An Open-Label, Multicenter, Follow-up Trial of ARGX-113-1904 to Evaluate the Safety, Tolerability, and Efficacy of Efgartigimod PH20 SC in Patients With Pemphigus
Phase: PHASE3
Conditions: Pemphigus Vulgaris, Pemphigus Foliaceus
Sponsor: argenx

 
 
 
 
Clinical Trial Protocol 
Protocol Title:  
An Open-Label, Multicenter, Follow-up Trial of ARGX-113-1904 
to Evaluate the Safety, Tolerability, and Efficacy of Efgartigimod 
PH20 SC in Patients With Pemphigus (ADDRESS+) 
Protocol Number:   
ARGX-113-1905 
Version Number:  
 
3.0 (Amendment 2) 
Compound:   
 
Efgartigimod (ARGX-113) 
Investigational Medicinal  Efgartigimod PH20 SC (efgartigimod coformulated with  
Product: 
recombinant human hyaluronidase PH20 [rHuPH20] for 
subcutaneous [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: 146526 
 
  
 
 
EudraCT: 2020-002917-16 
 
Date and Version:   
05 September 2022, Version 3.0 
 
 
System Version: 1.0, Status: Approved, Document ID: VV-TMF-86295

Clinical Trial Protocol ARGX-113-1905 v3.0 
 
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Efgartigimod PH20 SC 
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Sponsor’s Medical Contact: 
, MD, PhD 
argenx BV 
Industriepark Zwijnaarde 7 
9052 Zwijnaarde (Ghent) 
Belgium 
Office phone: 
 
Mobile phone: 
 
 
Contract Research Organization: Pharmaceutical Product Development (PPD) Global Ltd 
11 Granta Park, Great Abington 
Cambridge, CB21 6GQ 
United Kingdom 
Phone: +44 1223 374100 
 
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: 
MEA/APAC +44 1223 374 240 
North America +1 800 201 8725 
 
 
For drug safety reporting, contact the below email address: 
Safety Mailbox/Fax: 
Parexel email: 248700ADR@parexel.com 
Fax: 1-833-644-0806 
 
 
 
 
 
Confidentiality Statement 
The information in this document is confidential. It contains proprietary information of argenx BV 
(the sponsor). It is provided to you as an investigator or consultant for review by you, your staff, 
and the applicable Institutional Review Board/Independent Ethics Committee (IRB/IEC). 
Your acceptance of this document constitutes the agreement that you will not disclose the information 
contained herein to others without written authorization from the sponsor. 
System Version: 1.0, Status: Approved, Document ID: VV-TMF-86295

Clinical Trial Protocol ARGX-113-1905 v3.0 
 
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Notification: Possible Adaptations of Protocol During the COVID-19 Pandemic 
The aim of ARGX-113-1905 is to investigate a new subcutaneous (SC) treatment option for 
participants with pemphigus. This SC treatment consisting of efgartigimod coformulated with 
recombinant human hyaluronidase PH20 (rHuPH20) (called efgartigimod PH20 SC) could offer 
clinically significant benefits to pemphigus participants. 
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 (AEs) reported during 
argenx BV clinical trials. 
Due to the COVID-19 pandemic, it may not be possible to perform all assessments as planned 
for this trial (at the site, at the times indicated in the Schedule of Activities [SoA] in Section 1.3, 
or both).  
In order to provide participants with pemphigus the opportunity to continue the trial during the 
COVID-19 pandemic, an appendix with possible adaptations to ARGX-113-1905 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 to account for the possibility of efgartigimod administration in the 
participant’s home. This appendix is included in Section 10.11 (Appendix 11) of this protocol. 
System Version: 1.0, Status: Approved, Document ID: VV-TMF-86295

Clinical Trial Protocol ARGX-113-1905 v3.0 
 
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Signature of Sponsor 
 
Protocol Title:  
An Open-Label, Multicenter, Follow-up Trial of ARGX-113-1904 to 
Evaluate the Safety, Tolerability, and Efficacy of Efgartigimod PH20 
SC in Patients With Pemphigus (ADDRESS+) 
 
Protocol Number:  
ARGX-113-1905 
Acronym:  
ADDRESS+ 
Sponsor Representative:  
 
 
 
 
, MD, PhD 
Chief Medical Officer 
 
Date 
 
 
 
 
System Version: 1.0, Status: Approved, Document ID: VV-TMF-86295

Clinical Trial Protocol ARGX-113-1905 v3.0 
 
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SIGNATURE OF INVESTIGATOR 
PROTOCOL TITLE: 
An Open-Label, Multicenter, Follow-up Trial of ARGX-113-1904 
to Evaluate the Safety, Tolerability, and Efficacy of Efgartigimod 
PH20 SC in Patients With Pemphigus (ADDRESS+) 
PROTOCOL NO: 
ARGX-113-1905 
  
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 designated contract research 
organization (CRO). 
 
I have read this protocol in its entirety and agree to conduct the trial accordingly: 
 
Signature of Investigator: 
 
Date: 
 
Printed Name: 
 
 
 
Investigator Title: 
 
 
 
Name/Address of Site: 
 
 
 
 
 
 
 
 
 
 
 
System Version: 1.0, Status: Approved, Document ID: VV-TMF-86295

Clinical Trial Protocol ARGX-113-1905 v3.0 
 
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PROTOCOL AMENDMENT SUMMARY OF CHANGES 
DOCUMENT HISTORY 
Document 
Date of Issue 
Protocol Version 3.0 (v3.0), Amendment 2 
05 Sep 2022 
Protocol Version 2.0 (v2.0), Amendment 1 
05 Feb 2021 
Protocol Version 1.0 (v1.0) 
12 Aug 2020 
 
Amendment 2 (05 Sep 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 major changes from v2.0 to v3.0 of this protocol are summarized in the following table. 
Note that several of the identified changes were previously defined in an administrative letter 
for the protocol. Text that is formatted with a strikethrough line identifies protocol content that 
has been deleted, while text that is formatted in boldfaced italics identifies content that has been 
added. Minor editorial changes—including the correction of typographical errors, formatting 
inconsistencies, and wording choices—are not summarized in this table.   
Summary of Changes Between Protocol Version 2.0 and Protocol Version 3.0 
Section 
Description of Change 
Brief Rationale 
Sponsor’s Medical Contact 
, MD, PhD is now the 
sponsor’s medical contact for this study. 
Updated to reflect the 
sponsor’s current medical 
contact 
Signature of Sponsor 
, MD, PhD is now the 
sponsor signatory for this protocol. 
Updated to reflect the 
sponsor’s current chief 
medical officer 
1.1. Synopsis 
The upper limit of participants who can 
enter the trial (“up to 150”) has been 
deleted. 
Removed because the 
antecedent study 
ARGX-113-1904 has 
reopened enrollment, and 
participants who complete 
this study will be invited 
to roll over into 
ARGX-113-1905. Thus, 
the total number of 
participants may exceed 
150. 
3. OBJECTIVES AND ENDPOINTS 
Other sections impacted by this change: 
1.1. Synopsis 
“Anti-drug antibodies (ADA) to 
efgartigimod (serum levels)” 
was updated to: 
Updated for accuracy 
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Section 
Description of Change 
Brief Rationale 
“Incidence and prevalence of antidrug 
antibodies (ADA) against efgartigimod 
(serum levels)” 
4.1. Overall Design 
Other sections impacted by this change: 
1.1. Synopsis 
Section 1.3., Table 1 and Table 2: 
Schedule of Activities 
6.5.1. Concomitant Pemphigus Therapy 
Appendix 11, Table 8 and Table 9: 
Modified Schedule of Activities During 
COVID-19 Pandemic 
Item 1 in the list of clinical status 
categories at the end-of-study (EoS) of 
ARGX-113-1904 has been revised to 
“…CRmin or CRoff and are currently 
not in flare will be observed every 4 
weeks….” 
Revised to provide clear 
directives to investigators 
and site personnel about 
this group of participants 
who enter ARGX-113-
1905 
4.1. Overall Design 
Other sections impacted by this change: 
1.1. Synopsis 
6.5.1. Concomitant Pemphigus Therapy 
Item 4 in the list of clinical status 
categories at the EoS of ARGX-113-1904 
has been revised to “…absence of DC 
with oral prednisone 1.5 mg/kg/day for 
a minimum of 3 weeks, participants 
who roll over due to prednisone-related 
SAE who have not achieved DC, or 
flare between DC and achieving CRmin 
that is not controlled by 2 dose levels of 
OCS above the dose….” 
Revised to provide clear 
directives to investigators 
and site personnel about 
this group of participants 
who enter ARGX-113-
1905 
4.1. Overall Design 
Other sections impacted by this change: 
1.1. Synopsis 
6.5.1. Concomitant Pemphigus Therapy 
The instructions for tapering oral 
prednisone doses were clarified for: (1) 
participants who achieve DC with oral 
prednisone doses ≤0.5 mg/kg qd; (2) 
participants who achieve DC with oral 
prednisone doses >0.5 mg/kg qd or after 
having their oral prednisone dose 
escalated. 
Modified to provide clear 
instructions to 
investigators and site 
personnel about 
appropriate prednisone 
dose tapering based on 
the participant’s dose at 
the time they achieve DC 
4.1. Overall Design 
Other sections impacted by this change 
1.1. Synopsis 
4.2. Scientific Rationale for Trial Design 
6.5.1. Concomitant Pemphigus Therapy 
10.9. Appendix 9: Definition of Terms 
A note has been added to clarify that, 
when 10 mg/day oral prednisone is 
reached in ARGX-113-1904 or ARGX-
113-1905, this dose level must be 
maintained for 8 weeks until CRmin has 
been achieved. 
Modified to clarify the 
definition/characterization 
of CRmin in the study 
Section 1.3., Table 1: Schedule of 
Activities  
Other sections impacted by this change: 
8. TRIAL ASSESSMENTS AND 
PROCEDURES 
Appendix 11, Table 8: Modified 
Schedule of Activities During 
COVID-19 Pandemic 
• The time point for the EoT visit has 
been corrected. 
• The timing of visits and sample 
collection has been clarified 
(Section 8 and Tables 1 and 8, 
footnotes g, l, and n).  
Incorporated changes 
from an administrative 
letter dated 28 Oct 2021  
Section 1.3., Table 1 and Table 2: 
Schedule of Activities  
Other sections impacted by this change: 
8. TRIAL ASSESSMENTS AND 
The assessments to be performed during 
an unscheduled visit in case of new 
lesions, flare, AEs, or other safety 
reasons have been clarified. 
Revised for accuracy 
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Section 
Description of Change 
Brief Rationale 
PROCEDURES 
Appendix 11, Table 8 and Table 9: 
Modified Schedule of Activities During 
COVID-19 Pandemic 
A new table (Table 5) has been added in 
Section 8. TRIAL ASSESSMENTS 
AND PROCEDURES to outline the 
assessments to be performed during an 
unscheduled visit. 
Section 1.3., Table 1: Schedule of 
Activities  
Other sections impacted by this change: 
Appendix 11, Table 8: Modified 
Schedule of Activities During 
COVID-19 Pandemic 
The footnote reference for anti-Dsg-1 
and anti-Dsg-3 antibody assessments 
was removed. These assessments need 
to be performed as indicated in the SoA, 
regardless of whether the participant is 
receiving treatment with efgartigimod 
PH20 SC. 
Corrected for consistency 
Section 1.3., Table 1: Schedule of 
Activities  
Other sections impacted by this change: 
Appendix 11, Table 8: Modified 
Schedule of Activities During 
COVID-19 Pandemic 
Footnotes l and n were clarified to state 
that scheduled PK and PD samples are 
to be taken 4 weeks after CRmin even if 
a participant achieved CRmin in 
ARGX-113-1904. Similarly, blood 
samples for immunogenicity are to be 
taken 4 and 8 weeks after CRmin even if 
a participant achieved CRmin during 
ARGX-113-1904. 
Revised for accuracy 
Section 1.3., Table 1 and Table 2: 
Schedule of Activities  
Other sections impacted by this change: 
8.8.2. Immunological Profiling 
Appendix 11, Table 8 and Table 9: 
Modified Schedule of Activities During 
COVID-19 Pandemic 
The timing of samples for lymphocyte 
populations were updated for long-term 
immunological profiling. Samples will 
be taken at selected sites only: Sample 
collection is optional at on-site visits at 
W13 (±2 weeks), W26 (±2 weeks), W39 
(±2 weeks), W52 (±2 weeks) or 
EoT/ET, and EoS, and it is mandatory at 
on-site visits at W52 (±2 weeks) or 
EoT/ET and EoS for participants in 
CRmin or CRoff. 
Updated to obtain long-
term immunological 
profiling samples from 
participants in CRmin and 
CRoff  
Section 1.3., Table 1 and Table 2: 
Schedule of Activities  
Other sections impacted by this change: 
Appendix 11, Table 8 and Table 9: 
Modified Schedule of Activities During 
COVID-19 Pandemic 
An X was added in the column 
‘lymphocyte populations’ at V1 (at 
rollover) in line with other assessments 
scheduled at rollover and listed in the 
ARGX-113-1904 protocol at EoS/ED 
visit. 
Added for accuracy 
Section 1.3., Table 2: Schedule of 
Activities 
Other sections impacted by this change: 
Appendix 11, Table 9: Modified 
Schedule of Activities During 
COVID-19 Pandemic 
• Footnotes l and r were adjusted to 
refer to the EoS visit (instead of 
W60), because some participants will 
complete the study at W56. 
• Footnote m was modified to specify 
the timing of pregnancy tests: “A 
urine pregnancy test will be performed 
locally and at least once every 4 
weeks, at CR, and as of CR again 
every 4 weeks at on-site visits.”  
Revised for accuracy 
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Section 
Description of Change 
Brief Rationale 
Section 1.3., Table 2: Schedule 
of Activities 
Other sections impacted by this change: 
8. TRIAL ASSESSMENTS AND 
PROCEDURES 
Appendix 11, Table 9: Modified 
Schedule of Activities During 
COVID-19 Pandemic  
• An X was added in the column ‘On-
site visits every 4 weeks until W52 – 
After CRmin until W52’ for PK 
samples, which should also be taken 
4 weeks after CRmin (or at the next 
on-site visit), per footnote o. 
• The immunogenicity sampling 
adheres to footnote q; thus, “every 2 
weeks” was deleted in the table. 
• Footnotes b and c were modified to 
provide additional clarification about 
when the participant can begin 
receiving IMP at home visits. 
• Footnotes l, o, q, r, and s were revised 
to clarify the timing of visits and 
sample collection. 
• Footnote l was added in the row 
heading for Vaccination antibodies 
Incorporated changes 
from an administrative 
letter issued 28 Oct 2021 
2.3.1.Risk Assessment 
Other sections impacted by this change: 
2.3.2. Benefit Assessment 
8.4.8. Adverse Events of Special Interest 
The summary of the phase 2 study 
ARGX-113-1701 data was updated 
based on the final CSR.  
Updated based on a newly 
available final CSR for 
ARGX‑113‑1701 
5.1. Inclusion Criteria 
 
3A.i: 
Male participants must agree to use an 
acceptable method of contraception 
(as described in Section 10.4.2.2) and 
not donate sperm from signing the 
informed consent form (ICF) until the 
endlast dose of the studystudy drug. 
Guidance on 
contraception and sperm 
donation has been 
updated based on results 
from nonclinical 
reproductive toxicity 
studies 
5.1. Inclusion Criteria 
Other sections impacted by this change: 
Appendix 4: Section 10.4.2.1. Female 
Contraception for Women of 
Childbearing Potential 
3A.ii.  
• agree to use a highly effective or 
acceptable contraception method (as 
described in Section 10.4.2.1), which 
should be maintained at minimum 
until 90 days after the last dose of 
IMP 
Women of childbearing potential 
(WOCBP) must use a highly effective or 
acceptable contraception method, which 
should be maintained at minimum until 
90 days after the last dose of IMP. 
5.2. Exclusion Criteria 
Other sections impacted by this change: 
Appendix 4: Section 10.4.3. Collection 
of Pregnancy Information 
1A. Pregnant and lactating women and 
those intending to become pregnant 
during the trial or within 90 days 
after the last administration of IMP. 
Male participants will be instructed by 
the ICF to immediately inform the 
investigator if their partner becomes 
pregnant during the trial or up to 90 days 
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Section 
Description of Change 
Brief Rationale 
after they received the last dose of study 
drug. 
The investigator will collect pregnancy 
information on any female participant 
who becomes pregnant during the 
period of administration of IMP and up 
to 90 days after the participant received 
the last IMP. 
5.1. Inclusion Criteria 
The reference to a serum pregnancy test 
at screening was removed from 
inclusion criterion 3A.ii. 
Revised for accuracy 
(Screening is not 
applicable in this study.) 
6.2. Preparation/Handling/Storage/ 
Accountability 
Other sections impacted by this change: 
1.1. Synopsis 
4.1. Overall Design 
6.5.1. Concomitant Pemphigus Therapy 
Clarifications were added to indicate 
that more detail regarding the proper 
transport, storage, preparation, and 
administration of IMP is provided in the 
home guide.  
Modified to provide 
additional information 
about the IMP home 
guide 
8. TRIAL ASSESSMENTS AND 
PROCEDURES: Treatment Period 
The fourth paragraph of this section was 
revised to clarify the minimum duration 
that participants who had treatment 
failure during ARGX-113-1904 or flare 
after CRmin must continue on-site visits 
before they are permitted to begin home 
visits. 
Revised to provide clear 
directives to investigators 
and site personnel about 
scheduling home visits 
for these groups of 
participants 
8.3.8. Injection Site Reactions 
Injection site reactions (ISRs) will be 
monitored throughout the study. 
Section 8.3.8. Injection Site Reactions, 
includes information about ISRs 
observed during studies with 
efgartigimod PH20 SC. The following 
specific instructions for monitoring 
ISRs were added: 
An injection site reaction is any AE 
developing at the injection site. 
Localized injection site reactions are 
frequently observed in studies in which 
efgartigimod is comixed with rHuPH20 
and administered SC. The most 
frequently reported injection site 
reaction AEs are injection site 
erythema, injection site pain, and 
injection site swelling. Most are 
nonserious and mild (CTCAE grade 1) 
and do not lead to disruption in IMP 
administration.  
Any injection site reaction will be 
reported as an AE (Section 10.3.3). 
Certain types of local reactions could 
Updated for alignment 
across efgartigimod 
PH20 SC open-label 
extension study protocols 
regarding the monitoring 
of ISRs 
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Section 
Description of Change 
Brief Rationale 
be photographed and shared with the 
sponsor for review and assessment.  
As a routine precaution, participants 
should be trained or observed closely 
by a trained health care professional 
for any potential injection site reaction. 
8.4.1. Time Period and Frequency for 
Collecting AE and SAE Information 
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 10.3.3 and 
Section 10.3.4. 
Revised for accuracy and 
to clarify how and when 
AESIs must be reported 
(within 24 hours) 
Appendix 3: Section 10.3.4. Reporting of 
SAEs and AESIs 
 
The following text: 
All SAEs will be recorded on the paper 
SAE report form and the AE form on 
the eCRF. The investigator or 
designated site staff should check that 
all entered data are consistent. An alert 
email for the SAE report in the eCRF 
will then automatically be sent by email 
to the sponsor’s designated CRO safety 
mailbox via the EDC system. The paper 
SAE report form should be faxed or 
emailed to the sponsor’s designated 
CRO (see Safety Mailbox/Fax details on 
the title page of this protocol). 
Has been replaced with: 
• 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’s/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 Safety 
Mailbox/Fax details on page 2 of this 
protocol). 
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Section 
Description of Change 
Brief Rationale 
8.4.8. Adverse Events of Special Interest 
The text and Table 6 of this section have 
been updated to include the final results 
from ARGX-113-1701. The section 
previously included interim results from 
ARGX-113-1701. 
Updated to provide the 
results from the final 
ARGX-113-1701 CSR 
8.6. Pharmacodynamics 
The second paragraph of this section 
now includes the following sentence: 
IgG subtype analyses may be limited to 
a representative portion of study 
participants. 
Updated to account for 
the possibility that an 
upper limit will be placed 
on these analyses 
8.7. Immunogenicity 
The second paragraph of this section has 
been revised to provide specific details 
about the 3-tiered approach that is used 
for immunogenicity analysis. 
Revised following 
consultation with the 
sponsor’s Bioanalytics 
department 
10.2. Appendix 2: Table 7: Protocol-
Required Laboratory Assessments 
Other sections impacted by this change 
8.3.6. Clinical Safety Laboratory 
Assessments 
All Schedule of Activities Tables (ie, 
Tables 1, 2, 8, and 9) 
The urinalysis assessments that will be 
assessed and the relevant footnotes in all 
SoAs have been updated. 
Revised to eliminate 
urinalysis parameters that 
are not required 
Appendix 3: Section 10.3.4. Reporting of 
SAEs and AESIs 
Revised to update the SAE and AESI 
information that must be reported via 
the eDC system. 
Updated to include 
current requirements for 
data entry on the eDC 
system 
10.5. Appendix 5: Administrative 
Structure 
Information was updated for several 
contract research organizations that are 
performing analytical, sample storage, 
and data storage services for this study. 
Updated to reflect current 
information 
10.11. Appendix 11: Possible 
Adaptations of Trial Protocol During 
COVID-19 Pandemic: Mandatory Site 
Visits and Allowed Home Visits 
Instructions were added about vital sign 
measurements, blood/urine collection, 
and IMP administration when a home 
nurse cannot be identified or cannot 
travel to a participant’s home for a home 
visit. 
Revised for accuracy 
 
 
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TABLE OF CONTENTS 
SIGNATURE OF INVESTIGATOR ..............................................................................................5 
PROTOCOL AMENDMENT SUMMARY OF CHANGES ..........................................................6 
1. 
PROTOCOL SUMMARY ..........................................................................................19 
1.1. 
Synopsis ......................................................................................................................19 
1.2. 
Schema ........................................................................................................................27 
1.3. 
Schedule of Activities .................................................................................................28 
2. 
INTRODUCTION ......................................................................................................37 
2.1. 
Trial Rationale ............................................................................................................37 
2.2. 
Background .................................................................................................................38 
2.3. 
Benefit/Risk Assessment ............................................................................................41 
2.3.1. 
Risk Assessment .........................................................................................................41 
2.3.2. 
Benefit Assessment .....................................................................................................43 
2.3.3. 
Overall Benefit: Risk Conclusion ...............................................................................44 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................45 
4. 
TRIAL DESIGN .........................................................................................................47 
4.1. 
Overall Design ............................................................................................................47 
4.2. 
Scientific Rationale for Trial Design ..........................................................................50 
4.3. 
Justification for Dose ..................................................................................................51 
4.4. 
End of Study Definition ..............................................................................................52 
5. 
TRIAL POPULATION ..............................................................................................53 
5.1. 
Inclusion Criteria ........................................................................................................53 
5.2. 
Exclusion Criteria .......................................................................................................54 
5.3. 
Lifestyle Considerations .............................................................................................54 
5.4. 
Screen Failures ............................................................................................................54 
6. 
TRIAL INTERVENTION ..........................................................................................55 
6.1. 
Trial Intervention(s) Administered .............................................................................55 
6.2. 
Preparation/Handling/Storage/Accountability ............................................................57 
6.2.1. 
Preparation ..................................................................................................................57 
6.2.2. 
Handling .....................................................................................................................57 
6.2.3. 
Storage ........................................................................................................................57 
6.2.4. 
Accountability .............................................................................................................58 
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6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................................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 
6.4.3. 
Treatment of Overdose ...............................................................................................59 
6.5. 
Concomitant Therapy .................................................................................................59 
6.5.1. 
Concomitant Pemphigus Therapy ...............................................................................60 
6.5.2. 
Prohibited Medications and Therapy During the Trial ...............................................64 
6.6. 
Dose Modification ......................................................................................................64 
6.7. 
Intervention After the End of 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 .................................................................................................69 
8.3. 
Safety Assessments .....................................................................................................69 
8.3.1. 
Physical Examinations ................................................................................................70 
8.3.2. 
Height and Weight ......................................................................................................70 
8.3.3. 
Vital Signs ..................................................................................................................70 
8.3.4. 
Electrocardiography ....................................................................................................70 
8.3.5. 
Medical and Surgical History .....................................................................................71 
8.3.6. 
Clinical Safety Laboratory Assessments ....................................................................71 
8.3.6.1. 
Vaccination Antibodies Testing .................................................................................72 
8.3.6.2. 
Storage of Blood Samples in the Trial ........................................................................72 
8.3.7. 
Infections and Vaccinations ........................................................................................72 
8.3.8. 
Injection-site Reactions ..............................................................................................73 
8.3.9. 
Suicidal Ideation and Behavior Risk Monitoring .......................................................73 
8.3.10. 
Additional Safety Assessment ....................................................................................73 
8.4. 
Adverse Events and Serious Adverse Events .............................................................74 
8.4.1. 
Time Period and Frequency for Collecting AE and SAE Information .......................75 
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8.4.2. 
Method of Detecting AEs and SAEs ..........................................................................75 
8.4.3. 
Reporting of AEs and SAEs .......................................................................................75 
8.4.4. 
Follow-up of AEs and SAEs .......................................................................................76 
8.4.5. 
Regulatory Reporting Requirements for SAEs ...........................................................77 
8.4.6. 
Pregnancy ...................................................................................................................77 
8.4.7. 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying 
as Reportable AEs or SAEs for the Trial ....................................................................78 
8.4.8. 
Adverse Events of Special Interest .............................................................................78 
8.4.9. 
Infusion-Related Reactions .........................................................................................79 
8.4.10. 
Injection Site Reactions ..............................................................................................79 
8.5. 
Pharmacokinetics ........................................................................................................79 
8.6. 
Pharmacodynamics .....................................................................................................80 
8.7. 
Immunogenicity Assessments ....................................................................................80 
8.8. 
Exploratory Research ..................................................................................................80 
8.8.1. 
IgG Autoantibody Subtype and Specificity Study ......................................................80 
8.8.2. 
Immunological Profiling .............................................................................................81 
8.9. 
Imaging .......................................................................................................................81 
8.10. 
Medical Resource Utilization and Health Economics ................................................81 
8.11. 
Quality of Life and Patient-Reported Outcomes ........................................................81 
9. 
STATISTICAL CONSIDERATIONS .......................................................................83 
9.1. 
Statistical Methods ......................................................................................................83 
9.1.1. 
Statistical Methods and Plan .......................................................................................83 
9.1.2. 
Safety (Primary Endpoints) ........................................................................................83 
9.1.3. 
Secondary Endpoints ..................................................................................................83 
9.1.4. 
Pharmacodynamics, Pharmacokinetics, and Immunogenicity ...................................84 
9.2. 
Statistical Hypotheses .................................................................................................84 
9.3. 
Sample Size Determination ........................................................................................84 
9.4. 
Populations for Analysis .............................................................................................85 
9.5. 
Statistical Analyses .....................................................................................................85 
9.5.1. 
General Considerations ...............................................................................................85 
9.5.2. 
Participant Disposition ................................................................................................85 
9.5.3. 
Analysis Sets and Protocol Deviations .......................................................................85 
9.5.4. 
Demographic and Baseline Characteristics, and Concomitant Medication ................86 
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9.5.5. 
Primary Endpoint(s) ....................................................................................................86 
9.5.6. 
Secondary Endpoints ..................................................................................................86 
9.5.7. 
Other Endpoints ..........................................................................................................86 
9.5.8. 
Missing Data Handling ...............................................................................................86 
9.6. 
Interim Analyses .........................................................................................................87 
9.7. 
Data Safety Monitoring Board ....................................................................................87 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................88 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations ....................88 
10.1.1. 
Regulatory and Ethical Considerations ......................................................................88 
10.1.2. 
Financial Disclosure ...................................................................................................88 
10.1.3. 
Informed Consent Process ..........................................................................................89 
10.1.4. 
Data Protection ...........................................................................................................90 
10.1.5. 
Committees Structure .................................................................................................90 
10.1.5.1. 
Data Safety Monitoring Board ....................................................................................90 
10.1.6. 
Dissemination of Clinical Study Data ........................................................................91 
10.1.7. 
Data Quality Assurance ..............................................................................................91 
10.1.7.1. 
Data Handling and Record Keeping ...........................................................................92 
10.1.7.2. 
Quality Assurance Audit .............................................................................................92 
10.1.7.3. 
Quality Control ...........................................................................................................92 
10.1.8. 
Source Documents ......................................................................................................93 
10.1.9. 
Monitoring ..................................................................................................................94 
10.1.10. 
Data Management .......................................................................................................94 
10.1.11. 
Study and Site Start and Closure ................................................................................96 
10.1.12. 
Investigator Obligations ..............................................................................................96 
10.1.13. 
Protocol Signatures .....................................................................................................97 
10.1.14. 
Publication Policy .......................................................................................................97 
10.2. 
Appendix 2: Laboratory Tests ....................................................................................98 
10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ........................................................................99 
10.3.1. 
Definition of AE .........................................................................................................99 
10.3.2. 
Definition of SAE .....................................................................................................100 
10.3.3. 
Recording and Follow-Up of AE and/or SAE ..........................................................101 
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10.3.4. 
Reporting of SAEs and AESIs ..................................................................................103 
10.4. 
Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information ...............................................................................................................104 
10.4.1. 
Definitions ................................................................................................................104 
10.4.1.1. 
Woman of Childbearing Potential ............................................................................104 
10.4.2. 
Contraception Guidance ...........................................................................................104 
10.4.2.1. 
Female Contraception for Women of Childbearing Potential ..................................104 
10.4.2.2. 
Male Contraception ..................................................................................................105 
10.4.3. 
Collection of Pregnancy Information .......................................................................105 
10.4.3.1. 
Male Participants With Partners Who Become Pregnant .........................................105 
10.4.3.2. 
Female Participants Who Become Pregnant .............................................................106 
10.5. 
Appendix 5: Administrative Structure ......................................................................107 
10.6. 
Appendix 6: Pemphigus Disease Area Index (PDAI) Scoring System ....................108 
10.7. 
Appendix 7: EQ-5D-5L Scale ..................................................................................109 
10.8. 
Appendix 8: Autoimmune Bullous Disease Quality of Life (ABQOL) 
Questionnaire ............................................................................................................111 
10.9. 
Appendix 9: Definition of Terms .............................................................................114 
10.10. 
Appendix 10: Abbreviations .....................................................................................117 
10.11. 
Appendix 11: Possible Adaptations of Trial Protocol During COVID19 
Pandemic ...................................................................................................................120 
10.12. 
Appendix 12: Glucocorticoid Toxicity Index (GTI) ................................................136 
11. 
REFERENCES .........................................................................................................146 
 
LIST OF TABLES 
Table 1: 
Schedule of Activities for ARGX-113-1905 for Participants in CR, CR on 
Minimal Therapy, and CR off Therapy at Rollover From ARGX-113-1904 .............28 
Table 2: 
Schedule of Activities for ARGX-113-1905 for Participants Not in CR at 
Rollover From ARGX-113-1904, or Participants Experiencing Flare after 
CRmin or CRoff in ARGX-113-1905 ........................................................................32 
Table 3: 
Trial Interventions ......................................................................................................56 
Table 4: 
Concomitant Prednisone Equivalent Doses (in mg) by Body Weight .......................63 
Table 5: 
Assessments to be Performed During an Unscheduled Visita ....................................68 
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Table 6: 
ARGX-113-1701 Summary of Treatment-emergent Adverse Events in the 
Infections and Infestations System Organ Class by Preferred Term – Safety 
Analysis Set ................................................................................................................78 
Table 7:   Protocol-Required Laboratory Assessments...............................................................98 
Table 8: 
Modified Schedule of Activities During COVID-19 Pandemic for ARGX-
113-1905 for Participants in CR, CR on Minimal Therapy, and CR off 
Therapy at Rollover From ARGX-113-1904 ...........................................................127 
Table 9: 
Modified Schedule of Activities During COVID-19 Pandemic for ARGX-
113-1905 for Participants Not in CR at Rollover From ARGX-113-1904, or 
Participants Experiencing Flare after CRmin or CRoff in ARGX-113-1905 ...........131 
Table 10: Approach to Calculating the Baseline GTI 2.0 Score: Toxicities Assigned 
Weighted Scores from the C-GTI to Establish a Baseline GTI Score ......................136 
Table 11: Approach to Calculating the Changes in GTI 2.0 Score: Weighted Scores 
Assigned to Improvements or Worsenings in the C-GTI .........................................137 
Table 12: GTI 2.0 Specific List: 11 Domains (9 of Which are Shared by the C-GTI) 
and 23 Unique Items .................................................................................................138 
Table 13: Severity Categorization of Skin Manifestations by Grade .......................................140 
Table 14: Severity Categorization of Neuropsychiatric Manifestations by Grade ...................141 
 
LIST OF FIGURES 
Figure 1: 
ARGX-113-1905 Trial Design ...................................................................................27 
Figure 2: 
Impact of COVID-19 Pandemic on argenx BV Clinical Trials ................................122 
 
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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title:  
An Open-Label, Multicenter, Follow-up Trial of ARGX-113-1904 to Evaluate the Safety, 
Tolerability, and Efficacy of Efgartigimod PH20 SC in Patients With Pemphigus (ADDRESS+) 
Brief Title: 
Open-label follow-up trial of ARGX-113-1904 
Indication: 
Pemphigus 
Trial Sites/Countries: 
Global, multicenter trial using the same sites and countries as the antecedent trial 
ARGX-113-1904 
Target Population:  
Adult patients with moderate to severe pemphigus vulgaris (PV) or pemphigus foliaceus (PF) 
who participated in ARGX-113-1904 and roll over to ARGX-113-1905 
Investigational Medicinal Product (IMP), Dose, and Mode of Administration:   
Efgartigimod PH20 SC will be administered either weekly 1000 mg or
 mg on 
 and 
 followed by weekly 1000 mg with treatment being stopped upon achieving complete 
remission on minimal therapy (CRmin).  
Rationale: 
Pemphigus is a chronic disease and patients under treatment experience intermittent episodes of 
clinical remission and flare. The mainstays of therapy in PV are systemic corticosteroids and 
rituximab. Corticosteroids rapidly affect PV symptoms (3 to 4 weeks), but must be administered 
at high daily doses (eg, oral prednisone 1 to 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 possible dosage, by tapering gradually while 
keeping the disease in remission, is the therapeutic goal. Recently, rituximab has been approved 
by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) for 
the treatment of pemphigus in adults with moderate to severe PV. When administered as 
adjunctive treatment to a short course of prednisone, rituximab, while having a relatively late 
onset of action, has been 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 rituximab 
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intravenous (IV) frequently results in infusion-related reactions (IRRs) and adverse events (AEs), 
which may be of late onset.  
An innovative drug is needed for the treatment of PV and PF that has a fast onset of action (eg, 
early disease control [DC, defined as the absence of new lesions and the start of healing of 
established lesions], complete clinical remission [CR, defined as the absence of new lesions and 
complete healing of established lesions] within weeks), a strong prednisone sparing effect, and a 
favorable safety profile. 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. 
The antecedent trial ARGX-113-1904 intends to demonstrate that efgartigimod PH20 SC with an 
add-on therapy of oral prednisone at low doses would be a possible treatment modality for PV 
and PF that could lead to early disease remission at minimal prednisone dose. This trial has a 
treatment period of up to 30 weeks and provides a tailored dose regimen for participants by 
stopping investigational medicinal product (IMP) administration upon achieving CRmin (defined 
as the absence of new lesions and complete healing of established lesions while the participant 
receives minimal prednisone therapy of ≤10 mg/day for at least 2 months [8 weeks]). Note: when 
10 mg/day is reached in ARGX-113-1904 or ARGX-113-1905, this dose level must be maintained 
for 8 weeks until CRmin has been achieved. 
This trial provides extension of efgartigimod PH20 SC treatment and retreatment options 
for participants who have been randomized to the efgartigimod PH20 SC treatment arm in 
ARGX-113-1904, and the first treatment of efgartigimod PH20 SC and retreatment options 
for participants who had been randomized to the placebo arm in ARGX-113-1904. 
At the blinded rollover from ARGX-113-1904 into ARGX-113-1905, participants may be in 
different clinical stages of treatment. Participants may have achieved CRmin, participants may 
have achieved CR without meeting the minimal therapy criterion, participants may have 
achieved DC or 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) without having achieved 
CR, participants may have had treatment failure or a flare after having achieved CRmin. 
ARGX-113-1905 evaluates the ability to (further) taper prednisone therapy and achieve CR off 
therapy (CRoff), the ability to achieve CR and CRmin for participants who have not yet achieved 
CRmin, and the ability to treat flare; and assesses patient outcome measures and the safety, PD, 
PK, and immunogenicity of efgartigimod PH20 SC over the duration of the trial.  
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Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
• 
To assess the safety of treatment, extended 
treatment, and retreatment with 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 sign measurements, physical 
examinations, electrocardiograms (ECGs), 
and clinical laboratory safety evaluations  
Secondary 
• 
To evaluate the efficacy of efgartigimod 
PH20 SC treatment in PV and PF 
• 
Proportion of PV participants who achieve 
CRmin  
• 
Proportion of PV and PF participants who 
achieve CRmin  
• 
Time to DC 
• 
Time to CR 
• 
Time to CRmin  
• 
Time to CRoff 
• 
Time to flare 
• 
Rate of treatment failure 
• 
Rate of flare 
• 
Cumulative prednisone dose over the trial  
• 
Pemphigus Disease Area Index (PDAI) at 
each visit 
• 
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) 
score 
• 
Autoimmune Bullous Disease Quality of Life 
(ABQOL) score  
• 
To evaluate the pharmacokinetics (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 
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Objectives 
Endpoints 
• 
Anti-desmoglein (Dsg)-1 and -3 
autoantibodies serum levels 
• 
To evaluate the immunogenicity of 
efgartigimod in participants with PV or PF 
• 
Incidence and prevalence of antidrug 
antibodies (ADA) against efgartigimod 
(serum levels)  
• 
To explore feasibility of self-administration of 
efgartigimod PH20 SC 
• 
Percentage of participants who performed 
self-administration  
• 
Percentage of caregivers who administered 
the injection to the participant  
• 
Number of visits needed for the participant or 
caregiver to be competent to start 
administering efgartigimod PH20 SC  
• 
Frequency of self- or caregiver-supported 
administration at home 
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 
• 
To evaluate the immunogenicity of rHuPH20 
in participants with PV or PF 
• 
Antibodies produced against recombinant 
human hyaluronidase (rHuPH20) (plasma 
levels) 
Overall Design 
This is a prospective, multicenter, open-label extension (OLE) trial on the efficacy, safety, 
patient outcome measures, tolerability, immunogenicity, PK, and PD of efgartigimod PH20 SC 
in adult PV or PF participants, who participated in the antecedent trial ARGX-113-1904.  
Participants at the end of study (EoS) visit or early discontinuation (ED) visit in 
ARGX-113-1904 will be given the option to enroll into ARGX-113-1905 after confirmation of 
eligibility while retaining the blinding of ARGX-113-1904. For each participant, the date of the 
baseline visit in ARGX-113-1905 will be the same as the date of the EoS/ED visit in ARGX-
113-1904. 
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At baseline, participants will be treated according to their clinical status at EoS 
of ARGX-113-1904, as follows: 
1. Participants who have achieved CRmin or CRoff and are currently not in flare will be 
observed every 4 weeks through on-site visits without efgartigimod PH20 SC treatment. 
In participants who have achieved CRmin (oral prednisone ≤10 mg per day for 2 months 
[8 weeks]), prednisone tapering may be pursued upon investigator’s judgment until 
participants achieve CRoff. 
2. Participants in CR who have not achieved CRmin will receive weekly efgartigimod PH20 
SC administrations of 1000 mg while continuing the add-on therapy of oral prednisone 
until CRmin is achieved. Prednisone tapering may be pursued upon investigator's 
judgment until participants achieve CRoff. Participants will be treated through on-site 
visits or through home visits with an on-site visit once every 4 weeks. 
3. Participants who have achieved DC but not CR will receive weekly on-site 
administrations of 1000 mg efgartigimod PH20 SC with an add-on therapy of oral 
prednisone (Table 4) until CR has been achieved, and then will continue to receive 
weekly efgartigimod PH20 SC administrations of 1000 mg until CRmin is achieved 
either on site or through home visits with an on-site visit once every 4 weeks. 
4. Participants under certain conditions of treatment failure as defined below or participants 
with flare after having achieved CRmin, may roll over prematurely into ARGX-113-1905 
and will be treated with efgartigimod PH20 SC at a dose of 
mg on 
 and 
 
followed by weekly administrations of 1000 mg with an add-on therapy of oral 
prednisone until CRmin.  
The following types of treatment failure are considered here: 
• absence of DC with oral prednisone 1.5 mg/kg/day for a minimum of 3 weeks 
• participants who roll over due to prednisone-related SAE who have not achieved DC, 
or 
• flare between DC and achieving CRmin that is not controlled by 2 dose levels of OCS 
above the dose at which the flare is observed and that is at least 0.3 mg/kg/day 
(Table 4) 
In the absence of DC, participants will receive prednisone at the starting dose of 
1.5 mg/kg/day. In case of uncontrolled flare before CRmin, participants will receive, as 
starting dose, the last dose from ARGX-113-1904. In case of flare after CRmin, 
participants will receive a prednisone dose in line with the severity of the flare, with the 
recommendation of a minimum of 0.3 mg/kg/day when the flare is of mild severity 
(PDAI activity score <15) and of 0.5 mg/kg/day when the flare is moderate to severe 
(PDAI activity score ≥15). Dosing of efgartigimod PH20 SC will be done during on-site 
visits or home visits according to the Schedule of Activities (SoA) in Table 2.   
5. Participants who developed a prednisone-related SAE may prematurely roll over into 
ARGX-113-1905 and may be treated with efgartigimod PH20 SC through on-site or 
home visits according to the clinical statuses as described above. Concomitant prednisone 
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will be considered to fit the clinical statuses as described above if compatible with the 
nature and severity of the SAE, with a lower dose to no concomitant prednisone being 
considered otherwise.    
Participants or their caregivers (a person of legal age that the participant proposes to perform the 
administrations) may also self-administer efgartigimod PH20 SC after they have successfully 
completed self-administration training (in ARGX-113-1904 with at least 1 refresher training 
in ARGX-113-1905 or during ARGX-113-1905). All participants and/or their caregivers will 
receive a home guide for transport, storage, preparation, and administration of the IMP. 
At any postbaseline 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 (Table 4) 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 postbaseline visit before DC 
• Insufficient clinical change: the absence of DC after 3 to 4 weeks of the participant 
being treated at the starting baseline prednisone 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 
If DC is not attained after a minimum of 3 weeks of the participant receiving oral prednisone 
1.5 mg/kg qd, then the participant will be considered a treatment failure and will be withdrawn 
from the trial. 
For participants who achieve DC at a starting dose of 0.5 mg/kg qd or lower, the prednisone dose 
will be maintained at that starting dose qd until CR and 2 weeks thereafter, or EoC 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), that dose will be maintained until 2 weeks after achieving 
DC and then will be tapered (Table 4) in increments of 0.25 mg/kg every 2 weeks until the 
starting dose is achieved. This starting dose 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 4 weeks. Further tapering will be performed 
thereafter, as long as CR or EoC are sustained. 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 for at least 8 
weeks until CRmin is achieved. The prednisone dose can then be further tapered to reach CRoff 
according to the clinical judgment of the investigator. 
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At visits when at least 1 new lesion is observed or established lesions remain extensive without 
being defined as a flare (ie, 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), 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.  
In case of flare in the period between DC and CRmin, the prednisone dose will be increased 
to achieve DC again. 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 dose of OCS that is 2 dose levels above the dose at which the flare is 
observed and that is at least 0.3 mg/kg/day (Table 4) will be managed according to clinical 
judgment (ie, either receive a further increased prednisone dose or be withdrawn from the trial). 
Withdrawal of participants with a flare before CRmin will be defined as treatment failure.  
In case of flare after having achieved CRmin (ie, while being off efgartigimod treatment), 
participants will be immediately treated/retreated with a new cycle of efgartigimod PH20 SC. 
The first day of new efgartigimod treatment will define a new baseline for assessments of 
outcomes (DC, CR, etc) and prednisone escalation or tapering schedule.    
In the new treatment cycle, participants will be administered efgartigimod PH20 SC at a weekly 
dose of 
mg for the first  weeks, followed by weekly administrations of 1000 mg until 
CRmin. Oral prednisone will be administered at a dose chosen according to clinical judgment, 
with the recommendation of 0.3 mg/kg qd in the case of mild flare (PDAI activity score <15) and 
0.5 mg/kg qd in the case of moderate to severe flare (PDAI activity score ≥15). The treatment 
goal of a new treatment cycle is to first achieve DC again and therefore these participants will be 
treated accordingly (refer to Table 2 for the corresponding SoA). 
A new treatment cycle of efgartigimod PH20 SC can be initiated in eligible participants until 
week 44. In participants requiring a new treatment cycle of efgartigimod PH20 SC between 
weeks 45 and 49, the initiation will be optional and based on clinical judgment and participant 
consent. A new efgartigimod treatment cycle will not be permitted after week 49 to ensure a 
minimum of 4 weeks of efgartigimod treatment/cycle. 
Except for oral prednisone, no other systemic therapies (eg, immunosuppressants, IVIg, 
immunoadsorption, anti-CD20 biologics) will be permitted during the trial.  
Trial procedures will be performed per the SoA as detailed in Section 1.3 and Section 10.11. 
Disclosure Statement: ARGX-113-1905 is an open-label, multicenter, follow-up trial of 
ARGX-113-1904 to evaluate safety, tolerability, and efficacy of fixed doses of efgartigimod 
PH20 SC in participants with pemphigus. 
Number of Participants: All participants who were randomized into ARGX-113-1904 will be 
eligible to roll over to ARGX-113-1905. 
System Version: 1.0, Status: Approved, Document ID: VV-TMF-86295

Clinical Trial Protocol ARGX-113-1905 v3.0 
 
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Intervention Groups and Duration: Up to 60 weeks for participants who receive IMP 
administrations up to week 52 and with a follow-up period of up to 8 weeks after the last IMP 
administration. 
Data Safety Monitoring Board: Yes (Section 10.1.5.1) 
Definitions: 
• Complete clinical remission (CR): the absence of new lesions and complete healing 
of established lesions (except for postinflammatory 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 at ≤10 mg/day for at least 2 months (8 weeks). Note: when 10 mg/day is 
reached in ARGX-113-1904 or ARGX-113-1905, this dose level must be maintained 
for 8 weeks until CRmin has been achieved. 
• Complete remission off therapy (CRoff): the absence of new and established 
lesions completely healed while the participant is receiving no prednisone therapy 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: an increase of ≥5 points in the PDAI activity score, observed at 
any postbaseline 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: 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. 
• 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 flare will be recorded as new transient or new persistent lesions. Transient new 
lesions are defined as the presence of new lesions that heal within 1 week. Persistent 
new lesions are defined as the presence of new lesions that last more than 1 week. 
• Treatment failure: the absence of DC with oral prednisone 1.5 mg/kg/day for a 
minimum of 3 weeks, or flare before CRmin resulting in withdrawal of the 
participant. 
System Version: 1.0, Status: Approved, Document ID: VV-TMF-86295

Clinical Trial Protocol ARGX-113-1905 v3.0 
 
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1.3. 
Schedule of Activities 
Table 1: 
Schedule of Activities for ARGX-113-1905 for Participants in CR, CR on Minimal Therapy, and CR 
off Therapy at Rollover From ARGX-113-1904 
Trial period 
Open-label extension 
 
 
Follow-up 
Visit number 
V1 
Roll 
overa 
V1 
+ 4 
weeks 
V1   
+ 8 
weeks 
V1   
+ 12 
weeks 
V1   
+ 16 
weeks 
V1   
+ 20 
weeks 
V1    
+ 24 
weeks 
V1   
+ 28 
weeks 
V1   
+ 32 
weeks 
V1   
+ 36 
weeks 
V1   
+ 40 
weeks 
V1   
+ 44 
weeks 
V1   
+ 48 
weeks 
V1  
+ 51 weeks 
EoT/ET 
UNSb 
Safety 
follow-
up 1 
EoT/ET 
+ 4 weeksc 
Safety 
follow-
up 2 
EoT/ET 
+ 8 weeks 
EoSc 
Assessment/procedure 
±0 
days 
±2 daysd 
 
 
±3 
daysd 
±3 
daysd 
Informed consent  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weighte 
X 
 
 
 
 
 
Xe 
 
 
 
 
 
 
X 
 
 
 
ECGf,g 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
X 
 
X 
X 
Physical examination and 
vital signsf,h 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysisf,i 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xb 
X 
X 
Urine pregnancy testf,j 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xb 
X 
X 
Vaccination antibodiesf 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xb 
X 
X 
Blood sampling 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• clinical chemistry 
and hematologyf,k 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xb 
X 
X 
• anti-Dsg-1 and anti-
Dsg-3 antibodies 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xb 
X 
X 
System Version: 1.0, Status: Approved, Document ID: VV-TMF-86295

Clinical Trial Protocol ARGX-113-1905 v3.0 
 
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Efgartigimod PH20 SC 
 
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Trial period 
Open-label extension 
 
 
Follow-up 
Visit number 
V1 
Roll 
overa 
V1 
+ 4 
weeks 
V1   
+ 8 
weeks 
V1   
+ 12 
weeks 
V1   
+ 16 
weeks 
V1   
+ 20 
weeks 
V1    
+ 24 
weeks 
V1   
+ 28 
weeks 
V1   
+ 32 
weeks 
V1   
+ 36 
weeks 
V1   
+ 40 
weeks 
V1   
+ 44 
weeks 
V1   
+ 48 
weeks 
V1  
+ 51 weeks 
EoT/ET 
UNSb 
Safety 
follow-
up 1 
EoT/ET 
+ 4 weeksc 
Safety 
follow-
up 2 
EoT/ET 
+ 8 weeks 
EoSc 
Assessment/procedure 
±0 
days 
±2 daysd 
 
 
±3 
daysd 
±3 
daysd 
• PKl 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xb,m 
X 
X 
• Total IgG and IgG 
subtypesf,l 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xb 
X 
X 
• immunogenicityf,n 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
• IgG autoantibody 
subtypes and 
specificityf 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xb 
X 
X 
PDAIf 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ABQOLf,o 
X 
at CRmin (or the next on-site visit) 
X 
 
 
 
EQ-5D-5Lf,o 
X 
at CRmin (or the next on-site visit) 
X 
 
 
 
Disease assessmentf,p 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Lymphocyte populations 
(at selected sites)q 
X 
 
 
X 
 
 
X 
 
 
 
X 
 
 
X 
 
X 
X 
GTI 
X 
 
 
 
 
 
Xr 
 
 
 
 
 
 
Xr 
 
 
 
IMP self-administration 
trainings 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Efgartigimod PH20 SCt 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Prednisone taperu 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
System Version: 1.0, Status: Approved, Document ID: VV-TMF-86295

Clinical Trial Protocol ARGX-113-1905 v3.0 
 
05 Sep 2022 
Efgartigimod PH20 SC 
 
argenx 
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Trial period 
Open-label extension 
 
 
Follow-up 
Visit number 
V1 
Roll 
overa 
V1 
+ 4 
weeks 
V1   
+ 8 
weeks 
V1   
+ 12 
weeks 
V1   
+ 16 
weeks 
V1   
+ 20 
weeks 
V1    
+ 24 
weeks 
V1   
+ 28 
weeks 
V1   
+ 32 
weeks 
V1   
+ 36 
weeks 
V1   
+ 40 
weeks 
V1   
+ 44 
weeks 
V1   
+ 48 
weeks 
V1  
+ 51 weeks 
EoT/ET 
UNSb 
Safety 
follow-
up 1 
EoT/ET 
+ 4 weeksc 
Safety 
follow-
up 2 
EoT/ET 
+ 8 weeks 
EoSc 
Assessment/procedure 
±0 
days 
±2 daysd 
 
 
±3 
daysd 
±3 
daysd 
Concomitant 
therapies/procedures  
Continuous monitoring 
AE monitoring 
Continuous monitoring 
ABQOL=Autoimmune Bullous Disease Quality of Life; AE=adverse events; ALT=alanine aminotransferase; ALP=alkaline phosphatase; AST=aspartate 
aminotransferase; BMI=body mass index; BUN=blood urea nitrogen; CR=complete clinical remission; CRmin=CR on minimal therapy; CRP=C-reactive 
protein; DC=disease control; Dsg=desmoglein; ECG=electrocardiogram; EoC=end of consolidation; EoS=end of study; EoT=end of treatment; EQ-5D-
5L=EuroQol 5-dimension 5-level scale; ET=early termination; GGT=gamma-glutamyl transferase; GTI=Glucocorticoid Toxicity Index; IgG=immunoglobulin 
type G; IMP=investigational medicinal product; LDH=lactate dehydrogenase; LDL-C=low-density lipoprotein cholesterol; MCV=mean corpuscular volume; 
NAb=neutralizing antibody; PDAI=Pemphigus Disease Area Index; PD=pharmacodynamic; PK=pharmacokinetics; QTcF=Fridericia corrected QT interval; 
rHuPH20=recombinant human hyaluronidase PH20; RBC=red blood cells; SC=subcutaneous(ly); UNS=unscheduled visit; W=week; WBC=white blood cells; 
V=visit at site 
a For participants who roll over from ARGX-113-1904 to ARGX-113-1905, the baseline visit will occur for these participants at the same visit as the EoS/ED 
visit in study ARGX-113-1904. All assessments will be performed before IMP administration. 
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. Refer to Section 8 for more information. Participants with 
new lesions or flare after achieving CR should return to weekly on-site visits. Participants with flare who had achieved CRmin or CRoff should switch to the 
visit schedule outlined in Table 2. 
c Follow-up 1 will be the EoS visit for participants who ended treatment before W49 or 4 weeks before ET. Both follow-up visits will be required only for 
participants who continue to receive efgartigimod PH20 SC for at least 1 visit between W49 and W52 or during the last 4 weeks before ET. 
d Study visit windows are ±2 days during the treatment period and ±3 days for the follow-up visits. 
e Weight will be measured and BMI will be calculated accordingly, at the rollover visit, at W26 (or the next on-site visit if W26 does not coincide with an on-site 
visit) and W52. Weight will also be measured if there has been an obvious change since the last measurement. 
f Assessment or procedure will be completed predose at visits when IMP is administered. 
g The ECG will be recorded at baseline, every 3 months while receiving efgartigimod PH20 SC treatment, at CRmin (or the next on-site visit if CRmin is 
achieved during a week without an on-site visit), and at EoS. The ECG (heart rate, PR, QT, and QRS interval) will be read centrally, and QTcF and QTcB will 
be calculated. The ECG will be recorded only at baseline and EoS in participants not receiving efgartigimod. Additional ECGs may be performed at the 
discretion of the investigator during unscheduled visits. 
System Version: 1.0, Status: Approved, Document ID: VV-TMF-86295

Clinical Trial Protocol ARGX-113-1905 v3.0 
 
05 Sep 2022 
Efgartigimod PH20 SC 
 
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h A complete physical examination will be performed at each on-site visit. Vital sign measurements include systolic and diastolic blood pressure, heart rate, and 
body temperature. 
i 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 is abnormal). 
j A urine pregnancy test will be performed locally and at least once every 4 weeks. 
k Clinical blood laboratory tests will include hematology and blood chemistry at all visits. The hematology profile includes hemoglobin, hematocrit, MCV, RBC 
count, platelet count, and WBC count with differential. The blood chemistry profile includes sodium, potassium, calcium, HbA1c, creatinine, creatinine 
clearance, BUN, ALT, AST, total bilirubin, GGT, CRP, ALP, LDH, LDL-C, uric acid, total protein, and albumin. 
l PK and PD (total IgG and IgG subtypes) samples will be taken every 4 weeks as long as the participant is receiving efgartigimod PH20 SC treatment (until 
CRmin or the next on-site visit) and 4 weeks after CRmin (or the next on-site visit; this also applies if the participant achieved CRmin in ARGX-113-1904) or 
EoT. Blood samples will be taken predose (within 2 hours before the start of IMP administration during visits when IMP is administered).  
m At unscheduled visits, blood samples for PK will only be taken if IMP is administered. 
n Blood samples will be taken to test for immunogenicity to efgartigimod in serum and rHuPH20 in plasma every 4 weeks while the participant is receiving 
efgartigimod PH20 SC treatment (until CRmin or the next on-site visit) and 4 and 8 weeks after CRmin (or the next 2 on-site visits; this also applies if the 
participant achieved CRmin in ARGX-113-1904) or EoT. NAb will be tested for all confirmed positive immunogenicity samples. 
o Questionnaires are to be completed before any other assessment. 
p Disease assessment parameters include DC, EoC, CR, CRmin, CRoff, flare, and treatment failure. Participants who have achieved CR and have new lesions 
should come to the clinic for an unscheduled visit for disease assessment. 
q Samples for lymphocyte populations will be taken at selected sites only: optionally at on-site visits at W13 (±2 weeks), W26 (±2 weeks), W39 (±2 weeks), 
W52 (±2 weeks) or EoT/ET and EoS, and mandatory at on-site visits at W52 (±2 weeks) or EoT/ET and EoS for participants in CRmin or CRoff. 
r The GTI assessment will be performed at visit 1, W26 (or the next on-site visit), and W52. 
s Participants and/or their caregivers will be invited to receive at least 1 refresher training for self-administration, or caregiver-supported administration of IMP. 
Training will continue until deemed successfully completed by authorized staff. 
t Efgartigimod PH20 SC will be administered weekly at a dose of 1000 mg until CRmin. For IMP administrations between the scheduled site visits, the 
participant can choose between self-administration (if training successfully completed), home nurse visits, or return to the trial site for the SC injection only. 
Participants who have achieved CRmin or CRoff and are currently not in flare will be observed every 4 weeks without any further IMP administration until 
flare or EoS. Only for on-site visits and home nurse visits, participants should be followed up for safety monitoring for at least 1 hour after the first IMP 
administration, or followed by 15 minutes of observation for subsequent administrations and released according to their clinical status. The last planned IMP 
administration is at W52. If the participant withdraws from the study, efgartigimod PH20 SC will not be administered. 
u 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). 
 
 
 
System Version: 1.0, Status: Approved, Document ID: VV-TMF-86295

Clinical Trial Protocol ARGX-113-1905 v3.0 
 
05 Sep 2022 
Efgartigimod PH20 SC 
 
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Table 2: 
Schedule of Activities for ARGX-113-1905 for Participants Not in CR at Rollover From ARGX-113-1904, or 
Participants With Flare after CRmin or CRoff in ARGX-113-1905 
Trial period 
Open-label extension 
EoT/ET 
 
Follow-up 
V1a 
Observational 
visits 
IMP admin 
only visit 
Observational visits 
Visit Number 
 
Weekly on-site 
visits until CRb 
Weekly home 
or on-site visits 
until CRminc 
On-site visits 
every 4 weeks 
until CRmin 
On-site visits 
every 4 weeks 
until W52  
W52  
UNSd 
Safety 
follow-up 
1 
Safety 
follow-up 
2 
Trial Week 
Rollovera 
V1 + 7x 
CR until 
CRmin 
CR until CRmin 
After CRmin 
until W52 
W52 
EoT/ET  
+ 4 weekse 
EoT/ET 
+ 8 weeks 
EoSe 
Assessment/Procedure 
±0 days 
±2 daysf 
±2 days 
 
±3 daysf 
Informed consent  
X 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
X 
 
 
 
 
 
 
 
 
Weightg 
X 
Xg 
 
Xg 
Xg 
X 
 
 
 
ECGh,i 
X 
X 
 
X 
X 
X 
 
X 
X 
Physical examination 
and vital signsi,j 
X 
X 
 
X 
X 
X 
X 
X 
X 
Urinalysisi,k,l 
X 
X 
 
X 
X 
X 
Xd 
X 
X 
Urine pregnancy testi,m 
X 
X 
 
X 
X 
X 
Xd 
X 
X 
Vaccination antibodiesi,l 
X 
X 
 
X 
X 
X 
Xd 
X 
X 
Blood sampling 
 
 
 
 
 
 
 
 
 
• Clinical chemistry 
and hematologyi,l,n 
X 
X 
 
X 
X 
X 
Xd 
X 
X 
• anti-Dsg-1 and anti-
Dsg-3 antibodiesi,l 
X 
X 
 
X 
X 
X 
Xd 
X 
X 
System Version: 1.0, Status: Approved, Document ID: VV-TMF-86295

Clinical Trial Protocol ARGX-113-1905 v3.0 
 
05 Sep 2022 
Efgartigimod PH20 SC 
 
argenx 
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33 
Trial period 
Open-label extension 
EoT/ET 
 
Follow-up 
V1a 
Observational 
visits 
IMP admin 
only visit 
Observational visits 
Visit Number 
 
Weekly on-site 
visits until CRb 
Weekly home 
or on-site visits 
until CRminc 
On-site visits 
every 4 weeks 
until CRmin 
On-site visits 
every 4 weeks 
until W52  
W52  
UNSd 
Safety 
follow-up 
1 
Safety 
follow-up 
2 
Trial Week 
Rollovera 
V1 + 7x 
CR until 
CRmin 
CR until CRmin 
After CRmin 
until W52 
W52 
EoT/ET  
+ 4 weekse 
EoT/ET 
+ 8 weeks 
EoSe 
Assessment/Procedure 
±0 days 
±2 daysf 
±2 days 
 
±3 daysf 
• PKi,o 
X 
X 
 
X 
Xo 
X 
Xd,p 
X 
X 
• Total IgG and IgG 
subtypesi,o 
X 
X 
 
X 
X 
X 
Xd 
X 
X 
• immunogenicityi,q 
X 
X 
 
X 
X 
X 
 
X 
X 
• IgG autoantibody 
subtypes and 
specificityi 
X 
Xr 
 
X 
X 
X 
Xd 
X 
X 
PDAIi 
X 
X 
  
X 
X 
X 
X 
X 
X 
ABQOLi,s,t 
X 
Xs 
 
Xs 
Xs 
X 
 
 
 
EQ-5D-5Li,s,t 
X 
Xs 
 
Xs 
Xs 
X 
 
 
 
Disease assessmenti,u 
X 
X 
 
X 
X 
X 
X 
X 
X 
Photography (at selected 
sites)v 
X 
Xv 
 
 
 
X 
Xd,v 
 
 
Lymphocyte populations 
(at selected sites)w 
X 
Xw 
 
Xw 
Xw 
Xw 
 
X 
X 
GTIx 
X 
Xx 
 
Xx 
Xx 
X 
 
 
 
IMP self-administration 
trainingy 
X 
X 
X 
X 
X 
X 
 
 
 
System Version: 1.0, Status: Approved, Document ID: VV-TMF-86295

Clinical Trial Protocol ARGX-113-1905 v3.0 
 
05 Sep 2022 
Efgartigimod PH20 SC 
 
argenx 
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34 
Trial period 
Open-label extension 
EoT/ET 
 
Follow-up 
V1a 
Observational 
visits 
IMP admin 
only visit 
Observational visits 
Visit Number 
 
Weekly on-site 
visits until CRb 
Weekly home 
or on-site visits 
until CRminc 
On-site visits 
every 4 weeks 
until CRmin 
On-site visits 
every 4 weeks 
until W52  
W52  
UNSd 
Safety 
follow-up 
1 
Safety 
follow-up 
2 
Trial Week 
Rollovera 
V1 + 7x 
CR until 
CRmin 
CR until CRmin 
After CRmin 
until W52 
W52 
EoT/ET  
+ 4 weekse 
EoT/ET 
+ 8 weeks 
EoSe 
Assessment/Procedure 
±0 days 
±2 daysf 
±2 days 
 
±3 daysf 
Efgartigimod PH20 SCz 
Xz 
Xz 
X 
X 
 
X 
X 
 
 
Prednisone taperaa 
X 
X 
 
X 
X 
X 
X 
 
 
Concomitant therapies/ 
procedures  
Continuous monitoring 
AE monitoring 
Continuous monitoring 
ABQOL=Autoimmune Bullous Disease Quality of Life; AE=adverse event; ALT=alanine aminotransferase; ALP=alkaline phosphatase; AST=aspartate 
aminotransferase; BMI=body mass index; BUN=blood urea nitrogen; CR=complete clinical remission; CRmin=CR on minimal therapy; CRP=C-reactive 
protein; DC=disease control; Dsg=desmoglein; ECG=electrocardiogram; EoC=end of consolidation; EoS=end of study; EoT=end of treatment; EQ-5D-
5L=EuroQol 5-dimension 5-level scale; ET=early termination; GGT=gamma-glutamyl transferase; GTI=Glucocorticoid Toxicity Index; IgG=immunoglobulin 
type G; IMP=investigational medicinal product; LDH=lactate dehydrogenase; MCV=mean corpuscular volume; NAb=neutralizing antibody; 
PD=pharmacodynamic; PDAI=Pemphigus Disease Area Index; PK=pharmacokinetics; QTcF=Fridericia corrected QT interval; rHuPH20=recombinant human 
hyaluronidase PH20; RBC=red blood cells; SC=subcutaneous(ly); UNS=unscheduled visit; V=visit at site; V1 + 7x=visit 1 + 7 times x with ‘x’ being the weeks 
post V1 (eg, V1 + 7x3 is the visit at W3 [21 days post visit 1]); W=week; WBC=white blood cells 
a For participants who roll over from ARGX-113-1904 to ARGX-113-1905, the baseline visit will occur at the EoS/ED visit of ARGX-113-1904. All 
assessments are performed before IMP administration. 
b A minimum of 6 on-site visits (rollover (V1) to W6 or start of retreatment +5 weeks) is required before switching to home administrations, even if CR is 
reported earlier. 
c Home visits are allowed once a participant achieves CR but not before W7 or not before the start of retreatment +6 weeks. The investigator should call the 
participant every 2 weeks until CRmin to confirm the participant is still in CR and to determine the prednisone tapering schedule. 
d In case of suspected new lesions as reported by the participant, AEs, flare, or other safety reasons, the participant should come to the clinic. This may require an 
unscheduled visit. Depending on the reason for the visit, different assessments need to be performed. Refer to Section 8 for more information. 
e Follow-up 1 will be the EoS visit for participants who ended treatment before W49, or 4 weeks before ET. Both follow-up visits will be required only for 
participants who continue to receive efgartigimod PH20 SC for at least 1 visit between W49 and W52, or during the last 4 weeks before ET. 
f Study visit windows are ±2 days during the treatment period and ±3 days for the follow-up visits. 
System Version: 1.0, Status: Approved, Document ID: VV-TMF-86295

Clinical Trial Protocol ARGX-113-1905 v3.0 
 
05 Sep 2022 
Efgartigimod PH20 SC 
 
argenx 
Confidential 
35 
g Weight will be measured and BMI will be calculated accordingly, at the rollover visit, at W26 (or the next on-site visit if W26 does not coincide with an on-site 
visit) and W52. Weight will also be measured if there has been an obvious change since the last measurement. 
h The ECG will be recorded at baseline, at the start of retreatment and every 3 months (or the next on-site visit) while receiving efgartigimod PH20 SC treatment, 
at CRmin (or the next on-site visit if CRmin is achieved during a week without an on-site visit), and EoS. The ECG (heart rate, PR, QT, and QRS interval) will 
be read centrally, and QTcF and QTcB will be calculated. Additional ECGs may be performed at the discretion of the investigator during unscheduled visits. 
i Assessment or procedure will be completed predose at visits when IMP is administered. 
j A complete physical examination will be performed at each on-site visit. Vital sign measurements include systolic and diastolic blood pressure, heart rate, and 
body temperature. 
k 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 is abnormal). 
l Samples will be taken every week from rollover (V1) to W9 or start of retreatment +8 weeks, and then every 4 weeks and at the visit when CR is observed. 
Once CR is achieved, samples will be taken every 4 weeks at on-site visits until EoS. For participants achieving CR between rollover (V1) and W6 or the start 
of retreatment +5 weeks, samples will be taken weekly from rollover (V1) to W6 or start of retreatment +5 weeks, and then every 4 weeks during on-site visits 
until EoS. 
m A urine pregnancy test will be performed locally at least once every 4 weeks, at CR, and as of CR again every 4 weeks at on-site visits. 
n Clinical blood laboratory tests will include hematology and blood chemistry at all visits. The hematology profile includes hemoglobin, hematocrit, MCV, RBC 
count, platelet count, WBC count with differential. The blood chemistry profile includes sodium, potassium, calcium, HbA1c, creatinine, creatinine clearance, 
BUN, ALT, AST, total bilirubin, GGT, CRP, ALP, LDH, low-density lipoprotein cholesterol (LDL-C), uric acid, total protein, and albumin. 
o PK and PD (total IgG and IgG subtypes) samples will be taken every 4 weeks, at CR, and as of CR again every 4 weeks at on-site visits, as long as the 
participant is receiving efgartigimod PH20 SC treatment (until CRmin or the next on-site visit if CRmin is achieved during a week without an on-site visit), and 
4 weeks after CRmin (or the next on-site visit) or EoT. Blood will be taken predose (within 2 hours before the start of IMP administration during visits when 
IMP is administered). 
p Blood will be taken for PK assessment predose (within 2 hours before the start of IMP administration during visits when IMP is administered). At UNS visits, 
blood samples for PK analysis will be taken only if IMP is administered. 
q Blood will be taken to test for immunogenicity to efgartigimod in serum and to rHuPH20 in plasma every 4 weeks, at CR, and as of CR every 4 weeks at on-
site visits while the participant is receiving efgartigimod PH20 SC treatment (until CRmin or the next on-site visit if CRmin is achieved during a week without 
an on-site visit), and 4 and 8 weeks after CRmin (or the next 2 on-site visits) or EoT. NAb will be tested for all confirmed positive immunogenicity samples. 
r Blood will be taken every 4 weeks and at the visit when CR is observed for IgG autoantibody subtypes and specificity. Once CR is achieved, samples will be 
taken every 4 weeks at on-site visits until EoS. 
s The ABQOL and EQ-5D-5L will be administered at the start of retreatment, when achieving CRmin (or at the next on-site visit if CRmin is achieved during a 
week without an on-site visit), and at EoT/W52 only. 
t Questionnaires are to be completed before any other assessment. 
u Disease assessment parameters include DC, EoC, CR, CRmin, CRoff, flare, and treatment failure. Participants who have achieved CR and have new lesions 
should come to the clinic for a UNS visit for disease assessment. 
v 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 time points. 
w Samples for lymphocyte populations will be taken at selected sites only: optionally at on-site visits at W13 (±2 weeks), W26 (±2 weeks), W39 (±2 weeks), 
W52 (±2 weeks) or EoT/ET and EoS, and mandatory at on-site visits at W52 (±2 weeks) or EoT/ET and EoS for participants in CRmin or CRoff. 
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x The GTI assessment will be performed at visit 1, W26 (or the next on-site visit) and W52. 
y Participants and/or their caregivers will be invited to receive at least 1 refresher training for self-administration, or caregiver-supported administration of IMP. 
Training will continue until deemed successfully completed by authorized staff. 
z Efgartigimod PH20 SC will be administered subcutaneously weekly at a dose of 1000 mg until CRmin. In case of treatment failure in ARGX-113-1904, or 
flare while not receiving efgartigimod therapy, efgartigimod PH20 SC will be administered on 
 at a dose of 
mg, followed by weekly SC 
administrations of 1000 mg until CRmin. For IMP administrations between the scheduled visits (after achieving CR), the participant can choose between self-
administration (if training successfully completed), home nurse visits or return to the trial site for the SC injection only. Participants who have achieved CRmin 
or CRoff and are currently not in flare will be observed every 4 weeks without any further IMP administration until flare or EoS. Only for on-site visits and 
home nurse visits, participants should be followed up for safety monitoring for at least 1 hour after the first administration, or followed by 15 minutes of 
observation for subsequent administrations for safety monitoring and released according to their clinical status. The last planned IMP administration is at W52. 
If the participant withdraws from the study, efgartigimod PH20 SC will not be administered. 
aa 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 
This is a prospective, multicenter, open-label extension (OLE) trial on the efficacy, safety, 
patient outcome measures, tolerability, immunogenicity, PK, and PD of efgartigimod PH20 SC 
in adult PV or PF participants, who participated in the antecedent trial ARGX-113-1904. 
2.1. 
Trial Rationale 
Pemphigus is a chronic disease and patients under treatment experience intermittent episodes of 
clinical remission and flare. The mainstays of therapy in PV are systemic corticosteroids and 
rituximab. Corticosteroids rapidly affect PV symptoms (3 to 4 weeks), but must be administered 
at high daily doses (eg, oral prednisone 1 to 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, while having a relatively late onset of action, 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 rituximab IV frequently results in infusion-related reactions 
(IRRs) and adverse events (AEs), which may be of late onset.  
An innovative drug is needed for the treatment of PV and PF that has a fast onset of action (eg, 
early disease control [DC, defined as the absence of new lesions and the start of healing of 
established lesions], complete clinical remission [CR, defined as the absence of new lesions and 
complete healing of established lesions] within weeks), a strong prednisone sparing effect, and a 
favorable safety profile.  
The antecedent trial ARGX-113-1904 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 
which leads to early disease remission at minimal prednisone dose. The trial has a treatment 
phase of up to 30 weeks, and provides a tailored dose regimen for participants by stopping 
investigational medicinal product (IMP) administration upon achieving complete remission on 
minimal therapy (CRmin, defined as the absence of new lesions and complete healing of 
established lesions while the participant is receiving minimal prednisone therapy of ≤10 mg/day 
for at least 2 months [8 weeks]). Note: when 10 mg/day is reached in ARGX-113-1904 or 
ARGX-113-1905, this dose level must be maintained for 8 weeks until CRmin has been achieved. 
ARGX-113-1905 provides efgartigimod PH20 SC extended treatment and retreatment options 
for participants who were randomized to the efgartigimod PH20 SC treatment arm in 
ARGX-113-1904, and provides first efgartigimod PH20 SC treatment and retreatment options 
for participants who were randomized to the placebo treatment arm in ARGX-113-1904. 
At blinded rollover from ARGX-113-1904 into ARGX-113-1905, participants may be in 
different clinical stages: participants may have achieved CRmin; participants may have achieved 
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CR without meeting the minimal therapy criterion; participants may have achieved DC or EoC 
(the time at which no new lesions have developed for a minimum of 2 weeks and approximately 
80% of lesions have healed) without having achieved CR; participants may have had treatment 
failure or a flare after having achieved CRmin. 
ARGX-113-1905 evaluates the ability to (further) taper prednisone therapy and achieve CRoff 
(CRoff defined as the absence of new and established lesions completely healed while the 
participant is receiving no prednisone therapy for at least 2 months [8 weeks]), the ability to 
achieve CR and CRmin for participants who had not yet achieved CRmin, and the ability to treat 
flare; and assesses participant outcome measures and the safety, PD, PK, and immunogenicity of 
efgartigimod PH20 SC over the duration of the trial. 
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-3.28,29 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-1.22 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/million in Finland, to around 
1.5/million in France, 4 to 5/million in Italy, up to 8/million in Greece, and 16/million in Israel.1 
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).  
Both conditions are chronic and intractable, with 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 
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overrepresented in the PV population, in which the female-predominant thyroid diseases and 
rheumatoid arthritis are associated.2  
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 suprabasal 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.5  
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.3 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.4  
Because Dsg-1 is expressed in the superficial portion of the epidermis, PF participants 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 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 
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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 participant reaches rapidly minimal corticosteroid dose 
(prednisone ≤10 mg/day) or even no concomitant treatment (off prednisone therapy). 
The therapeutic management of participants 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, participants must be managed by referral centers, where 
they can be monitored carefully by experienced dermatologists. In many participants, 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 participants, consensual definitions of the most important clinical 
endpoints among national and international experts, 14 as well as regular guidelines for the 
diagnosis and treatment of these diseases are available.,9,10,14,23 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.13,24 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 the patient’s daily life.19  
According to the most recent international guideline,5 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.6,7,8 
Oral prednisone is the most commonly used corticosteroid. The starting oral prednisone dose is 
high, ranging from 1 to 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 to 4 weeks at the latest, the 
prednisone dose must be increased. In patients with very active disease, intravenous bolus of 
corticosteroids (eg, methylprednisolone) may be preferred, especially at the treatment initiation. 
Tapering of oral prednisone is initiated as soon as DC is achieved or up to the end of the 
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 patients with 
PV who were treated with prednisone could achieve a first complete remission on minimal dose 
after 12 months.25 Flare occurred frequently, ie, in 45% of the cases within 6 months. Finally, the 
common course of PV is one 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. 26 Meanwhile, the risk 
of corticosteroid-related side effects increased with treatment duration (osteoporosis, diabetes, 
hypertension, Cushing syndrome, cataract, glaucoma, infections, etc).27 Accordingly, most 
patients with PV 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 is primarily used in patients with refractory PV 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 to 
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 year9). 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 to 1 mg/kg per day according to disease severity10). 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 editions of the Investigator’s Brochures (IBs).  
2.3.1. 
Risk Assessment 
In clinical studies to date, efgartigimod has been well-tolerated in both healthy adult participants 
and in those 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 
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5 severe TEAEs, no action was taken on the drug dose for 3 participants; drug was withdrawn 
from the participant who had nonrelated grade 3 pneumonia; and the dose was interrupted for the 
participant who reported possibly related blood CPK increase. The most commonly reported 
TEAEs were nasopharyngitis, diarrhea, and headache, reported in 4 participants (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-113-1602 in participants with MG, no grade ≥3 TEAEs were reported 
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 
≥1 TEAE. Most TEAEs were of mild or moderate 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 hematoma 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 participants 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 participants 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 both healthy participants 
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and in those 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 ECG findings have been observed in 
clinical trials to date. 
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 rat and 
rabbit 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 rat 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 subcutaneous 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 co-administered 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 comixed with 2000 U/mL rHuPH20 was well-
tolerated by all participants. No deaths, serious adverse events (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%) participants 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) 
which was reported as moderate in severity. Dose-related effects were observed. All participants 
recovered from their TEAEs by the end of the study, except for 1 participant who had 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 participants (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 participants with 1 or more abnormalities at the injection site 
appeared to increase with increasing SC doses of efgartigimod comixed with rHuPH20. 
2.3.2. 
Benefit Assessment 
Efgartigimod has been shown to effectively reduce IgG antibodies and improve clinical 
outcomes in several clinical trials of healthy participants and those with pemphigus, MG, or ITP. 
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In the phase 2 trial ARGX-113-1701 in participants with pemphigus, the efficacy of efgartigimod 
is supported by pharmacodynamic effects (effects on IgG and 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 achieved DC with or 
without concomitant prednisone, while participants achieved CR when efgartigimod 
administration was combined with low-dose prednisone. Flare was prevented when efgartigimod 
was given at weekly intervals, before and after DC or CR.  
In Dec 2021, the FDA approved efgartigimod for the treatment of generalized myasthenia gravis 
(gMG) in adult patients who are anti-acetylcholine receptor antibody (AChR-Ab) seropositive. In 
the phase 2 trial (ARGX-113-1602) of gMG participants, 4 weekly IV infusions of 10 mg/kg 
efgartigimod led to statistically significant improvements in clinical scales and were well 
tolerated.11 Additionally, in a randomized, double-blinded, placebo-controlled, phase 3 trial in 
participants with MG (ARGX-113-1704), the primary endpoint was met: the percentage of 
AChR-Ab seropositive participants who, after the first treatment cycle, had reduction of ≥2 
points on the Myasthenia Gravis Activities of Daily Living (MG-ADL) total score compared to 
study entry baseline for ≥4 consecutive weeks, with the first ≥2-point reduction observed no later 
than 1 week after the last IMP infusion. 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 a phase 2 trial of patients with ITP (ARGX-113-1603), efgartigimod resulted in a rapid and 
marked reduction of IgG antibodies (maximum mean reduction of 65%) and of all IgG 
subtypes.12 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-treated participants achieving a platelet count of ≥50×109/L 
for more than 10 cumulative days compared to the placebo group. 
Efgartigimod PH20 SC (the same formulation used in pemphigus studies) is also under 
investigation in an ongoing phase 2 trial in patients with chronic inflammatory demyelinating 
polyneuropathy (CIDP) (ARGX-113-1802). 
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 participants with pemphigus. 
 
 
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3. 
OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary 
• 
To assess the safety of treatment, extended 
treatment, and retreatment with 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 sign measurements, physical 
examinations, electrocardiograms (ECGs), 
and clinical laboratory safety evaluations 
Secondary 
• 
To evaluate the efficacy of efgartigimod 
PH20 SC treatment in PV and PF 
• 
Proportion of PV participants who achieve 
CRmin  
• 
Proportion of PV and PF participants who 
achieve CRmin 
• 
Time to DC 
• 
Time to CR 
• 
Time to CRmin  
• 
Time to CRoff 
• 
Time to flare 
• 
Rate of treatment failure 
• 
Rate of flare 
• 
Cumulative prednisone dose over the trial  
• 
Pemphigus Disease Area Index (PDAI) at 
each visit 
• 
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) 
score 
• 
Autoimmune Bullous Disease Quality of Life 
(ABQOL) score  
• 
To evaluate the pharmacokinetics (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 
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Objectives 
Endpoints 
• 
To evaluate the immunogenicity of 
efgartigimod in participants with PV or PF 
• 
Incidence and prevalence of antidrug 
antibodies (ADA) against efgartigimod 
(serum levels) 
• 
To explore feasibility of self-administration of 
efgartigimod PH20 SC 
• 
Percentage of participants who performed 
self-administration  
• 
Percentage of caregivers who administered 
the injection to the participant  
• 
Number of visits needed for the participant or 
caregiver to be competent to start 
administering efgartigimod PH20 SC  
• 
Frequency of self- or caregiver-supported 
administration at home 
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 subclasses 
and autoantibody reactivity to Dsg domains 
and other antigens 
• 
Lymphocyte dynamic changes 
• 
To evaluate the immunogenicity of rHuPH20 
in participants with PV or PF 
• 
Immunogenicity to rHuPH20 (plasma levels) 
 
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In the absence of DC, participants will receive prednisone at the starting dose of 
1.5 mg/kg/day. In case of uncontrolled flare before CRmin, participants will receive, as 
starting dose, the last dose from ARGX-113-1904. In case of flare after CRmin, 
participants will receive a prednisone dose in line with the severity of the flare, with the 
recommendation of a minimum of 0.3 mg/kg/day when the flare is of mild severity 
(PDAI activity score <15) and of 0.5 mg/kg/day when the flare is moderate to severe 
(PDAI activity score ≥15). Dosing of efgartigimod PH20 SC will be done during on-site 
visits or home visits according to Table 2.   
5. Participants who developed a prednisone-related SAE may prematurely roll over into 
ARGX-113-1905 and may be treated with efgartigimod PH20 SC through on-site or 
home visits according to the clinical statuses as described above. Concomitant prednisone 
will be considered to fit the clinical statuses as described above as far as compatible with 
the nature and severity of the SAE, with a lower dose to no concomitant prednisone being 
considered otherwise.    
Participants or their caregivers (a person of legal age that the participant proposes to perform the 
administrations) may self-administer efgartigimod PH20 SC after they have successfully 
completed self-administration training (in ARGX-113-1904 with at least 1 refresher training in 
OLE trial ARGX-113-1905, or during ARGX-113-1905). All participants and/or their caregivers 
will receive a home guide for transport, storage, preparation, and administration of the IMP. 
At any postbaseline 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 (Table 4) 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 postbaseline visit before DC  
• Insufficient clinical change: the absence of DC after 3 to 4 weeks of the participant 
being treated at the starting baseline prednisone 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 
If DC is not attained after a minimum of 3 weeks of the participant receiving oral prednisone 
1.5 mg/kg qd, then the participant will be considered a treatment failure and will be withdrawn 
from the trial. 
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For participants who achieve DC at the starting dose of 0.5 mg/kg qd or lower, the prednisone 
dose will be maintained at that starting dose qd until CR and 2 weeks thereafter, or EoC 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), that dose will be maintained until 2 weeks after 
achieving DC and then will be tapered (Table 4) in increments of 0.25 mg/kg every 2 weeks until 
the starting dose is achieved. This starting dose 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 4 weeks. Further tapering will be 
performed thereafter, as long as CR or EoC are sustained. 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 for at least 
8 weeks until CRmin is achieved. The prednisone dose can then be further tapered to reach 
CRoff according to the clinical judgment of the investigator. 
At visits when at least 1 new lesion is observed or established lesions remain extensive without 
being defined as a flare (ie, 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), 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.  
In case of flare in the period between DC and CRmin, the prednisone dose will be increased to 
achieve DC again. 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 dose of OCS that is 2 dose levels above the dose at which the flare is 
observed and that is at least 0.3 mg/kg/day (Table 4) will be managed according to clinical 
judgment ie, either receive a further increased prednisone dose or be withdrawn from the trial. 
Withdrawal of participants with a flare before CRmin will be defined as treatment failure. 
In case of flare after having achieved CRmin (ie, while being off efgartigimod treatment), 
participants will be immediately treated/retreated with a new cycle of efgartigimod PH20 SC. 
The first day of new efgartigimod treatment will define a new baseline for assessments of 
outcomes (DC, CR, etc) and prednisone escalation or tapering schedule.    
In the new treatment cycle, participants will be administered efgartigimod PH20 SC at a weekly 
dose of 
 mg for the first
, followed by weekly SC administrations of 1000 mg until 
CRmin. Oral prednisone will be administered at a dose chosen according to clinical judgment, 
with the recommendation of 0.3 mg/kg qd in the case of mild flare (PDAI activity score <15) and 
0.5 mg/kg qd in the case of moderate to severe flare (PDAI activity score ≥15). The treatment 
goal of a new treatment cycle is to first achieve DC again and therefore these participants will be 
treated accordingly (Table 2).  
A new treatment cycle of efgartigimod PH20 SC can be initiated in eligible participants until 
week 44. In participants requiring a new treatment cycle of efgartigimod PH20 SC between 
weeks 45 and 49, the initiation will be optional and based on clinical judgment and participant 
consent. A new efgartigimod treatment cycle will not be permitted after week 49 to ensure a 
minimum of 4 weeks of efgartigimod treatment/cycle. 
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Except for oral prednisone, no other systemic therapies (eg, immunosuppressants, IVIg, 
immunoadsorption, anti-CD20 biologics) will be permitted during the trial.  
Trial procedures will be performed per the SoA as detailed in Section 1.3 and Section 10.11. 
4.2. 
Scientific Rationale for Trial Design 
Pemphigus is a chronic disease and patients under treatment have intermittent episodes of 
clinical remission and flare. 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, and 
using short courses at the lowest 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 adjunctive treatment to a short course of 
prednisone, rituximab, while having a relatively late onset of action, 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 rituximab IV frequently results in IRRs and AEs, which may 
be of late onset.  
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, and a favorable safety profile.  
Antecedent trial ARGX-113-1904 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 
which leads to early disease remission at minimal prednisone dose. The trial has a treatment 
phase of up to 30 weeks, and provides a tailored dose regimen for participants by stopping IMP 
administration upon achieving CRmin (defined as the absence of new lesions and complete 
healing of established lesions while the participant is receiving minimal prednisone therapy of 
≤10 mg/day for at least 2 months [8 weeks]). Note: when 10 mg/day is reached in 
ARGX-113-1904 or ARGX-113-1905, this dose level must be maintained for 8 weeks until CRmin 
has been achieved. 
Study ARGX-113-1905 provides efgartigimod PH20 SC extended and retreatment options 
for participants who were randomized to the efgartigimod PH20 SC treatment arm 
in ARGX-113-1904, and provides first treatment and retreatment options for participants 
who were randomized to the placebo treatment arm in study ARGX-113-1904. 
At blinded rollover from ARGX-113-1904 into ARGX-113-1905 participants may be in different 
clinical stages. Participants may have achieved CRmin, participants may have achieved CR 
without meeting the minimal therapy criterion, participants may have achieved DC or EoC (the 
time at which no new lesions have developed for a minimum of 2 weeks and approximately 80% 
of lesions have healed) without having achieved CR, participants may have had treatment failure 
or a flare after having achieved CRmin. 
ARGX-113-1905 evaluates the ability to (further) taper prednisone therapy and achieve CRoff, 
the ability to achieve CR and CRmin for participants who had not yet achieved CRmin, and the 
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ability to treat flare; and assesses patient outcome measures and the safety, PD, PK, and 
immunogenicity of efgartigimod PH20 SC over the duration of the trial. Duration of CR, time to 
CRoff and the effects of retreatment by the study drug will be specifically evaluated during the 
trial.  
4.3. 
Justification for Dose 
SC administration is highly preferred over an IV formulation for patients with pemphigus, given 
the expected need for weekly administration over prolonged durations. Therefore, efgartigimod 
with rHuPH20 will be administered SC weekly until CRmin; retreatment may be initiated in case 
of flare after having achieved CRmin. To achieve a fast PD effect and clinical response a dose of 
mg will be administered in the first 
, 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. 
ARGX-113-1701 showed that efgartigimod treatment resulted in a rapid DC with or without 
associated prednisone, as well as complete remission 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 of a reduction in time to a clinically relevant improvement. Subsequently, a 
lower weekly dose is expected to maintain improvement in this 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 from the phase 1 study in healthy participants, phase 2 studies of 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 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 
patients with pemphigus. 
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PK and PD data from 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 
on IgG levels as the 10 mg/kg IV dosed weekly, include area under the 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% 
confidence interval (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 1000 mg efgartigimod 
PH20 SC doses is comparable to that of 10 mg/kg IV efgartigimod. 
As pemphigus is a chronic disease, current therapies require chronic administration. In this trial, 
efgartigimod with rHuPH20 will be administered via the SC route in a flat dose in a new highly 
concentrated formulation, which may be more convenient for patients with pemphigus.  
In order to allow for a convenient SC administration with efgartigimod to achieve the targeted 
exposure and PD effect, efgartigimod will be coformulated with rHuPH20. This compound is 
being used in co-formulations with approved therapeutic antibodies to facilitate SC injection 
with volumes larger than 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. 
A 
 mg efgartigimod to be administered as
 SC injections 
coformulated with rHuPH20 has been selected for this trial. This dose is anticipated to achieve 
close to maximal IgG reduction within 
 as achieved by 1000 mg SC at steady state.  
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 EoT/ET visit and any follow-up visits (if applicable).  
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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 
have any of the exclusion criteria will not be eligible to receive any study 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 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 participated in ARGX-113-1904 and completed the study or has the 
defined criteria for rollover. 
3A. Contraceptive use by men and women should be consistent with local regulations 
regarding the methods of contraception for those participating in clinical trials and:  
i. Male participants: 
− Male participants must agree to use an acceptable method of contraception 
(as described in Section 10.4.2.2) from signing the informed consent form (ICF) 
until the last dose of the study drug. 
ii. Female participants: 
− Women of childbearing potential (WOCBP as defined in Section 10.4.1) must: 
▪ have a 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 Section 10.4.2.1), which should be maintained at minimum 
until after the last dose of IMP 
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5.2. 
Exclusion Criteria  
Participants are excluded from the trial if any of the following criteria apply: 
1A. Pregnant and lactating women and those intending to become pregnant during the trial 
2. 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 
3. Known hypersensitivity to any of the components of the administered treatments 
5.3. 
Lifestyle Considerations 
No lifestyle restrictions are required. 
5.4. 
Screen Failures 
Not applicable in this long-term extension trial. 
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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 participant according to the protocol.  
6.1. 
Trial Intervention(s) Administered 
A list of trial interventions is presented in Table 3. 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 (the thighs and the arms) may be 
chosen.   
Refer to the Pharmacy Manual and preparation guide for further details. Additionally, 
participants may receive oral prednisone (or equivalent such as prednisolone) as concomitant 
therapy (refer to Section 6.5.1).
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Table 3: 
Trial Interventions 
Intervention 
Efgartigimod PH20 SC 
Prednisone (or equivalent) 
Type  
Biologic 
Non-IMP 
Dose 
formulation 
Efgartigimod 165 mg/mL or 180 mg/mL 
+ 2000 U/mL rHuPH20 solution for SC 
injection to be dosed at a fixed dose of 
1000 mg per injection 
Prednisone/prednisolone tablets for oral 
administration  
Unit dose 
strength(s) 
165 mg/mL or 180 mg/mL 
Prednisone 1 mg, 5 mg, 10 mg, 20 mg, 
50 mg 
Prednisolone 5 mg 
Dosage level(s) 
Weekly 1000 mg administrations until 
CRmin, for participants in DC or CR at 
rollover from ARGX-113-1904.  
 mg administered in separate 
sites on 
 followed by 
weekly 1000 mg administrations until 
CRmin, for participants under treatment 
failure in ARGX-113-1904, or 
participants starting a new treatment 
cycle. 
Refer to Section 6.5.1  
Route of 
administration 
Abdominal SC injection(s); preferred 
sitea 
Oral administration 
Use 
Investigational drug 
Non-IMP or concomitant therapy 
IMP  
IMP 
Non-IMP 
Sourcing 
Provided by the sponsor to the trial site 
Provided by the sponsor to the trial site, 
or sourced locally 
Packaging and 
labeling 
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 requirement, or as 
magistral preparation upon prescription 
by the investigator 
CR=complete clinical remission; CRmin=complete remission on minimal therapy; DC=disease control; 
IMP=investigational medicinal product; SC=subcutaneous 
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 of efgartigimod PH20 SC (with efgartigimod at a 
concentration of 165 mg/mL or 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 the higher concentration of efgartigimod 
(180 mg/mL) reduces the dosing volume for each SC injection. 
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6.2. 
Preparation/Handling/Storage/Accountability 
6.2.1. 
Preparation 
Efgartigimod PH20 SC will be provided as a sterile, clear to opalescent, colorless to yellowish 
solution for SC injection in glass vials. 
Efgartigimod PH20 SC will be manufactured in accordance with Good Manufacturing Practice 
regulations. Refer to the Pharmacy Manual for information about IMP preparation, including the 
volume of efgartigimod PH20 SC to be administered. Instructions on preparation and 
administration of IMP will be included in the on-site guide and home guide. 
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 efgartigimod PH20 SC. 
Only participants enrolled in the trial may receive efgartigimod PH20 SC and only authorized 
and trained site staff may supply or administer efgartigimod PH20 SC. Participants or their 
caregivers may also self-administer efgartigimod PH20 SC after they have successfully 
completed self-administration training (in ARGX-113-1904 with at least 1 refresher training in 
trial ARGX-113-1905 or training during ARGX-113-1905). All participants and/or their 
caregivers will receive a home guide for transport, storage, preparation, and administration of the 
IMP. 
6.2.3. 
Storage 
Efgartigimod PH20 SC 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, who will also 
provide the investigator with the certificate of analysis, certificate of conformity, and European 
Union qualified person release documents. 
Efgartigimod PH20 SC 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 
efgartigimod PH20 SC assigned to the clinical site, in a locked, secure storage facility with 
access limited to those individuals authorized to dispense efgartigimod PH20 SC and maintained 
within the appropriate temperature ranges. 
Further guidance and information for the final disposition of unused efgartigimod PH20 SC are 
provided in the Pharmacy Manual. 
For home administrations, the participant (or caregiver) is responsible for the correct storage 
of the IMP at home. Participants will receive a home guide for transport, storage, preparation, 
and administration. 
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6.2.4. 
Accountability 
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for efgartigimod PH20 SC accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records). 
Detailed instructions on accountability of efgartigimod PH20 will be included in the Pharmacy 
Manual. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
ARGX-113-1905 is open-label. No trial team members from the investigating staff, the sponsor 
(except the sponsor’s clinical trial supplies team in ARGX-113-1904), and the sponsor’s 
designated CRO (except the specialty laboratories responsible for PK, PD, and immunogenicity 
analysis), will have access to the information related to IMP treatment assigned in ARGX113-
1904 until after database lock for ARGX-113-1904.  
The blinding of PK, PD, and immunogenicity data for ARGX-113-1905 will be maintained until 
database lock of the main trial ARGX-113-1904. 
An independent unblinded data safety monitoring board (DSMB), including an independent 
statistician, may review all safety data as specified in Section 10.1.5. 
6.4. 
Trial Intervention Compliance 
The participants are dosed by qualified approved personnel. They will receive efgartigimod 
PH20 SC 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 after 
they have successfully completed training (in ARGX-113-1904 with at least 1 refresher training 
in trial ARGX-113-1905 or training during ARGX-113-1905). The date and time of each dose 
administered at the site will be recorded in the source documents and recorded in the electronic 
case report form (eCRF). In the case of home administration, the home nurse will record the date 
and time of each dose administered in the source documents for recording on 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 
administration cannot be changed. All dates, start and end time of efgartigimod PH20 SC 
administration, and any deviations from the intended regimen must be recorded on the eCRF. 
A sponsor’s designated CRO 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 CRO 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. 
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Site personnel will be informed of medication errors to ensure accuracy going forward. The 
sponsor’s designated CRO monitor’s report will include details of any missed doses, medication 
errors (Section 6.4.3), treatment or scheduling errors, and the associated explanations. It will be 
evaluated if these medication 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 CRO 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. 
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 before review and documented approval of an amendment 
from the Institutional Review Board/Independent Ethics Committee (IRB/IEC) and regulatory 
authority 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. 
6.4.3. 
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 which was assigned to that participant per the 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 on 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. 
6.5. 
Concomitant Therapy 
All concomitant medications and procedures, whether allowed or not, must be recorded on the 
eCRF (including the name, indication for use, dose/schedule, start and stop dates). 
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6.5.1. 
Concomitant Pemphigus Therapy 
At baseline, participants will be treated according to their clinical status at EoS 
of ARGX-113-1904, as follows: 
1. Participants who have achieved CRmin or CRoff and are currently not in flare will be 
observed every 4 weeks through on-site visits without efgartigimod PH20 SC treatment. 
In participants who have achieved CRmin (oral prednisone ≤10 mg per day for 2 months 
[8 weeks]), prednisone tapering may be pursued upon investigator’s judgment until 
participants achieve CRoff. 
2. Participants in CR who have not achieved CRmin will receive weekly efgartigimod PH20 
SC administrations of 1000 mg while continuing the add-on therapy of oral prednisone 
until CRmin is achieved. Prednisone tapering may be pursued upon investigator's 
judgment until participants achieve CRoff. Participants will be treated through on-site 
visits, or through home visits with an on-site visit once every 4 weeks. 
3. Participants who have achieved DC but not CR will receive weekly on-site 
administrations of 1000 mg efgartigimod PH20 SC with an add-on therapy of oral 
prednisone (Table 4) until CR has been achieved, and then will continue to receive 
weekly efgartigimod PH20 SC administrations of 1000 mg until CRmin is achieved 
either on site or through home visits with an on-site visit once every 4 weeks. 
4. Participants under certain conditions of treatment failure as defined below or participants 
with flare after having achieved CRmin, may roll over prematurely into ARGX-113-1905 
and will be treated with efgartigimod PH20 SC at a dose of 
 on 
 
followed by weekly administrations of 1000 mg with an add-on therapy of oral 
prednisone until CRmin.  
The following types of treatment failure are considered here: 
• absence of DC with oral prednisone 1.5 mg/kg/day for a minimum of 3 weeks 
• participants who roll over due to prednisone-related SAE who have not achieved DC, 
or 
• flare between DC and achieving CRmin that is not controlled by 2 dose levels of OCS 
above the dose at which the flare is observed and that is at least 0.3 mg/kg/day 
(Table 4) 
In the absence of DC, participants will receive prednisone at the starting dose of 
1.5 mg/kg/day. In case of uncontrolled flare before CRmin, participants will receive, as 
starting dose, the last dose from ARGX-113-1904. In case of flare after CRmin, 
participants will receive a prednisone dose in line with the severity of the flare, with the 
recommendation of a minimum of 0.3 mg/kg/day when the flare is of mild severity 
(PDAI activity score <15) and of 0.5 mg/kg/day when the flare is moderate to severe 
(PDAI activity score ≥15). Dosing of efgartigimod PH20 SC will be done during on-site 
visits or home visits according to Table 2.   
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5. Participants who developed a prednisone-related SAE may prematurely roll over into 
ARGX-113-1905 and may be treated with efgartigimod PH20 SC through on-site or 
home visits according to the clinical statuses as described above. Concomitant prednisone 
will be considered to fit the clinical statuses as described above if compatible with the 
nature and severity of the SAE, with a lower dose to no concomitant prednisone being 
considered otherwise.    
Participants or their caregivers (a person of legal age that the participant proposes to perform the 
administrations) may also self-administer efgartigimod PH20 SC after they have successfully 
completed self-administration training (in ARGX-113-1904 with at least 1 refresher training 
in ARGX-113-1905 or during ARGX-113-1905). All participants and/or their caregivers will 
receive a home guide for transport, storage, preparation, and administration of the IMP. 
At any postbaseline 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 (Table 4) 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 postbaseline visit before DC  
• Insufficient clinical change: the absence of DC after 3 to 4 weeks of the participant 
being treated at the starting baseline prednisone 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, and be withdrawn from the trial. 
For participants who achieve DC at a starting dose of 0.5 mg/kg qd or lower, the prednisone dose 
will be maintained at that starting dose qd until CR and 2 weeks thereafter, or EoC 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), that dose will be maintained until 2 weeks after achieving 
DC and then will be tapered in increments of 0.25 mg/kg (Table 4) every 2 weeks until the 
starting dose is achieved. Then the starting dose 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 (defined as the time at which no new 
lesions have developed for a minimum of 2 weeks and approximately 80% of lesions have 
healed) for 4 weeks. Further tapering will be performed thereafter, as long as CR or EoC are 
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sustained. The rules for tapering are shown in Table 4. 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 for at least 
8 weeks until CRmin is achieved. The prednisone dose can then be further tapered to reach 
CRoff according to the clinical judgment of the investigator,. 
At visits when at least 1 new lesion is observed or established lesions remain extensive without 
being defined as a flare (ie, 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), 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.  
In case of flare in the period between DC and CRmin, the prednisone dose will be increased to 
achieve DC again. 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 dose of OCS that is 2 dose levels above the dose at which the flare is 
observed and that is at least 0.3 mg/kg/day (Table 4), will be managed according to clinical 
judgment, ie, either receive a further increased prednisone dose or be withdrawn from the trial. 
Withdrawal of participants with a flare before CRmin will be defined as treatment failure.  
In case of flare after having achieved CRmin and thus while being off efgartigimod treatment, 
participants will be immediately treated/retreated with a new cycle of efgartigimod PH20 SC. 
The first day of new efgartigimod treatment will define a new baseline for assessments of 
outcomes (DC, CR, etc) and prednisone escalation or tapering schedule.  
In the new treatment cycle, participants will be administered efgartigimod PH20 SC at a dose of 
 for the first
 followed by weekly administrations of 1000 mg until CRmin. Oral 
prednisone will be administered at a dose chosen according to clinical judgment, with the 
recommendation of 0.3 mg/kg qd in the case of mild flare (PDAI activity score <15) and 
0.5 mg/kg qd in the case of moderate to severe flare (PDAI activity score ≥15). The treatment 
goal of a new treatment cycle is to first achieve DC again and therefore these participants will be 
treated accordingly (Table 2 ). 
Except for oral prednisone, no other systemic therapies (eg, immunosuppressants, IVIg, 
immunoadsorption, anti-CD20 biologics) will be permitted during the trial.  
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 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 4: 
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 
125mg 
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 
<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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6.5.2. 
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 recommended dietary allowance (RDA)/dietary 
reference intake (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  
• Other investigational drug 
6.6. 
Dose Modification 
Not applicable 
6.7. 
Intervention After the End of the Trial 
After a participant has completed the trial or has withdrawn/discontinued early, the usual 
treatment will be administered, if required, according to the trial site’s standard of care and 
generally accepted medical practice depending on the participant’s individual needs. 
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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 study 
intervention. Participants who discontinue the trial early, will complete all the assessments listed 
for the end of treatment visit as in the SoA (Section 1.3) and will be followed up for 8 weeks for 
ongoing safety and efficacy monitoring after the last dose of IMP. 
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 early termination visit (equivalent to EoT 
visit) should be conducted, as shown in the SoA (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 8-week 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 EoT 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 early discontinuation from the trial include: 
• It is in the participant’s best interest – discussion with the medical monitor of the CRO 
and the sponsor’s medical director is encouraged before 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 becomes 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 
• 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 the participant 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, the participant 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 (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 were 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. 
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 informed consent form 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 pages on the eCRF. 
Immediate safety concerns should be discussed first with the CRO’s medical monitor 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. 
For participants who had treatment failure in ARGX-113-1904 or a flare after CRmin, a 
minimum of 6 on-site visits (rollover [V1] to W6 or start of retreatment +5 weeks) are required 
before switching to home administrations, even if CR is achieved earlier. Home visits are 
allowed once a participant achieves CR but not before week 7 or start of retreatment +6 weeks. 
The investigator should call the participant every 2 weeks until CRmin to confirm the participant 
is still in CR and determine the safety status, clinical status (eg, new lesions), and prednisone 
tapering schedule. 
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 (Section 8.4), 
and the recording of concomitant therapy and procedures (Section 8.3.5). 
At all visits, the efficacy and QoL assessments should be performed first, before any other 
trial-specific procedure with the only exception of obtaining informed consent at baseline. 
The EQ-5D-5L and ABQOL should be performed before all other efficacy assessments 
(Section 8.2).  
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 administration-only visit. At this visit assessments 
need to be performed as follows: 
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- 
Assessments as specified in Table 5 
Note: In case of new lesions or flare, the assessments indicated with an “*” in 
Table 5 should be performed only once at the visit where the new lesions or the flare 
are/is confirmed. The assessments with an “*” should not be repeated at subsequent 
visits (even if more new lesions develop at these subsequent visits or the flare is 
sustained) unless when the subsequent visits coincide with planned observational or 
IMP administration-only visits and the assessments are to be performed for those 
visits per the SoA (Section 1.3). 
- 
Assessments as specified for the planned observational or IMP-administration-only 
visit, 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, participants need to switch to the visit schedule outlined in Table 2 or 
if they entered ARG-113-1905 per Table 2, will be immediately retreated with a new cycle of 
efgartigimod PH20 SC. The first day of new efgartigimod treatment will define a new baseline 
for assessments of outcomes (DC, CR, etc) and prednisone escalation or tapering schedule. 
Table 5: 
Assessments to be Performed During an Unscheduled Visita 
 
Assessment 
Unscheduled visit – 
any reason other than 
new lesions or flare 
Unscheduled visit – 
new lesions 
Unscheduled visit – 
flare 
Physical examination & vital 
signs 
X 
X* 
X* 
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 
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 
 
 
X* 
Vaccination antibodies 
 
 
X* 
Total IgG (no IgG subtypes) 
X 
 
 
IgG autoantibody subtypes 
and cytokines 
 
 
X* 
Photography (at selected sites) 
Per the judgment of the 
investigator 
Per the judgment of the 
investigator 
Per the judgment of the 
investigator 
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Assessment 
Unscheduled visit – 
any reason other than 
new lesions or flare 
Unscheduled visit – 
new lesions 
Unscheduled visit – 
flare 
IMP administration 
If the visit coincides 
with a planned IMP-
administration only 
visit 
If the visit coincides 
with a planned IMP-
administration only 
visit 
If the visit coincides 
with a planned IMP-
administration only 
visit 
Prednisone taper 
X 
X 
X 
AE monitoring 
X 
X 
X 
Concomitant therapies 
X 
X 
X 
a The unscheduled visit can coincide with a planned observational or IMP administration-only visit. 
Treatment-Free Follow-Up Period 
Participants who reach week 52 or discontinue early will enter the treatment-free follow-up 
period of 8 weeks. Week 60 follow-up visit will only be required for those participants who were 
still receiving efgartigimod for at least 1 visit between week 49 and week 52. For participants 
who ended treatment before week 49, week 56 will be the end of study visit. 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 per local regulations, no source data verification will be 
performed on race and ethnicity.  
8.2. 
Efficacy Assessments 
The efficacy of the IMP will be assessed at on-site and home 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 every 2 weeks until CRmin is achieved to confirm the 
participant is still in CR. 
Additionally, the clinical activity of pemphigus will be assessed using the PDAI (Section 10.6), 
which has been developed by the International Pemphigus Committee.13,14 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 
severe disease have a PDAI activity score of ≥45. 
8.3. 
Safety Assessments 
The planned time points for all safety assessments are provided in the SoA (Section 1.3). 
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8.3.1. 
Physical Examinations 
Physical examinations will be performed at the time points indicated in the SoA (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. 
At all trial visits, new clinically significant abnormal or worsened preexisting conditions will be 
reported as an AE. 
8.3.2. 
Height and Weight 
Weight will be measured and body mass index (BMI) will be calculated accordingly, at the 
rollover visit, at W26 (or the next on-site visit if W26 does not coincide with an on-site visit) and 
W52. Weight will be remeasured if there has been an obvious change in weight since the last 
measurement. For the assessment of weight, participants will be required to remove their shoes 
and wear light indoor clothing. 
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 (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. 
At all trial visits, new clinically significant abnormal or worsened preexisting vital sign 
abnormalities will be reported as an AE. 
8.3.4. 
Electrocardiography 
ECGs will be performed at the time points indicated in the SoA (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. 
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At all trial visits, new clinically significant abnormal or worsened preexisting ECG abnormalities 
will be reported as an AE. 
8.3.5. 
Medical and Surgical History 
Medical and surgical history will not be collected for this trial. All data regarding medical 
and surgical history for participants rolling into ARGX-113-1905 will come from the 
ARGX-113-1904 database. 
8.3.6. 
Clinical Safety Laboratory Assessments 
Blood and urine samples for determination of clinical chemistry, hematology, urinalysis, and 
serology (ie, viral testing) will be collected and analyzed at a central lab as indicated in the SoA 
(Section 1.3) and Section 10.2. The urine sample for the pregnancy test will be analyzed locally. 
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 770 mL for the entire duration of the study (or up to 
1056 mL for participants participating in the immunological profiling). 
For all female participants of childbearing potential, a urine pregnancy test will be conducted and 
analyzed locally at the site at the visits specified in the SoA (Section 1.3).  
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, it may be documented accordingly without being reported as AE. 
The details of sampling, handling, storage, and transportation of the samples will be described in 
the laboratory manual (refer to Section 10.5 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). 
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• 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 results must be recorded in the CRF. 
8.3.6.1. 
Vaccination Antibodies Testing 
Serum samples collected at visits according to the SoA (Section 1.3) may be used to analyze 
vaccination antibodies and response to vaccines possibly given during the trial, if applicable. 
Data from testing of vaccination antibodies will not be part of the clinical database and will be 
described in a separate report. 
8.3.6.2. 
Storage of Blood Samples in the Trial 
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 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 
Patients with pemphigus are prone to developing infections, including those 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.  
The following measures before and during the study are highly recommended: 
• To initiate or renew administration of non-live, inactivated, polysaccharide or 
recombinant vaccines (eg, tetanus, hepatitis A, hepatitis B, shingles)  
• To vaccinate participants who are especially prone to or with a history of respiratory 
infections against Pneumococcus or Streptococcus pneumoniae 
• To vaccinate participants with seasonal vaccines (eg, influenza virus), especially those 
susceptible to enter the trial in the winter months 
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• To screen for possible infections (eg, respiratory, skin, mouth, eyes, nose and throat, 
genitals) and, if appropriate, initiate antibiotic treatment  
• 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 and, subsequently, the 
sponsor’s medical monitor. 
Any vaccination received during the study should be recorded on the eCRF with the brand name 
of the vaccine and the date of vaccine administration. 
8.3.8. 
Injection Site Reactions 
An injection site reaction is any AE developing at the injection site. Localized injection site 
reactions are frequently observed in studies in which efgartigimod is comixed with rHuPH20 and 
administered SC. The most frequently reported injection site reaction AEs are injection site 
erythema, injection site pain, and injection site swelling. Most are nonserious and mild (CTCAE 
grade 1) and do not lead to disruption in IMP administration.  
Any injection site reaction will be reported as an AE (Section 10.3.3). Certain types of local 
reactions could be photographed and shared with the sponsor for review and assessment.  
As a routine precaution, participants should be trained or observed closely by a trained health 
care professional for any potential injection site reaction.  
8.3.9. 
Suicidal Ideation and Behavior Risk Monitoring 
Not applicable. 
8.3.10. 
Additional Safety Assessment 
As an additional assessment of the impact of glucocorticoid morbidity, the Glucocorticoid 
Toxicity Index (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.20 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.21 In this new version, 
the weights derived in the initial GTI validation study are used to generate 2 scores from the 
composite GTI (C-GTI), ie, the Cumulative Worsening Score (CWS) and the Aggregate 
Improvement Score (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. 
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The GTI is composed of 2 components:  
• The 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), 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 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 10.12. 
8.4. 
Adverse Events and Serious Adverse Events 
Definitions of AE and SAE are provided in Section 10.3 as well as guidelines for assessing 
causality and relationship to IMP. 
AEs will 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 
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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 (refer to Section 7). 
An unexpected AE is any adverse drug event, which 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. 
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 ICF until end of treatment or the last 
follow-up visit at the time points specified in the SoA (Section 1.3). 
All SAEs and AESIs will be recorded and reported to the sponsor or designee immediately 
and under no circumstance should this exceed 24 hours, as indicated in Section 10.3.3 and 
Section 10.3.4. 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 the conclusion of 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, to corticosteroid (non-IMP) use, or to 
trial participation, 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 10.3.3. 
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. 
Reporting of AEs and SAEs 
All AEs that occur during the trial, from signature of the ICF until the last trial-related activity 
are to be recorded on the appropriate AE pages (either “serious” or “nonserious”) 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 on the eCRF. 
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Any SAE, including death due to any cause, which occurs during this trial after signature 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 8.4.4 and Section 10.3.3. 
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. 
8.4.4. 
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 to the last trial-related activity will be followed up until 
resolution, until the participant is lost to follow-up, or until the participant withdraws consent 
(as defined in Section 7). 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 
(Section 10.4). 
For SAEs, AESIs (Section 8.4.8), nonserious 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 10.3.3. 
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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, Institutional Review Boards (IRB)/Independent Ethics Committees 
(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, per applicable 
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, per their local regulatory requirements. 
8.4.6. 
Pregnancy 
If a pregnancy is reported, the investigator will record pregnancy information on the appropriate 
form and submit it to the sponsor within 24 hours of learning of the female participant or female 
partner of male participant (after obtaining the necessary signed informed consent from the 
female partner) who is pregnant (Section 10.4). 
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. 
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8.4.7. 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying 
as Reportable AEs or SAEs for the Trial 
Not applicable. 
8.4.8. 
Adverse Events of Special Interest  
An AESI (serious or nonserious, 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 on 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. 
The characteristics of infections in the phase 2 trial ARGX-113-1701 with efgartigimod in 
pemphigus patients are summarized in Table 6. A total of 32 TEAEs related to infections were 
reported in 21 (61.8%) participants; among them, 7 events in 5 (14.7%) patients were assessed as 
probably or possibly related to efgartigimod, and the remaining 25 events were assessed as not or 
unlikely related to efgartigimod. 
Table 6: 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 
Participants with at least 1 TEAE 
Infections and infestations 
Nasopharyngitis 
Urinary tract infection 
Rhinitis 
Bronchitis 
Gastroenteritis 
Impetigo 
Pustule 
Bacteriuria 
Candida infection 
Conjunctivitis 
Folliculitis 
Oral herpes 
16 (84.2) 60 
11 (57.9) 15 
0 
1 (5.3) 2 
0 
2 (10.5) 2 
1 (5.3) 1 
1 (5.3) 1 
1 (5.3) 2 
1 (5.3) 1 
0 
1 (5.3) 1 
0 
1 (5.3) 1 
13 (86.7) 61 
10 (66.7) 17 
4 (26.7) 4 
2 (13.3) 2 
2 (13.3) 3 
0 
1 (6.7) 1 
1 (6.7) 1 
0 
0 
1 (6.7) 1 
0 
1 (6.7) 1 
0 
29 (85.3) 121 
21 (61.8) 32 
4 (11.8) 4 
3 (8.8) 4 
2 (5.9) 3 
2 (5.9) 2 
2 (5.9) 2 
2 (5.9) 2 
1 (2.9) 2 
1 (2.9) 1 
1 (2.9) 1 
1 (2.9) 1 
1 (2.9) 1 
1 (2.9) 1 
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Efgartigimod 
(10 mg/kg IV) 
(N=19) 
n (%) e 
Efgartigimod 
(25 mg/kg IV) 
(N=15) 
n (%) e 
Overall 
(N=34) 
n (%) e 
Pneumonia 
Pulpitis dental 
Respiratory tract infection 
Sialoadenitis 
Skin infection 
Tonsillitis 
Tooth infection 
Upper respiratory tract infection 
1 (5.3) 1 
0 
1 (5.3) 1 
1 (5.3) 1 
0 
1 (5.3) 1 
0 
0 
0 
1 (6.7) 1 
0 
0 
1 (6.7) 1 
0 
1 (6.7) 1 
1 (6.7) 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 
1 (2.9) 1 
1 (2.9) 1 
Source: ARGX-113-1701 CSR Table 14.3.1.2  
TEAE=treatment-emergent adverse events; IV=intravenous; N/n=number of participants; e=number of events 
Notes: Percentages are based on the number of participants in the Safety Analysis Set. Adverse event terms are 
coded by system organ class and preferred term 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 
Per the current efgartigimod IB, IRRs are defined as AEs within the standardized Medical 
Dictionary for Regulatory Activities (MedDRA) queries (SMQs) for hypersensitivity, 
anaphylactic reaction, and extravasation (excluding implant); all broad search applied; and all 
AEs that occurred within 48 hours of an infusion.  
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 comixed with rHuPH20 in single-dose SC administrations was well-tolerated 
in healthy participants 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). 
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. 
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Concentrations of efgartigimod will be determined using a validated assay. 
8.6. 
Pharmacodynamics 
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 (within 
2 hours before IMP). 
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. 
Immunogenicity Assessments 
Blood samples to test for an immunogenic response against efgartigimod and rHuPH20 will be 
collected as indicated in the SoA (Section 1.3). Sampling will occur predose on IMP 
administration visits.  
All samples will be analyzed in a 3-tiered approach using validated immunogenicity methods. 
First, all samples will be evaluated in a screening assay (tier 1) and scored positive or negative. 
Second, screened positive samples will be evaluated in a confirmatory assay (tier 2) to assess the 
specificity of the immunogenicity response. The samples will be scored confirmed positive or 
confirmed negative. Samples confirmed positive in tier 2 will be further analyzed in a titration 
assay to characterize the magnitude of the antibody response and a neutralizing antibody (NAb) 
assay to assess the antibodies for neutralizing activity (tier 3). 
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. 
8.8. 
Exploratory Research 
8.8.1. 
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.15 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. 5,15,16  
Efgartigimod, an FcRn inhibitor that gives a targeted reduction of IgG antibodies of all 
subtypes,18 has been evaluated in the treatment of patients with MG,11 ITP,12 and pemphigus 
(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 Dsg-3 whole 
extracellular domains) with clinical observations. 
Blood samples for this exploratory research will be collected as indicated in the SoA 
(Section 1.3).  
8.8.2. 
Immunological Profiling 
Immunological profiling in the antecedent study ARGX-113-1904 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. Analysis in 
ARGX1131905 is restricted to specific analysis of lymphocyte populations in selected sites and a 
limited number of participants for long-term follow-up. Additionally, all patients in CRmin or 
CRoff will be sampled for lymphocyte populations at on-site visits at W52 (±2 weeks) or 
EoT/ET and EoS. 
Blood samples will be collected as indicated in the SoA (Section 1.3). 
8.9. 
Imaging 
For illustrative purposes, pictures of different anatomical regions may be taken at selected sites 
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 time points. 
Photography is generally accepted as routine practice for documenting dermatological conditions 
in medical practice. Photographs will be taken only at baseline for participants not in CR or with 
a flare 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. 
8.10. 
Medical Resource Utilization and Health Economics 
Refer to Section 8.11. 
8.11. 
Quality of Life and Patient-Reported Outcomes 
The participant will complete the patient-reported outcome instrument (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 (Section 10.7). 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) 
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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 the daily life of the patient (refer to Section 10.8).19  
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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. 
9.1. 
Statistical Methods 
9.1.1. 
Statistical Methods and Plan 
A detailed and comprehensive Statistical Analysis Plan (SAP) will be written and signed off 
before the interim and 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. 
Although this is an open-label trial, the blinding of PK, PD, and immunogenicity data for 
ARGX-113-1905 will be maintained until after database lock of ARGX-113-1904. A summary 
of the plan is described below.  
All comparisons of endpoints between prior treatment groups will be purely descriptive.  
9.1.2. 
Safety (Primary Endpoints) 
All clinical safety outcomes will be reported using descriptive statistics in the form of summary 
tables. Wherever it is suitable, respective graphical displays will be presented along with the 
summary tables. The main safety primary endpoints will be summaries from the following 
sections of each endpoint.  
• Incidence and severity of: 
− TEAEs 
− AESIs 
− SAEs  
• Vital signs and physical examination  
• ECG 
• Clinical laboratory test results (hematology, clinical chemistry, urinalysis) 
9.1.3. 
Secondary Endpoints 
All efficacy endpoints will be evaluated descriptively and presented as summary tables on 
following efficacy secondary endpoints. 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. 
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Efficacy Endpoints 
• Proportion of participants with PV who achieve CRmin  
• Proportion of participants with PV and PF who achieve CRmin  
• Time to DC  
• Time to CR  
• Time to CRmin  
• Time to CRoff  
• Time to flare  
• Rate of treatment failure  
• Rate of flare  
• Cumulative prednisone dose over the trial  
• PDAI at each visit  
Health-related Quality of Life  
• ABQOL score  
• EuroQol 5-Dimension 5-Level (EQ-5D-5L) Scale  
Treatment Self-administration  
• Percentage of participants who performed self-administration 
• Percentage of caregivers who administered the injection to the participant 
• Number of visits needed for the participant or caregiver to be competent to start 
administering efgartigimod PH20 SC 
• Frequency of self- or caregiver-supported administration at home  
Additionally, the health impact of glucocorticoid (GC) use in participants with PV or PF will be 
assessed using C-GTI and GTI-SL. 
9.1.4. 
Pharmacodynamics, Pharmacokinetics, and Immunogenicity 
Descriptive statistics will be provided for efgartigimod serum concentrations, PD levels (total 
IgG and subtypes), anti-Dsg1 and anti-Dsg3, and immunogenicity. 
9.2. 
Statistical Hypotheses 
Not applicable. There is no specific statistical hypothesis that will be tested in this open-label 
study. 
9.3. 
Sample Size Determination 
Not applicable for this OLE trial. 
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9.4. 
Populations for Analysis 
The following populations are defined: 
Population 
Description 
Safety set 
All participants who received at least 1 dose, or part of a dose, of IMP 
Rollover set 
All participants who rolled over from the ARGX-113-1904 study 
The safety set is used for safety analysis (except for the analysis of C-GTI and GTI-SL). In 
general, the rollover set is used for efficacy evaluation (according to the treatment the participant 
was randomized to in the ARGX-113-1904 study). All details on the specific analysis of an 
endpoint in a specific population will be provided in the SAP. 
9.5. 
Statistical Analyses 
The SAP will be finalized before 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 secondary 
endpoints. 
9.5.1. 
General Considerations 
The baseline value for study ARGX-113-1905 will be the value at the last visit in 
ARGX-113-1904.  
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. 
Participant Disposition 
Participant disposition will be summarized in a table. It will include the number of participants 
enrolled previously on placebo and efgartigimod in ARGX-113-1904, who 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 for the overall trial period and, where relevant, by previous treatment group. 
9.5.3. 
Analysis Sets and Protocol Deviations 
The number of participants for the analysis set will be presented as described in Section 9.4. 
Major protocol deviations, by previous treatment group in ARGX-113-1904, 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 (Section 9.1) and listed. 
9.5.5. 
Primary Endpoint(s) 
Exposures to IMP and prednisone will be summarized. The safety analysis will be analyzed 
overall but also by status at entry into ARGX-113-1905. 
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. AEs 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. Clinically significant laboratory abnormalities 
will be summarized descriptively. 
9.5.6. 
Secondary Endpoints 
All secondary endpoints will be presented with descriptive summary statistics. All data collected 
will be listed, together with derived variables. Graphical displays will show efficacy variables 
over time.  
Descriptive statistical methods will be used to analyze all secondary efficacy data. In addition, 
summaries for certain subgroups if defined will also be presented. For time to event endpoints, 
survival curves will be estimated using the Kaplan-Meier time to event method. Summary 
statistics and summary plots will be presented for all other endpoints including other endpoints 
including CWS and AIS (as components of C-GTI) and the complementary GTI-SL, QoL, PK, 
PD, immunogenicity, and self-administration. More details for the analysis of the endpoints will 
be described in the SAP. 
Analyses will not only refer to the baseline of ARGX-113-1905, but the baseline of 
ARGX1131904 will be used for specific analysis as stated in the SAP for this OLE trial. 
More detailed descriptions will be presented in the SAP of the study. 
9.5.7. 
Other Endpoints 
Results from the exploratory research will not be part of the clinical database and will be 
described in a separate report. 
9.5.8. 
Missing Data Handling 
Details on handling missing data will be provided in the SAP. 
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9.6. 
Interim Analyses  
Interim analyses may be performed in support of potential regulatory authority interactions. 
9.7. 
Data Safety Monitoring Board  
Refer to Section 10.1.5.  
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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
This study will be conducted 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, Investigator Brochure, 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 
before 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 study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/IEC 
• Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
• Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 536/2014 for clinical 
studies (if applicable), and all other applicable local regulations 
10.1.2. 
Financial Disclosure 
The sponsor will fund the study as outlined in the clinical study agreement. 
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The sponsor will obtain adequate global/local insurance for the study participants including the 
study participants for the required duration of time. 
The sponsor maintains an insurance coverage for this study in accordance with the laws and 
regulations of the countries in which the study is performed. Liability and insurance provisions 
for this study 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 
Before signing the ICF, the study participants will be instructed not to participate in any other 
clinical study that involves an intervention or collection of data until the completion of the 
current study. 
Any participant who provides informed consent is being 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 study, 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 study 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 study, that meets the requirements of 21 CFR 50, local regulations, ICH 
guidelines, Health Insurance Portability and Accountability Act requirements, where applicable, 
and the IRB/IEC or study center. 
The ICF will be used to explain the potential risks and benefits of study 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 study 
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 before any study-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 informed consent 
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document before the performance of any protocol procedures and before the administration of 
IMP. 
Participants must be re-consented to the most current version of the ICF(s) during their 
participation in the study. 
A signed and dated copy of the ICF(s) must be provided to the participant. 
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 which would make the participant identifiable will not be transferred.  
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the 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 only at baseline for participants not in CR or with 
a flare 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 study management. They will be supplemented by an 
independent statistician. The DSMB may unblind the data collected during ARGX-113-1904, 
for the sake of the participant's safety in the study. 
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 study by either the 
sponsor or the DSMB. The DSMB will advise the sponsor regarding continuation, modification, 
or termination of the study after every meeting. 
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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 Study Data 
The sponsor or designee, and auditor may access participant records for the purpose of 
monitoring this study, 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 level of protection. 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 study. 
The investigator is responsible for maintaining source documents. These will be made available 
for verification by the sponsor’s designated CRO monitor at each monitoring visit. The 
investigator must submit an eCRF for each participant, regardless of duration of participation or 
administration of IMP. All supportive documentation submitted with the eCRF, such as 
laboratory or hospital records, should be clearly identified with the study 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 study will be recorded on printed or 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 eCRF. 
The investigator must maintain accurate documentation (source data) that supports the 
information entered on the eCRF. Only if requested per local regulations, no source data 
verification will be performed on race and ethnicity. 
The investigator must permit study-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 study including quality 
checking of the data.  
The sponsor assumes accountability for actions delegated to other individuals (eg, CROs). 
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Study monitors will perform ongoing source data verification to confirm that data entered into 
the eCRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
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 study documents (records and 
documents pertaining to the conduct of this study 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 study site 
should plan on retaining such documents for approximately 25 years after study completion. The 
study 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. 
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 study is being 
conducted. Participant identification codes (participant names and corresponding study 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 before 
changing the location or status of any essential clinical study documents. The investigator must 
contact the sponsor before disposing of any study 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 
Study processes, study sites (including, but not limited to site visits, central laboratories, 
vendors), the study database, and study documentation may be subject to quality assurance audit 
during the course of the study 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 study. 
10.1.7.3. Quality Control 
Quality control will be applied to each stage of study-related activities. 
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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 CRO monitors of safety parameters and 
adherence to selection criteria 
• Data management quality control checks 
• Continuous data acquisition and cleaning 
• Quality control check of the clinical study report (CSR) 
• 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 
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 study-related 
documents including medical history and concomitant medication documentation to 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 on 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. 
Definition of what constitutes source data can be found in the source data agreement, defined per 
site and agreed upon between the CRO and the investigator. 
The investigator must maintain accurate documentation (source data) that supports the 
information entered on the eCRF. 
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Study monitors will perform ongoing source data verification to confirm that data entered into 
the eCRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted 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. The sponsor’s designated CRO monitors will work in 
accordance with the SOPs of the CRO. 
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 CRO 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 CRO monitor will perform an eCRF review, source document 
verification (wherever allowed per local regulations), and source document review. 
The source documentation agreement form describes the source data for the different data on the 
eCRF. This document should be completed and signed by the sponsor’s designated CRO 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 CRO 
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 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. 
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, per local 
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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. Appropriate training 
and security measures will be completed by the investigator and all designated site staff before 
the study is 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 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. Before 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 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. 
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 on the 
eCRF before it can be merged with the eCRF data into the clinical database. The CRO will 
provide a data management plan detailing this reconciliation. 
Adverse events, 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 (WHO DD). The generic 
name, the preferred name, and the WHO name will be assigned using the WHO DD thesaurus. 
The anatomical therapeutic chemical classes will be assigned to the prior and concomitant 
medications and procedures. Concomitant procedures will be coded according to the MedDRA 
thesaurus. 
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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, and any CRO(s) used in 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. 
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 CRO monitor and other 
contact personnel at the sponsor and the CRO are listed in the investigator study file provided to 
each site. 
The investigator is responsible for ensuring that all study site personnel, including 
subinvestigators, adhere to all applicable regulations and guidelines, including local laws and 
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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 which 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. Subinvestigators 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 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 
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 CSR. 
The CSR 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 before 
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 
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:   
Protocol-Required Laboratory Assessments 
Hematology 
Hemoglobin, hematocrit, mean corpuscular volume (MCV), red blood cell 
(RBC) count, platelet count, white blood cell (WBC) count with differential 
Clinical chemistry 
Sodium, potassium, calcium, HbA1c, creatinine, creatinine clearance, blood urea 
nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase 
(AST), total bilirubin, gamma-glutamyl transferase (GGT), low-density 
lipoprotein cholesterol (LDL-C), C-reactive protein (CRP), alkaline phosphatase 
(ALP), lactate dehydrogenase (LDH), uric acid, total protein, and albumin 
Urinalysis 
Specific gravity, pH, protein, glucose, ketones, blood, bilirubin, urobilinogen, 
nitrite, leukocyte esterase, and microscopic examination (if blood or protein is 
abnormal) 
Pharmacokinetics 
Serum levels of efgartigimod 
Pharmacodynamic markers 
Serum levels of total IgG and IgG subtypes (IgG1, IgG2, IgG3, and IgG4) and 
anti-Dsg-1 and anti-Dsg-3 autoantibodies  
Immunogenicity 
Serum levels of antidrug antibodies (ADA) to efgartigimod. Plasma levels of 
antibodies produced against recombinant human hyaluronidase (rHuPH20) to be 
tested in case of safety concerns. 
Local evaluations 
Urine pregnancy test 
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10.3. 
Appendix 3: Adverse Events: Definitions and Procedures 
for Recording, Evaluating, Follow-up, and Reporting 
10.3.1. 
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. 
 
Definitions of Unsolicited and Solicited AEs 
• 
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 nonserious 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 preexisting 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 preexisting disease(s) or condition(s) present or 
detected at the start of the study that do not worsen. 
10.3.2. 
Definition of SAE 
An 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 preexisting condition that did not worsen from baseline 
is 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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An 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. 
10.3.3. 
Recording and Follow-Up of AE and/or SAE 
AE and SAE Recording 
When an AE/SAE occurs, it is the responsibility of the investigator to review all documentation 
(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) 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 semicolon 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; and 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 participant’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 
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Assessment of Causality 
always make an assessment of causality for every event before the initial transmission of the SAE 
data. 
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 
the CIOMS. Unrelated and Unlikely will be merged into “Unrelated” and Related, Possible and 
Probable 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. 
10.3.4. 
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’s/designee’s safety mailbox via the eDC system.  
• The paper SAE report form will be faxed or emailed to the sponsor/designee (see Safety 
Mailbox/Fax details on page 2 of this protocol). 
 
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10.4. 
Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information 
10.4.1. 
Definitions 
10.4.1.1. 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 (eg, hysterectomy, bilateral salpingectomy, or bilateral oophorectomy). 
10.4.2. 
Contraception Guidance 
10.4.2.1. Female Contraception for Women of Childbearing Potential  
WOCBP must use 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:  
• Combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulation  
− Oral  
− Intravaginal  
− Transdermal  
• Progestogen-only hormonal contraception associated with inhibition of ovulation  
− Oral  
− Injectable  
− Implantable  
• Intrauterine device (IUD)  
• Intrauterine hormone-releasing system (IUS)  
• Bilateral tubal occlusion  
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• Vasectomized partner  
• Sexual abstinence 
Acceptable methods of contraception are: 
• Progestogen-only hormonal contraception in which inhibition of ovulation is not the 
primary mode of action 
− Oral 
− Injectable 
− Implantable 
• Male or female condom with or without spermicide 
• Cap, diaphragm, or sponge with spermicide 
10.4.2.2. Male Contraception 
An acceptable method of contraception is a condom. 
10.4.3. 
Collection of Pregnancy Information 
10.4.3.1. Male Participants With Partners Who Become Pregnant 
• Male participants will be instructed by 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 (refer to 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. 
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10.4.3.2. Female Participants Who Become Pregnant 
• 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 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 IMP treatment. 
− The participant should have the early termination assessments and enter the follow-up 
period. 
− All assessments for early termination (refer to Section 1.3) 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 (refer to 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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10.5. 
Appendix 5: Administrative Structure 
 
Central Laboratories 
Cerba Research NV 
Industriepark Zwijnaarde 3 
B-9052 Gent 
Belgium 
Analysis of Pharmacokinetics (PK) and Antidrug Antibodies (ADA) 
LGC 
Newmarket Road 
Fordham 
Cambridgeshire 
CB7 5WW 
United Kingdom 
Antibodies and Neutralizing Antibodies Against rHuPH20 
Labcorp Bioanalytical Services LLC 
8211 Scicor Drive, Suite B 
Indianapolis, IN 46214 
US 
Total IgG and IgG Subtypes 
Pharmaceutical Product Development (PPD) Central Lab 
2 Tesseneer Drive  
Highland Heights, KY 41076 
US 
Long-Term Storage of Pharmacokinetics-Pharmacodynamics (PK-PD) and Immunogenicity 
Azenta Life Science  
Im Leuschnerpark 1b 
64347 Griesheim 
Germany 
Central ECG Reading 
Clario 
1818 Market Street, Suite 2600 
Philadelphia, PA 19103 
US 
Trial Monitoring/Medical Monitoring 
PPD Global Ltd. 
11 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 
Urinalysis – 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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10.6. 
Appendix 6: Pemphigus Disease Area Index (PDAI) Scoring System 
 
Copyright © 2007 University of Pennsylvania; All Rights Reserved 
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10.7. 
Appendix 7: EQ-5D-5L Scale  
 
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10.8. 
Appendix 8: Autoimmune Bullous Disease Quality of Life (ABQOL) 
Questionnaire 
 
 
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10.9. 
Appendix 9: Definition of Terms 
Complete clinical remission (CR):  
The absence of new lesions and complete healing of established lesions (except for 
postinflammatory 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 at ≤10 mg/day for at least 2 months (8 weeks). Note: when 10 mg/day is 
reached in ARGX-113-1904 or ARGX-113-1905, this dose level must be maintained for 8 weeks 
until CRmin has been achieved. 
Complete remission off therapy (CRoff): 
The absence of new and established lesions completely healed while the participant is receiving 
no prednisone therapy for at least 2 months (8 weeks). 
Council for International Organizations of Medical Sciences: 
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 ADR/suspected unexpected serious adverse reaction in clinical trials. 
Contract research organization: 
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 the database 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, 
when appropriate, efficacy, and to make recommendations to the sponsor concerning the 
continuation, modification or termination of the trial. 
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Disease control (DC):  
The absence of new lesions and the start of healing of established lesions. 
Disease progression:  
Increase of ≥5 points in the PDAI activity score, observed at any postbaseline 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 (IRB/IEC): 
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 
participants 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 participants. 
Informed consent/informed consent form: 
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. 
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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. 
International Council for Harmonisation of Technical Requirements for Pharmaceuticals 
for Human Use (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. 
Protocol amendment: 
A written description of a change(s) to or formal clarification of a protocol. 
Randomization: 
Process of random attribution of treatment to participants 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 the presence of new lesions that heal 
within 1 week. Persistent new lesions are defined as the presence of 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:  
The absence of DC with oral prednisone 1.5 mg/kg/day for a minimum of 3 weeks, or flare 
before CRmin resulting in withdrawal of the participant. 
 
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10.10. 
Appendix 10: Abbreviations 
Abbreviation/Term 
Expansion/Definition 
ABQOL 
Autoimmune Bullous Disease Quality of Life 
ABSIS 
Autoimmune Bullous Skin disorder Intensity Score 
AChR-Ab 
acetylcholine receptor–antibody 
ADA 
antidrug antibodies 
ADR 
adverse drug reaction 
AE 
adverse event 
AESI 
adverse event of special interest 
AIS 
aggregate improvement score 
ALT 
alanine aminotransferase 
ALP 
alkaline phosphatase 
BMI 
body mass index 
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 Science 
CPK 
creatine phosphokinase 
CR 
complete clinical remission 
CRmin 
complete remission on minimal therapy 
CRO 
contract research organization 
CRoff 
complete remission off therapy 
CSR 
clinical study report 
CTCAE 
common terminology criteria for adverse events 
CWS 
cumulative worsening score 
DC 
disease control 
Dsg  
desmoglein  
DSMB 
data safety monitoring board 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
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Abbreviation/Term 
Expansion/Definition 
ED 
early discontinuation 
ENT 
ear-nose-throat 
EoC 
end of consolidation 
EoS 
end of study  
EoT 
end of treatment 
EQ-5D-5L 
EuroQol Five-Dimension Five-Level Scale 
ET 
early termination  
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 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use  
IEC 
Independent Ethics Committee  
IgG 
immunoglobulin gamma 
IMP 
investigational medicinal product 
IND  
investigational new drug  
IRB  
Institutional Review Board  
IRR 
infusion-related reaction 
IRT 
interactive response technology 
ITP 
immune thrombocytopenia 
IV 
intravenous 
IVIg 
IV immunoglobulin 
MCV 
mean corpuscular volume 
MedDRA  
Medical Dictionary for Regulatory Activities  
MG 
myasthenia gravis 
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Abbreviation/Term 
Expansion/Definition 
MG-ADL 
Myasthenia Gravis Activities of Daily Living  
NAb 
neutralizing antibodies 
OCS 
oral corticosteroids 
OLE 
open-label extension 
PD 
pharmacodynamic 
PDAI 
Pemphigus Disease Area Index 
PF 
pemphigus foliaceus 
PK 
pharmacokinetics 
PPD 
Pharmaceutical Product Development 
PPE 
personal protective equipment 
PT 
preferred term 
PV 
pemphigus vulgaris 
qd 
daily 
QoL 
quality of life 
QTcF 
Fridericia corrected QT interval 
rHuPH20 
recombinant human hyaluronidase PH20 
RBC 
red blood cell 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SC 
subcutaneous 
SoA 
schedule of activities 
SOC 
system organ class 
SOP 
standard operating procedure 
SUSAR 
suspected unexpected serious adverse reaction 
TEAE 
treatment-emergent adverse event 
US 
United States 
WBC 
white blood cell 
WHO 
World Health Organization 
WHO-DD 
World Health Organization Drug Dictionary 
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10.11. 
Appendix 11: Possible Adaptations of Trial Protocol During 
COVID-19 Pandemic 
Introduction 
The aim of ARGX-113-1905 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 those who have pemphigus. 
argenx BV has performed a critical assessment of the use of efgartigimod during the COVID-19 
pandemic. Based on the risk-benefit assessment, ARGX-113-1905 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 (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 to ensure the safety of the 
participant while simultaneously maintaining 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-113-1905 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 to 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 on 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 when he/she is in the trial, 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 before 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. 
The impact of the COVID-19 pandemic on argenx BV clinical trials is outlined in Figure 2. 
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Figure 2: 
Impact of COVID-19 Pandemic on argenx BV Clinical Trials 
 
 
 
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. 
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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, they can continue the trial and receive trial medication, 
provided that they have not received/are not receiving prohibited medication (Section 6.5.2). 
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 which are mandatory to be collected during the trial, are summarized 
below: 
Eligibility 
• ICF 
• Participation in ARGX-113-1904 
• Other parameters to confirm eligibility (refer 
to Section 5.1 and Section 5.2) 
Efficacy 
• Disease assessment (DC, EoC, CR, 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 
Schedule of Activities (SoA) in Section 1.3 and Table 8 and Table 9. 
• 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). 
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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 and other visits can be at home*: 
• Rollover Visit  
The rollover visit has to be be performed at the study site. If it is not possible to go to the study 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.  
• Start of retreatment in case of flare after CRmin (while being off efgartigimod therapy) 
Confirmation of flare and start of retreatment has to be performed at the trial site. If it is not possible 
to go to the trial site due to the COVID-19 situation, retreatment should not be initiated. 
• Other Trial Visits 
During the COVID-19 pandemic, study visits after the rollover visit or start of retreatment 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 AEs, concomitant 
medications, and their general wellbeing; the investigator will also perform efficacy assessments via 
the audio/video interview. 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 scheme below. 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 will be administered through self- or caregiver-supported 
administration, provided that the participant or caregiver has completed the training and has been 
deemed competent. 
• Week 52/EoT/ET 
The week 52/EoT/ET 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. 
 
                                                 
 
 
 
*Note that a “home visit” as described in this appendix could also be a visit at an alternative convenient location. 
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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) 
• 
AEs 
• 
Concomitant medication (including prednisone 
dosage) 
• 
Vital signs 
• 
IMP administration 
• 
Blood sampling  
• 
Urine collection 
Home nurse 
In person at participant’s 
homea 
AEs=adverse events; CR=complete clinical remission; DC=disease control; EoC=end of consolidation; 
ICF=informed consent form; IMP=investigational medicinal product 
a A “home visit” could also be a visit at an alternative convenient location. 
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, and ADA every 4 weeks for 
participants in CR. For those who are not in CR at rollover or are starting retreatment, blood 
samples will be collected weekly until week 6 and then every 4 weeks until week 60. 
Additionally, urine samples will be collected for urinalysis using the same schedule, and urine 
pregnancy testing will be performed every 4 weeks. 
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• ECG 
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 will be administered by authorized staff either at the site during scheduled visits or at home 
visits by a home nurse. In addition, participants or their caregivers may self-administer IMP after 
they have successfully completed self-administration training (in ARGX-113-1904 with at least 
1 refresher training in ARGX-113-1905, or training during ARGX-113-1905).  
Trial Endpoint 
The criteria for the trial endpoint for a participant as described in the main protocol, also apply to 
this appendix.
System Version: 1.0, Status: Approved, Document ID: VV-TMF-86295

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Table 8: 
Modified Schedule of Activities During COVID-19 Pandemic for ARGX-113-1905 for Participants in CR, 
CR on Minimal Therapy, and CR off Therapy at Rollover From ARGX-113-1904 
In the Schedule of Activities (SoA) tables for ARGX-113-1905 (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 
Open-label extension 
 
 
Follow-up 
Visit number 
V1 
Roll 
overa 
V1   
+ 4 
weeks 
V1   
+ 8 
weeks 
V1   
+ 12 
weeks 
V1   
+ 16 
weeks 
V1   
+ 20 
weeks 
V1    
+ 24 
weeks 
V1   
+ 28 
weeks 
V1   
+ 32 
weeks 
V1   
+ 36 
weeks 
V1   
+ 40 
weeks 
V1   
+ 44 
weeks 
V1   
+ 48 
weeks 
V1  
+ 51 weeks 
EoT/ET 
UNSb 
Safety 
follow-
up 1 
EoT/ET 
+ 4 weeksc 
Safety 
follow-
up 2 
EoT/ET 
+ 8 weeks 
EoSc 
Assessment/procedure 
±0 
days 
±2 daysd 
 
 
±3 daysd 
±3 daysd 
Informed consent  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weighte 
X 
 
 
 
 
 
Xe 
 
 
 
 
 
 
X 
 
 
 
ECGf,g 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
X 
 
X 
X 
Physical examination and 
vital signsf,h 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysisf,i 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xb 
X 
X 
Urine pregnancy testf,j 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xb 
X 
X 
Vaccination antibodiesf 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xb 
X 
X 
Blood sampling 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• clinical chemistry and 
hematologyf,k 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xb 
X 
X 
System Version: 1.0, Status: Approved, Document ID: VV-TMF-86295

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Trial period 
Open-label extension 
 
 
Follow-up 
Visit number 
V1 
Roll 
overa 
V1   
+ 4 
weeks 
V1   
+ 8 
weeks 
V1   
+ 12 
weeks 
V1   
+ 16 
weeks 
V1   
+ 20 
weeks 
V1    
+ 24 
weeks 
V1   
+ 28 
weeks 
V1   
+ 32 
weeks 
V1   
+ 36 
weeks 
V1   
+ 40 
weeks 
V1   
+ 44 
weeks 
V1   
+ 48 
weeks 
V1  
+ 51 weeks 
EoT/ET 
UNSb 
Safety 
follow-
up 1 
EoT/ET 
+ 4 weeksc 
Safety 
follow-
up 2 
EoT/ET 
+ 8 weeks 
EoSc 
Assessment/procedure 
±0 
days 
±2 daysd 
 
 
±3 daysd 
±3 daysd 
• anti-Dsg-1 and anti-
Dsg-3 antibodies 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xb 
X 
X 
• PKl 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xb,m 
X 
X 
• Total IgG and IgG 
subtypesf,l 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xb 
X 
X 
• immunogenicityf,n 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
• IgG autoantibody 
subtypes and 
specificityf 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xb 
X 
X 
PDAIf 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ABQOLf,o 
X 
at CRmin (or the next on-site visit) 
X 
 
 
 
EQ-5D-5Lf,o 
X 
at CRmin (or the next on-site visit) 
X 
 
 
 
Disease assessmentf,p 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Lymphocyte populations 
(at selected sites)q 
X 
 
 
X 
 
 
X 
 
 
 
X 
 
 
X 
 
X 
X 
GTI 
X 
 
 
 
 
 
Xr 
 
 
 
 
 
 
Xr 
 
 
 
IMP self-administration 
trainings 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Efgartigimod PH20 SCt 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
System Version: 1.0, Status: Approved, Document ID: VV-TMF-86295

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Trial period 
Open-label extension 
 
 
Follow-up 
Visit number 
V1 
Roll 
overa 
V1   
+ 4 
weeks 
V1   
+ 8 
weeks 
V1   
+ 12 
weeks 
V1   
+ 16 
weeks 
V1   
+ 20 
weeks 
V1    
+ 24 
weeks 
V1   
+ 28 
weeks 
V1   
+ 32 
weeks 
V1   
+ 36 
weeks 
V1   
+ 40 
weeks 
V1   
+ 44 
weeks 
V1   
+ 48 
weeks 
V1  
+ 51 weeks 
EoT/ET 
UNSb 
Safety 
follow-
up 1 
EoT/ET 
+ 4 weeksc 
Safety 
follow-
up 2 
EoT/ET 
+ 8 weeks 
EoSc 
Assessment/procedure 
±0 
days 
±2 daysd 
 
 
±3 daysd 
±3 daysd 
Prednisone taperu 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Concomitant 
therapies/procedures  
Continuous monitoring 
AE monitoring 
Continuous monitoring 
ABQOL=Autoimmune Bullous Disease Quality of Life; AE=adverse events; ALT=alanine aminotransferase; ALP=alkaline phosphatase; AST=aspartate 
aminotransferase; BMI=body mass index; BUN=blood urea nitrogen; CR=complete clinical remission; CRmin=CR on minimal therapy; CRP=C-reactive protein; 
DC=disease control; Dsg=desmoglein; ECG=electrocardiogram; EoC=end of consolidation; EoS=end of study; EoT=end of treatment; EQ-5D-5L=EuroQol 
5-dimension 5-level scale; ET=early termination; GGT=gamma-glutamyl transferase; GTI=Glucocorticoid Toxicity Index; IgG=immunoglobulin type G; 
IMP=investigational medicinal product; LDH=lactate dehydrogenase; LDL-C=low-density lipoprotein cholesterol; MCV=mean corpuscular volume; NAb=neutralizing 
antibody; PDAI=Pemphigus Disease Area Index; PD=pharmacodynamic; PK=pharmacokinetics; QTcF=Fridericia corrected QT interval; rHuPH20=recombinant 
human hyaluronidase PH20; RBC=red blood cells; SC=subcutaneous(ly); UNS=unscheduled visit; W=week; WBC=white blood cells; V=visit at site 
a For participants who roll over from ARGX-113-1904 to ARGX-113-1905, the baseline visit will occur for these participants at the same visit as the EoS/ED visit in 
study ARGX-113-1904. All assessments will be performed before IMP administration. 
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. Refer to Section 8 for more information. Participants with new 
lesions or flare after achieving CR should return to weekly on-site visits. Participants with flare who had achieved CRmin or CRoff should switch to the visit schedule 
outlined in Table 9. 
c Follow-up 1 will be the EoS visit for participants who ended treatment before W49 or 4 weeks before ET. Both follow-up visits will be required only for participants 
who continue to receive efgartigimod PH20 SC for at least 1 visit between W49 and W52 or during the last 4 weeks before ET. 
d Study visit windows are ±2 days during the treatment period and ±3 days for the follow-up visits. 
e Weight will be measured and BMI will be calculated accordingly, at the rollover visit, at W26 (or the next on-site visit if W26 does not coincide with an on-site visit) 
and W52. Weight will also be measured if there has been an obvious change since the last measurement. 
f Assessment or procedure will be completed predose at visits when IMP is administered. 
g The ECG will be recorded at baseline, every 3 months while receiving efgartigimod PH20 SC treatment, at CRmin (or the next on-site visit if CRmin is achieved 
during a week without an on-site visit), and at EoS. The ECG (heart rate, PR, QT, and QRS interval) will be read centrally, and QTcF and QTcB will be calculated. 
The ECG will be recorded only at baseline and EoS in participants not receiving efgartigimod. Additional ECGs may be performed at the discretion of the investigator 
during unscheduled visits. 
System Version: 1.0, Status: Approved, Document ID: VV-TMF-86295

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h A complete physical examination will be performed at each on-site visit. Vital sign measurements include systolic and diastolic blood pressure, heart rate, and body 
temperature. 
i 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 is abnormal). 
j A urine pregnancy test will be performed locally and at least once every 4 weeks. 
k Clinical blood laboratory tests will include hematology and blood chemistry at all visits. The hematology profile includes hemoglobin, hematocrit, MCV, RBC count, 
platelet count, and WBC count with differential. The blood chemistry profile includes sodium, potassium, calcium, HbA1c, creatinine, creatinine clearance, BUN, 
ALT, AST, total bilirubin, GGT, CRP, ALP, LDH, LDL-C, uric acid, total protein, and albumin. 
l PK and PD (total IgG and IgG subtypes) samples will be taken every 4 weeks as long as the participant is receiving efgartigimod PH20 SC treatment (until CRmin or 
the next on-site visit) and 4 weeks after CRmin (or the next on-site visit; this also applies if the participant achieved CRmin in ARGX-113-1904) or EoT. Blood 
samples will be taken predose (within 2 hours before the start of IMP administration during visits when IMP is administered). 
m At unscheduled visits, blood samples for PK will only be taken if IMP is administered. 
n Blood samples will be taken to test for immunogenicity to efgartigimod in serum and rHuPH20 in plasma every 4 weeks while the participant is receiving 
efgartigimod PH20 SC treatment (until CRmin or the next on-site visit) and 4 and 8 weeks after CRmin (or the next 2 on-site visits; this also applies if the participant 
achieved CRmin in ARGX-113-1904) or EoT. NAb will be tested for all confirmed positive immunogenicity samples. 
o Questionnaires are to be completed before any other assessment. 
p Disease assessment parameters include DC, EoC, CR, CRmin, CRoff, flare, and treatment failure. Participants who have achieved CR and have new lesions should 
come to the clinic for an unscheduled visit for disease assessment. 
q Samples for lymphocyte populations will be taken at selected sites only: optionally at on-site visits at W13 (±2 weeks), W26 (±2 weeks), W39 (±2 weeks), W52 (±2 
weeks) or EoT/ET and EoS, and mandatory at on-site visits at W52 (±2 weeks) or EoT/ET and EoS for participants in CRmin or CRoff. 
r The GTI assessment will be performed at visit 1, W26 (or the next on-site visit), and W52. 
s Participants and/or their caregivers will be invited to receive at least 1 refresher training for self-administration, or caregiver-supported administration of IMP. 
Training will continue until deemed successfully completed by authorized staff. 
t Efgartigimod PH20 SC will be administered weekly at a dose of 1000 mg until CRmin. For IMP administrations between the scheduled site visits, the participant can 
choose between self-administration (if training successfully completed), home nurse visits, or return to the trial site for the SC injection only. Participants who have 
achieved CRmin or CRoff and are currently not in flare will be observed every 4 weeks without any further IMP administration until flare or EoS. Only for on-site 
visits and home nurse visits, participants should be followed up for safety monitoring for at least 1 hour after the first IMP administration, or followed by 15 minutes 
of observation for subsequent administrations and released according to their clinical status. The last planned IMP administration is at W52. If the participant 
withdraws from the study, efgartigimod PH20 SC will not be administered. 
u 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). 
 
 
System Version: 1.0, Status: Approved, Document ID: VV-TMF-86295

Clinical Trial Protocol ARGX-113-1905 v3.0 
 
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Table 9: 
Modified Schedule of Activities During COVID-19 Pandemic for ARGX-113-1905 for Participants Not in CR 
at Rollover From ARGX-113-1904, or Participants With Flare after CRmin or CRoff in ARGX-113-1905 
In the Schedule of Activities (SoA) tables for ARGX-113-1905 (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 
Open-label extension 
EoT/ET 
 
Follow-up 
V1a 
Observational 
visits 
IMP admin 
only visit 
Observational visits 
Visit number 
 
Weekly on-site 
visits until CRb 
Weekly home 
or on-site visits 
until CRminc 
On-site visits 
every 4 weeks 
until CRmin 
On-site visits 
every 4 weeks 
until W52  
W52  
UNSd 
Safety 
follow-up 
1 
Safety 
follow-up 
2 
Trial week 
Rollovera 
V1 + 7x 
CR until 
CRmin 
CR until CRmin 
After CRmin 
until W52 
W52 
EoT/ET  
+ 4 weekse 
EoT/ET 
+ 8 weeks 
EoSe 
Assessment/procedure 
±0 days 
±2 daysf 
±2 days 
 
±3 daysf 
Informed consent  
X 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
X 
 
 
 
 
 
 
 
 
Weightg 
X 
Xg 
 
Xg 
Xg 
X 
 
 
 
ECGh,i 
X 
X 
 
X 
X 
X 
 
X 
X 
Physical examination and 
vital signsi,j 
X 
X 
 
X 
X 
X 
X 
X 
X 
Urinalysisi,k,l 
X 
X 
 
X 
X 
X 
Xd 
X 
X 
Urine pregnancy testi,m 
X 
X 
 
X 
X 
X 
Xd 
X 
X 
Vaccination antibodiesi,l 
X 
X 
 
X 
X 
X 
Xd 
X 
X 
System Version: 1.0, Status: Approved, Document ID: VV-TMF-86295

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Trial period 
Open-label extension 
EoT/ET 
 
Follow-up 
V1a 
Observational 
visits 
IMP admin 
only visit 
Observational visits 
Visit number 
 
Weekly on-site 
visits until CRb 
Weekly home 
or on-site visits 
until CRminc 
On-site visits 
every 4 weeks 
until CRmin 
On-site visits 
every 4 weeks 
until W52  
W52  
UNSd 
Safety 
follow-up 
1 
Safety 
follow-up 
2 
Trial week 
Rollovera 
V1 + 7x 
CR until 
CRmin 
CR until CRmin 
After CRmin 
until W52 
W52 
EoT/ET  
+ 4 weekse 
EoT/ET 
+ 8 weeks 
EoSe 
Assessment/procedure 
±0 days 
±2 daysf 
±2 days 
 
±3 daysf 
Blood sampling 
 
 
 
 
 
 
 
 
 
• Clinical chemistry and 
hematologyi,l,n 
X 
X 
 
X 
X 
X 
Xd 
X 
X 
• anti-Dsg-1 and anti-
Dsg-3 antibodiesi,l 
X 
X 
 
X 
X 
X 
Xd 
X 
X 
• PKi,o 
X 
X 
 
X 
Xo 
X 
Xd,p 
X 
X 
• Total IgG and IgG 
subtypesi,o 
X 
X 
 
X 
X 
X 
Xd 
X 
X 
• immunogenicityi,q 
X 
X 
 
X 
X 
X 
 
X 
X 
• IgG autoantibody 
subtypes and 
specificityi 
X 
Xr 
 
X 
X 
X 
Xd 
X 
X 
PDAIi 
X 
X 
  
X 
X 
X 
X 
X 
X 
ABQOLi,s,t 
X 
Xs 
 
Xs 
Xs 
X 
 
 
 
EQ-5D-5Li,s,t 
X 
Xs 
 
Xs 
Xs 
X 
 
 
 
Disease assessmenti,u 
X 
X 
 
X 
X 
X 
X 
X 
X 
System Version: 1.0, Status: Approved, Document ID: VV-TMF-86295

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Trial period 
Open-label extension 
EoT/ET 
 
Follow-up 
V1a 
Observational 
visits 
IMP admin 
only visit 
Observational visits 
Visit number 
 
Weekly on-site 
visits until CRb 
Weekly home 
or on-site visits 
until CRminc 
On-site visits 
every 4 weeks 
until CRmin 
On-site visits 
every 4 weeks 
until W52  
W52  
UNSd 
Safety 
follow-up 
1 
Safety 
follow-up 
2 
Trial week 
Rollovera 
V1 + 7x 
CR until 
CRmin 
CR until CRmin 
After CRmin 
until W52 
W52 
EoT/ET  
+ 4 weekse 
EoT/ET 
+ 8 weeks 
EoSe 
Assessment/procedure 
±0 days 
±2 daysf 
±2 days 
 
±3 daysf 
Photography (at selected 
sites)v 
X 
Xv 
 
 
 
X 
Xd,v 
 
 
Lymphocyte populations 
(at selected sites)w 
X 
Xw 
 
Xw 
Xw 
Xw 
 
X 
X 
GTIx 
X 
Xx 
 
Xx 
Xx 
X 
 
 
 
IMP self-administration 
trainingy 
X 
X 
X 
X 
X 
X 
 
 
 
Efgartigimod PH20 SCz 
Xz 
Xz 
X 
X 
 
X 
X 
 
 
Prednisone taperaa 
X 
X 
 
X 
X 
X 
X 
 
 
Concomitant therapies/ 
procedures  
Continuous monitoring 
AE monitoring 
Continuous monitoring 
ABQOL=Autoimmune Bullous Disease Quality of Life; AE=adverse event; ALT=alanine aminotransferase; ALP=alkaline phosphatase; AST=aspartate 
aminotransferase; BMI=body mass index; BUN=blood urea nitrogen; CR=complete clinical remission; CRmin=CR on minimal therapy; CRP=C-reactive protein; 
DC=disease control; Dsg=desmoglein; ECG=electrocardiogram; EoC=end of consolidation; EoS=end of study; EoT=end of treatment; EQ-5D-5L=EuroQol 5-
dimension 5-level scale; ET=early termination; GGT=gamma-glutamyl transferase; GTI=Glucocorticoid Toxicity Index; IgG=immunoglobulin type G; 
IMP=investigational medicinal product; LDH=lactate dehydrogenase; MCV=mean corpuscular volume; NAb=neutralizing antibody; PD=Pharmacodynamic; 
PDAI=Pemphigus Disease Area Index; PK=pharmacokinetics; QTcF=Fridericia corrected QT interval; rHuPH20=recombinant human hyaluronidase PH20; RBC=red 
blood cells; SC=subcutaneous(ly); UNS=unscheduled visit; V=visit at site; V1 + 7x=visit 1 + 7 times x with ‘x’ being the weeks post V1 (eg, V1 + 7x3 is the visit at 
W3 [21 days post visit 1]); W=week; WBC=white blood cells 
System Version: 1.0, Status: Approved, Document ID: VV-TMF-86295

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a For participants who roll over from ARGX-113-1904 to ARGX-113-1905, the baseline visit will occur at the EoS/ED visit of ARGX-113-1904. All assessments are 
performed before IMP administration. 
b A minimum of 6 on-site visits (rollover (V1) to W6 or start of retreatment +5 weeks) is required before switching to home administrations, even if CR is reported 
earlier. 
c Home visits are allowed once a participant achieves CR but not before W7 or not before the start of retreatment +6 weeks. The investigator should call the participant 
every 2 weeks until CRmin to confirm the participant is still in CR and to determine the prednisone tapering schedule. 
d In case of suspected new lesions as reported by the participant, AEs, flare, or other safety reasons, the participant should come to the clinic. This may require an 
unscheduled visit. Depending on the reason for the visit, different assessments need to be performed. Refer to Section 8 for more information. 
e Follow-up 1 will be the EoS visit for participants who ended treatment before W49, or 4 weeks before ET. Both follow-up visits will be required only for participants 
who continue to receive efgartigimod PH20 SC for at least 1 visit between W49 and W52, or during the last 4 weeks before ET. 
f Study visit windows are ±2 days during the treatment period and ±3 days for the follow-up visits. 
g Weight will be measured and BMI will be calculated accordingly, at the rollover visit, at W26 (or the next on-site visit if W26 does not coincide with an on-site visit) 
and W52. Weight will also be measured if there has been an obvious change since the last measurement. 
h The ECG will be recorded at baseline, at the start of retreatment and every 3 months (or the next on-site visit) while receiving efgartigimod PH20 SC treatment, at 
CRmin (or the next on-site visit if CRmin is achieved during a week without an on-site visit), and EoS. The ECG (heart rate, PR, QT, and QRS interval) will be read 
centrally, and QTcF and QTcB will be calculated. Additional ECGs may be performed at the discretion of the investigator during unscheduled visits. 
i Assessment or procedure will be completed predose at visits when IMP is administered. 
j A complete physical examination will be performed at each on-site visit. Vital sign measurements include systolic and diastolic blood pressure, heart rate, and body 
temperature. 
k 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 is abnormal). 
l Samples will be taken every week from rollover (V1) to W9 or start of retreatment +8 weeks, and then every 4 weeks and at the visit when CR is observed. Once CR 
is achieved, samples will be taken every 4 weeks at on-site visits until EoS. For participants achieving CR between rollover (V1) and W6 or the start of retreatment +5 
weeks, samples will be taken weekly from rollover (V1) to W6 or start of retreatment +5 weeks, and then every 4 weeks during on-site visits until EoS. 
m A urine pregnancy test will be performed locally at least once every 4 weeks, at CR, and as of CR again every 4 weeks at on-site visits. 
n Clinical blood laboratory tests will include hematology and blood chemistry at all visits. The hematology profile includes hemoglobin, hematocrit, MCV, RBC count, 
platelet count, WBC count with differential. The blood chemistry profile includes sodium, potassium, calcium, HbA1c, creatinine, creatinine clearance, BUN, ALT, 
AST, total bilirubin, GGT, CRP, ALP, LDH, low-density lipoprotein cholesterol (LDL-C), uric acid, total protein, and albumin. 
o PK and PD (total IgG and IgG subtypes) samples will be taken every 4 weeks, at CR, and as of CR again every 4 weeks at on-site visits, as long as the participant is 
receiving efgartigimod PH20 SC treatment (until CRmin or the next on-site visit if CRmin is achieved during a week without an on-site visit), and 4 weeks after 
CRmin (or the next on-site visit) or EoT. Blood will be taken predose (within 2 hours before the start of IMP administration during visits when IMP is administered). 
p Blood will be taken for PK assessment predose (within 2 hours before the start of IMP administration during visits when IMP is administered). At UNS visits, blood 
samples for PK analysis will be taken only if IMP is administered. 
q Blood will be taken to test for immunogenicity to efgartigimod in serum and to rHuPH20 in plasma every 4 weeks, at CR, and as of CR every 4 weeks at on-site visits 
while the participant is receiving efgartigimod PH20 SC treatment (until CRmin or the next on-site visit if CRmin is achieved during a week without an on-site visit), 
and 4 and 8 weeks after CRmin (or the next 2 on-site visits) or EoT. NAb will be tested for all confirmed positive immunogenicity samples. 
r Blood will be taken every 4 weeks and at the visit when CR is observed for IgG autoantibody subtypes and specificity. Once CR is achieved, samples will be taken 
every 4 weeks at on-site visits until EoS. 
System Version: 1.0, Status: Approved, Document ID: VV-TMF-86295

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s The ABQOL and EQ-5D-5L will be administered at the start of retreatment, when achieving CRmin (or at the next on-site visit if CRmin is achieved during a week 
without an on-site visit), and at EoT/W52 only. 
t Questionnaires are to be completed before any other assessment. 
u Disease assessment parameters include DC, EoC, CR, CRmin, CRoff, flare, and treatment failure. Participants who have achieved CR and have new lesions should 
come to the clinic for a UNS visit for disease assessment. 
v 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 time points. 
w Samples for lymphocyte populations will be taken at selected sites only: optionally at on-site visits at W13 (±2 weeks), W26 (±2 weeks), W39 (±2 weeks), W52 (±2 
weeks) or EoT/ET and EoS, and mandatory at on-site visits at W52 (±2 weeks) or EoT/ET and EoS for participants in CRmin or CRoff. 
x The GTI assessment will be performed at visit 1, W26 (or the next on-site visit) and W52. 
y Participants and/or their caregivers will be invited to receive at least 1 refresher training for self-administration, or caregiver-supported administration of IMP. 
Training will continue until deemed successfully completed by authorized staff. 
z Efgartigimod PH20 SC will be administered subcutaneously weekly at a dose of 1000 mg until CRmin. In case of treatment failure in ARGX-113-1904, or flare while 
not receiving efgartigimod therapy, efgartigimod PH20 SC will be administered on 
 mg, followed by weekly SC administrations of 
1000 mg until CRmin. For IMP administrations between the scheduled visits (after achieving CR), the participant can choose between self-administration (if training 
successfully completed), home nurse visits or return to the trial site for the SC injection only. Participants who have achieved CRmin or CRoff and are currently not in 
flare will be observed every 4 weeks without any further IMP administration until flare or EoS. Only for on-site visits and home nurse visits, participants should be 
followed up for safety monitoring for at least 1 hour after the first administration, or followed by 15 minutes of observation for subsequent administrations for safety 
monitoring and released according to their clinical status. The last planned IMP administration is at W52. If the participant withdraws from the study, efgartigimod 
PH20 SC will not be administered. 
aa 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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10.12. 
Appendix 12: Glucocorticoid Toxicity Index (GTI) 
Table 10: 
Approach to Calculating the Baseline GTI 2.0 Score: Toxicities Assigned 
Weighted Scores from the C-GTI to Establish a Baseline GTI Score 
 
*Bone/tendon will not be scored as part of the C-GTI. 
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Table 11: 
Approach to Calculating the Changes in GTI 2.0 Score: Weighted Scores 
Assigned to Improvements or Worsenings in the C-GTI 
 
*Bone health will not be scored as part of the C-GTI. 
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Table 12: 
GTI 2.0 Specific List: 11 Domains (9 of Which are Shared by the C-GTI) and 
23 Unique Items  
  
*Bone mineral density decreases >6% will not be reported.  
 
 
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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 
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Table 13: 
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) 
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% 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. 
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• 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. 
− 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 14: 
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. 
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− 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 one 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. 
− 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 
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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   
• 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). 
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• 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) 
• 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 an 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 
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• 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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11. 
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Signature Page for VV-TMF-86295 v1.0
Signature Page for VV-TMF-86295 v1.0
Reason for signing: Approved (eSignature)
Name: Luc Truyen
Role: Approver
Date of signature: 05-Sep-2022 06:56:31 GMT+0000
System Version: 1.0, Status: Approved, Document ID: VV-TMF-86295