory polyneuropathy
 Autonomic neuropathy (hypoglycemia unawareness, bladder or bowel problems, 
erectile dysfunction, and other autonomic nervous system issues) 
 Diabetic amyotrophy (muscle infarction) 
 Mononeuritis (eg, foot drop attributed to diabetic neuropathy or a diabetic sixth 
cranial nerve palsy) 


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 Diabetic retinopathy: any form of retinopathy associated with diabetes mellitus, 
including both non-proliferative and proliferative forms of diabetic retinopathy as 
well as diabetic macular edema. 
 These complications must be confirmed by an ophthalmologist
 Severe skin toxicity: any of the 3 following manifestations: 
 Grade 4 acneiform lesions: papules or pustules covering a percent of the BSA, 
which may or may not be associated with symptoms of pruritus or tenderness and 
are associated with extensive superinfection with IV antibiotics indicated or life-
threatening consequences 
 Grade 3 striae: covering >30% BSA or associated with ulceration 
 Grade 3 ulcers: combined area of ulcers >2cm or full-thickness skin loss 
involving damage to or necrosis of subcutaneous tissue that may extend down to 
fascia 
 Symptomatic adrenal insufficiency: symptoms resulting from failure of the adrenal 
cortex to produce sufficient cortisol and, in some cases, aldosterone 
 Psychosis: hallucinations, delusions, or disorganized thought processes (occurring in 
the absence of mania, delirium, or depression) 
 Steroid-induced violence: glucocorticoid-induced violence toward self or others 


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10.16. 
Appendix 16: Country-Specific Requirements 
10.16.1. 
China 
10.16.1.1. Section 1.3. Schedule of Activities - China 
Table 16:
Schedule of Activities for Trial ARGX-113-1904 – China
Trial Period 
Screening
Treatment
EoS/
EDa 
UNSb 
Follow-up 
V1(BL) 
V2 
Observational 
visits 
IMP admin 
only visit 
Observational visits 
Visit Number 
 
 
Weekly on-
site visits until 
CRc 
Weekly home 
or on-site 
visits until 
CRmind 
On-site visits 
every 4 weeks 
until CRmin 
On-site visits 
every 4 
weeks after 
CRmin until 
W31 
W31 
Follow-
up W34 
 
Follow-
up 
W38e 
 
Trial Day/Week 
D-21 
to D-1 
D1 
(W1) 
D8 
(W2) 
D15 (W3) 
until CR 
CR until 
CRmin 
CR until 
CRmin 
CRmin until 
W31 
W31 
EoS/ED 
+3W 
EoS/ED 
+7W 
Visit Window 
±0 days 
±2 daysf 
V1 + 7× ±2 daysf 
±2 
daysf 
±3 daysf
Assessment/
Procedure 
 
Informed consentg
X
Inclusion/exclusion 
criteria 
X 
X 
 
 
 
 
 
 
 
 
 
DIF/histopathologyh 
X
Concomitant 
therapies/procedures 
X 
Continuous monitoring 
Karnofsky 
performance score 
X 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
Height and weighti
X 
 
 
Xi
 
Xi
Xi
X 
 
 
 


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Trial Period 
Screening
Treatment 
EoS/
EDa
UNSb 
Follow-up 
V1(BL)
V2
Observational 
visits
IMP admin 
only visit
Observational visits
Visit Number 
 
 
Weekly on-
site visits until 
CRc 
Weekly home 
or on-site 
visits until 
CRmind 
On-site visits 
every 4 weeks 
until CRmin 
On-site visits 
every 4 
weeks after 
CRmin until 
W31 
W31 
Follow-
up W34 
 
Follow-
up 
W38e 
 
Trial Day/Week 
D-21 
to D-1 
D1
(W1)
D8
(W2)
D15 (W3) 
until CR 
CR until 
CRmin 
CR until 
CRmin 
CRmin until 
W31 
W31
EoS/ED 
+3W 
EoS/ED 
+7W 
Visit Window 
±0 days 
±2 daysf 
V1 + 7× ±2 daysf 
±2 
daysf 
±3 daysf
Physical 
examination and 
vital signsj,k 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
ECGj 
X 
 
 
Xl 
Xl 
 
X 
 
 
 
Medical and 
surgical history 
X 
 
 
 
 
 
 
 
 
 
 
Randomizationm
 
X 
 
 
 
 
 
 
 
 
 
Urinalysisj,n,o
X 
X 
X 
X 
 
X 
X 
X 
Xb
X 
X 
Urine pregnancy 
testj,p 
X
Xp 
 
X 
X 
X 
Xb 
X 
X 
Blood sampling: 
 
Active viral 
infection testq
X 
 
 
 
 
 
 
 
 
 
 
Serum pregnancy 
testr 
X
Clinical chemistry 
& hematologyj,o,s
X 
X 
X 
X 
 
X 
X 
X 
Xb 
X 
X 


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Trial Period 
Screening
Treatment 
EoS/
EDa
UNSb 
Follow-up 
V1(BL)
V2
Observational 
visits
IMP admin 
only visit
Observational visits
Visit Number 
 
 
Weekly on-
site visits until 
CRc 
Weekly home 
or on-site 
visits until 
CRmind 
On-site visits 
every 4 weeks 
until CRmin 
On-site visits 
every 4 
weeks after 
CRmin until 
W31 
W31 
Follow-
up W34 
 
Follow-
up 
W38e 
 
Trial Day/Week 
D-21 
to D-1 
D1
(W1)
D8
(W2)
D15 (W3) 
until CR 
CR until 
CRmin 
CR until 
CRmin 
CRmin until 
W31 
W31
EoS/ED 
+3W 
EoS/ED 
+7W 
Visit Window 
±0 days 
±2 daysf 
V1 + 7× ±2 daysf 
±2 
daysf 
±3 daysf
Tuberculosis 
QuantiFERON/IGR
A or equivalent 
testj,t 
X
Anti-Dsg-1 and 
anti-Dsg-3 
antibodiesj,o 
X 
X 
X 
X 
 
X 
X 
X 
Xb 
X 
X 
PKj,o,u
X
Xu 
X 
 
X 
X 
X 
Xb,u 
X
X
Total IgGj,o,v 
X
X
X
X
X
X
X
Xb
X 
X 
Immunogenicityj,w 
 
X 
 
X 
(every 2 weeks)
 
X 
X 
X 
 
X 
X 
QoL Assessments: 
 
EQ-5D-5Lj,x
 
X 
 
Xy
 
Xy
Xy
X
 
 
 
ABQOLj,x 
X
Xy
 
Xy
Xy
X
 
 
 
GTIj 
 
X 
 
Xz 
Xz 
Xz 
X 
 
 
 
IMP self-
administration 
trainingaa
 
 
 
X 
X 
 
 
 
 
 


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Trial Period 
Screening
Treatment 
EoS/ 
EDa
UNSb 
Follow-up 
V1(BL) 
V2
Observational 
visits 
IMP admin 
only visit
Observational visits
Visit Number 
 
 
Weekly on-
site visits until 
CRc 
Weekly home 
or on-site 
visits until 
CRmind 
On-site visits 
every 4 weeks 
until CRmin 
On-site visits 
every 4 
weeks after 
CRmin until 
W31 
W31 
Follow-
up W34 
 
Follow-
up 
W38e 
 
Trial Day/Week 
D-21 
to D-1 
D1
(W1) 
D8
(W2) 
D15 (W3) 
until CR 
CR until 
CRmin 
CR until 
CRmin 
CRmin until 
W31 
W31 
EoS/ED 
+3W 
EoS/ED 
+7W 
Visit Window 
±0 days 
±2 daysf 
V1 + 7× ±2 daysf 
±2 
daysf 
±3 daysf
IMP 
administrationbb
 
X 
 
X 
 
X 
X 
X 
 
 
Xb
 
 
PDAIj 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
Disease 
assessmentcc
 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
Prednisone taperdd 
X
X 
X 
X
X 
X 
X 
X 
AE monitoring
Continuous monitoring
ABQOL=Autoimmune Bullous Disease Quality of Life; admin=administration; BL=baseline; BMI=body mass index; CR=complete clinical remission; 
CRmin=CR on minimal therapy; D=day; DC=disease control; DIF=direct immunofluorescence; Dsg=desmoglein; ECG=electrocardiogram; ED=early 
discontinuation; EoC=end of consolidation; EoS=end of study; FSH=follicle-stimulating hormone; GTI=Glucocorticoid Toxicity Index; HLA=human leukocyte 
antigen; IgG=immunoglobulin G; ICF=informed consent form; IMP=investigational medicinal product; OLE=open-label extension; PDAI=Pemphigus Disease 
Area Index; PK=pharmacokinetics; RBC=red blood cells; UNS=unscheduled visit; WBC=white blood cells; W=week; V=visit 
a All participants will complete EoS/ED, which will be the end of the trial for participants who enroll in the OLE trial ARGX-113-1905. Participants who do not 
enroll in the OLE trial ARGX 113 1905 will complete the follow-up visits at W34 and W38. 
b In case of suspected new lesions as reported by the participants, AEs, flare or other safety reasons, participants should come to the clinic. This may require an 
unscheduled visit. Depending on the reason for the visit, different assessments need to be performed. See Section 8 for more information. Participants with new 
lesions or flare after achieving CR should return to weekly on-site visits until CR is achieved again. 
c A minimum of 6 on-site visits, V1(BL)/W1 to W6, are required before switching to home administrations, even if CR is achieved earlier than W6. The W7 visit 
is the first eligible “IMP administration only” visit (refer to column “Weekly home or on-site visits until CRmin”), at home or on-site, if CR is achieved 
between W1 and W6. 
d Home visits are allowed once participants achieve CR, but not before W7. The investigator should call the participant every 2 weeks until CRmin is achieved to 
confirm the participant is still in CR. On-site visits may continue at the investigator’s discretion. 


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e W38 (follow-up visit 2) is the end of the trial for participants who do not enroll in the OLE trial ARGX-113-1905. The W38 follow-up visit will only be 
required for those participants who were still receiving IMP at least once from W27 onward. For participants who ended treatment prior to W27, W34 will be 
the end of the trial. 
f Trial visit windows are ±2 days during the treatment period and ±3 days for follow-up visits. 
g No trial-related assessments can be initiated before the participant has provided a signed ICF.
h Only required if not available from medical history. 
i Height and weight will be measured (and BMI will be calculated accordingly) at screening, at week W15 (or the next on-site visit if W15 does not coincide 
with an on-site visit), and EoS/ED. Weight will also be measured if there has been an obvious change since the last measurement. 
j At visits in which IMP is administered, the assessment or procedure should be completed before dosing.
k A complete physical examination will be completed at each on-site visit. Vital sign measurements include systolic and diastolic blood pressure, heart rate, and 
body temperature. Supine blood pressure and heart rate will be measured using standard equipment after at least 10 minutes rest. 
l ECG to be taken at W12. If the W12 visit does not coincide with an on-site visit, then the assessment should be performed at the next on-site visit. ECG (heart 
rate, PR, QT, and QRS interval) will be read centrally. QTcF and QTcB will be calculated. 
m Randomization will take place on day 1 after all eligibility checks are confirmed (eg, PDAI) and before other baseline assessments are run, and prior to dosing. 
n Urinalysis will include specific gravity, pH, protein, glucose, ketones, blood, bilirubin, urobilinogen, nitrite, leukocyte esterase, and microscopic examination 
(if blood or protein test results are abnormal). 
o Samples will be taken every week from V1(BL)/W1 to W9 and then every 4 weeks and at the visit where CR is observed. Once CR is achieved, samples will 
be taken every 4 weeks at on-site visits until EoS/ED. For participants achieving CR between V1(BL)/W1 and W6, samples will be taken weekly from W1 to 
W6 and then every 4 weeks at on-site visits until EoS/ED. 
p A urine pregnancy test will be conducted and analyzed locally during on-site visits at least once every 4 weeks (before and after CR) and at the time of CR. 
q Viral testing for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), hepatitis B core antibody (anti-HBc), hepatitis B virus (HBV) 
DNA, hepatitis C virus (HCV) antibodies, HCV messenger RNA (mRNA), and human immunodeficiency virus (HIV) antibodies. 
r At screening, a serum pregnancy test must be performed in women of childbearing potential or FSH test to confirm postmenopausal status.
s Clinical blood laboratory tests will include hematology and blood chemistry at all visits and international normalized ratio (INR) or activated partial 
thromboplastin time (aPTT) at screening only. The hematology profile includes hemoglobin, hematocrit, mean corpuscular volume (MCV), RBC count, platelet 
count, WBC count with differential. The blood chemistry profile includes sodium, potassium, calcium, hemoglobin A1c (HbA1c), creatinine, creatinine 
clearance, blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, gamma-glutamyl transferase (GGT), 
C-reactive protein (CRP), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein 
cholesterol (HDL-C), total cholesterol, triglycerides, uric acid, total protein, and albumin. 
t At the discretion of investigator, additional testing may be performed to rule out active tuberculosis infection, including but not limited to chest computed 
tomography (CT) or X-ray. 
u For PK assessment, blood samples will be taken predose (within 2 hours before the start of IMP administration at visits where IMP is administered). An 
additional PK sample will be taken on D3 and on D11 (±1 day) until samples from 24 participants are obtained. At unscheduled visits blood samples for PK 
will only be taken if IMP is administered. 
v At screening, total IgG will be measured as part of inclusion and exclusion criteria. The pharmacodynamic (PD) biomarker total IgG will be measured centrally 
from a blood sample taken predose. 
w Anti-drug antibodies to efgartigimod (in serum samples) and antibodies against rHuPH20 (in plasma samples) will be tested predose every 2 weeks from 
V1(BL)/W1 to W9 and then every 4 weeks at on-site visits and at the visit where CR is observed. Once CR is achieved, samples will be taken every 4 weeks at 


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on-site visits until EoS/ED. For participants achieving CR between V1(BL)/W1 and W6, samples will be taken predose at V1(BL)/W1, W3, W5, the visit 
where CR is observed, W10, and then every 4 weeks at on-site visits until EoS/ED. Neutralizing antibodies (Nab) will be tested for all confirmed positive ADA 
samples. 
x Questionnaires are to be completed prior to any other activity.
y Assessments will be performed at baseline, after 4 weeks (W5), W15, and EoS/ED visits. If the W15 visit does not coincide with an on-site visit, then the 
assessment should be performed at the next on-site visit. 
z The GTI assessment will be performed only at baseline, W15 and EoS/ED. If W15 does not coincide with an on-site visit, then the assessment should be 
performed at the next on-site visit. 
aaParticipants will be trained to self-administer IMP (foreseen in the OLE trial; not in the ARGX-113-1904 trial) during the first 4 visits as of V3 when IMP is 
administered; thereafter, training for self-administration is optional (only if needed). 
bbIMP will be administered until CRmin. Participants should remain at the site for at least 1 hour after the first administration and 15 minutes after subsequent 
administrations for safety monitoring. Participants will be released according to their clinical status. Participants who experience treatment failure, or flare after 
achieving CR on minimal therapy, will be allowed to roll over into the OLE trial ARGX-113-1905 earlier than W31. Participants who do not roll over into trial 
ARGX-113-1905 will complete the treatment-free follow-up period.  
ccDisease assessment parameters include disease control (DC), end of consolidation (EoC), complete clinical remission (CR), complete remission on minimal 
therapy (CRmin), complete remission off therapy (CRoff), flare, and treatment failure. Participants who have achieved CR and have new lesions should come 
to the clinic for a UNS for disease assessment. 
dd Prednisone dose tapering will begin 2 weeks after achieving CR or 4 weeks after sustained EoC (thus, no new lesions have developed for a minimum of 6 
weeks and approximately 80% or more of lesions have healed). 
 
 


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10.16.1.2. Section 8.3.6. Clinical Safety Laboratory Assessments – China 
Blood and urine samples for determination of clinical chemistry, hematology, coagulation, 
urinalysis, serology (ie, viral testing), and tuberculosis QuantiFERON/IGRA test and other tests 
that have been approved in China with similar validity versus QuantiFERON (eg, T-SPOT) will 
be collected and analyzed as indicated in the SoA (refer to Section 10.16) and Section 10.16.1.3. 
In China, a certified laboratory will be used for clinical safety laboratory assessment. The urine 
sample for the pregnancy test will be analyzed locally. 
Participants may be rescreened (ie, redoing the full assessments as per SoA in Section 10.16) or 
retested once (ie, repeating 1 test, see Section 5.4) if still within the screening period. 
On days that IMP is administered, blood for laboratory assessments should be collected before 
dosing. 
Additional safety samples may be collected if clinically indicated, at the discretion of the 
investigator.
For all female participants of childbearing potential, a serum pregnancy test will be performed at 
screening (on the samples taken for clinical laboratory tests), and a urine pregnancy test will be 
conducted and analyzed locally at the site at the visits specified in the SoA (Section 10.16). A 
follicle-stimulating hormone (FSH) test will be run to confirm postmenopausal status and 
exclude that a woman is of childbearing potential; see Section 10.5. 
Clinical laboratory tests will be reviewed for results of potential clinical significance at all time 
points throughout the trial. The investigator will evaluate any change in laboratory values. If the 
investigator determines a laboratory abnormality to be clinically significant, it will be considered 
as a laboratory AE, however, if the abnormal laboratory value is consistent with a current 
diagnosis, then it may be documented accordingly without being reported as an AE.
The details of sampling, handling, storage, and transportation of the samples will be described in 
the Laboratory Manual. 
All laboratory tests with values considered clinically significantly abnormal during participation 
in the trial should be recorded as an AE and repeated until the values return to normal or baseline 
or are no longer considered clinically significant by the investigator or medical monitor. 
 If such values do not return to normal/baseline within a period of time judged 
reasonable by the investigator, then the etiology should be identified and the sponsor 
notified.
 All protocol-required laboratory assessments, as defined in Section 10.16.1.3, must be 
conducted in accordance with the Laboratory Manual and the SoA (Section 10.16).  
 If laboratory values from non-protocol specified laboratory assessments (except for 
total IgG; refer to Section 8.6) performed at the institution’s local laboratory require a 
change in participant management or are considered clinically significant by the 
investigator (eg, SAE or AE or dose modification), then the event must be recorded in 
the eCRF.  


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10.16.1.2.1.
Section 8.3.6.2. Storage of Blood Samples in the Trial - China
Upon approval from the Human Genetic Resources (HGR) in China and in compliance with 
local regulations, blood samples collected from Chinese participants may be used to validate 
methods to support the efgartigimod program. 
The storage duration and destruction of blood samples collected from Chinese participants will 
comply with HGR Administration of China (HGRAC) requirements and other relevant 
regulations. 
10.16.1.3. Section 10.2. Appendix 2: Laboratory Tests – Table 7 - China 
Table 17: 
Protocol-Required Laboratory Assessments - China 
Hematology 
Hemoglobin, hematocrit, MCV, RBC, platelet count, WBC with differential 
Clinical chemistry
Sodium, potassium, calcium, HbA1c, creatinine, creatinine clearance, BUN, 
ALT, AST, total bilirubin, GGT, LDL-C, CRP, ALP, LDH, HDL-C, total 
cholesterol, triglycerides, uric acid, total proteina, and albumina 
Coagulation 
INR or aPTT 
Urinalysis 
Specific gravity, pH, protein, glucose, ketones, blood, bilirubin, urobilinogen, 
nitrite, leukocyte esterase, and microscopic examination (if blood or protein test 
results are abnormal) 
Serology 
HIV antibodies (1 and 2), HBsAg, anti-HBs and anti-HBc, HBV DNA, HCV 
antibodies, HCV mRNA 
Other 
Serum human ß-HCG, FSH test, tuberculosis QuantiFERON/IGRA test (and 
other tests that have been approved in China with similar validity versus 
QuantiFERON, eg, T-SPOT), urine pregnancy test 
Pharmacokineticsa 
Serum levels of efgartigimod 
Pharmacodynamic 
markersa 
Serum levels of total IgG and anti-Dsg-1 and anti-Dsg-3 autoantibodies 
Immunogenicitya 
Serum levels of ADA to efgartigimod and plasma levels of antibodies against 
rHuPH20 
ß-HCG= ß subunit of  human chorionic gonadotrophin; ADA= antidrug antibodies; ALP= alkaline phosphatase; 
ALT= alanine aminotransferase; anti-Dsg-1=anti-desmoglein-1; anti-Dsg-3=anti-desmoglein-3; 
anti-HBs=antibodies to the surface antigens of the hepatitis B virus; anti-HBc= antibodies to the surface core 
antigens of the hepatitis B virus; aPTT= activated partial thromboplastin time; AST=aspartate aminotransferase; 
BUN=blood urea nitrogen; CRP=C-reactive protein; DNA= deoxyribonucleic acid; FSH=follicle-stimulating 
hormone GGT=gamma-glutamyl transferase; HbA1c= hemoglobin A1c; HBV=hepatitis B virus; HBsAg=hepatitis 
B surface antigen; HCV=hepatitis C virus; HDL-C=high-density lipoprotein cholesterol; HIV= human 
immunodeficiency viruses; IgG=immunoglobulin G; INR=international normalized ratio; LDH= lactate 
dehydrogenase; LDL-C=low-density lipoprotein cholesterol MCV=mean corpuscular volume; mRNA= messenger 
RNA; RBC= red blood cell; rHuPH20=recombinant human hyaluronidase; RNA=ribonucleic acid; WBC=white 
blood cell 
a PK, PD, immunogenicity, albumin, and total protein data will not be reported to the site. A system will be 
implemented that will alert the investigator of out-of-range albumin and total protein values, to allow for 
appropriate safety follow-up. 


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10.16.1.4. Section 10.14. Possible Adaptations of Trial Protocol During COVID-19 Pandemic - Table 10 - China 
Table 18:
Modified Schedule of Activities During COVID-19 Pandemic - China
In the SoA of the ARGX-113-1904 trial (see below), the mandatory assessments are indicated in red (X). The assessments that need to 
be performed only if feasible during the COVID-19 pandemic are indicated in black (X). At site visits, all assessments have to be 
performed (critical [X] and non-critical [X]), if operationally feasible. 
Trial Period 
Screening 
Treatment
EoS/
EDa 
UNSb 
Follow-up 
V1(BL) 
V2 
Observational 
visits 
IMP admin 
only visit 
Observational visits 
Visit Number 
 
 
Weekly on-
site visits until 
CRc
Weekly home 
or on-site 
visits until 
CRmind 
On-site visits 
every 4 weeks 
until CRmin 
On-site visits 
every 4 
weeks after 
CRmin until 
W31 
W31 
Follow-
up W34 
 
Follow-
up 
W38e
 
Trial Day/Week 
D-21 
to D-1 
D1 
(W1) 
D8 
(W2) 
D15 (W3) 
until CR 
CR until 
CRmin 
CR until 
CRmin 
CRmin until 
W31 
W31 
EoS/ED 
+3W 
EoS/ED 
+7W 
Visit Window 
±0 days 
±2 daysf
V1 + 7× ±2 daysf
±2 
daysf 
±3 daysf
Assessment/ 
Procedure 
 
Informed consentg
X
Inclusion/exclusion 
criteria 
X 
X 
 
 
 
 
 
 
 
 
 
DIF/histopathologyh 
X 
 
 
 
 
 
 
 
 
 
 
Concomitant 
therapies/procedures 
X 
Continuous monitoring 
Karnofsky 
performance score 
X 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
Height and weighti
X
Xi
 
Xi
Xi
X 
 
 
 


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Trial Period 
Screening
Treatment 
EoS/
EDa
UNSb 
Follow-up 
V1(BL)
V2
Observational 
visits
IMP admin 
only visit
Observational visits
Visit Number 
 
 
Weekly on-
site visits until 
CRc 
Weekly home 
or on-site 
visits until 
CRmind 
On-site visits 
every 4 weeks 
until CRmin 
On-site visits 
every 4 
weeks after 
CRmin until 
W31 
W31 
Follow-
up W34 
 
Follow-
up 
W38e 
 
Trial Day/Week 
D-21 
to D-1 
D1
(W1)
D8
(W2)
D15 (W3) 
until CR 
CR until 
CRmin 
CR until 
CRmin 
CRmin until 
W31 
W31
EoS/ED 
+3W 
EoS/ED 
+7W 
Visit Window 
±0 days 
±2 daysf 
V1 + 7× ±2 daysf 
±2 
daysf 
±3 daysf
Physical 
examination and 
vital signsj,k 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
ECGj 
X 
 
 
Xl 
Xl 
 
X 
 
 
 
Medical and 
surgical history 
X 
 
 
 
 
 
 
 
 
 
 
Randomizationm
 
X 
 
 
 
 
 
 
 
 
 
Urinalysisj,n,o
X 
X 
X 
X 
 
X 
X 
X 
Xb
X 
X 
Urine pregnancy 
testj,p 
X
Xp 
 
X 
X 
X 
Xb 
X 
X 
Blood sampling: 
 
Active viral 
infection testq
X 
 
 
 
 
 
 
 
 
 
 
Serum pregnancy 
testr 
X
Clinical chemistry 
& hematologyj,o,s
X 
X 
X 
X 
 
X 
X 
X 
Xb 
X 
X 


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Trial Period 
Screening
Treatment 
EoS/
EDa
UNSb 
Follow-up 
V1(BL)
V2
Observational 
visits
IMP admin 
only visit
Observational visits
Visit Number 
 
 
Weekly on-
site visits until 
CRc 
Weekly home 
or on-site 
visits until 
CRmind 
On-site visits 
every 4 weeks 
until CRmin 
On-site visits 
every 4 
weeks after 
CRmin until 
W31 
W31 
Follow-
up W34 
 
Follow-
up 
W38e 
 
Trial Day/Week 
D-21 
to D-1 
D1
(W1)
D8
(W2)
D15 (W3) 
until CR 
CR until 
CRmin 
CR until 
CRmin 
CRmin until 
W31 
W31
EoS/ED 
+3W 
EoS/ED 
+7W 
Visit Window 
±0 days 
±2 daysf 
V1 + 7× ±2 daysf 
±2 
daysf 
±3 daysf
Tuberculosis 
QuantiFERON/IGR
A or equivalent 
testj,t 
X
Anti-Dsg-1 and 
anti-Dsg-3 
antibodiesj,o 
X 
X 
X 
X 
 
X 
X 
X 
Xb 
X 
X 
PKj,o,u
X
Xu 
X 
 
X 
X 
X 
Xb,u 
X
X
Total IgGj,o,v 
X
X
X
X
X
X
X
Xb
X 
X 
Immunogenicityj,w 
 
X 
 
X 
(every 2 weeks)
 
X 
X 
X 
 
X 
X 
QoL Assessments: 
 
EQ-5D-5Lj,x
 
X 
 
Xy
 
Xy
Xy
X
 
 
 
ABQOLj,x 
X
Xy
 
Xy
Xy
X
 
 
 
GTIj 
 
X 
 
Xz 
Xz 
Xz 
X 
 
 
 
IMP self-
administration 
trainingaa
 
 
 
X 
X 
 
 
 
 
 


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Trial Period 
Screening
Treatment 
EoS/ 
EDa
UNSb 
Follow-up 
V1(BL) 
V2
Observational 
visits 
IMP admin 
only visit
Observational visits
Visit Number 
 
 
Weekly on-
site visits until 
CRc 
Weekly home 
or on-site 
visits until 
CRmind 
On-site visits 
every 4 weeks 
until CRmin 
On-site visits 
every 4 
weeks after 
CRmin until 
W31 
W31 
Follow-
up W34 
 
Follow-
up 
W38e 
 
Trial Day/Week 
D-21 
to D-1 
D1
(W1) 
D8
(W2) 
D15 (W3) 
until CR 
CR until 
CRmin 
CR until 
CRmin 
CRmin until 
W31 
W31 
EoS/ED 
+3W 
EoS/ED 
+7W 
Visit Window 
±0 days 
±2 daysf 
V1 + 7× ±2 daysf 
±2 
daysf 
±3 daysf
IMP 
administrationbb
 
X 
 
X 
 
X 
X 
X 
 
 
Xb
 
 
PDAIj 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
Disease 
assessmentcc
 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
Prednisone taperdd 
X
X 
X 
X
X 
X 
X 
X 
AE monitoring
Continuous monitoring
ABQOL=Autoimmune Bullous Disease Quality of Life; admin=administration; BL=baseline; BMI=body mass index; CR=complete clinical remission; 
CRmin=CR on minimal therapy; D=day; DC=disease control; DIF=direct immunofluorescence; Dsg=desmoglein; ECG=electrocardiogram; ED=early 
discontinuation; EoC=end of consolidation; EoS=end of study; EQ-5D-5L=EuroQol 5-dimension 5-level; FSH=follicle-stimulating hormone; 
GTI=Glucocorticoid Toxicity Index; HLA=human leukocyte antigen; IgG=immunoglobulin G; ICF=informed consent form; IMP=investigational medicinal 
product; OLE=open-label extension; PDAI=Pemphigus Disease Area Index; PK=pharmacokinetics; RBC=red blood cells; UNS=unscheduled visit; WBC=white 
blood cells; W=week; V=visit 
a All participants will complete EoS/ED, which will be the end of the trial for participants who enroll in the OLE trial ARGX-113-1905. Participants who do not 
enroll in the OLE trial ARGX 113 1905 will complete the follow-up visits at W34 and W38. 
b In case of suspected new lesions, as reported by the participants, AEs, flare or other safety reasons, participants should come to the clinic. This may require an 
unscheduled visit. Depending on the reason for the visit, different assessments should be performed. See Section 8 for more information. Participants with new 
lesions or flare after achieving CR should return to weekly on-site visits until CR is achieved again. 
c A minimum of 6 on-site visits, V1(BL)/W1 to W6, are required before switching to home administrations, even if CR is achieved earlier than W6. The W7 visit 
is the first eligible “IMP administration only” visit (refer to column “Weekly home or on-site visits until CRmin”), at home or on-site, if CR is achieved 
between W1 and W6. 


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d Home visits are allowed once participants achieve CR, but not before W7. The investigator should call the participant every 2 weeks until CRmin is achieved to 
confirm the participant is still in CR. On-site visits may continue at the investigator’s discretion. 
e W38 (follow-up visit 2) is the end of the trial for participants who do not enroll in the OLE trial ARGX-113-1905. The W38 follow-up visit will only be 
required for those participants who were still receiving IMP at least once from W27 onward. For participants who ended treatment prior to W27, W34 will be 
the end of the trial. 
f Trial visit windows are ±2 days during the treatment period and ±3 days for follow-up visits. 
g No trial-related assessments can be initiated before the participant has provided a signed ICF. 
h Only required if not available from medical history. 
i Height and weight will be measured (and BMI will be calculated accordingly) at screening, at week W15 (or the next on-site visit if W15 does not coincide 
with an on-site visit), and EoS/ED. Weight will also be measured if there has been an obvious change since the last measurement. 
j At visits in which IMP is administered, the assessment or procedure should be completed before dosing. 
k A complete physical examination will be completed at each on-site visit. Vital sign measurements include systolic and diastolic blood pressure, heart rate, and 
body temperature. Supine blood pressure and heart rate will be measured using standard equipment after at least 10 minutes rest. 
l ECG to be taken at W12. If the W12 visit does not coincide with an on-site visit, then the assessment should be performed at the next on-site visit. ECG (heart 
rate, PR, QT, and QRS interval) will be read centrally. QTcF and QTcB will be calculated. 
m Randomization will take place on day 1 after all eligibility checks are confirmed (eg, PDAI) and before other baseline assessments are run, and prior to dosing. 
n Urinalysis will include specific gravity, pH, protein, glucose, ketones, blood, bilirubin, urobilinogen, nitrite, leukocyte esterase, and microscopic examination 
(if blood or protein test results are abnormal). 
o Samples will be taken every week from V1(BL)/W1 to W9 and then every 4 weeks and at the visit where CR is observed. Once CR is achieved, samples will 
be taken every 4 weeks at on-site visits until EoS/ED. For participants achieving CR between V1(BL)/W1 and W6, samples will be taken weekly from W1 to 
W6 and then every 4 weeks at on-site visits until EoS/ED. 
p A urine pregnancy test will be conducted and analyzed locally during on-site visits at least once every 4 weeks (before and after CR) and at the time of CR. 
q Viral testing for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), hepatitis B core antibody (anti-HBc), hepatitis B virus (HBV) 
DNA, hepatitis C virus (HCV) antibodies, HCV messenger RNA (mRNA), and human immunodeficiency virus (HIV) antibodies. 
r At screening, a serum pregnancy test must be performed in women of childbearing potential or FSH test to confirm postmenopausal status. 
s Clinical blood laboratory tests will include hematology and blood chemistry at all visits and international normalized ratio (INR) or activated partial 
thromboplastin time (aPTT) at screening only. The hematology profile includes hemoglobin, hematocrit, mean corpuscular volume (MCV), RBC count, platelet 
count, WBC count with differential. The blood chemistry profile includes sodium, potassium, calcium, hemoglobin A1c (HbA1c), creatinine, creatinine 
clearance, blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, gamma-glutamyl transferase (GGT), 
C-reactive protein (CRP), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein 
cholesterol (HDL-C), total cholesterol, triglycerides, uric acid, total protein, and albumin. 
t At the discretion of investigator, additional testing may be performed to rule out active tuberculosis infection, including but not limited to chest computed 
tomography (CT) or X-ray. 
u For PK assessment, blood samples will be taken predose (within 2 hours before the start of IMP administration at visits where IMP is administered). An 
additional PK sample will be taken on D3 and on D11 (±1 day) until samples from 24 participants are obtained. At unscheduled visits blood samples for PK 
will only be taken if IMP is administered. 
v At screening, total IgG will be measured as part of inclusion and exclusion criteria. The pharmacodynamic (PD) biomarker total IgG will be measured centrally 
from a blood sample taken predose. 


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w Anti-drug antibodies to efgartigimod (in serum samples) and antibodies against rHuPH20 (in plasma samples) will be tested predose every 2 weeks from 
V1(BL)/W1 to W9 and then every 4 weeks at on-site visits and at the visit where CR is observed. Once CR is achieved, samples will be taken every 4 weeks at 
on-site visits until EoS/ED. For participants achieving CR between V1(BL)/W1 and W6, samples will be taken predose at V1(BL)/W1, W3, W5, the visit 
where CR is observed, W10, and then every 4 weeks at on-site visits until EoS/ED. Neutralizing antibodies (Nab) will be tested for all confirmed positive ADA 
samples. 
x Questionnaires are to be completed prior to any other activity.
y Assessments will be performed at baseline, after 4 weeks (W5), W15, and EoS/ED visits. If the W15 visit does not coincide with an on-site visit, then the 
assessment should be performed at the next on-site visit. 
z The GTI assessment will be performed only at baseline, W15 and EoS/ED. If W15 does not coincide with an on-site visit, then the assessment should be 
performed at the next on-site visit. 
aaParticipants will be trained to self-administer IMP (foreseen in the OLE trial; not in the ARGX-113-1904 trial) during the first 4 visits as of V3 when IMP is 
administered; thereafter, training for self-administration is optional (only if needed). 
bb IMP will be administered until CRmin. Participants who do not roll over into trial ARGX-113-1905 will complete the treatment-free follow-up period. 
Participants should remain at the site for at least 1 hour after the first administration and 15 minutes for subsequent administrations for safety monitoring. 
Participants will be released according to their clinical status. Participants who experience treatment failure, or flare after achieving CR on minimal therapy, 
will be allowed to roll over into the OLE trial ARGX-113-1905 earlier than W31.  
cc Disease assessment parameters include disease control (DC), end of consolidation (EoC), complete clinical remission (CR), complete remission on minimal 
therapy (CRmin), complete remission off therapy (CRoff), flare, and treatment failure. Participants who have achieved CR and have new lesions should come 
to the clinic for a UNS for disease assessment. 
ddPrednisone dose tapering will begin 2 weeks after achieving CR or 4 weeks after sustained EoC (thus, no new lesions have developed for a minimum of 6 
weeks and approximately 80% or more of lesions have healed). 


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10.16.2. 
Germany 
10.16.2.1. Section 1.3: Schedule of Activities – Post-Administration Safety Monitoring – 
Germany 
To ensure proper safety monitoring, participants should remain at the site for at least 1 hour after 
the first administration. In Germany, participants should remain at the site for at least 30 minutes 
after the 5 subsequent administrations and for 15 minutes after all administrations thereafter. 
Participants will be released according to their clinical status. 
 
 


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11.
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19. Qian Y, Jeong JS, Abdeladhim M, et al. IgE anti-LJM11 sand flu salivary antigen may 
herald the onset of fogo selvagem in endemic Brazilian regions. J Invest Dermatol 
2015;135(3):913-915. 
20. Baican A, Baican C, Chiriac G, et al. Pemphigus vulgaris is the most common 
autoimmune bullous disease in Northwestern Romania. Int J Dermatol 2010;49(7):768-
774.
21. Zhao CY, Murrell DF. Pemphigus vulgaris: and evidence-based treatment update. Drugs 
2015;75(3):271-284. 
22. Schmidt E, Sticherling M, Sardy M, et al. S2k guidelines for the treatment of pemphigus 
vulgaris/foliaceus and bullous pemphigoid: 2019 update. J Dtsch Dermatol Ges 
2020;18(5):516-526. 
23. Harman KE, Brown D, Exton LS, et al. British Association of Dermatologists' guidelines 
for the management of pemphigus vulgaris 2017. Br J Dermatol 2017-177(5):1170-1201. 
24. Murrell DF, Pena S, Joly P, et al. Diagnosis and management of pemphigus: 
Recommendations of an international panel of experts. J Am Acad Dermatol 
2020;82(3):575-585.e.1. 
25. Hebert V, Boulard C, Houivet E, et al. Large international validation of ABSIS and PDAI 
pemphigus severity scores. J Invest Dermatol 2019;139(1):31-37. 
26. Amagai M, Ikeda S, Shimizu H, et al. A randomized double-blind trial of intravenous 
immunoglobulin for pemphigus. J Am Acad Dermatol 2009;60(4):595-603. 
27. Rosenbach M, Murrell DF, Bystryn JC, et al. Reliability and convergent validity of two 
outcome instruments for pemphigus. J Invest Dermatol 2009;129:2404-2410. 
28. Rahbar Z, Daneshpazhooh M, Mirshams-Shahshahani M, et al. Pemphigus disease 
activity measurements: pemphigus disease area index, autoimmune bullous skin disorder 
intensity score, and pemphigus vulgaris activity score. JAMA Dermatol 2014;150(3):266-
272. 
29. Sebaratnam DF, Hanna AM, Chee SN, et al. Development of a quality-of-life instrument 
for autoimmune bullous disease: the Autoimmune Bullous Disease Quality of Life 
questionnaire. JAMA Dermatol 2013;149(10):1186-1191. 


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09 Dec 2022
Efgartigimod PH20 SC 
argenx 
Confidential 
168 
30. Ratnam KV, Phay KL, Tan CK. Pemphigus therapy with oral prednisolone regimens. A 
5-year study. Int J Dermatol 1990;29(5):363-367. 
31. Czernik A, Bystryn JC. Improvement of intravenous immunoglobulin therapy for bullous 
pemphigoid by adding immunosuppressive agents: marked improvement in depletion of 
circulating autoantibodies. Arch Dermatol 2008;144(5):658-661. 
32. Chaidemenos G, Apalla Z, Koussidou T, Papagarifallou I, Ioannides D. High dose oral 
prednisone vs. prednisone plus azathioprine for the treatment of oral pemphigus: a 
retrospective, bi-centre, comparative study. J Eur Acad Dermatol Venereol 
2011;25(2):206-210. 
33. Beissert S, Mimouni D, Kanwar AJ, Solomons N, Kalia V, Anhalt GJ. Treating 
pemphigus vulgaris with prednisone and mycophenolate mofetil: a multicenter, 
randomized, placebo-controlled trial. J Invest Dermatol 2010;130(8):2041-2048.
34. Mimouni D, Bar H, Gdalevich M, Katzenelson V, David M. Pemphigus, analysis of 155 
patients. J Eur Acad Dermatol Venereol 2010;24(8):947-952. 
35. Wormser D, Chen DM, Brunetta PG, et al. Cumulative oral corticosteroid use increases 
risk of glucocorticoid-related adverse events in patients with newly diagnosed 
pemphigus. J Am Acad Dermatol 2017;77(2):379-381. 
36. Howard JF Jr, Bril V, Burns TM, et al. Randomized phase 2 study of FcRn antagonist 
efgartigimod in generalized myasthenia gravis. Neurology 2019;92(23):e2661-e2673. 
37. Newland AC, Sanchez-Gonzalez B, Rejto L, et al. Phase 2 study of efgartigimod, a novel 
FcRn antagonist, in adult patients with primary immune thrombocytopenia. Am J 
Hematol 2020;95(2):178-187. 
38. Miloslavsky EM, Naden RP, Bijlsma JWJ, et al. Development of a Glucocorticoid 
Toxicity Index (GTI) using multicriteria decision analysis. Ann Rheum Dis. 2017;76:543-
546. 
39. McDowell PJ, Stone JH, Zhang, Y, et al. Quantification of glucocorticoid-associated 
morbidity in severe asthma using the Glucocorticoid Toxicity Index. J Allergy Clin 
Immunol. 2021;9(1):365-372. 
40. Kasperkiewicz M, Ellebrecht CT, Takahashi H, et al. Pemphigus. Nat Rev Dis Primers
2017;3:17026. 
41. Ahmed AR, Carrozzo M, Caux F, et al. Monopathogenic vs multipathogenic explanations 
of pemphigus pathophysiology. Exp Dermatol 2016;25(11):839-846. 
42. Schmidt E, Kasperkiewicz M, Joly P. Pemphigus. Lancet 2019;394:882-894. 
43. Ulrichts P, Guglietta A, Dreier T, et al. Neonatal Fc receptor antagonist efgartigimod 
safely and sustainably reduces IgGs in humans. J Clin Invest 2018;128:4372-4386. 
44. Harrington DP, Fleming TR. A class of rank test procedures for censored survival data. 
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45. Neuenschwander B, Capkun-Niggli G, Branson M, Spiegelhalter DJ. Summarizing 
historical information on controls in clinical trials. Clin Trials 2010;7(1):5-18. 



SAP_001.pdf: 
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ARGX-113-1904
Protocol:
ARGX-113-1904
SGS CR number:
BE-80-2000062
Development phase:
Phase 3
Sponsor:
argenx BV
Analysis purpose:
Final analysis
SAP version number:
Final 2.0
SAP version date:
22NOV2023




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Final 2.0 of 22NOV2023
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PROTOCOL HISTORY 
ARGX-113-1904
Protocol:
Version or ID
Date 
(ddMMMyyyy)
Impact of the changes on the statistical 
analysis
Final 1.0
22JUL2020
NAP
Final 2.0 
(Amendment 1)
10FEB2021
NAP
Final 3.0 
(Amendment 2)
18MAY2021
NAP
Final 4.0 
(Amendment 3)
09JUN2022
NAP


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LIST OF ABBREVIATIONS 
1904
ARGX-113-1904
1905
ARGX-113-1905
Ab
Antibody
ABQOL 
Autoimmune Bullous Disease Quality of Life 
ADA
anti-drug antibodies 
ADaM
analysis data model
AE
adverse event
AESI
adverse events of special interest 
AIS 
aggregate improvement score 
ALQ
above the limit of quantification
ANCOVA
Analysis of covariance 
ATC
Anatomical-Therapeutic-Chemical
BMI 
body mass index 
Bpm
beats per minute
BLQ
below the limit of quantification
C-GTI 
Composite Glucocorticoid Toxicity Index 
CMH
Cochran-Mantel-Haenszel
CR
clinical remission
CRF
case report form
CRmin
complete remission on minimal therapy
CRoff 
complete remission off prednisone therapy 
CSP
Clinical study protocol
CTCAE
Common Terminology Criteria for Adverse Events
CWS 
cumulative worsening score 
DBP
diastolic blood pressure
DC
disease control 
Dsg 
desmoglein 
DY
relative day
ECG
Electrocardiogram
ED 
early discontinuation 
EoC
end of consolidation 


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EoS 
end of study 
EQ-5D-5L 
EuroQol 5-Dimension 5-Level Scale 
FU
Follow-up
GM
Geometric mean
GSD
Geometric standard deviation
GTI 
Glucocorticoid Toxicity Index 
GTI-SL 
Glucocorticoid Toxicity Index Specific List
HR
heart rate
ICE
Intercurrent event
ICF
informed consent form
ICH
International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use
IgG
immunoglobin G
IMP
investigational medicinal product
IRR
Injection-related reaction 
ISR
Injection site reaction
IV 
intravenous 
IVIg 
immunoglobulins given intravenously 
LOCF
Last Observation Carried Forward
MedDRA
Medical Dictionary for Regulatory Activities
MMRM
Mixed model for repeated measurements
NCI 
National Cancer Institute 
NCPD 
normalized cumulative prednisone dose 
NAb
neutralizing antibody 
OLE
open-label extension
PD
Pharmacodynamics
PDAI 
Pemphigus Disease Area Index 
PK
Pharmacokinetics
PF
pemphigus foliaceus
PT 
preferred term 
PV
pemphigus vulgaris
rHuPH20 
recombinant human hyaluronidase PH20 
QoL
quality of life


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QTc
corrected QT interval
QTcB
QTcF
SAE
serious adverse event
SAF
safety analysis set
SAP
statistical analysis plan
SBP
systolic blood pressure
SC
subcutaneous
SCR
all screened participants analysis set
SD
standard deviation
SE
standard error
SGS CR
SGS Clinical Research
SOC
system organ class
SOP
standard operating procedure
STAT
statistics
TEAE
treatment-emergent adverse event
WHO-DD
World Health Organization Drug Dictionary


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DEFINITION OF TERMS 
case report form 
(CRF)
A printed, optical, or electronic document in which 
protocol required information is recorded for each study
participant.
Display
Analysis table, figure or listing.
Phase
Interval of time in the planned conduct of a study that is 
associated with a specific purpose: for example, screening, 
treatment, follow-up.
IMP
Pharmaceutical form of an active ingredient or placebo, 
being tested or used as a reference in a clinical study.
treatment-emergent 
abnormality
Any post-baseline abnormality that was not present at 
baseline (e.g. hemoglobin normal at baseline and grade 1 
post-baseline; glucose low at baseline and high post-
baseline; QTcF ]450; 480] ms at baseline and >500 ms 
post-baseline).
Complete clinical 
remission (CR)
The absence of new lesions and complete healing of 
established lesions (except for post-inflammatory 
hyperpigmentation or erythema from resolving lesions).
Complete remission 
on minimal therapy 
(CRmin)
The absence of new and established lesions completely 
healed while the participant is receiving prednisone therapy 
Complete remission 
off prednisone 
therapy (CRoff)
The absence of new and established lesions completely 
healed while the participant is receiving no prednisone 
therapy (or the equivalent) for at least 2 months (8 weeks).
Disease control (DC)
The absence of new lesions and the start of healing of 
established lesions.
Disease progression
at any post-baseline visit before DC.


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End of consolidation 
(EoC)
The time at which no new lesions have developed for a 
minimum of 2 weeks and approximately 80% of lesions have 
healed.
Flare
Appearance of 3 or more new lesions in a 4-week period 
that do not heal spontaneously within 1 week or the 
extension of established lesions, in a participant who had 
achieved DC.
Treatment failure
Absence of DC with oral prednisone 1.5 mg/kg/day for a 
minimum of 3 weeks, or flare between DC and CRmin that 
is not controlled by a dose that is 2 dose levels above the 
dose at which the flare is observed and that is of at least 0.3 
mg/kg qd, or the occurrence of an SAE considered related 
to prednisone by the investigator.


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TABLE OF CONTENTS 
Statistical analysis plan ............................................................................................... 1
Signature page .............................................................................................................. 2
Protocol history ............................................................................................................ 3
List of abbreviations .................................................................................................... 4
Definition of terms ....................................................................................................... 7
Table of Contents ......................................................................................................... 9
1.
Introduction ....................................................................................................... 13
1.1
Study objectives.............................................................................................13
1.2
Study design ..................................................................................................14
1.3
Expected sample size.....................................................................................15
1.4
Software.........................................................................................................15
1.5
Validation model ...........................................................................................15
2.
General methodology......................................................................................... 16
2.1
Analysis sets ..................................................................................................16
2.1.1
Analysis sets....................................................................................16
2.1.2
As planned versus as actual analysis...............................................16
2.2
Phases and time points...................................................................................17
2.2.1
Analysis Phases and Periods ...........................................................17
2.2.2
Baseline and change from baseline .................................................18
2.2.3
Relative day.....................................................................................18
2.2.4
Analysis visits .................................................................................19
2.2.5
Worst-case.......................................................................................21
2.3
Imputation and rounding rules.......................................................................21
2.3.1
Missing values.................................................................................21
2.3.2
Handling partially or completely missing dates in calculations......22
2.3.3
Values below or above a threshold .................................................22
2.3.4
Rounding of derived variables ........................................................22
2.3.5
Outliers............................................................................................22
2.4
Presentation of results....................................................................................23
2.4.1
Calculation of descriptive statistics and percentages ......................23
2.4.2
Presentation of treatments ...............................................................24
2.4.3
Order in tables and listings..............................................................24


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3.
General characteristics analyses ...................................................................... 25
3.1
Participant disposition ...................................................................................25
3.1.1
Available data..................................................................................25
3.1.2
Presentation of results .....................................................................25
3.2
Demographic and other baseline characteristics ...........................................25
3.2.1
Available data..................................................................................25
3.2.2
Derivation rules...............................................................................26
3.2.3
Presentation of results .....................................................................26
3.3
Medical history and concomitant diseases ....................................................27
3.3.1
Available data..................................................................................27
3.3.2
Derivation rules...............................................................................27
3.3.3
Presentation of results .....................................................................27
3.4
Prior and concomitant therapies and procedures...........................................27
3.4.1
Available data..................................................................................27
3.4.2
Derivation rules...............................................................................27
3.4.3
Presentation of results .....................................................................28
3.5
IMP and prednisone administration...............................................................28
3.5.1
Available data..................................................................................28
3.5.2
Derivation rules...............................................................................29
3.5.3
Presentation of results .....................................................................31
4.
Efficacy, pharmacokinetic, Pharmacodynamic and immunogenicity 
analyses ......................................................................................................... 32
4.1
Efficacy and quality of life............................................................................32
4.1.1
Available data..................................................................................32
4.1.2
Endpoints and derivation rules........................................................32
4.1.3
Presentation of results and statistical analysis.................................37
4.1.4
Fixed-Sequence testing procedure ..................................................40
4.1.5
Subgroup analyses for efficacy .......................................................41
4.2
Pharmacokinetics...........................................................................................42
4.2.1
Available data..................................................................................42
4.2.2
Derivation rules...............................................................................43
4.2.3
Presentation of results .....................................................................43
4.3
Pharmacodynamics........................................................................................43


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4.3.1
Available data..................................................................................43
4.3.2
Derivation rules...............................................................................43
4.3.3
Presentation of results .....................................................................44
4.4
Immunogenicity.............................................................................................44
4.4.1
Available data..................................................................................44
4.4.2
Derivation rules...............................................................................46
4.4.3
Presentation of results .....................................................................50
5.
Safety analyses ................................................................................................... 52
5.1
Adverse events...............................................................................................52
5.1.1
Available data..................................................................................52
5.1.2
Derivation rules...............................................................................52
5.1.3
Presentation of results .....................................................................53
5.2
Clinical laboratory evaluation .......................................................................55
5.2.1
Available data..................................................................................55
5.2.2
Derivation rules...............................................................................56
5.2.3
Presentation of results .....................................................................56
5.3
Vital signs......................................................................................................57
5.3.1
Available data..................................................................................57
5.3.2
Derivation rules...............................................................................57
5.3.3
Presentation of results .....................................................................57
5.4
Electrocardiograms........................................................................................57
5.4.1
Available data..................................................................................57
5.4.2
Derivation rules...............................................................................58
5.4.3
Presentation of results .....................................................................58
5.5
Physical examinations ...................................................................................59
5.5.1
Available data..................................................................................59
5.5.2
Presentation of results .....................................................................59
6.
Changes to the planned analysis ....................................................................... 60
6.1
Changes not covered by protocol amendments before database lock ...........60
6.2
Changes not covered by protocol amendments after database lock..............61
6.3
Changes to the final statistical analysis plan .................................................61
7.
References ........................................................................................................... 62
8.
List of tables and listings ................................................................................... 63
8.1
Tables ............................................................................................................63


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8.2
Listings ..........................................................................................................74
9.
Appendices ......................................................................................................... 76
9.1
Main Intercurrent Events (ICE).....................................................................76
9.1.1
Immunosuppressants or dapsone at therapeutic doses for at least 4 
weeks in total in the last 12 weeks before achieving CRmin..........76
9.1.2
achieving CRmin.............................................................................76
9.1.3
Immunoadsorption or plasma exchange (at least 1 procedure) before 
achieving CRmin.............................................................................76
9.1.4
Rituximab or other anti-CD20 biologics (at least 1 infusion) before 
achieving CRmin.............................................................................77
9.1.5
IV or IM corticosteroids..................................................................77
9.1.6
Tetracyclines administered at least 100 mg/day for at least 2 weeks 
in total..............................................................................................77
9.1.7
Any interventional study drug under development for pemphigus 
given before achieving CRmin........................................................77
9.2
SAS CODE....................................................................................................78
9.2.1
MMRM model.................................................................................78
9.2.2
ANCOVA model.............................................................................78
9.2.3
Time to event analysis: stratified Fleming-Harrington weighted 
logrank test ......................................................................................78
9.2.4
Time to event analysis: logrank test................................................78
9.2.5
Cochran-Mantel-Haenszel test with Klingenberg midpoint and CI79
9.2.6
Cox Proportional Hazard regression model ....................................80
9.2.7
Stratified Mann-Whitney test..........................................................80
9.3
GTI: Derivation of CWS and AIS.................................................................81
9.3.1
Allocate weights..............................................................................81
9.3.2
CWS and AIS calculation ...............................................................87
9.4
Toxicity grades (CTCAE, v5.0) ....................................................................88
9.5
Schedule of assessments................................................................................92


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1.
INTRODUCTION 
This statistical analysis plan (SAP) describes the final statistical analyses to be 
performed for study ARGX-113-1904 (BE-80-2000062).
This SAP covers the efficacy, safety, pharmacokinetic (PK), pharmacodynamic (PD),
immunogenicity and general characteristics of the statistical analysis. It specifies the 
analysis displays to be presented and describes the methods and procedures in a more 
elaborated way than in the statistical methods section of the protocol. Analyses of 
exploratory endpoints are not in scope of this SAP.
The statistical analysis will process and present the results following the International 
Council for Harmonisation of Technical Requirements for Pharmaceuticals for 
Human Use (ICH) standards, in particular the ICH-E3, ICH-E6, and ICH-E9 
guidelines.
1.1
STUDY OBJECTIVES 
According to the ARGX-113-1904 protocol, the primary objective of this study is to
demonstrate the efficacy of efgartigimod PH20 SC compared to placebo in the 
treatment of participants with pemphigus vulgaris (PV).
The secondary objectives of study are:
To demonstrate the efficacy of efgartigimod PH20 SC in the treatment 
of participants with PV or pemphigus foliaceus (PF).
To assess the safety of efgartigimod PH20 SC in participants with PV or
PF.
To assess the health impact of glucocorticoid (GC) use in participants
with PV or PF.
To evaluate the effects of efgartigimod PH20 SC on quality of life 
(QoL) in participants with PV or PF.
To evaluate the PK of efgartigimod PH20 SC in participants with PV or 
PF.
To evaluate the PD of efgartigimod PH20 SC in participants with PV or 
PF.
To evaluate the immunogenicity of efgartigimod PH20 SC in 
participants with PV or PF.
To evaluate the competency of participants or caregivers to self-
administer efgartigimod PH20 SC.
The exploratory objectives include the following but are out of scope of this SAP:
To evaluate the disease-specific genetic background and effects of 
efgartigimod PH20 SC on the serological and immunological profiles of 
participants with PV or PF.
To evaluate the effects of efgartigimod PH20 SC on markers of 
pemphigus pathology in skin of participants with PV or PF.
 


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1.2
STUDY DESIGN 
This study is a prospective, multicenter, randomized, double-blinded, placebo-
controlled study to investigate the efficacy, safety, participant outcome measures, 
tolerability, immunogenicity, PK, and PD of efgartigimod PH20 SC in adult 
participants with PV or PF.
The study comprises a screening period of up to 3 weeks, a treatment period of up to 
30 weeks, and an 8-week follow-up period for participants who do not enrol into the 
open-label extension (OLE) study ARGX-113-1905.
After confirmation of eligibility, participants will be randomized in a 2:1 ratio to 
receive efgartigimod PH20 SC or placebo, as follows:
Efgartigimod PH20 SC will be administered on day 1 and day 8 at a 
dose of 
 mg, followed by weekly administrations of 1000 mg until 
CRmin is observed. Efgartigimod PH20 SC will be administered at on-
site visits until CR, with a minimum of 6 weekly on-site visits. After 
achieving CR, efgartigimod PH20 SC will be administered at on-site 
visits or at home by a nurse until CR on minimal therapy is achieved.
Placebo (vehicle with 2000 U/mL of rHuPH20) SC will be administered 
using the same regimen.
CR is defined as the absence of new lesions and complete healing of established 
lesions (except for post-inflammatory hyperpigmentation or erythema from resolving 
lesions). CRmin is defined as the absence of new lesions and complete healing of 
established lesions while the participant is receiving minimal prednisone therapy of 
Randomization will be stratified by disease status (relapsing and newly diagnosed), 
disease severity (PDAI activity score <30 and PDAI activ
weight (<77.5 kg and 77.5 kg) at baseline. Participants with severe PV or PF (PDAI 
study population.
All participants, regardless of treatment assignment, will concomitantly receive oral 
prednisone (or equivalent such as prednisolone) at 0.5 mg/kg qd starting dose. Except 
for oral prednisone (or equivalent), no other systemic therapies (eg,
immunosuppressants, IVIg, immunoadsorption, anti-CD20 biologics) will be 
permitted during the study.
Participants who experience treatment failure, or flare after achieving CRmin, will be 
allowed to roll over into the OLE study ARGX-113-1905 earlier than week 30. 
Participants who do not roll over into study ARGX-113-1905 will complete an 8-
week treatment-free follow-up period. Participants experiencing an SAE related to 
prednisone in ARGX-113-1904 are considered treatment failures and may also 
benefit from an early roll over to the OLE, according to clinical judgment of the 
investigators.
 


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1.3
EXPECTED SAMPLE SIZE 
Approximately 213 participants with PV or PF will be randomized as follows for 
1904 study:
Approximately 183 participants with PV will be randomized in a 2:1 
ratio to receive efgartigimod PH20 SC or placebo, respectively
Up to approximately 30 participants with PF may be randomized in a 
2:1 ratio to receive efgartigimod PH20 SC or placebo, respectively
All participants who were randomized into ARGX-113-1904 will be eligible to roll
over to study 1905.
1.4
SOFTWARE 
SAS version 9.4 or later will be used for programming. 
1.5
VALIDATION MODEL 
SGS Clinical Research (SGS CR) statistics (STAT) and pharmacokinetics (PK)
standard operating procedures (SOPs) and work instructions (WIs) as effective at the 
project start will be followed throughout the project, provided the applicable 
regulatory requirements are still met.
Analysis Data Model (ADaM) datasets (except subject-level analysis dataset 
[ADSL]), analysis tables and listings will be reviewed by an independent person 
(model B validation). ADaM dataset ADSL and the primary endpoint will be 
reviewed through independent programming (model C validation).


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2.
GENERAL METHODOLOGY 
2.1
ANALYSIS SETS 
The following analysis sets will be considered in the statistical analysis:
All screened 
participants set (SCR):
participants who signed an informed consent to
participate in the study
Modified Intent-to-treat
analysis set (mITT):
all participants who were randomized into the study and 
received at least one dose, or part of a dose, of IMP 
Per Protocol set (PP):
all participants in the mITT population for whom no 
major protocol deviations affecting the efficacy and data 
validity were reported
Safety analysis set 
(SAF):
all participants who were randomized into the study and 
received at least one dose, or part of a dose, of IMP 
PK analysis set (PK)
all participants in the safety analysis set for whom at 
least one post-baseline serum PK concentration is 
available
PD analysis set (PD)
all participants in the safety analysis set for whom at 
least one post-baseline serum PD concentration is 
available
Note: Having signed an informed consent is defined as having a complete informed 
consent signature date in the database.
The efficacy analyses will be done on the mITT analysis set. The analyses of primary 
and key secondary efficacy endpoints will be repeated on the PP analysis set. The 
general characteristics and safety analyses will be done on the safety analysis set. PK 
analysis will be performed on the PK analysis set. PD analysis will be done on the PD 
analysis set. Immunogenicity will be analyzed on the safety analysis set.
All analyses on the mITT and PP analysis set will be performed according to the
planned randomization group. All other analyses will be performed according to the
actual received IMP.


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2.2
PHASES AND TIME POINTS 
All events and assessments will be allocated to phases and periods as defined below.
Table 1: Phase definition 
Phase
Period
Start
End
Screening
Date of signing the informed consent form 
(ICF), with 00:00 added as time part a
First IMP administration date/time
1 minute
Treatment
On Treatment
First IMP administration date/time
Last IMP administration date with 
23:59 added as time part.
Off Treatment
End of on treatment period + 1 minute
For participants who roll over to 
study 1905, date of study
termination (of study 1904), with 
23:59 added as time part.
For participants who do not roll
over to study 1905, date of end of 
study/early discontinuation visit b,
with 23:59 added as time part.
For participants who do not roll
over to study 1905 and have no end 
of study/early discontinuation visit,
date of treatment discontinuation
(of study 1904), with 23:59 added 
as time part.
Following phase is only applicable for participants in the treatment phase who do not roll over to study 1905.
Follow-up
End of treatment phase + 1 minute
Date of study termination (of study
1904), with 23:59 added as time 
part.
a
For rescreened participants without new IC signed the rescreening visit date is used as start of screening phase
b
Treatment phase lasts until EoS/ED also if a participant may be off treatment after CRmin
Per definition and for each participant, the first phase starts on the date of the earliest 
available ICF signature, and the last available phase ends on the date of study
termination with 23:59 added as time part.
Adverse events and concomitant medications will be allocated to phases (
also to
periods) as described in sections 5.1.2 and 3.4.2 respectively. All other assessments 
will be allocated to phases based on the assessment date/time. 
A set of subperiods will be derived within the treatment phase, to support the analysis 
of treatment-emergent adverse events (TEAEs) versus post-TEAEs, as defined in 
Table 2 below.


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Table 2: Subperiod definition for AE
Subperiod
Start
End
Treatment 
emergent 1
Treatment period start date/time
(see Table 1)
Date of first EFG where the next 
EFG is at least 61 days later 
+ 60 daysa
Post-treatment 
emergent 1
End date/time of previous subperiod
+ 1 minute
Start date/time of next subperiod
- 1 minute
Treatment 
emergent 2
First EFG date/time following the start 
of previous post-treatment emergent
subperiod
Date of first EFG where the next 
EFG is at least 61 days later 
+ 60 daysa
Post-treatment 
emergent 2
End date/time of previous subperiod 
+ 1 minute
Start date/time of next subperiod 
- 1 minute
Etc.b
EFG = efgartigimod (administration)
a
With 23:59 added as time part
b
Repeat until the last subperiod
The end date/time of the last subperiod within a period will be the end date/time of the period as defined in Table 
1.
In case of (partially) missing date/time fields disabling allocation, the visit label will 
be used to allocate to the correct phase. If this is not possible (unscheduled visits or 
visits on a turning point between phases), assessments will be allocated to the
treatment phase unless the available parts of the assessments start or stop date/time 
provide evidence for allocating to a non-treatment phase.
The baseline value will be the last available and non-missing value prior to the first 
dose of study medication. Assessments on day 1 without time collection or with time 
information exactly equal to the time of first IMP administration and which are 
planned predose will be considered as predose.
Change from baseline at time point t is defined as:
value at time point t baseline value
Percentage change from baseline at time point t is defined as:
100*([value at time point t baseline value] / baseline value)
Relative days in the study (ADY) will be calculated according to the following rule:
Concerned date < reference date: ADY = concerned date reference date
ADY = concerned date reference date + 1
Unless stated otherwise, the reference date is the date of first administration of IMP.


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Additionally relative days in the phase/period (ADYP) will be calculated using the 
first day of the phase/period as reference date (date of first IMP for screening phase). 
Per definition ADY=ADYP for the screening.
All assessments, including unscheduled assessments, will be allocated to analysis 
windows as defined below. Tables and listings will present the analysis windows, not 
the case report form (CRF) visits. Allocation of assessments will be done using their 
relative day (ADYP, see section 2.2.3). Visit windows are the mid-point between the 
scheduled study days for each visit.
Table 3: Analysis visits 
Following analysis visits are allocated based on ADYP using start of phase as 
reference day.
Phase
Analysis window
Target ADYP
Lower limit ADYP
Upper limit ADYP
Screening
Screening
-21
-INF
1
Treatment
Baseline
1
-INF
1[1]
Week 1
8
1[1]
11
Week 2
15
12
18
Week 3
22
19
25
Week (3+ x[2])
22 + (x[2]*7 days)
19 + (x[2]*7 days)
25 + (x[2]*7 days)
Week 29
204
201
207
Week 30
211
208
End day of treatment 
phase
Follow-up
FU Week 3
21
1
35
FU Week 7
49
36
End of follow-up 
phase
[1]
An assessment on Day 1 will be attributed to Baseline in case it is before the first IMP administration, to Week 1
otherwise. 
[2]
.25


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Table 4: Additional analysis visits for PD, Albumin, LDL-C and PDAI
Additionally following analysis visits are allocated based on ADYP using start of 
period as reference day.
Phase
Period
Analysis window
Target 
ADYP
Lower limit 
ADYP
Upper limit 
ADYP
Treatment
On treatment
Baseline 
1
-INF
1[1]
Week 1
8
1[1]
11
Week 2
15
12
18
Week 3
22
19
25
Week (3+ x[2])
22 + (x[2]*7 
days)
19 + (x[2]*7
days)
25 + (x[2]*7
days)
Week 30
211
208
Last IMP 
administration 
date
Off treatment
Week 1
8
1
11
Week 2
15
12
18
Week 3
22
19
25
Week (3+ x[2])
22 + (x[2]*7 
days)
19 + (x[2]*7
days)
25 + (x[2]*7
days)
Week 30
211
208
End day of 
treatment 
phase
[1]
An assessment on Day 1 will be attributed to Baseline in case it is before the first IMP administration, to Week 1
otherwise. 
[2]
.26 
Per parameter and analysis window, the value closest to the target ADYP will be used 
in analysis tables, other values will only be listed. If more than one value is located at 
the same distance from the target, then the latest in time will be selected. The value 
latest in time will be identified using, in order of preference, the assessment time, the 
visit label or the group identifier (if applicable). For immunogenicity assessments, 
missing values resulting in an unavailable ADA/NAb status are given the lowest 
priority when the selection is made. For other assessments, missing values are 
removed before the selection is made. 
Partially missing assessment dates disabling allocation to analysis windows will not 
be imputed and thus these assessments will not be considered in the per-timepoint 
analysis. Note that these assessments are included in analyses on worst-case.


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As the schedule of assessments is dependent of CR and consequently varies between 
participants, data might get spread over time for the 4-weekly visits after CR. 
Therefore some visit windows will be changed for some parameters:
1. For ABQOL and EQ-5D-5L
Week 14 (wide range): from ADYP=96 until ADYP=123
Week 30 (wide range): from ADYP= 124 until ADYP=end of treatment 
phase
Additional visit window: Endpoint: last record post baseline.
2. For GTI
Week 14 (wide range): from ADYP=61 until ADYP=137 with target on 
ADYP=99
Week 30 (wide range): from ADYP=173 until ADYP= end of treatment 
phase with target on ADYP=211
Other assessments will be allocated as in table 3 but will not be presented 
in the tables (only in listings).
Additional visit window: Overall: last record post baseline.
3. For ECG
Week 11 (wide range): from ADYP=75 until ADYP=102
The same rules for record selection as for the regular visit windows will be applied in 
case of more records occur in the same window. 
A worst-case analysis visit will be created for parameters for which abnormalities 
and/or toxicity grades are defined to summarize values considered as the worst-case. 
For abnormalities it is derived per parameter and in case both the lowest and the
highest values are considered abnormal, a participant can have 2 worst-case analysis 
visits for a same parameter. For toxicity grades the worst-case is the value associated 
to the highest toxicity grade and is derived per parameter and toxicity direction
(hypo/hyper).
All non-missing post-baseline values, including unscheduled assessments and follow-
up visits, will be considered when deriving the worst-case analysis visit.
2.3
IMPUTATION AND ROUNDING RULES 
For imputation on missing values related to efficacy, see appropriate section of the 
applicable efficacy endpoint.


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Partially missing date of diagnosis and of disease onset will be imputed as follows:
Missing day will be imputed with first day of the month
Missing day and month will be imputed with 1JAN
If the imputed date of diagnosis is before the date of disease onset, date of diagnosis 
will be imputed with date of disease onset.
If the imputed date of disease onset is after the date of diagnosis, date of disease onset 
will be imputed with date of diagnosis.
Safety values expressed as below (or above) the detection limit will be imputed by the 
value of the detection limit itself. Listings will always show the non-imputed values.
Total IgG and IgG subtype values expressed as below or above the limit of
quantification (BLQ or ALQ, respectively) will not be imputed. For anti-Dsg-1/Dsg-
3, BLQ and ALQ values will be imputed by the value of the detection limit itself.
Listings will always show the non-imputed values.
PK concentrations BLQ will be flagged as such in the listings. For descriptive 
statistical analysis, all BLQ values will be set to zero. For ALQ values, all ALQ 
values will be set to the upper limit of quantification for descriptive analysis. Listings 
will always present the original value.
Anti-drug antibodies (ADA) against efgartigimod: titer of positive ADA samples 
y 1. 
Antibodies (Ab) against rHuPH20: titer of positive rHuPH20 Ab samples reported as 
Neutralizing antibodies (NAb) against rHuPH20: titer of positive rHuPH20 NAb 
d by 100. 
Derived variables will be rounded to the appropriate number of decimals at display 
level:
Cumulative prednisone dose will be rounded to 0 decimals.
BMI and time since diagnosis will be rounded to 1 decimal.
eGFR and NCPD will be rounded to 2 decimals.
There will be no outlier detection. All measured values will be included in the 
analyses.


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2.4
PRESENTATION OF RESULTS 
Region/country specific outputs will be created to support region/country specific 
submissions.
Specifically, all descriptive outputs described in this SAP will be repeated by region 
(Japanese / Non-Japanese as defined in the study protocol) to support the J-MAA 
submission. The definition of a Japanese participant in the protocol is a participant 
whose parents and 4 grandparents are Japanese, who has the Japanese nationality, was 
born in Japan, has not lived outside of Japan for a total of >10 years, and currently 
lives in Japan. 
To support the Chinese submission, all outputs described in this SAP will be repeated 
for the following two subpopulations: Mainland Chinese and East Asian. Mainland 
Chinese is defined as any participant enrolled by an investigational site located in 
mainland China and with a ra
Asian
enrolled by an investigational site located in East Asia (China, Japan), and with a race 
s and Pharmacodynamics analyses
described in sections 4.2 and 4.3 (except the Japanese-specific analysis) will be 
repeated for the complement of the Mainland Chinese and East Asian subgroups (i.e. 
Non-Mainland Chinese and Non-East Asian).
To support the EU submission, all outputs described in this SAP will be repeated for 
the participants with a history of relapsing disease. This subgroup includes
participants that met the following inclusion criteria in the protocol of study ARGX-
113-1904:
since disease onset, and off prednisone therapy ± a conventional 
immunosuppressant (eg, azathioprine, cyclophosphamide, methotrexate, 
mycophenolate mofetil) or dapsone. 
since disease onset, and receiving a tapered dose of oral prednisone (or 
equivalent), provided that prednisone has been given at stable dose ± a 
conventional immunosuppressant (eg, azathioprine, cyclophosphamide, 
methotrexate, mycophenolate mofetil) or dapsone for at least 2 weeks and 
participants are fit to start prednisone treatment at 0.5 mg/kg qd at baseline. 
For continuous variables, full descriptive statistics will only be presented if there are 
at least 2 non-missing observations. Alternatively, only the number of non-missing 
data points and mean are shown.
Descriptive statistics will include the number of non-missing data points, the 
arithmetic mean, the standard deviation (SD), the standard error (SE), the median, 
minimum, Q1, Q3 and maximum.
Descriptive statistics for immunogenicity titer values will also include geometric 
mean (GM) and geometric standard deviation (GSD).


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Mean, median, Q1 and Q3, geometric mean (GM) and geometric standard deviation 
(GSD) will be presented with one more decimal place than the individual values, with
maximum 4 decimal places. SD and SE will be presented with 2 more decimal places 
than the individual values, with maximum 5 decimal places. Minimum and maximum 
will be presented with the same number of decimal places than the individual values,
with maximum 3 decimal places. GM and GSD of percent changes from baseline are
presented with one decimal.
Descriptive statistics for PK concentrations will include n (number of observed 
values), arithmetic mean, SD, median, minimum and maximum, and the coefficient of
variation (CV%). Serum concentrations will be presented with 3 significant digits in 
without the decimals. The descriptive statistics should be rounded to the same number 
of significant digits as the individual values. If more than half of the values are BLQ, 
arithmetic mean will be set to BLQ and SD and CV% will not be calculated.
For event-type safety data, the number and percentage of participants with an event,
and the number of events will be shown. The denominator will be all participants in 
the analysis set per treatment and phase
.
For frequency tabulations and cross-tabulations, the denominator will be all 
participants in the analysis set per treatment. For tables where results are shown by 
analysis visit, the denominator will be all participants in the analysis set per treatment 
and per analysis visit. Missing values will never be included in the denominator count 
when computing percentages. For cross-tabulations of post-baseline results versus 
.
The following treatment labels will be used in the tables and listings: 
EFG PH20 SC
PBO PH20 SC
In the general characteristics analysis, a grand total will be added to summarize all 
participants over treatments. Grand totals will be shown last.
All tables and figures will be presented per treatment, unless specified otherwise. In 
by visit displays, worst-case will be shown last, if present.
In listings for general characteristics, results will be ordered by treatment and 
participant, unless specified otherwise.
All other listings will be ordered by treatment, participant, analysis visit and time 
point, unless specified otherwise.
In tables showing several parameters, each parameter will begin on a new page and 
parameters will be sorted alphabetically, within the parameter category if applicable.
The Efgartigimod treatment group will always be shown first, then the Placebo 
treatment group.


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3.
GENERAL CHARACTERISTICS ANALYSES 
3.1
PARTICIPANT DISPOSITION 
The following participant data will be tabulated:
The number of participants in each analysis set.
The number and percentage of participants for each phase and analysis 
visit.
Descriptive statistics of the phase duration, calculated as phase end date 
phase start date + 1 day.
presented for participants with/without treatment failure.
The number and percentage of participants who completed or 
discontinued the study as documented on the study termination page and 
the number and percentage of participants for each study discontinuation 
reason.
The number and percentage of participants who completed or 
discontinued the treatment as documented on the end of treatment page 
and the number and percentage of participants for each treatment 
discontinuation reason.
The number and percentage of participants who roll over to study 
ARGX-113-1905 and the number and percentage of participants by 
reason not rolling over (i.e
to
).
All information collected in the CRF concerning treatment allocation and study and 
treatment discontinuation will be listed.
Tables to be produced for the topline results (see list of output in 8.1) will be 
presented for all participants (PV+PF) as well as for PV participants and PF 
participants separately.
3.2
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS 
The following parameters will be available:
Demographics: sex at birth, age at informed consent, race and ethnicity
(if collection permitted), region, childbearing potential, height, weight 
and BMI at screening, year of birth, date of signing ICF (listed only).


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Baseline disease characteristics: date of pemphigus onset (listed only),
date of pemphigus diagnosis, pemphigus type (vulgaris/foliaceus) and 
subtype (mucosal-dominant / mucocutaneous / cutaneous), type of 
procedure used for confirmation of diagnosis (cutaneous histology / 
direct immunofluorescence / indirect immunofluorescence / ELISA), 
relapsing (yes / no), newly diagnosed (yes / no), number of relapses (if 
applicable), prior use of immunosuppressants (yes / no), prior use of 
rituximab (yes / no), PDAI activity score and PDAI total score at 
baseline, baseline severity [PDAI activity <30/ 30 as well as PDAI
activity score 15-44 (moderate), 45 (severe)], ABQOL total score at 
baseline, Karnofsky performance score,
anti-Dsg 
antibodies (aDsg1 only, aDsg3 only, both aDsg1 and aDsg3, neither 
aDsg1 nor aDsg3), prednisone equivalent dose per body weight at 
baseline (mg/kg/day), prednisone equivalent dose at baseline (mg/day)
and stratification factors (as randomized).
The following parameters will be derived:
Time since pemphigus diagnosis (months): (date of first IMP
date of 
diagnosis)*12/365.25
Notes: 
o
Partially missing dates will be imputed as detailed in section 2.3.2.
o
Result will be rounded as detailed in section 2.3.4 .
Prior use of immunosuppressants is defined as use of medications with
IMP administration
Prior use of rituximab is defined as use of medication with CMDECOD 
Derivation of prednisone equivalent dose is detailed in section 3.5.2.
Since day 1 can be considered as a transition day, prednisone equivalent 
dose on day 2 will be used as baseline.
Region: North America (USA), Europe (Bulgaria, France, Hungary, 
Germany, Greece, Italy, Poland, Romania, Spain, UK), Asia (China, 
India, Japan), Rest of world (Australia, Georgia, Russian Federation, 
Serbia, Turkey, Ukraine)
Demographics will be presented using descriptive statistics for age, height, weight 
and BMI at screening and frequency tabulations for sex, childbearing potential,
weight at baseline (<77.5 kg,
, geographical region, race and ethnicity.
Baseline disease characteristics will be presented using descriptive statistics for time 
since diagnosis (overall and for newly diagnosed subjects and subjects relapsing),
number of relapses, PDAI activity score and PDAI total score at baseline, ABQOL 


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total score at baseline, Karnofsky performance score and prednisone dose; frequency 
tabulations for all other parameters.
Descriptive analyses will be presented for all participants (PV+PF) as well as for PV 
participants and PF participants separately.
All demographic data and baseline disease characteristics will be listed. 
3.3
MEDICAL HISTORY AND CONCOMITANT DISEASES 
Medical history findings are coded using the medical dictionary for regulatory 
activities (MedDRA) into system organ classes and preferred terms. For each finding, 
a start and stop date or ongoing flag is collected. The MedDRA version will be 
updated to the latest one until the database lock of 1904.
Medical history finding: not ongoing at screening, ended before date of signing 
informed consent.
Concomitant disease: medical history condition still ongoing at screening.
Medical history and concomitant diseases will be tabulated separately. Both tables
will show:
The number and percentage of participants with findings
The number and percentage of participants with findings by system 
organ class (SOC) and preferred term (PT)
All medical history (not ongoing at screening) and concomitant disease (still ongoing 
at screening) data will be listed.
3.4
PRIOR AND CONCOMITANT THERAPIES AND PROCEDURES 
All therapies are coded using WHO-DD. Anatomical-Therapeutic-Chemical (ATC)
selection is performed to select the most appropriate medication class. For the 
selected class, ATC coding up to level 4 is available in the clinical database. For each 
therapy, a start date or prior flag and stop date or ongoing flag are collected.
Procedures are coded using the medical dictionary for regulatory activities 
(MedDRA) into preferred terms. For each finding, the indication and a start and stop 
date are collected.
Based on their start and stop date, therapies and procedures will be allocated into one 
or both of the following categories:


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Prior: any therapy/procedure that strictly started before the first dose.
Concomitant: any therapy/procedure that was taken on or after the first 
dose.
A medication that started before the first dose date and continued during the study 
will be classified as both prior and concomitant.
Therapies/procedures with (partially) missing date(time)s will be allocated to each 
category unless the available parts of the therapy/procedure start or stop date(time)
provide evidence not to do so.
Intercurrent events of unallowed therapies that may influence efficacy are defined as:
Immunosuppressants at therapeutic doses for at least 4 weeks in total
IVIg/SCIg at immunomodula
Immunoadsorption or plasma exchange, at least 1 procedure
Rituximab or other anti-CD20 biologics, at least 1 infusion
IV or IM corticosteroids 
Tetracyclines at least 100 mg/day for at least 2 weeks in total
Any interventional study drug under development for pemphigus
Note: if dose is missing and/or period of intake cannot be derived, it is still 
considered an intercurrent event.
Details on the derivation of intercurrent events are provided in Appendix 9.1. More 
information how these intercurrent events are handled can be found in the efficacy 
section 4.1.
Prior and concomitant therapies will be tabulated (separately), by ATC class (level 1 
and 3) and generic term. Concomitant therapies will exclude oral Prednisone and 
equivalent medications administered for pemphigus; these will be presented 
separately.
Tables to be produced for the topline results (see list of output in 8.1) will be 
presented for all participants (PV+PF) as well as for PV participants.
All prior and concomitant therapies/procedures data will be listed with detailed 
information about ATC classes.
3.5
IMP AND PREDNISONE ADMINISTRATION 
For each IMP administration and for prednisone administration, the start and end 
date/times, doses (per administration), dose units and volume with units (for IMP 
only) will be recorded.
Participants/caregivers may follow a self-administration training. Visits at which 
training took place and reasons for not following a training are recorded.


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The following parameters will be derived for IMP administration:
Number of administrations: sum of all administrations of study drug.
administrations are expected on day 1 and day 8.
Number of 
 doses: i.e. daily doses of 
mg 
administrations 
of 1000 mg).
The following parameters will be derived for IMP self-administration by participant 
and by caregiver:
Number of participants/caregivers receiving the self-administration 
training.
Number of training visits received by participant/caregiver.
Number of participants/caregivers who were adequately trained and 
capable to self-administer efgartigimod.
Number of training visits before being considered capable to self-
administer.
Normalised cumulative Prednisone dose (NCPD) will be calculated based on 
prednisone equivalent doses (Schimmer e.a., 2015, and Liu e.a., 2013). Prednisone 
equivalent dose is calculated as [dose of ATC]*[equivalence factor 
prednisone]/[equivalence factor ATC]. Following [equivalence factors] are used:


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Betamethasone [1.5]
Cortisone [37.5]
Deflazacort [15]
Dexamethasone [1.5]
Fluocortolone [10]
Hydrocortisone [30]
Methylprednisolone [8]
Methylprednisolone acetate [8]
Methylprednisolone sodium succinate [8]
Paramethasone [4]
Prednisolone [10]
Prednisolone acetate [10]
Prednisolone sodium succinate [10]
Prednisone [10]
Prednisone acetate [10]
Prednylidene [12]
Rimexolone [20]
Triamcinolone [8]
Example: calculation of equivalent dosage of 12 mg methylprednisolone: 12*10/8=
15 mg prednisone.
Only systemic use of oral medication is included.
NCPD (mg/kg/day) is calculated for different periods as [the sum of (equivalent doses
taking into account daily dose frequency)/(body weight in kg)]/(period duration in 
days) with body weight of visit closest before or at each start of prednisone equivalent 
medication record. If for a given day of analysis period, no record exists in the CRF 
indicating prednisone use that day, the dose will be assumed to be 0 mg. NCPD will 
be calculated with and without considering main intercurrent events (see efficacy 
section 4.1.2.2). Additionally the cumulative prednisone dose (in mg) over these 
periods will be calculated. Following periods are considered (including start and end 
of the period):
Whole planned treatment phase, defined as the period from Day 1 to 
Day 218 (regardless of whether the assessment is on treatment or follow 
up phase)
Start of treatment phase until CR in participants who achieved CR (up to 
Day 218)
Start of treatment phase until CRmin in participants who achieved 
CRmin (up to Day 218)
Days with prednisone equivalent dose <=10 mg and <=20 mg will be flagged in the 
analysis dataset. The number of days with prednisone equivalent dose <= 10 mg in 


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the treatment phase will be calculated as well as the proportion of days <= 10 mg in 
the treatment phase (=100 * number of days <=10 mg /duration of treatment phase).
Number of administrations and number of 
doses will be summarized using 
descriptive statistics. Analysis on NCPD is described in the efficacy section 4.1.2.2.
Number of days and proportion of days with prednisone equivalent dose <= 10 mg 
are analysed in the same way as NCPD, except for the subgroup analyses where only 
results will be presented for the disease type subgroup.
All study drug administration data will be listed. Also a detailed listing of prednisone 
administration and NCPD will be provided including prednisone equivalent doses 
with body weight at intake, dates of ICE, CR, CRmin and EoS.
Frequency tabulations with percentages will be produced for:
Number of participants/caregivers receiving the self-administration 
training (denominator is all participants in SAF)
Number of training visits received (denominator is number of 
participants/caregivers receiving training)
Number of participants/caregivers who were adequately trained and 
capable to self-administer efgartigimod (denominator is number of 
participants/caregivers receiving training)
Number of training visits before being considered capable to self-
administer (denominator is number of participants/caregivers receiving 
training)
Number of administrations by administrator and location (at home/on-
site) per visit and overall
Tables to be produced for the topline results (see list of output in 8.1) will be 
presented for all participants (PV+PF) as well as for PV participants. Tables on IMP 
administration will also be presented for PF participants separately.
Line plots for the mean daily prednisone dose (mg) and mean cumulative prednisone 
dose (g) over time will be produced for all participants (PV+PF) as well as for PV 
participants. These plots will be produced under the following approaches for 
handling missing data:  
a) complete case analysis; 
b) last observation carried forward; 
c) baseline observation carried forward.


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4.
EFFICACY, PHARMACOKINETIC, 
PHARMACODYNAMIC AND IMMUNOGENICITY 
ANALYSES 
4.1
EFFICACY AND QUALITY OF LIFE 
Efficacy will be evaluated by assessments of PDAI, DC, EoC, CR, CRmin, complete 
remission off prednisone therapy (CRoff), cumulative prednisone dose, flares and 
treatment failure. Quality of life will be measured using Autoimmune Bullous 
Disease Quality of life (ABQOL) Questionnaire and EuroQoL 5-Dimension 5-
Levels- (EQ-5D-5L) Scale. The health impact of glucocorticoid (GC) use will be 
measured using the Glucocorticoid Toxicity Index (GTI) (see section 9.3).
The analysis of primary and key secondary endpoints will be repeated on the PP set. 
In addition, these analyses will also be repeated on the mITT population excluding 
data impacted by the conflict in Ukraine, i.e. excluding participants from Ukraine that 
have not completed the study by the onset of conflict (24Feb2022). All the above 
repetitions will be performed on the primary estimand only.
For all references to weeks, analysis visits are considered as described in section 2.2.4
unless specified otherwise. If multiple assessments fall within the same analysis 
window, only the assessment closest to the target date will be considered unless 
specified otherwise. Other assessments within this window will only be listed and not 
considered in the below analyses. Only the time to response endpoint (see section
4.1.2.2) will be derived using all possible measurements and not only the one closest 
to the target of the analysis visit. Visits during the treatment and FU phase will be 
considered defining the different responses, unless mentioned otherwise.
The primary endpoint is the proportion of PV participants having achieved CRmin (as 
assessed by the investigator) within 30 weeks. A stratified Cochran-Mantel-Haenszel 
(CMH) test will be calculated with the stratification factors of disease status, disease 
severity, and body weight at randomization.
Disease activity relative day will be calculated as specified in Section 2.2.3. Any 
CRmin achieved with a relative day up to day 218 is counted as a primary endpoint 
response. CRmin cases achieved for the first time after day 218 will not be 
considered.
The main analysis on the primary endpoint
approach
in case of main intercurrent events. This strategy implies that when a main 
intercurrent event (ICE) occurs, a participant is considered a non-responder. This 
happens in the following situations:


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Intercurrent medications (see section 3.4.2) before CRmin
o
Immunosuppressants or dapsone at therapeutic doses for at least 4 
weeks in total in the last 12 weeks before achieving CRmin
o
IVIg/SCIg
before 
achieving CRmin
o
Immunoadsorption or plasma exchange (at least 1 procedure) before 
achieving CRmin
o
Rituximab or other anti-CD20 biologics (at least 1 infusion) before 
achieving CRmin
o
IV or IM corticosteroids administered (at least 1 administration, any 
dose) once the participant has achieved minimal prednisone (or 
prednisone equivalent) dose of <= 10 mg/day (i.e., during the 8 week 
period required in the protocol to confirm the CRmin status) or
administered at any moment before achieving CRmin in any of the 
three following situations:
a) more than 60 mg for 3 consecutive days 
b) more than 40 mg for 4 consecutive days 
c) more than 7 days in total
o
Tetracyclines administered at least 100 mg/day for at least 2 weeks in
total in the last 10 weeks before achieving CRmin
o
Any interventional study drug under development for pemphigus
given before achieving CRmin
Discontinuation of IMP before CRmin due to lack of efficacy
Death
The conditions on intercurrent medications above are tailored for the primary 
endpoint (CRmin). Conditions on intercurrent medications based on medication type, 
minimal dosing and minimal duration apply to the secondary endpoints below with
composite strategy or hypothetical strategy. However, conditions on intercurrent 
medications
x
CRmin only. Details on the derivation of intercurrent events are provided in 
Appendix 9.1.
Missing values for reasons other than the main intercurrent events, will be imputed as 
follows:
all CR assessments missing: CRmin = non-response
CRmin never ticked: CRmin = non-response
CRmin is ticked but date of CRmin is missing: date for CRmin will be 
imputed by disease assessment visit date 
A supplementary analysis for this primary analysis on mITT 
the occurrence of the intercurrent event is considered
irrelevant: CRmin as assessed by the investigator is used regardless of whether or not 
the intercurrent event occurs. Missing values for reasons other than the main 
intercurrent events will be handled as stated above for the primary estimand.


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A landmark analysis will be performed as a supplementary analysis, i.e. proportion of 
PV participants having achieved CRmin (as assessed by the investigator) at 30 weeks 
(weeks 22-30 CR on minimal therapy). This implies that a responder is defined as a 
participant tha
week 30. Disease activity relative day will be calculated as specified in Section 2.2.3.
If the disease status at week 30 analysis visit (see Section 2.2.4) is not missing, then 
that disease status will be used. If the disease status at week 30 analysis visit is 
missing but disease status at any analysis visits from week 26 to week 29 is not 
missing the last non-missing analysis visit assessment from week 26 will be used. If 
all disease status assessments at the analysis windows for week 26 to week 30 are 
missing, then CRmin at week 30 is No.
will be applied.
Accordingly, use of intercurrent medication or permanent IMP discontinuation due to 
lack of efficacy before or at week 30 will be considered as a non-responder regardless 
the outcome of the algorithm above. 
Additionally, a sensitivity analysis on this landmark analysis will be performed as 
above without using the week 26 to week 29 data to impute any potential missing 
disease status at week 30.
The following key secondary endpoints, which will be tested in the mITT population
in hierarchical order (see section 4.1.4), are defined as:
1) The proportion of PV+PF participants that have achieved CRmin within 30 weeks
using the same stratified CMH as for the primary endpoint. As this first key 
secondary endpoint is similar to the primary endpoint, the same approach for 
handling the main ICEs (both composite strategy and treatment policy strategy), as 
suggested for the primary analysis, will be applied.
2) Normalised cumulative Prednisone dose (NCPD, mg/kg/day) over the whole 
planned treatment phase in PV participants, will be analyzed by an analysis of 
covariance (ANCOVA) model to compare both treatment groups. Only actual 
administrations of prednisone are considered (not as scheduled). The model will 
include treatment and the stratification variables will be considered as factors. 
Main intercurrent events are handled using the hypothetical strategy, that is, as 
follows:
Intercurrent medications (see section 3.4.2): stop calculating cumulative 
dose after ICE. In case 'immunosuppressants for at least 4 weeks in total'
is the ICE, use end of the 4 weeks IC medication as stop for cumulative 
dose calculation.
ICE, use end of the 2 weeks IC medication as stop for cumulative dose 
corticosteroids ' is the ICE, use the first 
day of this IC medication as stop for cumulative dose calculation. 
Discontinuation of IMP before CRmin due to lack of efficacy: stop 
calculating cumulative dose after this ICE.
Details on the derivation of intercurrent events are provided in Appendix 9.1.


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A non-parametric stratified Mann-Whitney test will be performed as sensitivity
analysis.
A supplementary analysis for this secondary endpoint
the occurrence of the intercurrent event is considered irrelevant: 
NCPD is calculated regardless of whether or not the intercurrent event occurs.
3) Time to CR in PV participants, calculated as the difference between the first date 
CR was achieved and the first IMP administration date.
Time to CR (days) = date (first CR) - first IMP date + 1
Main intercurrent events are handled as follows (composite strategy):
Intercurrent medications (see section 3.4.2) before CR: participant is
assumed to not reach CR until the theoretical end of the study and is 
censored at day 218.
Discontinuation of IMP before CR due to lack of efficacy: participant is
assumed to not reach CR until the theoretical end of the study and is 
censored at day 218.
Participants without any disease assessment are censored at day 1. Participants with 
disease assessment but not achieving CR in the period from Day 1 to Day 218 and 
without intercurrent event in that period are censored at the earliest of day 218 and 
the end of treatment + FU phase.
A supplementary analysis for this secondary endpoint
the occurrence of the intercurrent event is considered irrelevant: Time
to CR is calculated regardless of whether or not the intercurrent event occurs.
4) Time to DC in PV participants, calculated as the difference between the first date 
DC was achieved and the first IMP administration date. Similar calculations, ICE 
handling and censoring rules are applied as for 'time to CR' (composite strategy).
A supplementary analysis for this secondary endpoint
the occurrence of the intercurrent event is considered irrelevant: time 
to DC is calculated regardless of whether or not the intercurrent event occurs.
Both time to event endpoints will be statistically evaluated using the stratified 
Fleming-Harrington weighted logrank statistic FH (1,0), with the stratification factors 
disease status, disease severity, and body weight at randomization. For both, Kaplan-
Meier survival plots by treatment arm will be produced (as in-text figures only).
5) NCPD over the whole planned treatment phase in all participants: same derivation 
as second key secondary endpoint (composite strategy and treatment policy strategy) 
but for all participants.
6) Time to DC in all participants: same derivation as fourth key secondary endpoint 
(composite strategy) but for all participants.
7) Time to CR in all participants: same derivation as third key secondary endpoint 
(composite strategy) but for all participants.


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All other secondary endpoints will be analyzed using the mITT population. Analyses 
related to data in the period after an event (CRmin, DC) can only be performed in 
participants with that event.
1. Proportion of PF participants who achieve CRmin within 30 weeks: same 
derivation as for the primary endpoint (composite strategy) but then for PF 
participants.
2. Time to CRmin in PV, PF and all participants: same derivation as third key 
secondary endpoint (composite strategy) but using date of achieving CRmin.
Time to CRmin is defined as the time to the moment that the participant achieves 
CRmin status defined as complete remission while receiving prednisone therapy 
at 10 mg/day or less for at least 8 weeks, based on the assessment of the 
investigator. The 8-week period with minimal prednisone necessary to confirm 
CRmin is included as part of this time period. For example, a participant that 
achieves complete remission with prednisone <= 10 mg/day at week 15 for the 
first time and maintains this status for 8 weeks will have a time to CRmin of 15 + 
8 = 23 weeks.
3. Proportion of participants achieving DC in PV, PF and all participants (composite 
strategy)
4. Proportion of participants achieving CR in PV, PF and all participants (composite 
strategy)
For all subsequent secondary endpoints a treatment policy strategy is applied ignoring 
ICEs.
5. Proportion of treatment failures as assessed by the investigator in PV and in all
participants. Specific reasons for treatment failure can be derived as follows in 
following order: 
absence of DC: if participant didn't achieve DC as assessed by the 
investigator
prednisone related SAE: occurrence of an SAE after DC considered 
related to prednisone by the investigator
flare: if previous 2 reasons are not applicable, the reason must be a flare 
between DC and CRmin that is not controlled by a prednisone dose that 
is 2 dose levels above the dose at which the flare is observed and that is 
a least 0.3mg/kg qd
Failure is defined for the whole treatment phase.
6. Number of flares in PV and in all participants: count number of flares as assessed 
by the investigator. A new flare only emerges after a new DC. Number of flares 
are counted over the whole treatment + follow-up phase, between first DC and 
CRmin (or end of treatment period for participants without CRmin) and after 
CRmin. The initial flare at baseline (if applicable) is not counted.
7. Time to first flare from first DC in PV and in all participants is calculated as (visit 
date of flare)-(date of first DC)+1. Similarly time to first flare from first CR and 
time to first flare from CRmin will be calculated as (visit date of flare)-(date of 
first CR and date of CRmin respectively)+1.


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8. Proportion of PV and all participants with at least one flare after DC. The same 
periods are considered as for number of flares: i.e. whole treatment + follow-up
phase, between first DC and CRmin (or end of treatment period for participants
without CRmin) and after CRmin.
9. Duration of CRmin in PV, PF and in all participants: count the number of weeks 
CRmin is maintained. I.e. participant remains without a lesion after CRmin and 
score=0 maintained. The 8-week period with minimal prednisone necessary to 
confirm CRmin is included as part of this duration. Participant is censored at EoS 
if still on CRmin at end of treatment phase (or follow-up phase if applicable).
10. PDAI at each visit in PV and in all participants: PDAI activity subscores
(mucosal, skin and scalp), PDAI activity score and PDAI total score are assessed 
by the investigator at each visit. Data after the first occurrence of an intercurrent 
event will also be used (treatment policy strategy). Missing data (intermittent as a 
result of the scattered way of data collection and non-intermittent as a result of 
study discontinuation), will be imputed using last observation carried forward 
(LOCF).
11. QoL in PV and in all participants: ABQOL (17 items) and EQ-5D-5L (i.e., 
mobility, self-care, usual activities, pain/discomfort, anxiety/depression and VAS)
are assessed by the investigator at baseline, Week 4, Week 14 and at EoS. A total 
ABQOL score is calculated as the sum of all 17 items score 0 to 3 with higher 
score indicating worse condition. Missing items are imputed with the average 
score of the present items if at least half (9) of the items are present. The total 
score is rounded to the highest integer.
12. C-GTI in PV and in all participants: Composite Glucocorticoid Toxicity Index 
comprises the Aggregate Improvement Score (AIS) and the Cumulative 
Worsening Score (CWS) (health impact of GC) and is measured at baseline,
Week 14 and EoS/ED. AIS and CWS are calculated for the first 14 week period
(W14), for the last 16 week period (W30) and for the treatment phase overall
(Overall). The last post-baseline assessment (Overall) is considered as the overall 
CWS/AIS and is calculated as a cumulative score over all post-baseline 
timepoints. The complementary GTI specific list (GTI-SL) will only be listed.
Wherever the stratification factors will be used in the efficacy analyses, the eCRF
values of these will be used and not the ones coming from the randomization. Also
for participants randomized without disease status, disease severity and body weight
stratification, i.e. Japanese and PF participants, these factors will be derived from the 
eCRF in order to include these participants in the statistical models.
For the analysis of the PF only population, all stratified models/tests for binary and 
survival endpoints will only be stratified by the following 2 strata: relapsing vs.
newly-diagnosed.
Examples of SAS code for the statistical analysis procedures are provided in 
Appendix 9.1.5.


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Frequency tabulations will be provided of the percentage of PV participants having 
achieved CRmin within 30 weeks (primary endpoint). The table will be repeated for
subgroups including treatment differences in proportions with 95% Wald CI, and 
overall (PV+PF participants).
A stratified CMH test will be calculated with the stratification factors of disease 
status, disease severity, and body weight at randomization; the strata-adjusted 
difference in proportions with the Klingenberg midpoint and 95% confidence interval 
and 2-sided CMH test p-value will be provided as well as an adjusted common OR 
with its 95% confidence interval. Homogeneity of the odds ratios will be tested by 
me
A supplementary analysis using the treatment policy strategy will be done for PV 
participants and overall.
The supplementary landmark analysis at week 30 will be performed on the mITT 
population for PV participants and overall using the stratified CMH test. 
Summary statistics on NCPD, cumulative prednisone dose, number of days and 
proportion of days with prednisone equivalent dose <= 10 mg will be provided for PV 
participants and an ANCOVA model with factors for treatment and the stratification 
variables will be applied on NCPD over the whole treatment phase only. Least square 
(LS) means and standard error (SE) with 95% 2-sided CI for placebo and 
efgartigimod will be reported, along with the difference in LS means of IMP vs 
placebo (with SE), 95% 2-sided CI, and 2-sided p-value. A non-parametric stratified 
Mann-Whitney test will be performed as sensitivity for PV participants. The 2-sided
p-value resulting from this hypothesis test will signify whether the null hypothesis 
that the distributions of the NCPD for both treatment arms are identical can be 
A
supplementary analysis using the treatment policy strategy applying the same 
ANOVA model will be done.
The table with summary statistics on NCPD will be repeated by subgroups, for PF 
participants and overall.
Time to CR and Time to DC will be descriptively presented with median times, 
quantiles and number and percentage of participants censored and with event. In 
addition, Kaplan-Meier survival plots by treatment arm will be produced (as in-text 
figures only). Both treatment groups will be compared using the stratified Fleming-
Harrington weighted logrank statistic FH (1,0). Also the Cox proportional hazard 
model will be used: the model will include treatment as fixed effects and stratification 
factors as covariates. The HR for efgartigimod vs. placebo will be provided, along 
with the associated 95% 2-sided Wald-type CI and 2-sided p-value. The table will be 
produced for PV participants and overall. The descriptive statistics will also be 
presented by subgroups.
Duration of CRmin and o
4.1.2.3 will be descriptively presented and treatment groups will 
be compared using the logrank statistic.


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Frequency tabulations will be provided for the percentages of treatment failure and its
different reasons. Failure rates will be compared using the same CMH-test as for the 
primary endpoint analysis.
Proportion of participants achieving DC and CR and proportion of participants with 
flare will be tabulated and treatment groups will be compared using the same CMH-
test as for the primary endpoint analysis.
Descriptive statistics for PDAI on absolute values, changes from baseline and percent 
changes from baseline will be calculated per timepoint. Results will be presented 
separately for observed data and LOCF imputed data. Changes from baseline on
LOCF imputed data will be compared between treatment arms at each analysis visit 
using an ANCOVA model with factors for treatment, baseline value and the 
stratification variables. Least square (LS) means and standard error (SE) with 95% 2-
sided CI for placebo and efgartigimod will be reported, along with the difference in 
LS means of IMP vs placebo (with SE), 95% 2-sided CI, and 2-sided p-value.
The number of flares will be descriptively presented and analyzed by the same 
ANCOVA model as for the NCPD analysis. Time to the first flare will be presented 
and analyzed in the same way as time to CR or time to DC, however using the 
logrank statistic.
Frequency tabulations will be provided for the percentages of participants within each 
outcome of QoL questionnaire items (ABQOL and EQ-5D-5L). Additionally
cumulative percentages (starting with the best outcome result) will be calculated. 
Descriptive statistics will be provided for the total ABQOL score and for the EQ-5D-
5L VAS score. Changes from baseline will be analyzed by means of a mixed model 
for repeated measurements (MMRM). The model will include treatment, visit and 
treatment by visit interaction terms as fixed effects, with baseline value, interaction of 
baseline value with visit, and stratification factors as covariates. Within-subject 
correlation will be modeled by assuming an unstructured covariance matrix (UN) for 
the error terms and Kenward-Roger degrees of freedom method will be used. Least 
square means and SE with 95% 2-sided CI for placebo and efgartigimod will be 
reported, along with the difference in LS means of IMP vs placebo (with SE), 95% 2-
sided CI, and 2-sided p-value. 
If the default Newton Raphson algorithm used by SAS PROC MIXED fails to 
converge, the following will be tried to avoid lack of convergence while maintaining 
an unstructured variance: 
A. The Fisher scoring algorithm (via the SCORING = 5 option of the PROC 
MIXED statement) will be used to obtain the initial values of covariance 
parameters.
B. If the above fails, the no-diagonal factor analytic structure will be used which 
effectively performs the Cholesky decomposition via the TYPE=FA0(V) option 
of the REPEATED statement, where V is the total number of distinct visits in the 
response vector (counting only rows where all model components are non-
missing).
C. If all the above fails, the variance-and-correlations parameterization will be 
attempted using TYPE =UNR.


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In the rare case where all the above fails, the following covariance structures will be 
tested for convergence (in order): toeph, arh(1), csh, toep, ar(1) and cs. However, if 
one of these simpler covariance structures is used, this needs to be implemented in 
combination with sandwich variance estimator (EMPIRICAL option).
Descriptive statistics will be provided for the C-GTI scores AIS and CWS; treatment 
groups will be compared using the same ANCOVA model and stratified Mann-
Whitney test as for the NCPD analysis. C-GTI will be analysed on complete cases:
i.e. participants with C-GTI at least at baseline and post-baseline. Participants where 
first post-baseline GTI improvements/worsening have not been obtained with respect 
to the baseline moment but with respect to a later moment (i.e. no GTI assessment at 
baseline visit) are excluded from analyses and are only listed.
To control the type I error for the primary and secondary endpoints (alpha controlled), 
the primary efficacy endpoint will be tested at the 5% 2-sided alpha level and will act 
as gatekeeper for the testing of secondary endpoints. The primary endpoint and 
secondary endpoints will be tested in a strict hierarchical order as listed below to
control the type I error (for definitions see section 4.1.2.1 and 4.1.2.2). If a certain 
endpoint turns out to be non-significant at the 5% significance level, subsequent
endpoints will no longer be evaluated.
1.
Primary endpoint: the proportion of PV participants who achieve CRmin within 
30 weeks using composite strategy approach
2.
Proportion of PV+PF participants that have achieved CRmin within 30 weeks
using composite strategy approach
3.
NCPD in PV participants using hypothetical strategy approach
4.
Time to CR in PV participants using composite strategy approach
5.
Time to DC in PV participants using composite strategy approach
6.
NCPD in PV+PF participants using hypothetical strategy approach
7.
Time to CR in PV+PF participants using composite strategy approach
8.
Time to DC in PV+PF participants using composite strategy approach
The individual per-endpoint tables will only show unadjusted p-values. A fixed-
sequence testing procedure table will be produced. This table will show both 
unadjusted p-values and p-values adjusted for multiplicity. For a given endpoint, the 
adjusted-for-multiplicity p-value is calculated as the maximum between its 
unadjusted p-value and the highest of all unadjusted p-values tested before.


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Subgroups are defined based on the following categorizing factors:
Gender (Male, Female)
Age (18 -< 65, 65 -<75, >=75 years)
Weight at screening (<50, 50-<75, 75 -< 100, 100 -<125, >= 125 kg)
BMI at screening (Underweight: < 18.5 kg/m2, Normal weight: 18.5 -<
25 kg/m2, Overweight: 25 -< 30 kg/m2, Obese: >= 30 kg/m2)
Race (Asian, Black or African American, White, Other)
Baseline eGFR (Normal: >= 90 mL/min/1.73m2, Mildly impaired: 60 -
<90 mL/min/1.73m2, Moderately impaired: 30 -< 60 mL/min/1.73m2,
Severely impaired: <30 mL/min/1.73m2)
Disease type (PV/PF) and PV subtype (mucosal-dominant vs 
(muco-)cutaneous)
Disease status (relapsing vs newly diagnosed)
Disease severity (PDAI activity score <30 and PDAI activity score 
); moderate (15<=PDAI <=44) vs severe (PDAI 45)
Region (North America; Europe; Asia; Rest of World)
Subgroup analyses will be performed on the primary and key secondary efficacy 
endpoints on the mITT population.


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Following table summarizes the analyses:
Table 5: Summary of analyses
Endpoint
PV
PFf
All
(PV+PF)
Strategy
Proportion CRmin
X1,c,p
X
X2,c,p,s
C+T
NCPD
X2,c,p
X
X2,s
H+T
Time to CR
X2,c,p
X
X2,s
C+T
Time to DC
X2, c,p
X
X2,s
C+T
Time to CRmin
X
X
X
C
Proportion DC / CR
X
X
X
C
Proportion treatment failure
X
X
T
Number of flares (incidence 
rate)
X
X
T
Proportion of participants 
with flare
X
X
T
Time to first flare
X
X
T
Duration of CRmin
X
X
X
T
PDAI, QoL, C-GTI
X
X
T
1 Primary endpoint
2 Key secondary endpoint
c Besides main analysis also supplementary analysis will be performed.
f PF as part of subgroup analysis or as separate analysis. 
p Also analysis on PP analysis set and mITT excluding data impacted by 
the conflict in Ukraine will be performed.
s Also subgroup analyses will be performed.
C=composite strategy (taking into account ICEs)
H=hypothetical strategy (taking into account ICEs)
T=treatment policy strategy (ignoring ICEs)
4.2
PHARMACOKINETICS 
Blood samples will be collected for the determination of efgartigimod concentration 
at the time points indicated in the schedule of assessments (see section 9.5). Sampling 
will be done predose on IMP administration visits (within 2 hours before IMP). 
An additional PK sample will be taken on day 3 and on day 11 (±1 day) until samples 
from 24 participants are obtained.


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PK data obtained during off treatment period from participants who achieved CRmin 
(ie, no longer receiving weekly administrations of IMP) will not be included in the 
descriptive statistics. 
In addition, following PK samples will be excluded from the descriptive statistics
based on time since previous IMP:
When PK samples are taken outside the visit windows. The study visit 
windows are ±2 days, i.e. if PK sample is not within last IMP+7 days ±
2 days. On Day 3 and Day 11 the visit window is ±1 day (ie, ±24h).
When a predose sample is taken after IMP administration.
When the IMP administration prior to the scheduled PK sample is 
missed (not applicable for Day 1).
A remark with reason for exclusion of the timepoint will be added in the appropriate 
listing.
PK concentrations will be reported in ng/mL by the lab and will be converted to 
ug/mL for analyses.
Individual concentration data and actual blood sampling times from dose 
administration for PK assessments will be listed.
Descriptive statistics per time point on concentration data will be presented in tables. 
4.3
PHARMACODYNAMICS 
The following pharmacodynamic markers will be measured in serum: total 
immunoglobulin G (IgG), IgG subtypes (IgG1, IgG2, IgG3, and IgG4) and anti-Dsg-
1/ Dsg-3 antibodies.
Changes and percent changes vs baseline will be calculated. Participants with a 
baseline value below the limit of quantification (BLQ) will be excluded when 
computing the change from baseline and the percent change from baseline. Values of
anti-Dsg-1/Dsg-3 above or below limit of quantification will be imputed by the upper 
or lower limit of quantification respectively. This will be explained by a footnote in 
the appropriate tables. Limits of quantification are provided by the lab. For total IgG 
and IgG subtypes, no imputation will be applied. Listings will always show the non-
imputed values.
In addition, for all pharmacodynamic endpoints, descriptive statistics of the actual 
vales will also include GM and GSD. GM and GSD are not applicable for descriptive 
statistics of the absolute changes from baseline. For these selected endpoints, 
descriptive statistics of percent changes from baseline will also include GM and GSD. 
GM and GSD of percent changes from baseline are calculated as 100x
-1}


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as log(aval)-log(base).
All pharmacodynamic endpoints will be summarized by means of descriptive 
statistics at each analysis visit. Actual values, changes from baseline and percent 
changes from baseline will be tabulated. Also, the same subgroup analyses will be 
performed as for efficacy.
4.4
IMMUNOGENICITY 
Blood samples will be collected for the determination of anti-drug antibodies (ADA) 
to efgartigimod (in serum samples) and antibodies against rHuPH20 (in plasma 
samples) at the time points indicated in the schedule of assessments (see section 9.5).
Immunogenicity samples are analyzed in a 3-tiered approach:
All samples are evaluated in the ADA screening assay and are scored as 
ADA screening positive or negative.
If a sample scored positive in the ADA screening assay, it is further 
evaluated in the confirmatory assay and is scored confirmed positive 
(positive immunodepletion) or confirmed negative (negative 
immunodepletion).
If a sample is scored as confirmed positive, the samples are further 
characterized in the ADA titration assay (to determine titer) and are also 
further analyzed in the Nab assay to confirm neutralizing activity. For 
Nab against efgartigimod, a screening assay is performed and results 
will be reported as negative or positive. For Nab against rHuPH20, the 
screening Nab assay is followed by a titer Nab assay in case the sample 
screened positive.
If available, a titer result will be reported for the ADA confirmed positive samples. 
However, a titer result is not always available:
In case the ADA confirmed positive sample could not be run in the 
titration assay (e.g., due to insufficient sample volume/quality to 
immuno-depletion
positive. 
If a sample is negative in the titration assay, it will be reported as 
confirmed positive in the second tier. 
If a sample 
ADA sample status is ADA unevaluable.
An overview of this 3-tiered approach and all possible ADA sample results that will 
be reported by the laboratory is given below. From these reported ADA sample












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rHuPH20 NAb unevaluable participant = participant classified as rHuPH20 NAb
unevaluable or with missing baseline rHuPH20 NAb sample or without post-baseline 
rHuPH20 NAb samples
NAb incidence = percentage of participants with participant
-
-
of evaluable participants). 
NAb prevalence = percentage of participants with participant classification 
-
-
-
(denominator: number of evaluable participants).
Analyses will be done for ADA against efgartigimod and antibodies against 
rHuPH20.
Frequency tabulations (number and percentages) will be provided with ADA or
rHuPH20 Ab negative/positive/unevaluable samples per analysis visit. These tables 
will be presented by ADA or rHuPH20 Ab participant category.
Frequency tabulations (number and percentages) will be provided by treatment on:
Participants per ADA or rHuPH20 Ab participant classification
Prevalence and incidence of ADA or rHuPH20 Ab
ADA or rHuPH20 Ab unevaluable participants
ADA or rHuPH20 Ab baseline positive/negative samples
For details on the definitions, see the above section 4.4.2.1. and 4.4.2.2.
The above frequency tabulations will be repeated for NAb assay using the definitions 
as defined in section 4.4.2.3. and 4.4.2.4.
In addition, a frequency tabulation (number and percentages) will be provided for:
NAb against efgartigimod positive participants within the ADA participant
classification (Treatment-unaffected ADA, Treatment-induced ADA, 
Treatment-boosted ADA, ADA Negative, ADA Unevaluable)
NAb against rHuPH20 Ab positive participants within the rHuPH20 Ab
participant classification
rHuPH20 Ab positive participants within efgartigimod ADA participant
classification
Correlation tables by ADA and NAb participant classification against efgartigimod 
and by rHuPH20 Ab will be provided for the following parameters for PV and PF 
participants combined:


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Mean (SD) drug concentration over time 
Mean (SE) percent change from baseline in total IgG
Overall Treatment-Emergent Adverse Events by MedDRA System 
Organ Class and Preferred Term by Overall Anti-Drug Antibodies 
Participant Classification 
Overall Serious Treatment-Emergent Adverse Events by MedDRA 
System Organ Class and Preferred Term by Overall Anti-Drug 
Antibodies Participant Classification 
Overall Injection-related reactions by Overall Anti-Drug Antibodies 
Participant Classification 
Overall Injection site reactions by Overall Anti-Drug Antibodies 
Participant Classification 
Proportion of participants with CRmin within 30 weeks*
* Difference in proportion responders between each of the 4 categories versus ADA 
Negative, NAb baseline neg post-baseline neg and rHuPH20 Ab Negative, 
including 95% exact confidence interval will be calculated.
ADA titer values against efgartigimod and rHuPH20 Ab titer values will be 
summarized by means of descriptive statistics by ADA participant classification or
rHuPH20 Ab participant classification respectively.
All available data on ADA and NAb against efgartigimod, rHuPH20 Ab and 
rHuPH20 NAb will be listed, showing also the sample status and participant
classification. 


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5.
SAFETY ANALYSES 
5.1
ADVERSE EVENTS 
Adverse events (AEs) are coded into SOC and PT using the latest version of the 
MedDRA available at the moment of the database lock. For each AE, start and stop 
date/times are collected as well as severity (NCI CTCAE v5.0), a seriousness flag, 
treatment relatedness, relatedness to procedures, action taken towards the IMP,
outcome, and AE of special interest (AESI) category (infection).
Treatment-emergent adverse events (TEAE) are defined as AEs starting on or after 
first administration of any IMP up through 60 days after the last administration of the 
IMP prior to the AE. Post-TEAEs are AEs starting after first administration of IMP 
that are not TEAEs.
Based on their start date/time, AEs will be allocated to the phase during which they 
started. Each AE will therefore be reported in only one phase. In case the AE start 
date/time is incomplete or missing and the AE could consequently be allocated to 
more than one phase, a worst-case allocation will be done as detailed below:
Treatment phase vs. non-treatment phase: the AE will be allocated to the 
treatment phase unless the available parts of the AE start or stop 
date/time provide evidence for allocating to the non-treatment phase.
A death case is defined as an A
An AE for which the IMP was discontinued is defined as an AE with action taken 
Treatment relatedness will be dichotomized as follows in tables:
Treatment related: related, probably related, possibly related or missing
Not treatment related: not related, unlikely related
Adverse events of special interest will be defined using MedDRA system organ class 
Injection-related reactions (IRRs) will be defined as all AEs with MedDRA preferred 
terms that are listed in either:
Hypersensitivity standardized MedDRA query (SMQ) (broad selection)
Anaphylactic reaction (SMQ) (broad selection)
Extravasation events (injections, infusions and implants) (SMQ) (broad 
selection), excluding implants
AND occurring within 48 hours of an administration, or within 2 days in case no AE 
start time is available. In case of (partially) missing AE start date, the AE will be 
considered as an IRR, unless the available parts of the AE start date provide evidence 
it did not occur within 48 hours of an injection.


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Injection site reactions (ISR) will be defined as all AEs with a MedDRA high level 
term of "Injection site reaction", regardless of the time of AE onset relative to an 
administration.
AE onset and duration will be calculated as follows when start and stop dates are 
fully known:
AE onset day (vs. first administration) = 
o
AE start date 
date of first administration: AE start date date of first 
IMP administration + 1 day
o
AE start date < date of first administration: AE start date date of first 
IMP administration
AE duration (days) = 
o
AE end date AE start date + 1 day
o
Study completion date or Study discontinuation date
AE start date + 
1 day (when the AE start date is fully known but the AE is not 
resolved at the end of the study)
Event rates per 100 participant years of follow-up (PYFU) will be calculated as
100*number of events/PYFU, with:
PYFU overall (in years) will be calculated as [the sum over all
participants of the study duration calculated as (last phase end date 
first IMP date + 1 day)]/365.25.
PYFU for TEAEs (in years) will be calculated as [the sum over all 
participants of all period durations during which an AE is considered to 
be treatment-emergent]/365.25.
PYFU for post-TEAEs (in years) will be calculated as [the sum over all 
participants of all period durations during which an AE is considered to 
be post-treatment-emergent]/365.25.
Incidence rates per 100 participant years of follow-up (PYFU) will be calculated as 
100*number of participants with events/PYFU.
Unless mentioned otherwise, tables will present TEAEs only. 
The TEAE tables will be presented for the treatment and follow-up phase combined.


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An overview table will show the number and percentage of participants with at least 
one event, the incidence rate per 100 participant years of follow-up and the number of 
events and event rate per 100 participant years of follow-up for the following:
TEAEs
Treatment related TEAEs
Serious TEAEs
Serious treatment related TEAEs
Serious prednisone related TEAEs
TEAEs related to prednisone
TEAEs related to study procedures
TEAEs for which the IMP was discontinued 
TEAEs for which the IMP was interrupted
TEAEs of special interest
Treatment related TEAEs of special interest
TE IRR events
Serious TE IRR events
TE ISR events
Fatal TEAEs
The overview table will be repeated specifically for ISR events, omitting the records 
related to TEAEs of special interest, prednisone-related TEAEs, IRR events and ISR 
events.
A summary table by MedDRA system organ class and preferred term will show the 
number and percentage of participants with at least one event, the incidence rate per 
100 participant years of follow-up and the number of events and the event rate per 
100 participant years of follow-up.
The overview and summary tables mentioned above, will present:
TEAEs
post-TEAEs
overall AEs (i.e., all AEs in the treatment + follow-up phase)


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Separate tables will be prepared for the following:
Most common (>=5% in any group) TEAEs
Treatment related TEAEs
Serious TEAEs
Serious treatment related TEAEs
Serious prednisone related TEAEs
3 TEAEs
TEAEs related to prednisone
TEAEs related to study procedures
TEAEs for which the IMP was discontinued 
TEAEs of special interest
Treatment related TEAEs of special interest
TE IRR events
Serious TE IRR events
TE ISR events
All AEs, including pre-treatment events will be listed.
5.2
CLINICAL LABORATORY EVALUATION 
Per protocol, the following laboratory parameters are expected:
Biochemistry: sodium, potassium, calcium (total), HbA1c, creatinine, 
creatinine clearance (adjusted for BSA), blood urea nitrogen (BUN), 
alanine aminotransferase (ALT), aspartate aminotransferase (AST), total 
bilirubin, gamma-glutamyl transferase (GGT), low-density lipoprotein-
cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C),
total cholesterol, triglycerides, C-reactive protein (CRP), alkaline 
phosphatase (AP), lactate dehydrogenase (LDH), uric acid, total protein, 
and albumin.
Hematology: hemoglobin, hematocrit, mean corpuscular volume 
(MCV), red blood cell (RBC) count, platelet count, white blood cell 
(WBC) count with differential.
Urinalysis: color, clarity/appearance, specific gravity, pH, protein, 
glucose, ketones, blood, bilirubin, urobilinogen, nitrite, leukocyte 
esterase, and microscopic examination of RBC, WBC, casts, crystals, 
and bacteria.
Specialty laboratory parameters: apolipoprotein B (apoB), lipoprotein 
A, fibrinogen, von Willebrand factor, D-dimer, proprotein convertase 
subtilisin/kexin type 9 serine protease (PCSK9).
Normal ranges are available as provided by the laboratory.


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Toxicity grades will be computed according to the National Cancer Institute (NCI)
common terminology criteria for adverse events (CTCAE) toxicity grading list
(version 5.0). The implementation of these toxicity grades for analysis is presented in
appendix 9.4. Only the parameters described in appendix 9.4 will be computed, 
according to the declared limits for each grade.
The following abnormality categories will be defined for parameters with no toxicity 
grade available:
Low: value < lower limit of normal range
range
High: value > upper limit of normal range
Notes:
Classification will be done by using non-imputed values and limits as 
reported in standardized units in the clinical database: a value <X where 
X equals the lower limit of normal range will be classified as low. A 
value X with normal range <X will be classified as high.
For the worst-case analysis visits as defined in section 2.2.5, an 
additional category low + high is defined in case there are both low and 
high post-baseline values. 
The statistical analysis will present results in standardized units, except creatinine 
clearance which is presented in original units (ml/min/1.73m2).
Continuous laboratory parameters will be summarized by means of descriptive 
statistics at each analysis visit. Actual values and changes from baseline will be 
shown in the same table. For albumin and low-density lipoprotein-cholesterol (LDL-
C) also percent changes vs baseline will be shown.
Laboratory abnormalities will be presented as a cross-tabulation of the abnormality at 
each post-baseline analysis visit and at the worst-case analysis visit versus the 
baseline abnormality. This table will also show numbers of participants with 
treatment-emergent abnormalities (see Definition of terms). The denominator for the 
percentage is the total number of participants per treatment and per analysis visit in 
the safety analysis set.
Laboratory toxicity grades will be presented as a cross-tabulation (shift table) of the 
toxicity (NCI CTCAE grades) at each post-baseline analysis visit and at the worst-
case analysis visit versus the baseline toxicity. This table will also show numbers and 
cumulative numbers over decreasing toxicity grading of participants with treatment-
emergent toxicities. The denominator for the percentage is the total number of 
participants per treatment and per analysis visit in the safety analysis set. Parameters 


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having toxicity grades defined in both directions (hypo and hyper) will be shown by 
direction.
All laboratory data will be listed, but only for participants with any post-baseline 
abnormality.
5.3
VITAL SIGNS 
The following vital signs parameters are collected: systolic (SBP) and diastolic blood 
pressure (DBP), heart rate, body temperature and weight.
Abnormalities are defined in below table.
SBP 
(mmHg)
DBP 
(mmHg)
Temperature 
(°C)
Low
<90
<45
<35.8
Normal
90-150
45-90
35.8-37.5
High
>150
>90
>37.5
Note: For the worst-case analysis visits, as defined in section 2.2.5, an additional 
category low + high is defined in case there are both low and high post-baseline 
values.
BMI will only be used in the C-GTI derivations.
VS parameters (without BMI) will be summarized by means of descriptive statistics 
at each analysis visit. Actual values and changes from baseline will be shown in the 
same table.
Abnormalities will be presented as a cross-tabulation of the abnormality at each 
post-baseline analysis visit and at the worst-case analysis visit versus the baseline 
abnormality. This table will also show numbers of participants with treatment-
emergent abnormalities (see Definition of terms).
All vital signs data will be listed, but only for participants with any post-baseline 
abnormality or any reading determined as clinically significant by the investigator.
5.4
ELECTROCARDIOGRAMS 
The following electrocardiogram (ECG) parameters will be collected: heart rate (HR), 
QRS interval, PR interval, QT interval, QTcF and QTcB.


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Abnormalities for HR, QRS and PR interval are defined in below table.
HR (bpm)
PR (ms)
QRS (ms)
Low
<40
<120
-
Normal
40-100
120-220
0-120
High
>100
>220
>120
Note: For the worst-case analysis visit, as defined in section 2.2.5, an additional 
category low + high is defined in case there are both low and high post-baseline 
values.
For QTcB and QTcF interval (ms), the following categories are defined:
Actual values:
o
450 (normal)
o
]450; 480]
o
]480; 500]
o
> 500
Changes:
o
o
]30; 60]
o
> 60
Note: The worst-case, as defined in section 2.2.5, is the highest post-baseline value 
and associated change. 
Uncorrected QT interval will only be listed.
Continuous ECG parameters will be summarized by means of descriptive statistics at 
each analysis visit. Actual values and changes from baseline will be shown in the 
same table.
Abnormalities of the actual values will be presented as a cross-tabulation of the 
abnormality at each post-baseline analysis visit, and at the worst-case analysis visit 
versus the baseline abnormality. This table will also show numbers and cumulative
numbers over decreasing abnormalities (QTcF and QTcB only) of participants with 
treatment-emergent abnormalities. The denominator for the percentage is the total 
number of participants per treatment and per analysis visit in the safety analysis set.
Abnormalities of the QTcF and QTcB changes from baseline will be presented as a
tabulation of the change from baseline abnormality at each post-baseline analysis visit 
and at the worst-case analysis visit. This table will also show cumulative numbers 
over decreasing change from baseline abnormalities of participants. The denominator 
for the percentage is the total number of participants per treatment and per analysis 
visit in the safety analysis set.


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All ECG data will be listed, but only for participants with any post-baseline 
abnormality.
5.5
PHYSICAL EXAMINATIONS 
Physical examination results per body system will be available.
Abnormal physical examination results will be listed.


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6.
CHANGES TO THE PLANNED ANALYSIS 
6.1
CHANGES NOT COVERED BY PROTOCOL AMENDMENTS BEFORE 
DATABASE LOCK 
Analysis visit labels deviate from the visit labels in the schedule of assessments of the 
protocol to accommodate the example in the ICH E3 guideline annex III.
NCPD, time to CR and time to DC for PV+PF participants are added to the fixed-
sequence testing procedure.
NCPD (mg/kg/day) is calculated for different periods as [the sum of (equivalent doses 
taking into account daily dose frequency)/(body weight in kg)]/(period duration in 
days) with body weight of visit closest before or at each start of prednisone equivalent 
medication record instead of using weight at baseline.
The following extra analyses will be conducted, which are not covered in the clinical 
study protocol (CSP):
-
Cox proportional hazard model on time to event endpoints
-
Stratified Mann-Whitney test on NCPD and GTI endpoints
-
Selected endpoints on the subset of PF participants
The following extra endpoints will be derived, which are not covered in the CSP (see 
section 4.1.2.3 and 3.5.2):
-
Time to CRmin
-
NCPD defined for different periods
-
Cumulative prednisone dose (mg) over different periods
-
Time to first flare for different periods
-
Proportions of participants with DC/CR
-
Duration of CRmin
The CSP pre-specified a list of medications whose use is to be considered an 
intercurrent event to be handled using the composite strategy. These medications 
were: immunosuppressants or dapsone, IVIg at immunomodulating doses, 
immunoadsorption or plasma exchange, rituximab or anti-CD20 biologics and IV 
corticosteroids. In this SAP, the following therapies, not mentioned in the CSP, have 
also been added as intercurrent events to be handled with the composite strategy: 
tetracyclines and any interventional study drug under development for pemphigus.
The following analysis, covered in the CSP, will not be performed since no 
comparable historical data are available for the control arm in the PF literature:
-
The magnitude of the effect of efgartigimod PH20 SC compared to placebo in 
the PF subpopulation will be evaluated using the posterior distribution of the 
treatment effect (difference between efgartigimod PH20 SC and placebo) 
obtained in a Bayesian analysis. This Bayesian analysis will incorporate 
historical data for the placebo in an informative maximum a posteriori 
probability estimate prior with robustness modifier.


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6.2
CHANGES NOT COVERED BY PROTOCOL AMENDMENTS AFTER 
DATABASE LOCK 
Not applicable.
6.3
CHANGES TO THE FINAL STATISTICAL ANALYSIS PLAN 
Not applicable.


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7.
REFERENCES 
ICH-E3 Structure and Content of Clinical Study Reports, 01 July 1996.
ICH Topic E6(R1) Guideline for Good Clinical Practice Step 4, 10 June 
1996.
ICH Topic E9 Statistical Principles for Clinical Trials Step 5 Note for 
Guidance on Statistical Principles for Clinical Trials (CPMP/ICH/363/96), 
September 1998.
ICH E9 (R1) addendum on estimands and sensitivity analysis in clinical trials 
to the guideline on statistical principles for clinical trials Step 5
(EMA/CHMP/ICH/436221/2017) 17 February 2020.
National Cancer Institute. Common Terminology Criteria for Adverse Events 
(CTCAE) Version 5.0, November 2017.
G. Shankar, S. Arkin, L. Cocea et al. Assessment and Reporting of the 
Clinical Immunogenicity of Therapeutic Proteins and Peptides
Harmonized 
Terminology and Tactical Recommendations
AAPS J. 2014:16(4):658-673.
Lu K, Mehrotra D. Specification of covariance structure in longitudinal data 
analysis for randomized clinical trials. Statistics in Medicine. 2010; 29: 474-
488. DOI: 10.1002/sim.3820.
Schimmer B.P., & Funder J.W. (2015). Acth, adrenal steroids, and 
pharmacology of the adrenal cortex. Brunton L.L., & Chabner B.A., & 
Knollmann B.C.(Eds.), Goodman & Gilman's: The Pharmacological Basis of 
Therapeutics, 12e. McGraw Hill. 
Liu, D., Ahmet, A., Ward, L., Krishnamoorthy, P., Mandelcorn, E. D., Leigh, 
R., Brown, J. P., Cohen, A., & Kim, H. (2013). A practical guide to the 
monitoring and management of the complications of systemic corticosteroid 
therapy. Allergy, asthma, and clinical immunology : official journal of the 
Canadian Society of Allergy and Clinical Immunology, 9(1), 30.


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8.
LIST OF TABLES AND LISTINGS 
8.1
TABLES  
Note: tables to be produced for the topline results (TL) are indicated in last column
GENERAL CHARACTERISTICS 
 
14.1.1.1
Analysis Sets
SCR
TL
14.1.1.2
Summary of Disposition 
SCR
TL
14.1.1.3
Participant Disposition by Country and Site
SAF
14.1.1.4
Participant Disposition by Analysis Visits
SAF
14.1.1.5
Analysis Phase/Period Duration
SAF
TL
14.1.1.6
Treatment Discontinuation
SAF
TL
14.1.1.7
Study Discontinuation
SCR
TL
14.1.1.8
Major Protocol Deviations
SAF
14.1.1.9
Minor Protocol Deviations
SAF
14.1.2.1
Demographic Data
SAF
TL
14.1.2.2
Baseline Disease Characteristics
SAF
TL
14.1.2.3
Medical History
SAF
14.1.2.4
Concomitant Diseases
SAF
14.1.2.5
Prior Therapies by ATC Class (Level 1 and 3) and 
Generic Term
SAF
TL
14.1.2.6
Concomitant Therapies by ATC Class (Level 1 and 3) and 
Generic Term
SAF
14.1.2.7
Intercurrent Events of Unallowed Therapies that may 
Influence Efficacy by ATC Class (Level 1 and 3) and 
Generic Term
SAF
14.1.2.8
Concomitant Prednisone Administration for Pemphigus
by ATC Class (Level 1 and 3) and Generic Term
SAF
TL
14.1.2.9
IMP Administration
SAF
TL
14.1.2.10
IMP Self Administration Training of Participants
SAF
14.1.2.11
IMP Self Administration Training of Caregivers
SAF
14.1.2.12
Type of IMP Administration
SAF
EFFICACY
14.2.1.1.1
Overview of Primary and Key Secondary Endpoints -
mITT
mITT
TL
14.2.1.1.2.1
Proportion of PV Participants Who Achieved CRmin -
Cochran-Mantel-Haenszel - mITT-PV
mITT
TL


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14.2.1.1.2.2
Proportion of PV Participants Who Achieved CRmin -
Cochran-Mantel-Haenszel (Supplementary Analysis:
Treatment Policy) - mITT-PV
mITT
14.2.1.1.2.3
Proportion of PV Participants Who Achieved CRmin -
Cochran-Mantel-Haenszel - PP-PV
PP
14.2.1.1.2.4
Proportion of PV Participants Who Achieved CRmin -
Cochran-Mantel-Haenszel - mITT Excluding Data 
Impacted by the Conflict in Ukraine-PV
mITT
14.2.1.1.3.1
Proportion of PV Participants Who Achieved CRmin at 
30 Weeks Landmark - Cochran-Mantel-Haenszel - mITT-
PV
mITT
TL
14.2.1.1.3.2
Proportion of PV Participants Who Achieved CRmin at 
30 Weeks Landmark (Sensitivity Analysis) - Cochran-
Mantel-Haenszel - mITT-PV
mITT
14.2.1.2.1.1
Proportion of PV+PF Participants Who Achieved CRmin
- Cochran-Mantel-Haenszel - mITT
mITT
TL
14.2.1.2.1.2
Proportion of PV+PF Participants Who Achieved CRmin
- Cochran-Mantel-Haenszel (Supplementary Analysis:
Treatment Policy) - mITT
mITT
14.2.1.2.1.3
Proportion of PV+PF Participants Who Achieved CRmin
- Cochran-Mantel-Haenszel - PP
PP
14.2.1.2.1.4
Proportion of PV+PF Participants Who Achieved CRmin
- Cochran-Mantel-Haenszel - mITT Excluding Data 
Impacted by the Conflict in Ukraine
mITT
14.2.1.2.1.5
Proportion of PV+PF Participants Who Achieved CRmin 
at 30 Weeks Landmark - Cochran-Mantel-Haenszel -
mITT
mITT
TL
14.2.1.2.1.6
Proportion of PV+PF Participants Who Achieved CRmin 
at 30 Weeks Landmark (Sensitivity Analysis) - Cochran-
Mantel-Haenszel - mITT
mITT
14.2.1.2.1.7
Proportion of PF Participants Who Achieved CRmin -
Cochran-Mantel-Haenszel - mITT-PF
mITT
TL
14.2.1.2.1.8
Proportion of PF Participants Who Achieved CRmin at 30 
Weeks Landmark - Cochran-Mantel-Haenszel - mITT-PF
mITT
TL
14.2.1.2.2.1
NCPD in PV Participants: Descriptive Statistics - mITT-
PV
mITT
TL
14.2.1.2.2.2
NCPD over Planned Treatment Phase in PV Participants:
ANCOVA - mITT-PV
mITT
TL
14.2.1.2.2.3
NCPD in PV Participants: Descriptive Statistics -
(Supplementary Analysis: Treatment Policy) - mITT-PV
mITT


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14.2.1.2.2.4
NCPD over Planned Treatment Phase in PV Participants:
ANCOVA (Supplementary Analysis: Treatment Policy) -
mITT-PV
mITT
14.2.1.2.2.5
NCPD in PV Participants: Descriptive Statistics - PP-PV
PP
14.2.1.2.2.6
NCPD over Planned Treatment Phase in PV Participants:
ANCOVA - PP-PV
PP
14.2.1.2.2.7
NCPD in PV Participants: Descriptive Statistics - mITT 
Excluding Data Impacted by the Conflict in Ukraine-PV
mITT
14.2.1.2.2.8
NCPD over Planned Treatment Phase in PV Participants: 
ANCOVA - mITT Excluding Data Impacted by the 
Conflict in Ukraine-PV
mITT
14.2.1.2.2.9
NCPD over Planned Treatment Phase in PV Participants: 
Stratified Mann-Whitney test - mITT-PV
mITT
14.2.1.2.2.10
NCPD in PF Participants: Descriptive Statistics mITT-
PF
mITT
TL
14.2.1.2.2.11
NCPD over Planned Treatment Phase in PF Participants: 
ANCOVA
mITT-PF
mITT
TL
14.2.1.2.2.12
NCPD in PV+PF Participants: Descriptive Statistics -
mITT
mITT
TL
14.2.1.2.2.13
NCPD over Planned Treatment Phase in PV+PF 
Participants: ANCOVA - mITT
mITT
TL
14.2.1.2.2.14
Cumulative Prednisone dose in PV Participants: 
Descriptive Statistics - mITT-PV
mITT
14.2.1.2.2.15
Cumulative Prednisone dose in PV+PF Participants: 
Descriptive Statistics - mITT
mITT
14.2.1.2.3.1
Time to DC in PV Participants: Descriptive Statistics -
Logrank Test - mITT-PV
mITT
TL
14.2.1.2.3.2
Time to DC in PV Participants: Cox Regression - mITT-
PV
mITT
TL
14.2.1.2.3.3
Time to DC in PV Participants: Descriptive Statistics 
(Supplementary Analysis: Treatment Policy) - Logrank 
Test - mITT-PV
mITT
14.2.1.2.3.4
Time to DC in PV Participants (Supplementary Analysis: 
Treatment Policy): Cox Regression - mITT-PV
mITT
14.2.1.2.3.5
Time to DC in PV Participants: Descriptive Statistics -
Logrank Test - PP-PV
PP
14.2.1.2.3.6
Time to DC in PV Participants: Descriptive Statistics -
Logrank Test - mITT Excluding Data Impacted by the 
Conflict in Ukraine-PV
mITT


Statistical Analysis Plan
ARGX-113-1904
Final analysis
Final 2.0 of 22NOV2023
Page 66 of 98
14.2.1.2.3.7
Time to DC in PF Participants: Descriptive Statistics -
Logrank Test mITT-PF
mITT
TL
14.2.1.2.3.8
Time to DC in PV+PF Participants: Descriptive Statistics 
- Logrank Test - mITT
mITT
TL
14.2.1.2.3.9
Time to DC in PV+PF Participants: Cox Regression -
mITT
mITT
TL
14.2.1.2.4.1
Time to CR in PV Participants: Descriptive Statistics -
Logrank Test - mITT-PV
mITT
TL
14.2.1.2.4.2
Time to CR in PV Participants: Cox Regression - mITT-
PV
mITT
TL
14.2.1.2.4.3
Time to CR in PV Participants: Descriptive Statistics 
(Supplementary Analysis: Treatment Policy) - Logrank 
Test - mITT-PV
mITT
14.2.1.2.4.4
Time to CR in PV Participants (Supplementary Analysis: 
Treatment Policy): Cox Regression - mITT-PV
mITT
14.2.1.2.4.5
Time to CR in PV Participants: Descriptive Statistics -
Logrank Test - PP-PV
PP
14.2.1.2.4.6
Time to CR in PV Participants: Descriptive Statistics -
Logrank Test - mITT Excluding Data Impacted by the 
Conflict in Ukraine-PV
mITT
14.2.1.2.4.7
Time to CR in PF Participants: Descriptive Statistics -
Logrank Test - mITT-PF
mITT
TL
14.2.1.2.4.8
Time to CR in PV+PF Participants: Descriptive Statistics 
- Logrank Test - mITT
mITT
TL
14.2.1.2.4.9
Time to CR in PV+PF Participants: Cox Regression -
mITT
mITT
TL
14.2.1.2.5.1
Proportion of Participants Who Achieved CRmin - mITT 
- by Subgroups
mITT
TL
14.2.1.2.5.2
Proportion of PV Participants Who Achieved CRmin
mITT-PV - by Subgroups
mITT
TL
14.2.1.2.5.3
NCPD: Descriptive Statistics - mITT - by Subgroups
mITT
14.2.1.2.5.4
Time to DC: Descriptive Statistics - mITT - by Subgroups
mITT
14.2.1.2.5.5
Time to CR: Descriptive Statistics - mITT - by Subgroups
mITT
14.2.1.3.1.1
Time to CRmin in PV Participants: Descriptive Statistics -
Logrank Test - mITT-PV
mITT
TL
14.2.1.3.1.2
Time to CRmin in PF Participants: Descriptive Statistics -
Logrank Test - mITT-PF
mITT
TL


Statistical Analysis Plan
ARGX-113-1904
Final analysis
Final 2.0 of 22NOV2023
Page 67 of 98
14.2.1.3.1.3
Time to CRmin in PF+PV Participants: Descriptive 
Statistics - Logrank Test - mITT
mITT
TL
14.2.1.3.2.1
Proportion of PV Participants Who Achieved DC -
Cochran-Mantel-Haenszel - mITT-PV
mITT
14.2.1.3.2.2
Proportion of PF Participants Who Achieved DC - mITT-
PF
mITT
14.2.1.3.2.3
Proportion of PV+PF Participants Who Achieved DC -
Cochran-Mantel-Haenszel - mITT
mITT
14.2.1.3.3.1
Proportion of PV Participants Who Achieved CR -
Cochran-Mantel-Haenszel - mITT-PV
mITT
14.2.1.3.3.2
Proportion of PF Participants Who Achieved CR - mITT-
PF
mITT
14.2.1.3.3.3
Proportion of PV+PF Participants Who Achieved CR -
Cochran-Mantel-Haenszel - mITT
mITT
14.2.1.3.4.1
Proportion of Treatment Failures in PV Participants -
Cochran-Mantel-Haenszel - mITT-PV
mITT
14.2.1.3.4.2
Reason of Treatment Failures in PV Participants -
Tabulation - mITT-PV
mITT
14.2.1.3.4.3
Proportion of Treatment Failures in PV+PF Participants -
Cochran-Mantel-Haenszel - mITT
mITT
14.2.1.3.4.4
Reason of Treatment Failures in PV+PF Participants -
Tabulation - mITT
mITT
14.2.1.3.5.1
Number of Flares in PV Participants: Descriptive 
Statistics - mITT-PV
mITT
14.2.1.3.5.2
Number of Flares in PV Participants: ANCOVA - mITT-
PV
mITT
14.2.1.3.5.3
Time to First Flare in PV Participants: Descriptive 
Statistics - Logrank Test - mITT-PV
mITT
TL
14.2.1.3.5.4
Proportion of PV Participants with Flare - Cochran-
Mantel-Haenszel - mITT-PV
mITT
14.2.1.3.5.5
Number of Flares in PV+PF Participants: Descriptive 
Statistics - mITT
mITT
14.2.1.3.5.6
Number of Flares in PV+PF Participants: ANCOVA -
mITT
mITT
14.2.1.3.5.7
Time to First Flare in PV+PF Participants: Descriptive 
Statistics - Logrank Test - mITT
mITT
TL
14.2.1.3.5.8
Proportion of PV+PF Participants with Flare - Cochran-
Mantel-Haenszel - mITT
mITT


Statistical Analysis Plan
ARGX-113-1904
Final analysis
Final 2.0 of 22NOV2023
Page 68 of 98
14.2.1.3.5.9
Time to First Flare in PF Participants: Descriptive 
Statistics - Logrank Test mITT-PF
mITT
TL
14.2.1.3.6.1
Duration of CRmin in PV Participants: Descriptive 
Statistics - Logrank Test - mITT-PV
mITT
14.2.1.3.6.2
Duration of CRmin in PF Participants: Descriptive 
Statistics - Logrank Test - mITT-PF
mITT
14.2.1.3.6.3
Duration of CRmin in PV+PF Participants: Descriptive 
Statistics - Logrank Test - mITT
mITT
14.2.1.3.7.1
PDAI in PV Participants: Descriptive Statistics of Actual 
Values, Changes from Baseline and Percent Changes from 
Baseline on LOCF by Visit - mITT-PV
mITT
TL
14.2.1.3.7.2
PDAI in PV Participants: Descriptive Statistics of Actual 
Values, Changes from Baseline and Percent Changes from 
Baseline by Period and Visit - mITT-PV
mITT
14.2.1.3.7.3
PDAI in PV Participants: ANCOVA on LOCF Changes 
from Baseline by Visit - mITT-PV
mITT
TL
14.2.1.3.7.4
PDAI in PF Participants: Descriptive Statistics of Actual 
Values, Changes from Baseline and Percent Changes from 
Baseline on LOCF by Visit mITT-PF
mITT
TL
14.2.1.3.7.5
PDAI in PF Participants: ANCOVA on LOCF Changes 
from Baseline by Visit
mITT-PF
mITT
TL
14.2.1.3.7.6
PDAI in PV+PF Participants: Descriptive Statistics of 
Actual Values, Changes from Baseline and Percent 
Changes from Baseline on LOCF by Visit - mITT
mITT
TL
14.2.1.3.7.7
PDAI in PV+PF Participants: Descriptive Statistics of 
Actual Values, Changes from Baseline and Percent 
Changes from Baseline by Period and Visit - mITT
mITT
14.2.1.3.7.8
PDAI in PV+PF Participants: ANCOVA on LOCF 
Changes from Baseline by Visit - mITT
mITT
TL
14.2.1.3.8.1
C-GTI in PV Participants: Descriptive Statistics of CWS 
and AIS at Week 14, Week 30 and Overall - mITT-PV
mITT
14.2.1.3.8.2
C-GTI in PV Participants: ANCOVA on CWS and AIS at 
Week 14, Week 30 and Overall - mITT-PV
mITT
14.2.1.3.8.3
C-GTI in PV Participants: Stratified Mann-Whitney test 
on CWS and AIS at Week 14, Week 30 and Overall -
mITT-PV
mITT
14.2.1.3.8.4
C-GTI in PV+PF Participants: Descriptive Statistics of
CWS and AIS at Week 14, Week 30 and Overall - mITT
mITT
14.2.1.3.8.5
C-GTI in PV+PF Participants: ANCOVA on CWS and 
AIS at Week 14, Week 30 and Overall - mITT
mITT


Statistical Analysis Plan
ARGX-113-1904
Final analysis
Final 2.0 of 22NOV2023
Page 69 of 98
14.2.1.3.8.6
C-GTI in PV+PF Participants: Stratified Mann-Whitney 
test on CWS and AIS at Week 14, Week 30 and Overall -
mITT
mITT
14.2.1.4.1.1
ABQOL in PV Participants: Frequency Tabulation of 17 
Items by Visit - mITT-PV
mITT
14.2.1.4.1.2
ABQOL in PV Participants: Descriptive Statistics of
Actual Values and Changes from Baseline by Visit in 
ABQOL Total Score - mITT-PV
mITT
14.2.1.4.1.3
ABQOL in PV Participants: MMRM on Changes from
Baseline in ABQOL Total Score - mITT-PV
mITT
14.2.1.4.1.4
ABQOL in PV+PF Participants: Frequency Tabulation of 
17 Items by Visit - mITT
mITT
14.2.1.4.1.5
ABQOL in PV+PF Participants: Descriptive Statistics of
Actual Values and Changes from Baseline by Visit in 
ABQOL Total Score - mITT
mITT
14.2.1.4.1.6
ABQOL in PV+PF Participants: MMRM on Changes 
from Baseline in ABQOL Total Score - mITT
mITT
14.2.1.4.2.1
EQ-5D-5L in PV Participants: Frequency Tabulation of 5 
Dimensions by Visit - mITT-PV
mITT
14.2.1.4.2.2
EQ-5D-5L in PV Participants: Descriptive Statistics of
Actual Values and Changes from Baseline by Visit in 
VAS Score - mITT-PV
mITT
14.2.1.4.2.3
EQ-5D-5L in PV Participants: MMRM on Changes from
Baseline in VAS Score - mITT-PV
mITT
14.2.1.4.2.4
EQ-5D-5L in PV+PF Participants: Frequency Tabulation 
of 5 Dimensions by Visit - mITT
mITT
14.2.1.4.2.5
EQ-5D-5L in PV+PF Participants: Descriptive Statistics 
of Actual Values and Changes from Baseline by Visit in 
VAS Score - mITT
mITT
14.2.1.4.2.6
EQ-5D-5L in PV+PF Participants: MMRM on Changes 
from Baseline in VAS Score - mITT
mITT
PHARMACOKINETICS
14.2.2.1
Descriptive Statistics of Efgartigimod Serum 
Concentrations over Time
PK
PHARMACODYNAMICS
14.2.3.1
Descriptive Statistics of Actual Values, Changes from 
Baseline and Percent Changes from Baseline in Total IgG 
Level and IgG Subtype Levels by Visit
PD


Statistical Analysis Plan
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Final analysis
Final 2.0 of 22NOV2023
Page 70 of 98
14.2.3.2
Descriptive Statistics of Actual Values, Changes from 
Baseline and Percent Changes from Baseline in Total IgG 
Level and IgG Subtype Levels by Visit - by Subgroups
PD
14.2.3.3
Descriptive Statistics of Actual Values, Changes from 
Baseline and Percent Changes from Baseline in anti-Dsg-
1/-3 Antibodies by Visit
PD
14.2.3.4
Descriptive Statistics of Actual Values, Changes from 
Baseline and Percent Changes from Baseline in anti-Dsg-
1/-3 Antibodies by Visit - by Subgroups
PD
IMMUNOGENICITY
14.2.4.1.1
ADA-EFG: Anti-Drug Antibodies to Efgartigimod 
Sample Classification by Analysis Visit by Overall Anti-
Drug Antibodies Participant Classification
SAF
14.2.4.1.2
ADA-EFG: Anti-Drug Antibodies to Efgartigimod 
Participant Classification, Prevalence and Incidence
SAF
14.2.4.1.3
NAb-EFG: Neutralizing Antibodies to Efgartigimod 
Sample Classification by Analysis Visit by Overall 
Neutralizing Antibodies Participant Classification
SAF
14.2.4.1.4
NAb-EFG: Neutralizing Antibodies to Efgartigimod 
Participant Classification, Prevalence and Incidence 
SAF
14.2.4.1.5
Ab-PH20: Antibodies to PH20 Sample Classification by 
Analysis Visit by Overall PH20 Anti-Drug Antibodies 
Participant Classification
SAF
14.2.4.1.6
Ab-PH20: Antibodies to PH20 Participant Classification, 
Prevalence and Incidence
SAF
14.2.4.1.7
NAb-PH20: Neutralizing Antibodies to PH20 Sample 
Classification by Analysis Visit by Overall PH20 
Neutralizing Antibodies Participant Classification
SAF
14.2.4.1.8
NAb-PH20: Neutralizing Antibodies to PH20 Participant 
Classification, Prevalence and Incidence
SAF
14.2.4.2.1
NAb-EFG: Neutralizing Antibodies Positives to 
Efgartigimod Participant Classification by Overall 
Efgartigimod Anti-Drug Antibodies Participant 
Classification
SAF
14.2.4.2.2
NAb-PH20: Neutralizing Antibodies Positives to PH20 
Participant Classification by Overall PH20 Antibodies 
Participant Classification
SAF
14.2.4.2.3
Ab-PH20: Antibodies Positives to PH20 Participant 
Classification by Overall Efgartigimod Anti-Drug 
Antibodies Participant Classification
SAF


Statistical Analysis Plan
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Final analysis
Final 2.0 of 22NOV2023
Page 71 of 98
14.2.4.3.1
ADA-EFG: Mean Drug Concentration over Time by 
Overall ADA Participant Classification
SAF
14.2.4.3.2
ADA-EFG: Mean Percent Change from Baseline in Total 
IgG over Time by Overall ADA Participant Classification
SAF
14.2.4.3.3
ADA-EFG: Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term by 
Overall ADA Participant Classification
SAF
14.2.4.3.4
ADA-EFG: Serious Treatment-Emergent Adverse Events 
by MedDRA System Organ Class and Preferred Term by 
Overall ADA Participant Classification
SAF
14.2.4.3.5
ADA-EFG: Injection Site Reactions by Overall ADA 
Participant Classification
SAF
14.2.4.3.6
ADA-EFG: Injection-Related Reactions by Overall ADA 
Participant Classification
SAF
14.2.4.3.7
ADA-EFG: Proportion of Participants with CRmin within 
30 weeks by Overall ADA Participant Classification
SAF
14.2.4.4.1
NAb-EFG: Mean Drug Concentration over Time by 
Overall NAb Participant Classification
SAF
14.2.4.4.2
NAb-EFG: Mean Percent Change from Baseline in Total 
IgG over Time by Overall NAb Participant Classification
SAF
14.2.4.4.3
NAb-EFG: Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term by 
Overall NAb Participant Classification
SAF
14.2.4.4.4
NAb-EFG: Serious Treatment-Emergent Adverse Events 
by MedDRA System Organ Class and Preferred Term by 
Overall NAb Participant Classification
SAF
14.2.4.4.5
NAb-EFG: Injection Site Reactions by Overall NAb 
Participant Classification
SAF
14.2.4.4.6
NAb-EFG: Injection-Related Reactions by Overall NAb 
Participant Classification
SAF
14.2.4.4.7
NAb-EFG: Proportion of Participants with CRmin within 
30 weeks by Overall NAb Participant Classification
SAF
14.2.4.5.1
Ab-PH20: Mean Drug Concentration over Time by 
Overall Ab-PH20 Participant Classification
SAF
14.2.4.5.2
Ab-PH20: Mean Percent Change from Baseline in Total 
IgG over Time by Overall Ab-PH20 Participant 
Classification
SAF
14.2.4.5.3
Ab-PH20: Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term by 
Overall Ab-PH20 Participant Classification
SAF


Statistical Analysis Plan
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Final analysis
Final 2.0 of 22NOV2023
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14.2.4.5.4
Ab-PH20: Serious Treatment-Emergent Adverse Events 
by MedDRA System Organ Class and Preferred Term by 
Overall Ab-PH20 Participant Classification
SAF
14.2.4.5.5
Ab-PH20: Injection Site Reactions by Overall Ab-PH20 
Participant Classification
SAF
14.2.4.5.6
Ab-PH20: Injection-Related Reactions by Overall Ab-
PH20 Participant Classification
SAF
14.2.4.5.7
Ab-PH20: Proportion of Participants with CRmin within 
30 weeks by Overall Ab-PH20 Participant Classification
SAF
14.2.4.6.1
ADA-EFG: Descriptive Statistics of ADA Against 
Efgartigimod Titer Values by ADA Participant
Classification Against Efgartigimod
SAF
14.2.4.6.2
Ab-PH20: Descriptive Statistics of Ab Against PH20
Titer Values by Ab-PH20 Participant Classification
SAF
SAFETY 
 
ADVERSE EVENTS 
 
14.3.1.1
Adverse Events Overview
SAF
TL
14.3.1.2
Treatment-Emergent and Post-Treatment Emergent 
Adverse Events by MedDRA System Organ Class and 
Preferred Term
SAF
TL
14.3.1.3
Most Common (>=5% in Any Group) Treatment-
Emergent Adverse Events by MedDRA System Organ 
Class and Preferred Term
SAF
TL
14.3.1.4
Treatment Related Treatment-Emergent Adverse Events 
by MedDRA System Organ Class and Preferred Term
SAF
14.3.1.5
Serious Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term
SAF
TL
14.3.1.6
Serious Treatment Related Treatment-Emergent Adverse 
Events by MedDRA System Organ Class and Preferred 
Term
SAF
14.3.1.7
Serious Prednisone Related Treatment-Emergent Adverse 
Events by MedDRA System Organ Class and Preferred 
Term
SAF
14.3.1.8
Grade 3 or More Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term
SAF
TL
14.3.1.9
Treatment Related Grade 3 or More Treatment-Emergent 
Adverse Events by MedDRA System Organ Class and 
Preferred Term
SAF
14.3.1.10
Prednisone Related Treatment-Emergent Adverse Events 
by MedDRA System Organ Class and Preferred Term
SAF
TL


Statistical Analysis Plan
ARGX-113-1904
Final analysis
Final 2.0 of 22NOV2023
Page 73 of 98
14.3.1.11
Procedures Related Treatment-Emergent Adverse Events 
by MedDRA System Organ Class and Preferred Term
SAF
14.3.1.12
Treatment-Emergent Adverse Events Leading to 
Discontinuation of IMP by MedDRA System Organ Class 
and Preferred Term
SAF
TL
14.3.1.13
Treatment-Emergent Adverse Events of Special Interest 
by MedDRA System Organ Class and Preferred Term
SAF
TL
14.3.1.14
Treatment Related Treatment-Emergent Adverse Events 
of Special Interest by MedDRA System Organ Class and 
Preferred Term
SAF
14.3.1.15.1
Treatment-Emergent Injection Site Reaction - Overview
SAF
TL
14.3.1.15.2
Treatment-Emergent Injection Site Reactions by 
MedDRA System Organ Class and Preferred Term
SAF
TL
14.3.1.16.1
Treatment-Emergent Injection-Related Reactions by 
MedDRA System Organ Class and Preferred Term
SAF
14.3.1.16.2
Serious Treatment-Emergent Injection-Related Reactions 
by MedDRA System Organ Class and Preferred Term
SAF
LABORATORY DATA 
 
14.3.2.1
Descriptive Statistics of Laboratory Test Actual Values
and Changes from Baseline
SAF
14.3.2.2
Descriptive Statistics of Albumin and Low-Density 
Lipoprotein-Cholesterol (LDL-C) Actual Values, Changes 
from Baseline and Percent Changes from Baseline
SAF
14.3.2.3
Cross-Tabulation of Laboratory Abnormalities Versus 
Baseline Over Time
SAF
14.3.2.4
Cross-Tabulation of Laboratory Toxicity Grades Versus 
Baseline Over Time
SAF
VITAL SIGNS 
 
14.3.3.1
Descriptive Statistics of Vital Signs Actual Values and 
Changes from Baseline
SAF
14.3.3.2
Cross-Tabulation of Vital Signs Abnormalities Versus 
Baseline Over Time
SAF
ECG 
 
14.3.4.1
Descriptive Statistics of ECG Actual Values and Changes 
from Baseline
SAF
14.3.4.2
Cross-Tabulation of ECG Abnormalities Versus Baseline
Over Time
SAF
14.3.4.3
Cross-Tabulation of QTcB/QTcF Abnormalities Versus 
Baseline Over Time
SAF


Statistical Analysis Plan
ARGX-113-1904
Final analysis
Final 2.0 of 22NOV2023
Page 74 of 98
14.3.4.4
Tabulation of QTc Change Abnormalities Over Time
SAF
8.2
LISTINGS 
GENERAL CHARACTERISTICS 
16.2.1.1
Analysis Sets
SCR
16.2.1.2
Study and Treatment Discontinuation
SAF
16.2.1.3
Study Visits
SAF
16.2.2.1
Protocol Deviations
SAF
16.2.2.2
Violations on Eligibility Criteria
SAF
16.2.2.3
No-Treatment Participants
SCR minus 
SAF
16.2.2.4
Covid-19 Related Comments
SAF
16.2.4.1
Demographic Data
SAF
16.2.4.2
Baseline Disease Characteristics
SAF
16.2.4.3
Medical History and Concomitant Disease
SAF
16.2.4.4
Prior and Concomitant Therapies 
SAF
16.2.4.5
Prior and Concomitant Procedures 
SAF
16.2.4.6
Main Intercurrent Events
SAF
16.2.5.1
IMP Administration
SAF
16.2.5.2
Prednisone Administration and Cumulative Dose
SAF
16.2.5.3
NCPD and Cumulative Dose Until Endpoints
SAF
16.2.5.4
IMP Self Administration Training
SAF
PHARMACOKINETICS
16.2.5.5
Individual Efgartigimod Serum Concentrations and Actual 
Blood Sampling Times
PK
EFFICACY
16.2.6.1
Disease Status and Flares
mITT
16.2.6.2
Disease Status: Derived Parameters
mITT
16.2.6.3
Lesion Assessment
mITT
16.2.6.4
PDAI
mITT
16.2.6.5
ABQOL
mITT
16.2.6.6
EQ-5D-5L
mITT
16.2.6.7
C-GTI
mITT
16.2.6.8
GTI Specific List
mITT


Statistical Analysis Plan
ARGX-113-1904
Final analysis
Final 2.0 of 22NOV2023
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PHARMACODYNAMICS
16.2.6.9
Total IgG and IgG Subtypes
PD
16.2.6.10
Anti-Dsg-1/-3 Antibodies
PD
IMMUNOGENICITY
16.2.6.11
Efgartigimod Anti-drug Antibodies and Neutralizing 
Antibodies
SAF
16.2.6.12
PH20 Anti-drug Antibodies and Neutralizing Antibodies
SAF
SAFETY 
ADVERSE EVENTS
16.2.7.1
Adverse Events
SAF
16.2.7.2
Serious Adverse Events
SAF
16.2.7.3
Fatal Adverse Events 
SAF
16.2.7.4
Treatment-Emergent Adverse Events Leading to 
Discontinuation of IMP
SAF
16.2.7.5
Adverse Events of Special Interest
SAF
16.2.7.6
Adverse Events: Coding Information
SAF
LABORATORY DATA 
16.2.8.1
Laboratory Test Results for Participants with Abnormal 
Values
SAF
VITAL SIGNS 
16.2.9.1
Vital Signs Results for Participants with Abnormal Values
SAF
ECG 
16.2.10.1
ECG Results for Participants with Abnormal Values
SAF
PHYSICAL EXAMINATION 
16.2.11.1
Physical Examination Abnormalities
SAF


Statistical Analysis Plan
ARGX-113-1904
Final analysis
Final 2.0 of 22NOV2023
Page 76 of 98
9.
APPENDICES 
9.1
MAIN INTERCURRENT EVENTS (ICE) 
The conditions below are tailored for the primary endpoint (CRmin). Conditions 
based on medication type, minimal dosing and minimal duration apply to the other 
endpoints with composite strategy or hypothetical strategy. However, conditions like 
only. For these 
strategies, NCPD is calculated until and excluding the first day of ICE unless 
specified otherwise.
Azathioprine, at least 1 mg/kg/day
Mycophenolate mofetil, at least 2 g/day
Mycophenolic acid, at least 1000 mg/day
Mycophenolate mofetil hydrochloride, at least 2 g/day
Cyclophosphamide, at least 1 mg/kg/day, or IV pulse 500 mg/month
Methotrexate (sodium), at least 5 mg/week (in Japan), whereas 10 
mg/week in Europe
Ciclosporin, at least 3 mg/kg/day
Dapsone, at least 1 mg/kg/day
Hydroxychloroquine sulfate, at least 400mg/day
Thalidomide, at least 50mg/day
For CRmin and time to CRmin these events should occur in the last 12 
weeks before CRmin to be considered as an ICE. NCPD is calculated until 
and including the last day of the applicable 4 weeks intake.
o
or
o
or
nti-D
Immunoglobulin 
.
Plasmapheresis or mmunoadsorption therapy as PRDECOD, at least 
one cycle


Statistical Analysis Plan
ARGX-113-1904
Final analysis
Final 2.0 of 22NOV2023
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Rituximab, at least one cycle of 1 g or 375 mg/m2
Obinutuzumab
Ofatumumab
Ocrelizumab
Ibritumomab tiuxetan
Veltuzumab
Tocilizumab
administered (at least 1 administration, any dose) once the participant 
has achieved minimal prednisone (or prednisone equivalent) dose of <=
10 mg/day (i.e., during the 8 week period required in the protocol to 
confirm the CRmin status) or administered at any moment before 
achieving CRmin in any of the three following situations:
a) more than 60 mg of prednisone equivalent for 3 consecutive days 
b) more than 40 mg of prednisone equivalent for 4 consecutive days 
c) more than 7 days in total
H02 CORTICOSTEROIDS FOR 
or
For endpoints other than CRmin and time to CRmin, any administration of 
this type of medication is to be considered as an ICE.
medications with 
For CRmin and time to CRmin these events should occur in the last 10 
weeks before CRmin to be considered as an ICE. NCPD is calculated until 
and including the last day of the applicable 2 weeks intake.
medications under development for pemphigus will be evaluated during 
the course of the study
 


Statistical Analysis Plan
ARGX-113-1904
Final analysis
Final 2.0 of 22NOV2023
Page 78 of 98
9.2
SAS CODE 
Calculate &meanbase. as mean of base of all unique participants in FAS.
Note: this is the script for NCPD. For other variables this code needs to be adapted 
according the model specifications in section 4.1. For example, for PDAI, the 
dependent variable is CHG and the baseline value needs to be added to the set of 
covariables.


Statistical Analysis Plan
ARGX-113-1904
Final analysis
Final 2.0 of 22NOV2023
Page 79 of 98


Statistical Analysis Plan
ARGX-113-1904
Final analysis
Final 2.0 of 22NOV2023
Page 80 of 98
 


Statistical Analysis Plan
ARGX-113-1904
Final analysis
Final 2.0 of 22NOV2023
Page 81 of 98
9.3
GTI: DERIVATION OF CWS AND AIS 
Weights per item are attributed as specified below. GTI at Wx is evaluated versus 
previous GTI assessment. The first time point is referred to as start (or previous) and 
the second time point within each comparison is referred to as follow-up (or current).
Increase, decrease or no change in medication intake compared to previous 
assessment are checked in the GTI assessment. A missing evaluation, including for 
external data, will be considered as no change with weight=0.
External GTI data (i.e. LDL/HbA1c/BP and BMI) are allocated to a GTI assessment
based on dates. The last available value of these external data since previous GTI 
assessment will be used.
Changes from severe to moderate do not have any impact on calculation of 
CWS/AIS. Severe outcome on an item however is captured on the specific list (SL).
Moderate decrease in the direction of the normal range [<25 kg/ m2] by 
at least 5 BMI units
-36
Minor decrease in the direction of the normal range [<25 kg/ m2] by 
more than 2 but less than 5 BMI units
-21
No significant change (BMI remains within +/- 2 BMI units compared 
with start) OR BMI remains <25 kg/ m2
0
Minor increase in BMI (increase by more than 2 but less than 5 BMI 
2]) 
21
Moderate increase in BMI (increase by at least 5 BMI units above
2])
36


Statistical Analysis Plan
ARGX-113-1904
Final analysis
Final 2.0 of 22NOV2023
Page 82 of 98
Moderate improvement in glucose tolerance:
-44
o
HbA1c declined >10% from start AND medication decrease 
Minor improvement in glucose tolerance:
-32
o
HbA1c declined >10% from start AND no medication increase 
(unchanged or missing
o
HbA1c within 10% of start AND decrease in diabetic medication
o
HbA1c < 5.7 AND decrease in diabetic medication AND HbA1c 
increased >10%
No significant change in glucose tolerance:
0
o
HbA1c within 10% of start or (start and follow-up) HbA1c < 5.7 
AND no change in medication (or missing)
o
HbA1c increased > 10% of start AND a decrease in medication 
AND follow-
o
HbA1c decreased by > 10% of start AND an increase in 
medication 
Minor worsening of glucose tolerance or medication status:
32
o
HbA1c increased >10% of start AND no change in medication 
(or missing) AND follow-
o
HbA1c within 10% of start AND increase in diabetic medication
Moderate worsening of glucose tolerance despite increased diabetic 
treatment:
44
o
HbA1c increased >10% of start AND an increase in diabetic 
medication AND follow-
Note: changes in medication for glucose control, used in the above weight 
derivations, are assessed as a GTI specific question.


Statistical Analysis Plan
ARGX-113-1904
Final analysis
Final 2.0 of 22NOV2023
Page 83 of 98
Moderate improvement in BP:
-44
o
Decrease in either systolic or diastolic BP of >10% of start AND 
medication decr
Minor improvement in BP:
-19
o
Decrease in either systolic or diastolic BP of >10% of start AND 
no medication increase (unchanged or missing) AND start 
o
Systolic AND diastolic BP within 10% of start AND a decrease 
in medication 
o
Systolic BP < 120 and diastolic BP < 85 (both start and end) 
AND a decrease in medication 
No significant change in BP: 
0
o
Systolic AND diastolic BP within 10% of start or (start and 
follow-up) systolic / diastolic BP < 120/85 resp AND no change 
in medication (or missing)
o
Increase in systolic or diastolic BP >10% of start AND a 
decrease in medication AND follow-
or  diastolic BP 
o
Decrease in systolic or diastolic BP of > 10% of start AND an 
Minor worsening of BP:
19
o
Increase in systolic or diastolic BP >10% of start AND no 
change in medication (or missing) AND follow-up systolic BP 
o
Systolic AND diastolic BP within 10% of start AND an increase 
in medication 
o
Systolic BP < 120 and diastolic BP < 85 (both start and end)  
AND an increase in medication  
Moderate worsening of BP despite treatment
44
o
Increase in systolic or diastolic BP >10% of start AND an 
increase in medication AND follow-
Notes: 
1. changes in medication for BP control, used in the above weight derivations, are 
assessed as a GTI specific question. 
2.
diastolic BP. In case of both an increase and decrease occurs, this is considered as no 
change in BP and the score will be based on the change in medication (score = +/-19
for increase/decrease, score = 0 for no change).


Statistical Analysis Plan
ARGX-113-1904
Final analysis
Final 2.0 of 22NOV2023
Page 84 of 98
3. Hypertensive Emergency = Y or PRES = Y at current visit is provided a score 44 
regardless of the value at previous visit
Moderate improvement in lipids: 
-30
o
Decrease in LDL concentration >10% of start AND medication 
decrease
Minor improvement in lipids: 
-10
o
Decrease in LDL concentration >10% of start AND no change in 
medication (or missing) AND start above target range 
o
LDL within 10% of start AND decrease in medication
No significant change in lipids:
0
o
LDL within 10% of start AND no change in medication (or 
missing)
o
Increase in LDL > 10% of start AND decrease in medication 
o
Decrease in LDL > 10% of start AND no medication change (or 
missing) AND start LDL below or equal target range
o
Decrease in LDL > 10% of start AND increase in medication 
Minor worsening of LDL or medication status: 
10
o
Increase in LDL >10% of start AND no change in medication 
(or missing)
o
LDL within 10% of start of start AND increase in medication
Worsening of LDL despite treatment:
30
o
Increase in LDL >10% of start AND an increase in medication
Notes: 
1. changes in medication for lipid control, used in the above weight derivations, are 
assessed as a GTI specific question. 
2. target range for LDL is 1.81mmol/L
Moderate/severe weakness to none: 
-63
Moderate/severe weakness to mild weakness:
-54
Mild weakness to none: 
-9
No significant change:
0
None to mild weakness: 
9
Mild to Moderate/severe weakness:
54
None to Moderate/severe weakness:
63


Statistical Analysis Plan
ARGX-113-1904
Final analysis
Final 2.0 of 22NOV2023
Page 85 of 98
Allocate weights for each of the 5 subitems : acneiform rash, easy bruising, hirsutism, 
atrophy/striae, erosions/tears/ulcerations
Moderate/severe to none: 
-26
Moderate/severe to minor:
-18
Minor to none: 
-8
No significant change:
0
None to minor: 
8
minor to moderate/severe: 
18
None to moderate/severe:
26
Note: minor and mild or used fully interchangeable.
For the derivation from the grading to severe, moderate, minor (or mild): see table
underneath:
Minor/Mild
Moderate
Severe (Specific Domain)
Acneiform rash (Grades 1-2)
Acneiform rash (Grade 3)
Acneiform rash (Grade 4)
Easy bruising (Grade 1)
Easy bruising (Grade 2)
Hirsutism (Grade 1)
Hirsutism (Grade 2)
Atrophy/Striae (Grade 1)
Atrophy/Striae (Grade 2)
Atrophy/Striae (Grade 3)
Erosions/Tears/Ulcerations 
(Grade 1)
Erosions/Tears/Ulcerations 
(Grade 2)
Erosions/Tears/Ulcerations 
(Grade 3)


Statistical Analysis Plan
ARGX-113-1904
Final analysis
Final 2.0 of 22NOV2023
Page 86 of 98
Allocate weights for each of the 4 subitems : insomnia, mania, cognitive impairment, 
depression
Moderate/severe to none: 
-74
Moderate/severe to minor:
-63
Minor to none:
-11
No significant change:
0
None to minor: 
11
Minor to moderate/severe: 
63
None to moderate/severe:
74
Notes: 
1. presence of psychosis or glucocorticoid-induced violence (as captured in the GTI 
specific list) always has weight=74. Disappearance of psychosis or glucocorticoid-
induced violence has weight=-74.
2. minor and mild or used fully interchangeable
For the derivation from the grading to severe, moderate, minor (or mild): see table 
underneath:
Minor/Mild
Moderate
Severe (Specific Domain)
Insomnia (Grade 1)
Insomnia (Grade 2)
Mania (Grade 1)
Mania (Grade 2)
Mania (Grade 3)
Cognitive impairment (Grade 
1)
Cognitive impairment (Grade 
2)
Cognitive impairment (Grade 
3)
Depression (Grade 1)
Depression (Grade 2)
Depression (Grade 3)
No significant infection: 
0
Specific infections < Grade 3 (oral or vaginal candidiasis, 
uncomplicated zoster):
19
Grade 3, 4, or 5 or complicated herpes zoster: 
93
Note: 
Special case domain: each infection is a distinct event, so infections only have 
worsening. That means that a subject may have Infection grade 3 at W14 and again at 
W30 and the subjects may be assigned a score of 93 for the worsening from W14 to 
W30 
W30.


Statistical Analysis Plan
ARGX-113-1904
Final analysis
Final 2.0 of 22NOV2023
Page 87 of 98
The CWS is calculated as the sum of the worsening items: i.e. with weights >0. For 
the items with subitems, i.e. skin toxicity and neuropsychiatric effects, only the 
subitem with the highest positive weight is used. As an example, if neither insomnia
nor depression were present at the start of the GTI interval but there is mild insomnia 
and moderate depression present at post-baseline, then only the moderate depression 
is used for the neuropsychiatric weight (+74 points).
In the CWS calculation, the most severe infection in every GTI interval is scored (so 
in case of 2 periods, the score for an infection is counted twice for the overall CWS).
CWS is calculated at W14 and at W30 as the sum of the worsening items in all post-
baseline timepoints up to that timepoint respectively. The overall CWS is the sum of
all worsening items over all post-baseline timepoints.
With the AIS, improvement as well as worsening is included in the calculations of the 
sum of the items. For the items with subitems, i.e. skin toxicity and neuropsychiatric 
effects, only the subitem with the highest positive weight is used as well as the 
subitem with the lowest negative weight is used. For example: if the highest positive 
skin subitem is +26 and the highest negative skin subitem is -18, then skin weight for 
AIS is +8.
AIS is calculated at W14 and at W30 as the sum of the items in all post-baseline 
timepoints up to that timepoint respectively. The overall AIS is the sum over all post-
baseline timepoints.


Statistical Analysis Plan
Below table documents how the Common Terminology Criteria for Adverse Events CTCAE, v5.0: November 27, 2017 is implemented in the 
statistical analysis.
CTCAE, v5.0: November 27, 2017
Amylase (pancreatic)
>1.0-1.5 *ULN
>1.5-2.0 *ULN
>2.0-5.0 *ULN
>5.0 *ULN
Alanine amino transferase
>1-3 *ULN
>3-5 *ULN
>5-20 *ULN
>20 *ULN
Albumin
g/L
<LLN-30
<30-20
<20
-
g/dL
<LLN-3
<3-2
<2
-
Alkaline phosphatase
>1.0-2.5 *ULN
>2.5-5.0 *ULN
>5.0-20.0 *ULN
>20.0 *ULN
Aspartate amino transferase
>1-3 *ULN
>3-5 *ULN
>5-20 *ULN
>20 *ULN
Bilirubin (total)
>1.0-1.5 *ULN
>1.5-3.0 *ULN
>3.0-10.0 *ULN
>10.0 *ULN
Calcium (ionized) low
mmol/L
<LLN-1.0
<1.0-0.9
<0.9-0.8
<0.8
mg/dL
<LLN-4.0
<4.0-3.6
<3.6-3.2
<3.2
Calcium (ionized) high
mmol/L
>ULN-1.5
>1.5-1.6
>1.6-1.8
>1.8
mg/dL
>ULN-6.0
>6.0-6.4
>6.4-7.2
>7.2
Calcium (corrected) low
mmol/L
<LLN-2.00
<2.00-1.75
<1.75-1.50
<1.50
mg/dL
<LLN-8
<8-7
<7-6
<6
Calcium (corrected) high
mmol/L
>ULN-2.9
>2.9-3.1
>3.1-3.4
>3.4


Statistical Analysis Plan
mg/dL
>ULN-11.5
>11.5-12.5
>12.5-13.5
>13.5
Cholesterol
mmol/L
>ULN-7.75
>7.75-10.34
>10.34-12.92
>12.92
mg/dL
>ULN-300
>300-400
>400-500
>500
Creatine kinase
>1.0-2.5 *ULN
>2.5-5.0 *ULN
>5.0-10.0 *ULN
>10.0 *ULN
Creatinine
>1.0-1.5 *ULN
>1.5-3.0 *ULN
>3.0-6.0 *ULN
>6.0 *ULN
Gamma-glutamyl transferase
>1.0-2.5 *ULN
>2.5-5.0 *ULN
>5.0-20.0 *ULN
>20.0 *ULN
Glucose (fasting) low [1]
mmol/L
<LLN-3.0
<3.0-2.2
<2.2-1.7
<1.7
mg/dL
<LLN-55
<55-40
<40-30
<30
Lipase
>1.0-1.5 *ULN
>1.5-2.0 *ULN
>2.0-5.0 *ULN
>5.0 *ULN
Magnesium low
mmol/L
<LLN-0.5
<0.5-0.4
<0.4-0.3
<0.3
mg/dL
<LLN-1.2
<1.2-0.9
<0.9-0.7
<0.7
Magnesium high
mmol/L
>ULN-1.23
-
>1.23-3.30
>3.30
mg/dL
>ULN-3.0
-
>3.0-8.0
>8.0
Potassium low
mmol/L
-
<LLN-3.0
<3.0-2.5
<2.5
mEq/L
-
<LLN-3.0
<3.0-2.5
<2.5
Potassium high
mmol/L
>ULN-5.5
>5.5-6.0
>6.0-7.0
>7.0
mEq/L
>ULN-5.5
>5.5-6.0
>6.0-7.0
>7.0
Sodium low
mmol/L
<LLN-130
-
<130-120
<120


Statistical Analysis Plan
mEq/L
<LLN-130
-
<130-120
<120
Sodium high
mmol/L
>ULN-150
>150-155
>155-160
>160
mEq/L
>ULN-150
>150-155
>155-160
>160
Triglycerides
mmol/L
1.71-3.42
>3.42-5.70
>5.70-11.4
>11.4
mg/dL
150-300
>300-500
>500-1000
>1000
Partial thromboplastin time (activated or 
not specified
>1.0-1.5 *ULN
>1.5-2.5 *ULN
>2.5 *ULN
-
CD4 count
giga/L
<LLN-0.50
<0.50-0.20
<0.20-0.05
<0.05
counts/mm
<LLN-500
<500-200
<200-50
<50
Fibrinogen
<1.00-0.75 *LLN
<0.75-0.50 *LLN
<0.50-0.25 *LLN
<0.25 *LLN
International normalized ratio
>1.2-1.5 *ULN
>1.5-2.5 *ULN
>2.5 *ULN
-
Lymphocytes (absolute count) low
giga/L
<LLN-0.80
<0.80-0.50
<0.50-0.20
<0.20
counts/mm
<LLN-800
<800-500
<500-200
<200
Lymphocytes (absolute count) high
giga/L
-
>4-20
>20
-
counts/mm
-
>4000-20000
>20000
-
Neutrophils (absolute count) 
giga/L
<LLN-1.5
<1.5-1.0
<1.0-0.5
<0.5
counts/mm
<LLN-1500
<1500-1000
<1000-500
<500
Platelets
giga/L
<LLN-75
<75-50
<50-25
<25
counts/mm
<LLN-75000
<75000-50000
<50000-25000
<25000


Statistical Analysis Plan
White blood cells
giga/L
<LLN-3
<3-2
<2-1
<1
counts/mm
<LLN-3000
<3000-2000
<2000-1000
<1000
[1] Grade definition will also be applied when the fasting conditions into which the sample was drawn have not been declared (e.g. unscheduled 
samples, unknown), when only (a) sporadic result(s) for the parameter was (were) non-fasting (usually unscheduled samples), and in case of 
scheduled post-meal samples on a same day (e.g. 4 hours after dose and after a meal).
Note: In case ULN/LLN is higher/lower than the upper/lower limit of grade 1 (or even higher grades), ULN/LLN will be ignored and only the fixed 
values of CTCAE will be considered. In case ULN/LLN is missing, a grade will only be derived if the value leaves no doubt on which grade is to be 
assigned.


Statistical Analysis Plan


Statistical Analysis Plan


Statistical Analysis Plan




Statistical Analysis Plan


Statistical Analysis Plan


Statistical Analysis Plan