A Phase 3, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Trial to Evaluate the Efficacy and the Safety of Efgartigimod (ARGX-113) PH20 Subcutaneous in Adult Patients With Primary Immune Thrombocytopenia
Phase: PHASE3
Conditions: Primary Immune Thrombocytopenia
Sponsor: argenx

Clinical Trial Protocol ARGX-113-2004 v6.0 
 
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Efgartigimod PH20 SC 
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Confidential 
1 
 
Clinical Trial Protocol 
 
 
Protocol Title: 
A Phase 3, Multicenter, Randomized, Double-Blinded, 
Placebo-Controlled Trial to Evaluate the Efficacy and the Safety of 
Efgartigimod (ARGX-113) PH20 Subcutaneous in Adult Patients 
With Primary Immune Thrombocytopenia 
Protocol Number: 
ARGX-113-2004 
Protocol Version: 
6.0 
Amendment Number: 
5 
Compound: 
ARGX-113/Efgartigimod 
Trial Phase: 
3 
Short Title: 
Not applicable 
Acronym: 
ADVANCESC 
Sponsor Name: 
argenx BV 
Legal Registered Address: Industriepark Zwijnaarde 7 
 
9052 Zwijnaarde 
 
Belgium 
 
Phone: +32 9 310 34 00 
 
Fax: +32 9 310 34 99 
 
Regulatory Agency Identifier Number(s): 
 
IND
 
 
EudraCT 2020-004032-21 
Date:  
06 Apr 2023 
System Version: 1.0, Status: Approved, Document ID: VV-TMF-95336

Clinical Trial Protocol ARGX-113-2004 v6.0 
 
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Sponsor’s Medical Contact: 
 
 
argenx BV 
 
Industriepark Zwijnaarde 7 
 
9052 Zwijnaarde (Ghent) 
 
Belgium 
 
Phone: Office: 
 
 
Mobile: 
 
 
Contract Research Organization: ICON plc 
 
South County Business Park 
 
Leopardstown 
 
Dublin 18 
 
Ireland 
 
Phone: +353 (1) 291 2000 
 
The following additional numbers are also available for urgent contact: 
24-Hour Urgent Medical 
Helpline Number: 
(+1) 857 957 5013 
For the country-specific toll-free AT&T Direct Access code, 
please always refer to the latest version available on 
https://icophone.iconplc.com/ under “24/7 Medical Help Desk” 
 
For drug safety reporting, contact the email address below: 
Safety Mailbox/Fax: 
 
Email: safety@argenx.com  
 
Fax: (+1) 833 874 7325 
 
 
Confidentiality Statement 
The information contained in this medium is the property of argenx BV and/or its subsidiaries 
(jointly “argenx”) and is confidential and proprietary. Without prior authorization from argenx, 
information contained herein may not be used, reproduced, divulged, published, or otherwise 
disclosed to anyone.  
 
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Clinical Trial Protocol ARGX-113-2004 v6.0 
 
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Sponsor Signatory: 
 
 
 
 
 
 
 
 
See appended signature page 
 
, MD, PhD 
Chief Medical Officer 
 
Date 
 
 
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Clinical Trial Protocol ARGX-113-2004 v6.0 
 
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SIGNATURE OF INVESTIGATOR 
PROTOCOL TITLE: 
A Phase 3, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Trial to Evaluate the 
Efficacy and the Safety of Efgartigimod (ARGX-113) PH20 Subcutaneous in Adult Patients 
With Primary Immune Thrombocytopenia 
PROTOCOL NO./ALIAS: ARGX-113-2004/ ADVANCESC 
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 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: 
 
 
 
 
 
 
 
 
 
 
 
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PROTOCOL AMENDMENT SUMMARY OF CHANGES 
DOCUMENT HISTORY 
Document history for global protocol 
Date 
v6.0 Amendment 5 
06 Apr 2023 
v5.0 Amendment 4 
17 Feb 2023 
v4.0 Amendment 3 
15 Jul 2022 
v3.0 Amendment 2 
16 Jul 2021 
v2.0 Amendment 1 
12 Jan 2021 
v1.0 Original Protocol  
12 Sep 2020 
Amendment 5 (06 Apr 2023) 
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 This Amendment 
The primary reason for amendment 4 (v5.0, 17 Feb 2023) was to implement recommendations 
from the data safety monitoring board (DSMB) to modify the exclusion criterion regarding 
medical history of thromboembolic events and to require a mandatory discontinuation from trial 
intervention for participants who have an initial or recurrent malignancy. Editorial changes were 
included to help with readability. 
The reason for amendment 5 (v6.0) is that the protocol is still under the Directive 2001/20/EC 
and it will not transition to the new Regulation (EU) No 536/2014 of the European Parliament 
and the Council of the European Union. 
The protocol amendment Summary of Changes table for the previous amendments can be found 
in Section 10.12. 
The major changes from protocol v4.0 to v5.0 and v5.0 to v6.0 are summarized in the following 
table. Refer to Section 10.11 for any undefined abbreviations. 
 
 
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Section 
Description of change 
Brief rationale 
Version 6.0 
Protocol Amendment 
Summary of Changes 
The substantiality assessment was 
revised from referring to Article 2 §2 
(13) of the Regulation (EU) No 
536/2014 of the European 
Parliament and the Council of the 
European Union to Article 10(a) of 
Directive 2001/20/EC of the 
European Parliament and the 
Council of the European Union. 
This protocol is still under the 
directive and it will not transition to 
the new regulations. 
Version 5.0 
5.2, Exclusion Criteria, 
Criterion 12 
10.4, Appendix 4: 
Washout Requirements 
Before First IMP 
Administration 
The exclusion criterion and washout 
period for serious thromboembolic 
events was updated. The prohibited 
period for any major thrombotic or 
embolic event (eg, myocardial 
infarction, stroke, deep venous 
thrombosis, or pulmonary embolism) 
was revised from within 12 months 
to within 5 years before 
randomization. 
Exclusion criterion 12 was 
renumbered as 12a. 
The DSMB monitoring the 
ARGX-113 ITP program 
recommended a revision to the 
washout period for the exclusion of 
participants with serious 
thromboembolic events. 
7.1, Discontinuation of 
Trial Intervention 
Language was added to clarify that 
any participant developing a new or 
recurrent malignancy except basal 
cell carcinoma will discontinue trial 
treatment regardless of the 
relationship to IMP. 
The DSMB monitoring the 
ARGX-113 ITP program 
recommended a mandatory 
discontinuation from trial 
intervention for trial participants 
with an initial or recurrent 
malignancy. 
1.3, Schedule of 
Activities, Table 1 
10.9, Appendix 9, 
Table 5, Schedule of 
Activities 
8.6, Pharmacokinetics 
Footnote n regarding when 
PK/PD/ADA samples should be 
collected was revised from within 
2 hours to within the same day, 
before IMP administration. 
Table 4 was renumbered as Table 5. 
The revision allows additional 
flexibility for trial sites. 
2.3.1, Risk Assessment 
Table 2 of potential risks and 
mitigation strategies was added. 
The table succinctly addresses the 
trial risks and mitigation strategies. 
5.1, Inclusion Criteria, 
Criterion 8b 
10.6.2, Contraception 
Guidance 
The contraception requirement for 
male participants was removed. 
Inclusion criterion 8a was 
renumbered as 8b. 
Section 10.6.2.2 Male Contraception 
was deleted. 
This global change was made to all 
ARGX-113 studies based on 
emerging nonclinical data indicating 
that efgartigimod has a low risk of 
teratogenicity/fetotoxicity. 
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3, Objectives and 
Endpoints 
9.5.7, Other Secondary 
Endpoint Analyses Not 
Subject to Alpha 
Control 
An efficacy objective was added to 
compare efgartigimod PH20 SC to 
placebo PH20 SC in IWG response 
and initial response, measuring the 
proportions of participants with an 
IWG response, an IWG complete 
response, and an initial response. 
The revision was made to align with 
the SAP. 
3, Objectives and 
Endpoints 
8.12, Immunogenicity 
Assessments 
10.3, Appendix 3, 
Table 4 
Text reading “and titers of NAb 
against efgartigimod and/or 
rHuPH20 in the overall population” 
was revised to “and titers of NAb 
against rHuPH20 in the overall 
population.” 
Table 3 was renumbered as Table 4. 
The text was not correct. Titers are 
determined for only the PH20 NAb 
assay, not the efgartigimod NAb 
assay. 
8.3.2, Vital Signs 
Instructions for taking blood 
pressure were amended to include 
that participants should be seated and 
rested. 
The updated instructions match site 
practices and prevent protocol 
deviations. 
10.4, Appendix 4: 
Washout Requirements 
Before First IMP 
Administration 
Anti-CD20 therapy (eg, rituximab) 
with a washout of 6 months before 
randomization was added. 
This requirement was added to 
match inclusion criterion 7. 
2.2, Background 
1.1, Synopsis 
ARGX-113-1801 was added to the 
list of sources of clinical history. 
Additional data were available in 
ARGX-113-1801 to support product 
development. 
2.3.2, Benefit 
Assessment 
Lengthy description was replaced 
with language that directs the reader 
to the benefit/risk assessment in the 
current IB. 
The IB is the primary repository for 
updated product data. 
5.1, Inclusion Criteria, 
Criterion 2 
The age of consent inclusion 
criterion was revised to state that 
participants should be at least the 
local legal age of consent for clinical 
trials when signing the ICF. 
Inclusion criterion 2 was renumbered 
as 2a. 
The revision matches global 
requirements for the legal 
participation age. 
8.3.5, Clinical Safety 
Laboratory 
Assessments 
10.2, Appendix 2: 
Clinical Laboratory 
Tests 
Language was added describing 
blinding of albumin and urine total 
protein (quantitative) values and 
noting that an alert system will 
notify the investigator to ensure 
appropriate safety follow up. 
The DSMB monitoring the 
ARGX-113 ITP program advised 
that serum albumin and total protein 
results should remain blinded for the 
trial sites. 
10.7, Appendix 7: 
Administrative 
Structure 
The vendor name LGC was 
revised to DDS. 
The change was made to reflect the 
legal name of the vendor. 
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TABLE OF CONTENTS 
PROTOCOL AMENDMENT SUMMARY OF CHANGES ..........................................................5 
1. 
PROTOCOL SUMMARY ..........................................................................................14 
1.1. 
Synopsis ......................................................................................................................14 
1.2. 
Schema ........................................................................................................................22 
1.3. 
Schedule of Activities .................................................................................................23 
2. 
INTRODUCTION ......................................................................................................26 
2.1. 
Trial Rationale ............................................................................................................26 
2.2. 
Background .................................................................................................................27 
2.3. 
Benefit/Risk Assessment ............................................................................................28 
2.3.1. 
Risk Assessment .........................................................................................................28 
2.3.2. 
Benefit Assessment .....................................................................................................29 
2.3.3. 
Overall Benefit: Risk Conclusion ...............................................................................29 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................30 
4. 
TRIAL DESIGN .........................................................................................................34 
4.1. 
Overall Design ............................................................................................................34 
4.2. 
Scientific Rationale for Trial Design ..........................................................................35 
4.2.1. 
Participant Input into Design ......................................................................................35 
4.3. 
Justification for Dose ..................................................................................................35 
4.4. 
End of Trial Definition ...............................................................................................36 
5. 
TRIAL POPULATION ..............................................................................................37 
5.1. 
Inclusion Criteria ........................................................................................................37 
5.2. 
Exclusion Criteria .......................................................................................................38 
5.3. 
Lifestyle Considerations .............................................................................................40 
5.3.1. 
Meals and Dietary Restrictions ...................................................................................40 
5.3.2. 
Caffeine, Alcohol, and Tobacco .................................................................................40 
5.3.3. 
Activity .......................................................................................................................40 
5.4. 
Screen Failures, Retesting, and Rescreening ..............................................................40 
6. 
TRIAL INTERVENTION ..........................................................................................42 
6.1. 
Trial Intervention(s) Administered .............................................................................42 
6.2. 
Preparation/Handling/Storage/Accountability/Packaging ..........................................43 
6.2.1. 
Preparation ..................................................................................................................43 
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6.2.2. 
Handling .....................................................................................................................43 
6.2.3. 
Storage ........................................................................................................................43 
6.2.4. 
Accountability .............................................................................................................44 
6.2.5. 
Packaging and Labeling ..............................................................................................44 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................................44 
6.3.1. 
Emergency Unblinding ...............................................................................................44 
6.4. 
Trial Intervention Compliance ....................................................................................45 
6.4.1. 
Handling Missed Doses of the Investigational Medicinal Product ............................45 
6.4.2. 
Protocol Deviations ....................................................................................................46 
6.5. 
Screening and Treatment ............................................................................................46 
6.6. 
Prior and Concomitant Therapy ..................................................................................47 
6.6.1. 
Concurrent ITP Therapy .............................................................................................47 
6.6.2. 
Prohibited Medications and Therapy Before Randomization ....................................48 
6.6.3. 
Prohibited Medications and Therapy During the Trial ...............................................48 
6.6.4. 
Rescue Therapy ..........................................................................................................49 
6.7. 
Dose Modification ......................................................................................................50 
6.8. 
Intervention After the End of the Trial .......................................................................50 
7. 
DISCONTINUATION OF TRIAL INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................52 
7.1. 
Discontinuation of Trial Intervention .........................................................................52 
7.1.1. 
Temporary Discontinuation ........................................................................................52 
7.1.2. 
Rechallenge .................................................................................................................52 
7.2. 
Participant Discontinuation/Withdrawal From the Trial ............................................52 
7.3. 
Completion of the Trial ..............................................................................................53 
7.4. 
Lost to Follow-up .......................................................................................................53 
8. 
TRIAL ASSESSMENTS AND PROCEDURES .......................................................55 
8.1. 
Demography ...............................................................................................................55 
8.2. 
Efficacy Assessments .................................................................................................55 
8.2.1. 
56 
8.2.2. 
General Bleeding Assessment ....................................................................................56 
8.3. 
Safety Assessments .....................................................................................................56 
8.3.1. 
Physical Examinations ................................................................................................56 
8.3.2. 
Vital Signs ..................................................................................................................57 
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8.3.3. 
Electrocardiograms .....................................................................................................57 
8.3.4. 
Medical and Surgical History .....................................................................................57 
8.3.5. 
Clinical Safety Laboratory Assessments ....................................................................58 
8.3.5.1. 
Storage of Blood Samples in the Trial ........................................................................59 
8.3.6. 
Suicidal Ideation and Behavior Risk Monitoring .......................................................59 
8.3.7. 
Visit Reminder/Participant Identification Card ..........................................................59 
8.4. 
Adverse Events and Serious Adverse Events .............................................................60 
8.4.1. 
Time Period and Frequency for Collecting Adverse Event and Serious 
Adverse Event Information .........................................................................................60 
8.4.2. 
Method of Detecting Adverse Events and Serious Adverse Events ...........................61 
8.4.3. 
Reporting of Adverse Events and Serious Adverse Events ........................................61 
8.4.4. 
Follow-up of Adverse Events and Serious Adverse Events .......................................61 
8.4.5. 
Regulatory Reporting Requirements for Serious Adverse Events .............................62 
8.4.6. 
Pregnancy ...................................................................................................................62 
8.4.7. 
Cardiovascular and Death Events ...............................................................................63 
8.4.8. 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as 
Reportable Adverse Events or Serious Adverse Events .............................................63 
8.4.9. 
Adverse Events of Special Interest .............................................................................63 
8.5. 
Treatment of Overdose or Medication Error ..............................................................63 
8.6. 
Pharmacokinetics ........................................................................................................64 
8.7. 
Pharmacodynamics .....................................................................................................64 
8.8. 
 
8.9. 
Hospitalization for ITP Management .........................................................................65 
8.10. 
Genetics ......................................................................................................................65 
8.11. 
Biomarkers ..................................................................................................................65 
8.12. 
Immunogenicity Assessments ....................................................................................65 
8.13. 
Health Economics/Medical Resource Utilization .......................................................66 
8.14. 
Quality-of-Life and Patient-Reported Outcomes ........................................................66 
9. 
STATISTICAL CONSIDERATIONS .......................................................................67 
9.1. 
Statistical Methods ......................................................................................................67 
9.1.1. 
Summary Tables, Figures, and Listings .....................................................................67 
9.1.2. 
Hypothesis Testing and Confidence Intervals ............................................................67 
9.2. 
Statistical Hypotheses .................................................................................................67 
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9.3. 
Sample Size Determination ........................................................................................68 
9.4. 
Populations for Analyses ............................................................................................68 
9.5. 
Statistical Analyses .....................................................................................................68 
9.5.1. 
General Considerations ...............................................................................................69 
9.5.2. 
Participant Disposition ................................................................................................69 
9.5.3. 
Analysis Sets and Protocol Deviations .......................................................................69 
9.5.4. 
Demographic and Baseline Characteristics, and Concomitant Medication ................69 
9.5.5. 
Primary Endpoint ........................................................................................................69 
9.5.5.1. 
Definition of the Estimand for the Primary Endpoint ................................................69 
9.5.5.2. 
Handling of Main Intercurrent Events ........................................................................70 
9.5.5.3. 
Estimation of Treatment Effect and Statistical Inference ...........................................70 
9.5.5.4. 
Handling of Missing Data ...........................................................................................70 
9.5.5.5. 
Complementary Analyses ...........................................................................................70 
9.5.6. 
Key Secondary Endpoint Analyses Subject to Alpha Control ...................................70 
9.5.7. 
Other Secondary Endpoint Analyses Not Subject to Alpha Control ..........................72 
9.5.8. 
Exploratory Endpoints ................................................................................................73 
9.5.9. 
Safety Analyses ..........................................................................................................73 
9.5.10. 
Other Analyses ............................................................................................................73 
9.5.10.1. 
Pharmacodynamics, Pharmacokinetics, and Immunogenicity ...................................73 
9.6. 
Interim Analyses .........................................................................................................73 
9.7. 
Data Monitoring Committee .......................................................................................73 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................74 
10.1. 
Appendix 1: Regulatory, Ethical, and Trial Oversight Considerations ......................74 
10.1.1. 
Regulatory and Ethical Considerations ......................................................................74 
10.1.2. 
Financial Disclosure ...................................................................................................75 
10.1.3. 
Informed Consent Process ..........................................................................................75 
10.1.4. 
Data Protection ...........................................................................................................77 
10.1.5. 
Committees Structure .................................................................................................78 
10.1.5.1. 
Data Safety Monitoring Board ....................................................................................78 
10.1.6. 
Dissemination of Clinical Trial Data ..........................................................................78 
10.1.7. 
Data Quality Assurance ..............................................................................................79 
10.1.7.1. 
Data Handling and Record Keeping ...........................................................................79 
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10.1.7.2. 
Quality Assurance Audit .............................................................................................80 
10.1.7.3. 
Quality Control ...........................................................................................................80 
10.1.8. 
Source Documents ......................................................................................................81 
10.1.9. 
Monitoring ..................................................................................................................81 
10.1.10. 
Data Management .......................................................................................................82 
10.1.11. 
Trial and Site Start and Closure ..................................................................................83 
10.1.12. 
Investigator Obligations ..............................................................................................84 
10.1.13. 
Sponsor Signatures .....................................................................................................84 
10.1.14. 
Publication Policy .......................................................................................................85 
10.2. 
Appendix 2: Clinical Laboratory Tests .......................................................................86 
10.3. 
Appendix 3: Pharmacokinetic, Pharmacodynamic, and Immunogenicity 
Assessments ................................................................................................................87 
10.4. 
Appendix 4: Washout Requirements Before First IMP Administration ....................88 
10.5. 
Appendix 5: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ........................................................................89 
10.5.1. 
Definition of Adverse Event .......................................................................................89 
10.5.2. 
Definition of Serious Adverse Event ..........................................................................91 
10.5.3. 
Recording and Follow-up of Adverse Events and/or Serious Adverse Events ..........92 
10.5.4. 
Reporting of Serious Adverse Events .........................................................................94 
10.6. 
Appendix 6: Contraceptive Guidance and Collection of Pregnancy 
Information .................................................................................................................95 
10.6.1. 
Definitions ..................................................................................................................95 
10.6.1.1. 
Woman of Childbearing Potential ..............................................................................95 
10.6.2. 
Contraception Guidance .............................................................................................95 
10.6.2.1. 
Female Contraception For Women of Childbearing Potential ...................................95 
10.6.3. 
Collection of Pregnancy Information .........................................................................96 
10.6.3.1. 
Male Participants With Partners Who Become Pregnant ...........................................96 
10.6.3.2. 
Female Participants Who Become Pregnant ...............................................................96 
10.7. 
Appendix 7: Administrative Structure ........................................................................98 
10.8. 
Appendix 8: World Health Organization Bleeding Scale .........................................100 
10.9. 
Appendix 9: Possible Adaptations of Trial Protocol During COVID-19 
Pandemic ...................................................................................................................102 
10.10. 
Appendix 10: Definition of Terms ...........................................................................113 
10.11. 
Appendix 11: Abbreviations .....................................................................................116 
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10.12. 
Appendix 12: Protocol Amendment History ............................................................118 
Amendment 4 (17 Feb 2023) .......................................................................................................118 
Amendment 3 (15 Jul 2022) ........................................................................................................120 
Amendment 2 (16 Jul 2021) ........................................................................................................123 
Amendment 1 (12 Jan 2021) ........................................................................................................135 
11. 
REFERENCES .........................................................................................................151 
 
LIST OF TABLES 
Table 1: 
Schedule of Activities .................................................................................................23 
Table 2: 
Potential Risks and Mitigation Strategies ...................................................................28 
Table 3: 
Protocol-Required Laboratory Assessments...............................................................86 
Table 4: 
Protocol-Required Pharmacokinetic, Pharmacodynamic, and 
Immunogenicity Assessments ....................................................................................87 
Table 5: 
Schedule of Activities ...............................................................................................110 
 
LIST OF FIGURES 
Figure 1: 
Decision Tree for the Treatment of Participants .......................................................104 
 
 
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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: 
A Phase 3, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Trial to Evaluate the 
Efficacy and the Safety of Efgartigimod (ARGX-113) PH20 Subcutaneous in Adult Patients 
With Primary Immune Thrombocytopenia 
Short Title: 
Not applicable 
Indication: 
Primary immune thrombocytopenia (ITP) 
Trial Sites/Countries: 
This is a global, multicenter trial 
Target Population: 
Adult patients with persistent or chronic primary ITP, who have an average platelet count of 
<30×109/L, and, at the start of the trial taking concurrent ITP treatment(s) and having received at 
least 1 prior therapy for ITP in the past, or not taking treatment for ITP but having received at 
least 2 prior treatments for ITP. 
Test Product, Dose, and Mode of Administration: 
Test product: 
Efgartigimod 180 mg/mL coformulated with 2000 U/mL recombinant human hyaluronidase 
PH20 (rHuPH20) for subcutaneous (SC) administration (efgartigimod PH20 SC) 
Dose: 
Each dose of efgartigimod PH20 SC will include 1000 mg efgartigimod per injection. 
Mode of administration: 
Subcutaneous injection 
Comparator, Dose, and Mode of Administration: 
Comparator:  
Placebo PH20 SC 
Dose: 
Placebo with rHuPH20 for SC administration (placebo PH20 SC) 
Mode of administration: 
Subcutaneous injection 
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Rationale: 
This phase 3 trial aims to evaluate the efficacy, safety, and effect on the quality of life (QoL) and 
patient-reported outcomes (PRO) of efgartigimod PH20 administered as SC injections in adult 
patients with primary ITP who have had an insufficient response or who are intolerant to existing 
ITP treatments, evidenced by an average platelet count that is below the clinically accepted level 
for intervention (<30×10⁹/L). 
Participants classified as having persistent primary ITP (between 3 and 12 months since 
diagnosis) and chronic primary ITP (greater than 12 months since diagnosis) will be recruited. 
The diagnosis of primary ITP should be supported by a response to a prior ITP therapy other 
than thrombopoietin receptor agonists (TPO-RAs). At the start of the trial, the participants are 
either taking concurrent ITP treatment(s) and have received at least 1 prior therapy for ITP in the 
past, or the participants are not taking treatment for ITP but have received at least 2 prior 
treatments for ITP. If participants are receiving concurrent ITP therapies at baseline, these 
therapies should have been maintained at a stable dose and dosing frequency for 4 weeks before 
randomization. 
Treatments for ITP are often used in combination and efgartigimod has the potential to be used 
in combination with other ITP therapies or offer a new stand-alone modality. Therefore, 
participants with and without concurrent ITP therapy will be enrolled. Experience to date of 
efgartigimod treatment in combination with steroids and immunosuppressants in phase 2 and 
phase 3 trials in primary ITP and myasthenia gravis (MG) have not raised any safety concerns 
with these combinations of treatments. 
Results of the phase 1 trials in healthy subjects (ARGX-113-1501, ARGX-113-1702), the phase 
2 trials in participants with ITP (ARGX-113-1603) and MG (ARGX-113-1602), the phase 3 
trials in participants with MG (ARGX-113-1704 and ARGX-113-1705) and ITP 
(ARGX-113-1801), as well as pharmacokinetic/pharmacodynamic (PK/PD) modeling analysis, 
indicate that a dose of 10 mg/kg efgartigimod, administered weekly (qw) through intravenous 
(IV) infusion achieved close to maximal immunoglobulin G (IgG) reduction (PD effect), resulted 
in a reduction of pathogenic autoantibodies, and was associated with clinical efficacy in both 
participants with ITP and participants with MG. Furthermore, this dose was safe and well-
tolerated in all populations. 
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. rHuPH20 is being 
used in coformulations with approved therapeutic antibodies to facilitate SC injection with 
volumes larger than 2 mL. 
In designing the current phase 3 trial, a dose of 1000 mg efgartigimod administered as qw or 
every other week (q2w) SC injections coformulated with rHuPH20 was predicted to result in a 
comparable effect on IgG levels as with 10 mg/kg IV administered qw or q2w. 
No significant safety findings have been identified to date with efgartigimod administered SC in 
combination with rHuPH20 in completed or ongoing trials. 
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Objectives and Endpoints 
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary 
• To evaluate the efficacy of efgartigimod 
PH20 SC compared to placebo PH20 SC 
in achieving a sustained platelet count 
response in patients with chronic 
primary ITP, with a sustained platelet 
count response defined as platelet counts 
of ≥50×109/L for at least 4 of the 6 visits 
between week 19 and week 24 of the 
trial 
 
Note: “week” instead of “visit” is used 
in the endpoints, ensuring that the 
platelet count of the end-of-treatment 
visit is regarded as week 24 platelet 
count (eg, platelet count after 19 weeks 
of treatment corresponds with platelet 
count of visit 20) 
• Proportion of patients with chronic ITP 
with a sustained platelet count response 
defined as achieving platelet counts of 
≥50×109/L for at least 4 of the 6 visits 
between week 19 and week 24 of the trial 
Secondary 
• To evaluate the efficacy of 
efgartigimod PH20 SC compared to 
placebo PH20 SC in overall platelet 
count response 
• Extent of disease control defined as the 
number of cumulative weeks over the 
planned 24-week treatment period with 
platelet counts of ≥50×109/L in the chronic 
ITP population 
(Key Secondary Endpoint 1) 
• Proportion of patients in the overall 
population (chronic and persistent ITP) 
with a sustained platelet count response 
defined as achieving platelet counts of 
≥50×109/L for at least 4 of the 6 visits 
between week 19 and week 24 
(Key Secondary Endpoint 2) 
• Proportion of patients in the overall 
population achieving platelet counts of 
≥50×109/L for at least 6 of the 8 visits 
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between week 17 and 24 of the trial 
(Key Secondary Endpoint 3) 
• Proportion of patients in the overall 
population with overall platelet response 
defined as achieving a platelet count of 
≥50×109/L on at least 4 occasions at any 
time during the 24-week treatment period 
• Extent of disease control defined as the 
number of cumulative weeks until week 12 
with platelet counts of ≥50×109/L in the 
overall population 
• Proportion of patients in the overall 
population with overall platelet response 
defined as achieving a platelet count of 
≥50×109/L on at least 4 occasions at any 
time until week 12 
• Mean change from baseline in platelet 
count at each visit in the overall population 
• Time to response defined as the time to 
achieve 2 consecutive platelet counts of 
≥50×109/L in the overall population 
• The number of cumulative weeks over the 
planned 24-week treatment period with 
platelet counts of ≥30×109/L and 
≥20×109/L above baseline in the overall 
population 
• In patients with baseline platelet count of 
<15×109/L, the number of cumulative 
weeks over the planned 24-week treatment 
period with platelet counts of ≥30×109/L 
and ≥20×109/L above baseline in the overall 
population 
• To evaluate the incidence and severity 
of bleeding events while receiving 
treatment with efgartigimod PH20 SC 
compared to placebo PH20 SC 
• Incidence and severity of the World Health 
Organization (WHO)-classified bleeding 
events in the overall population 
(Key Secondary Endpoint 4) 
• To evaluate the efficacy of efgartigimod 
PH20 SC compared to placebo PH20 SC 
in International Working Group (IWG) 
response 
• Proportion of patients with an IWG 
response 
• Proportion of patients with an IWG 
complete response 
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• Proportion of patients with an initial 
response 
• To evaluate the safety and tolerability of 
efgartigimod PH20 SC administered qw 
or q2w compared to placebo PH20 SC 
• Incidence and severity of adverse events 
(AEs), AEs of special interest (AESIs), and 
serious AEs (SAEs) in the overall 
population 
• Vital signs, electrocardiogram (ECG), and 
laboratory assessments in the overall 
population 
• To evaluate the use of rescue treatment 
and changes in concurrent ITP therapy 
while receiving treatment with 
efgartigimod PH20 SC compared to 
placebo PH20 SC 
• Rate of receipt of rescue therapy (rescue per 
patient per month) in the overall population 
• Proportion of patients for whom dose and/or 
frequency of concurrent ITP therapies have 
increased at week 12 or later in the overall 
population 
• To evaluate the effects of 
efgartigimod PH20 SC treatment on 
QoL measures and PRO compared to 
placebo PH20 SC 
• Change from baseline in PRO (Functional 
Assessment of Chronic Illness Therapy 
Fatigue Scale [FACIT-Fatigue], Functional 
Assessment of Cancer Therapy 
questionnaire-Th6 [Fact-Th6]) and QoL 
(Short Form-36 [SF-36]) at planned visits in 
the overall population 
• To assess the immunogenicity of 
efgartigimod and rHuPH20 
• Incidence and prevalence of antibodies to 
efgartigimod and/or rHuPH20 in the overall 
population 
• Titers of antibodies to efgartigimod and/or 
rHuPH20 in the overall population 
• Presence of neutralizing antibodies (NAb) 
against efgartigimod and/or rHuPH20, and 
titers of NAb against rHuPH20 in the 
overall population 
• To assess the PK of efgartigimod PH20 
SC 
• Serum efgartigimod concentration observed 
predose (Ctrough) in the overall population 
• To assess the PD effects of efgartigimod 
PH20 SC 
• Pharmacodynamics markers: total IgG and 
antiplatelet antibody levels in the overall 
population 
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Exploratory 
• 
 
 
 
 
 
 
• 
 
 
 
 
 
 
 
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• 
 
 
 
 
 
 
 
Overall Design: 
This is a phase 3, multicenter, randomized, double-blinded, placebo-controlled, parallel-group 
trial to evaluate the efficacy, safety, and effect on QoL/PRO of efgartigimod PH20 SC treatment 
in adult patients with primary ITP. 
The target population is adult patients with persistent or chronic primary ITP, having an average 
platelet count of <30×109/L, and, at the start of the trial taking concurrent ITP treatment(s) and 
having received at least 1 prior therapy for ITP in the past, or not taking treatment for ITP but 
having received at least 2 prior treatments for ITP. If participants are receiving concurrent ITP 
therapies at baseline, these therapies should have been maintained at a stable dose and dosing 
frequency for 4 weeks before randomization. 
Disclosure Statement: 
ARGX-113-2004 is a double-blinded, randomized, parallel-group trial to evaluate the efficacy, 
safety, and effect on QoL/PRO of fixed doses of efgartigimod PH20 SC, compared to 
placebo PH20 SC. 
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Number of Participants: 
Approximately 180 participants with chronic ITP and up to 39 participants with persistent ITP 
will be randomized in a 2:1 ratio to receive efgartigimod PH20 SC or placebo PH20 SC, 
respectively. Recruitment will end when 180 participants with chronic ITP have been 
randomized. 
Participants will be stratified according to the following factors: 
• History of splenectomy (yes versus no) 
• Receiving concurrent ITP therapies at baseline (yes versus no) 
Intervention Groups and Duration: 
The total maximum trial duration per participant is up to 35 weeks: 
• Up to 2 weeks of screening 
• 24 weeks treatment period 
• End-of-treatment visit: 1 week after visit 24 
• 8 weeks of follow-up 
After confirmation of eligibility, the participants enter a 24-week treatment period and will be 
randomized to receive efgartigimod PH20 SC or placebo PH20 SC, qw from visits 1 to 4 and 
then from visits 5 to 16 either qw or q2w, adjusted according to their platelet counts. From 
visits 17 to 24, participants will be fixed on the dose schedule they were receiving at visit 16 or 
at the last visit at which the investigational medicinal product (IMP) was administered before 
visit 16 (ie, either qw or q2w). 
All participants or their caregivers (as defined in Section 10.10) will be invited to receive 
training to (self-)administer the IMP while under supervision at least 4 times in the last 
10 weeks, until they are capable of and comfortable with the (self-)administration 
([self-]administration without supervision is foreseen only in the open-label extension trial 
ARGX-113-2005, not in ARGX-113-2004). 
If the participant or his/her caregiver successfully completes the training to the satisfaction of the 
authorized staff, the participant or his/her caregiver, then the participant or his/her caregiver may 
administer the next injections at the trial site under the supervision of the authorized staff. The 
training must be documented in the participant’s source documents and eCRF. 
Participants who complete the 24-week randomized trial period will perform the 
end-of-treatment visit and can enter the open-label extension trial, ARGX-113-2005. If a 
participant has had an SAE during ARGX-113-2004, his/her eligibility for ARGX-113-2005 
should be evaluated by the investigator. The platelet counts from ARGX-113-2004 will be taken 
into account to assess dosing frequency in ARGX-113-2005. 
Participants who complete the 24-week trial period but do not enter the open-label extension 
trial, or participants who discontinue the trial early, with the exception of participants who 
withdraw their consent, will be followed up for 8 weeks for ongoing safety and efficacy 
monitoring. 
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For participants who discontinue the trial early, all the assessments listed for the early 
discontinuation visit specified in the Schedule of Activities (Section 1.3), will be performed. 
Data Monitoring Committee: yes (see Section 10.1.5.1) 
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1.2. 
Schema 
 
Efgartigimod PH20 SC=efgartigimod coformulated with rHuPH20 for subcutaneous administration; EoT=end-of-treatment visit; ITP=immune 
thrombocytopenia; Placebo PH20 SC=placebo with rHuPH20 for subcutaneous administration; rHuPH20=recombinant human hyaluronidase PH20 
a The dosing frequency can be changed from weekly to biweekly if the participant has platelet counts ≥100×109/L for 3 out of 4 consecutive visits (the fourth 
visit being the current visit) and has a platelet count of ≥100×109/L at the last of these 4 visits—OR—for 3 consecutive visits. 
b As of week 12, the start or an increase in the dose and/or schedule of permitted concurrent ITP therapy is allowed for participants who have an “insufficient 
response” (ie, no platelet count of ≥30×109/L in any of the visits during the last 4 weeks). These participants will be considered “nonresponders” for the 
primary endpoint analysis. 
 
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and the predose platelet count on the day of randomization (visit 1). If the third count is not available from the 3 preceding months, this third platelet count can 
be obtained during the screening period. 
 
 
e If available at baseline. 
f Height will only be measured at the screening visit. 
g If IMP is administered, the ECG will be performed after the IMP administration. 
h Laboratory assessments include all parameters mentioned in Section 10.2. On days that IMP is administered, samples for laboratory assessments should be 
collected before dosing, unless otherwise requested. 
i At the screening visit, if the investigator detects 1 or more screening laboratory abnormalities which are not aligned with the medical history and clinical 
evaluation of the participant, the result(s) should be confirmed if still within the screening window. For rescreening criteria see Section 5.4. 
j Only for women of childbearing potential. 
k At the screening visit, the total IgG level must be determined by the central laboratory (exclusion criterion 9). 
l Only for women of non-childbearing potential. 
m To maintain the blind, the IgG testing cannot be performed locally. 
n To be collected predose, on the day of IMP administration. 
o If the visit does not coincide with an IMP administration, then the assessment should be performed at the next IMP visit. 
p If the visit does not coincide with an IMP administration, then the assessment should NOT be performed. 
 
. 
r Randomization to be completed before administration of IMP. 
s Participants or their caregivers will be invited to receive training to (self-)administer the IMP while under supervision at least 4 times in the last 10 weeks, until 
they are capable of and comfortable with the (self-)administration ([self-]administration without supervision is foreseen only in the open-label extension trial 
ARGX-113-2005, not in ARGX-113-2004). 
t To be obtained before initiation of the IMP administration training. 
u The IMP (efgartigimod PH20 SC or placebo PH20 SC) will be administered as an SC injection at each IMP administration visit. Participants will remain at the 
trial site for at least 30 minutes following the end of the injection for routine safety monitoring based on the participant’s clinical status. Assessment of the 
dosing regimen as described in Section 6.5 will be applied. 
v Adverse events, procedures, and intake of concomitant medication(s) will be monitored continuously from signing the ICF until the last trial-related activity, 
unless the participant withdraws consent. In case of early discontinuation, any adverse events/serious adverse events should be assessed until the participant has 
ended the trial or until satisfactory resolution or stabilization. All available vaccination history will be recorded as part of the participant’s prior medication for 
vaccinations received in the past, or concomitant medication for vaccinations received during the trial. 
 
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2. 
INTRODUCTION 
2.1. 
Trial Rationale 
This phase 3 trial aims to evaluate the efficacy, safety, and effect on quality of life 
(QoL)/patient-reported outcomes (PRO) of efgartigimod coformulated with recombinant 
human hyaluronidase PH20 (rHuPH20) for subcutaneous (SC) administration (efgartigimod 
PH20 SC) in adult patients with primary immune thrombocytopenia (ITP) who have had an 
insufficient response or who are intolerant to existing ITP treatments, evidenced by an 
average platelet count that is below the clinically accepted level for intervention (<30×10⁹/L). 
Participants classified as having persistent primary ITP (between 3 and 12 months since 
diagnosis) and chronic primary ITP (greater than 12 months since diagnosis) will be 
recruited. The diagnosis of primary ITP should be supported by a response to a prior ITP 
therapy other than thrombopoietin receptor agonists (TPO-RAs). At the start of the trial, the 
participants are either taking concurrent ITP treatment(s) and have received at least 1 prior 
therapy for ITP in the past, or the participants are not taking treatment for ITP but have 
received at least 2 prior treatments for ITP. If participants are receiving concurrent ITP 
therapies at baseline, these therapies should have been maintained at a stable dose and dosing 
frequency for 4 weeks before randomization. 
Treatments for ITP are often used in combination, and efgartigimod has the potential to be 
used in combination with other ITP therapies or offer a new stand-alone modality. Therefore, 
participants with and without concurrent ITP therapy will be enrolled. Experience to date of 
efgartigimod treatment in combination with steroids and immunosuppressants in phase 2 and 
phase 3 trials in primary ITP and myasthenia gravis (MG) have not raised any safety 
concerns with these combinations of treatments. 
This trial will utilize an SC dose schedule aiming to maximize the pharmacodynamic (PD) 
effect (ie, reduction in immunoglobulin G [IgG] levels, including autoantibody levels) and 
seeking to result in an improvement in platelet count. In participants who achieve a 
prespecified threshold of maintained platelet count, the frequency of efgartigimod PH20 SC 
administration will be altered (ie, increased or decreased) according to prespecified criteria, 
after which the frequency of administration will be unchanged for the last 7 weeks (visits 17 
to 24) of trial treatment. Assessment of the dosing regimen as described in Section 6.5 will be 
applied. The aim is to achieve the maximum possible proportion of participants with a 
platelet count improvement and then assess whether this can be sustained in the last 6 weeks 
of trial treatment. 
To allow for a convenient SC administration, efgartigimod will be coformulated with 
rHuPH20. rHuPH20 is being used in coformulations with approved therapeutic antibodies to 
facilitate SC injection with volumes larger than 2 mL. 
In clinical trials, efgartigimod in combination with rHuPH20 administered SC has been 
generally safe and well tolerated with no significant safety issues identified. 
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2.2. 
Background 
Efgartigimod (ARGX-113) is a modified human IgG1-derived crystallized fragment (Fc) that 
binds with nanomolar affinity to the human neonatal crystallized fragment receptor (FcRn). 
Efgartigimod encompasses IgG1 residues D221-K447 (EU numbering scheme) and has been 
modified with antibody that enhances IgG degradation (ABDEG) technology1 to increase its 
affinity for FcRn at both physiological and acidic pH, resulting in a blockage of FcRn-
mediated recycling of IgGs. 
Given the essential role of the FcRn in IgG homeostasis, inhibiting this FcRn function, as is 
achieved by efgartigimod, leads to rapid degradation of all IgGs, including disease associated 
autoantibodies of the IgG isotype. This approach is thought to result in alleviation of signs 
and symptoms in IgG-driven autoimmune diseases. 
Phase 2 trials in participants with primary ITP (ARGX-113-1603), generalized myasthenia 
gravis (gMG; ARGX-113-1602), and pemphigus (ARGX-113-1701), and phase 3 trials in 
participants with gMG (ARGX-113-1704 and ARGX-113-1705) and ITP (ARGX-113-1801) 
have indicated that efgartigimod formulation for IV administration (efgartigimod IV) is well-
tolerated; induces a specific, rapid, and profound PD effect (ie, reduction in IgG levels, 
including autoantibody levels); and is associated with improvement in clinical signs and 
symptoms in patients with primary ITP2 and gMG (see Section 2.1). 
A detailed description of the chemistry, pharmacology, efficacy, and safety of efgartigimod 
is provided in the Investigator’s Brochure (IB). 
Primary ITP is an acquired autoimmune bleeding disorder characterized by an isolated low 
platelet count (<100×109/L) in the absence of other causes or disorders associated with 
thrombocytopenia.3 The prevalence of ITP is estimated at 9.5 per 100 000 adults, and 
incidence rates have been reported at 3.3 per 100 000 adults/year.4 In adults, the prevalence 
of ITP increases with age.5 Adult ITP can persist for years. Even with best available care, 
patients rarely achieve long-term remission, and often require multiple treatment options.6 
Immune thrombocytopenia can be described based on the duration of disease: newly 
diagnosed (within 3 months of diagnosis), persistent (between 3 and 12 months from 
diagnosis), and chronic (lasting for more than 12 months).3 
In primary ITP, platelet destruction and impaired platelet production are driven by IgG 
autoantibodies targeting surface receptors on platelets and their progenitor cells. The 
resulting, often severe, thrombocytopenia may be accompanied by a variety of clinical 
manifestations including evidence of bleeding in the skin and mucosa, and risk of serious 
intracranial and gastrointestinal bleeding complications. The highest concern is the risk of 
significant bleeding, such as intracranial hemorrhage. The 5-year fatal hemorrhage rate is 
higher in older patients with ITP, especially in those with comorbid conditions.6-8 Other 
clinically significant concerns include complications from internal bleeding and elevated risk 
of arterial thrombosis and venous thromboembolism.9 Immune thrombocytopenia is also 
associated with fatigue, reported in up to 39% of adults with ITP,4 as well as with impaired 
QoL. These comorbidities interfere with work and social life, which can lead to feelings of 
embarrassment, isolation, and sexual inadequacy.6-8 
Several drugs and medical procedures are routinely used in the management of ITP. First-line 
therapy in primary ITP is corticosteroids, as well as normal immunoglobulins given IV 
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(IVIg) and anti-D. Second-line treatments include broad immunosuppressants and TPO-RAs. 
There is limited evidence to guide the use of these treatments, as described in the American 
Society of Hematology guideline (ASH).10 There is very limited evidence to guide a 
sequence of treatments for patients who have recurrent or persistent thrombocytopenia 
associated with bleeding after an initial treatment course with corticosteroids (or IVIg or 
anti-D). Patients may cycle through different treatment regimens seeking any that is 
efficacious and tolerable. Immune thrombocytopenia remains a chronic disease despite the 
availability of several treatments with differing mechanisms of action. According to the ASH 
ITP guidelines only splenectomy has provided evidence of remission at 1 year. Additionally, 
a significant proportion of patients develops resistance to treatment. Furthermore, existing 
treatments are associated with burdensome side effects limiting their use (eg, long-term 
steroid treatment) and/or concern about use in patient populations (eg, TPO-RAs in patients 
with elevated cardiovascular risk). 
Targeted and selective IgG reduction, as achieved by efgartigimod, has the potential as an 
effective new treatment in ITP given the central role of IgG antiplatelet autoantibodies in the 
pathophysiology of ITP. It represents a novel mechanism of action distinct from that of other 
existing treatments which are either broadly immunosuppressive or stimulate thrombopoiesis. 
In the current trial, efgartigimod is coformulated with the permeation enhancer rHuPH20 
(efgartigimod PH20 SC). rHuPH20 acts as a spreading factor that increases the dispersion 
and absorption of other coadministered drugs and allows SC dosing of greater volumes than 
without rHuPH20. Subcutaneous injections of rHuPH20 with fluids, small molecules, 
peptides, and proteins (eg, IgG) were well-tolerated in all clinical trial populations studied to 
date.  
2.3. 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits, risks, and reasonably 
expected adverse events (AEs) of efgartigimod may be found in the current efgartigimod IB. 
2.3.1. 
Risk Assessment 
Table 2: 
Potential Risks and Mitigation Strategies 
Potential clinically 
significant risk  
Summary of data/rationale for risk Mitigation strategy 
Serious infection 
Efgartigimod reduces IgG levels, 
potentially hindering immune 
response and increasing the risk for 
infection. 
Exclude participants with clinically 
significant active infection not 
sufficiently resolved in the 
investigator’s opinion (Section 5.2). 
Infections are considered AESIs 
(Section 8.4.9). Monitor for 
infections and temporarily interrupt 
IMP dosing as specified in 
Section 7.1. 
Injection-related 
reactions 
All therapeutic proteins can elicit 
immune responses, potentially 
resulting in hypersensitivity or 
Monitor participants during 
administration and for 30 minutes 
thereafter for clinical signs and 
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Potential clinically 
significant risk  
Summary of data/rationale for risk Mitigation strategy 
allergic reactions such as rash, 
urticaria, angioedema, serum 
sickness, and anaphylactoid or 
anaphylactic reactions.  
symptoms of injection-related 
reactions. 
Injection-related reactions are 
considered AEs. 
Injection-site 
reactions 
Most AEs have been mild, transient 
injection-site reactions, including 
erythema, pain, bruising, pruritus, 
burning, tenderness, edema, 
induration, irritation, paresthesia, 
numbness, and rash. Moderate 
injection-site reactions occurring less 
include burning, erythema, pain, and 
numbness. Mild to moderate 
headache is commonly reported. 
Localized injection-site reactions are 
frequently observed in studies in 
which efgartigimod is comixed with 
PH20 and administered SC. 
Continuously monitor participants 
for injection-site reactions. 
Injection-site reactions are 
considered AEs (Section 8.3.1). 
AE=adverse event; AESI=adverse event of special interest; IgG=immunoglobulin G; IMP=investigational 
medicinal product; SC=subcutaneous 
2.3.2. 
Benefit Assessment 
More detailed information about the known and expected benefits and risks of efgartigimod 
and reasonably expected AEs can be found in the current version of the IB. 
2.3.3. 
Overall Benefit: Risk Conclusion 
The favorable balance between risks and anticipated efficacy/benefits supports the use of 
efgartigimod PH20 SC in clinical development. 
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3. 
OBJECTIVES AND ENDPOINTS 
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary 
• To evaluate the efficacy of 
efgartigimod PH20 SC compared to 
placebo PH20 SC in achieving a 
sustained platelet count response in 
patients with chronic primary ITP, with 
a sustained platelet count response 
defined as platelet counts of ≥50×109/L 
for at least 4 of the 6 visits between 
week 19 and week 24 of the trial 
 
Note: “week” instead of “visit” is used 
in the endpoints, ensuring that the 
platelet count of the end-of-treatment 
visit is regarded as week 24 platelet 
count (eg, platelet count after 19 weeks 
of treatment corresponds with platelet 
count of visit 20) 
• Proportion of patients with chronic ITP 
with a sustained platelet count response 
defined as achieving platelet counts of 
≥50×109/L for at least 4 of the 6 visits 
between week 19 and week 24 of the 
trial 
Secondary 
• To evaluate the efficacy of 
efgartigimod PH20 SC compared to 
placebo PH20 SC in overall platelet 
count response 
• Extent of disease control defined as the 
number of cumulative weeks over the 
planned 24-week treatment period with 
platelet counts of ≥50×109/L in the 
chronic ITP population 
(Key Secondary Endpoint 1) 
• Proportion of patients in the overall 
population (chronic and persistent ITP) 
with a sustained platelet count response 
defined as achieving platelet counts of 
≥50×109/L for at least 4 of the 6 visits 
between week 19 and week 24 
(Key Secondary Endpoint 2) 
• Proportion of patients in the overall 
population achieving platelet counts of 
≥50×109/L for at least 6 of the 8 visits 
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between week 17 and 24 of the trial 
(Key Secondary Endpoint 3) 
• Proportion of patients in the overall 
population with overall platelet response 
defined as achieving a platelet count of 
≥50×109/L on at least 4 occasions at any 
time during the 24-week treatment 
period 
• Extent of disease control defined as the 
number of cumulative weeks until 
week 12 with platelet counts of 
≥50×109/L in the overall population 
• Proportion of patients in the overall 
population with overall platelet response 
defined as achieving a platelet count of 
≥50×109/L on at least 4 occasions at any 
time until week 12 
• Mean change from baseline in platelet 
count at each visit in the overall 
population 
• Time to response defined as the time to 
achieve 2 consecutive platelet counts of 
≥50×109/L in the overall population 
• The number of cumulative weeks over 
the planned 24-week treatment period 
with platelet counts of ≥30×109/L and 
≥20×109/L above baseline in the overall 
population 
• In patients with baseline platelet count 
of <15×109/L, the number of cumulative 
weeks over the planned 24-week 
treatment period with platelet counts of 
≥30×109/L and ≥20×109/L above 
baseline in the overall population 
• To evaluate the incidence and severity 
of bleeding events while receiving 
treatment with efgartigimod PH20 SC 
compared to placebo PH20 SC 
• Incidence and severity of the World 
Health Organization (WHO)-classified 
bleeding events in the overall population 
(Key Secondary Endpoint 4) 
• To evaluate the efficacy of 
efgartigimod PH20 SC compared to 
• Proportion of patients with an IWG 
response 
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placebo PH20 SC in International 
Working Group (IWG) response 
• Proportion of patients with an IWG 
complete response 
• Proportion of patients with an initial 
response 
• To evaluate the safety and tolerability 
of efgartigimod PH20 SC administered 
qw or every other week (q2w) 
compared to placebo PH20 SC 
• Incidence and severity of AEs, AEs of 
special interest (AESIs), and SAEs in 
the overall population 
• Vital signs, ECG, and laboratory 
assessments in the overall population 
• To evaluate the use of rescue treatment 
and changes in concurrent ITP therapy 
while receiving treatment with 
efgartigimod PH20 SC compared to 
placebo PH20 SC 
• Rate of receipt of rescue therapy (rescue 
per patient per month) in the overall 
population 
• Proportion of patients for whom dose 
and/or frequency of concurrent ITP 
therapies have increased at week 12 or 
later in the overall population 
• To evaluate the effects of efgartigimod 
PH20 SC treatment on QoL measures 
and PRO compared to 
placebo PH20 SC 
• Change from baseline in PRO 
(Functional Assessment of Chronic 
Illness Therapy Fatigue Scale 
[FACIT-Fatigue], Functional 
Assessment of Cancer Therapy 
questionnaire-Th6 [Fact-Th6]) and QoL 
(Short Form-36 [SF-36]) at planned 
visits in the overall population 
• To assess the immunogenicity of 
efgartigimod and rHuPH20 
• Incidence and prevalence of antibodies 
to efgartigimod and/or rHuPH20 in the 
overall population 
• Titers of antibodies to efgartigimod 
and/or rHuPH20 in the overall 
population 
• Presence of neutralizing antibodies 
(NAb) against efgartigimod and/or 
rHuPH20, and titers of NAb against 
rHuPH20 in the overall population 
• To assess the PK of efgartigimod PH20 
SC 
• Serum efgartigimod concentration 
observed predose (Ctrough) in the overall 
population 
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• To assess the PD effects of 
efgartigimod PH20 SC 
• Pharmacodynamics markers: total IgG 
and antiplatelet antibody levels in the 
overall population 
Exploratory 
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• 
 
 
 
 
 
 
 
 
 
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4. 
TRIAL DESIGN 
4.1. 
Overall Design 
This is a phase 3, multicenter, randomized, double-blinded, placebo-controlled, 
parallel-group trial to evaluate the efficacy, safety, and effect on QoL/PRO of efgartigimod 
PH20 SC treatment in adult patients with primary ITP. 
The total maximum trial duration per participant is up to 35 weeks: 
− Up to 2 weeks of screening 
− 24 weeks treatment period 
− End-of-treatment visit: 1 week after visit 24 
− 8 weeks of follow-up 
The target population is adult patients with persistent or chronic primary ITP, having an 
average platelet count of <30×109/L, and, at the start of the trial taking concurrent ITP 
treatment(s) and having received at least 1 prior therapy for ITP in the past, or not taking 
treatment for ITP but having received at least 2 prior treatments for ITP. If participants are 
receiving concurrent ITP therapies at baseline, these therapies should have been maintained 
at a stable dose and dosing frequency for 4 weeks before randomization. 
As of week 12, the start or an increase in the dose and/or schedule of permitted concurrent 
ITP therapy is allowed for participants who have an “insufficient response” (ie, no platelet 
count of ≥30×109/L in any of the visits during the last 4 weeks). These participants will be 
considered as “nonresponders” for the primary endpoint analysis. 
After confirmation of eligibility, the participants enter a 24-week treatment period and will 
be randomized to receive efgartigimod PH20 SC or placebo PH20 SC, qw from visits 1 to 4, 
and then from visits 5 to 16 either qw or q2w, adjusted according to their platelet counts. 
From visits 17 to 24, participants will be fixed on the dose schedule they were receiving at 
visit 16 or at the last visit at which IMP was administered before visit 16 (ie, either qw or 
q2w). 
Participants completing the 24-week randomized trial period will perform the 
end-of-treatment visit and can enter the open-label extension trial, ARGX-113-2005. If a 
participant has had an SAE during ARGX-113-2004, his/her eligibility for ARGX-113-2005 
should be evaluated by the investigator. The platelet counts from ARGX-113-2004 will be 
taken into account to assess the dosing frequency in ARGX-113-2005. 
Participants who complete the 24-week trial period but who do not enter the open-label 
extension trial, or participants who discontinue the trial early, with the exception of 
participants who withdraw their consent, will be followed for 8 weeks for ongoing safety and 
efficacy monitoring. 
For participants who discontinue the trial early, all the assessments listed for the early 
discontinuation visit as specified in the Schedule of Activities (SoA, Section 1.3), will be 
performed. 
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All participants or their caregivers (as defined in Section 10.10) will be invited to receive 
training to (self-)administer the IMP while under supervision at least 4 times in the last 
10 weeks, until they are capable of and comfortable with the (self-)administration 
([self-]administration without supervision is foreseen only in the open-label extension trial 
ARGX-113-2005, not in ARGX-113-2004) as specified in the SoA in Section 1.3. 
If the participant or his/her caregiver successfully completes the training to the satisfaction of 
the authorized staff, the participant or his/her caregiver, then the participant or his/her 
caregiver may administer the next injections at the trial site under the supervision of the 
authorized staff. The training must be documented in the participant’s source documents and 
eCRF. 
4.2. 
Scientific Rationale for Trial Design 
In the current trial, efgartigimod PH20 SC or placebo PH20 SC will be administered in 
participants with primary ITP, with the aim to evaluate the efficacy, safety, and effect on 
QoL/PRO of efgartigimod PH20 SC versus placebo PH20 SC. 
This trial is designed as a randomized, double-blinded trial to evaluate the effect of fixed 
doses of efgartigimod PH20 SC compared to placebo PH20 SC. The trial consists of a 
treatment period where all participants will initially receive qw SC injections from visits 1 
to 4. From visits 5 to 16, the dosing frequency can be altered (ie, increased or decreased) 
according to specified rules. 
 
 
 
 explored. 
4.2.1. 
Participant Input into Design 
Not applicable. 
4.3. 
Justification for Dose 
Results of the phase 1 studies in healthy subjects (ARGX-113-1501, ARGX-113-1702), the 
phase 2 trials in participants with primary ITP and participants with gMG, the phase 3 trials 
in MG, as well as PK/PD modeling analysis, indicate that a dose of 10 mg/kg efgartigimod, 
administered qw through IV infusion achieved close to maximal IgG reduction (PD effect), 
resulted in a reduction of pathogenic autoantibodies, and was associated with clinical 
efficacy in both participants with ITP and participants with gMG. Furthermore, this dose was 
safe and well-tolerated in all populations. 
The selected SC dose targets a similar PD effect compared with the 10 mg/kg IV dose, 
anticipating a similar clinical response. PK/PD modeling indicated that qw or q2w doses of 
efgartigimod PH20 SC 1000 mg result in a comparable effect on IgG levels as with 10 mg/kg 
IV administered qw or q2w. No body weight effect was found to be statistically significant 
on either PK or PD parameters. 
No significant safety findings have been identified to date with efgartigimod administered SC 
in combination with rHuPH20 in trials with healthy participants, participants with gMG, 
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participants with primary ITP, participants with CIDP, or participants with pemphigus 
(vulgaris or foliaceus). 
4.4. 
End of Trial Definition 
The end of trial is defined as the last participant’s last visit in ARGX-113-2004. 
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5. 
TRIAL POPULATION 
Participants who do not meet all the inclusion criteria or who meet any of the exclusion 
criteria will not be eligible to receive any trial medication. 
The criteria for screening and enrollment are to be followed explicitly. If it is noted that a 
participant who does not meet 1 or more of the inclusion criteria and/or meets 1 or more of 
the exclusion criteria was inadvertently enrolled and dosed, the sponsor’s designated contract 
research organization (CRO) (medical) monitor 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 base. 
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 and provide written informed 
consent (including consent for the use and disclosure of research-related health 
information), willing and able to comply with the trial protocol procedures (including 
attending the required trial visits) 
2a. Is at least the local legal age of consent for clinical studies when signing the ICF. 
3. Confirmed diagnosis of primary ITP made at least 3 months before randomization 
and based on the American Society of Hematology Criteria, and no known etiology 
for thrombocytopenia 
4. Diagnosis supported by a response to a prior ITP therapy (other than TPO-RAs), in 
the opinion of the investigator 
5. Mean platelet count of <30×109/L from at least 3 documented, qualifying counts 
within the 3 preceding months where at least 2 of the qualifying counts must be taken 
during the screening period: 1 platelet count collected during the screening period and 
the predose platelet count on the day of randomization (visit 1). If the third count is 
not available from the 3 preceding months, this third platelet count can be obtained 
during the screening period. 
6. A documented history of a platelet count of <30×109/L before screening 
7. At the start of the trial, the participant is either receiving concurrent ITP treatment(s) 
and has received at least 1 prior therapy for ITP in the past, or the participant does not 
take treatment for ITP (see note) but has received at least 2 prior treatments for ITP. 
Participants receiving permitted concurrent ITP treatment(s) at baseline must have 
been stable in dose and frequency for at least 4 weeks before randomization. 
Permitted concurrent ITP medications include corticosteroids, danazol, vinca 
alkaloids, oral immunosuppressants, dapsone, fostamatinib, and/or oral TPO-RAs. 
Note: Participants not receiving concurrent ITP therapy are also eligible for the trial if 
they have not received prior ITP therapy for at least 4 weeks before baseline, and 
6 months in case of prior ITP therapy with an anti-CD20 therapy (eg, rituximab). 
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8b. Agree to use contraceptive measures consistent with local regulations and the 
following: 
Female participants of childbearing potential (defined in Section 10.6.1.1) must have 
a negative serum pregnancy test at screening and a negative urine pregnancy test at 
baseline before receiving IMP. Contraceptive requirements are provided in 
Section 10.6.2.1. 
5.2. 
Exclusion Criteria 
Participants are excluded from the trial if any of the following criteria apply: 
1. Secondary ITP/thrombocytopenia associated with another condition, eg, lymphoma, 
chronic lymphocytic leukemia, viral infection, hepatitis, induced or alloimmune 
thrombocytopenia, thrombocytopenia associated with myeloid dysplasia, or 
hematopoietic stem cell transplant 
2. Use of anticoagulants (eg, vitamin K antagonists, direct oral anticoagulants) within 
4 weeks prior to randomization 
3. Use of any transfusions within 4 weeks prior to randomization 
4. Use of Ig (IV, SC, or intramuscular route) or plasmapheresis (PLEX) within 4 weeks 
prior to randomization 
5. Use of romiplostim within 4 weeks prior to randomization 
6. Undergone splenectomy less than 4 weeks prior to randomization 
7. Use of an investigational product within 3 months or 5 half-lives (whichever is 
longer) before the first dose of the IMP 
8. Use of any monoclonal antibody or Fc fusion proteins, other than those previously 
indicated, within 6 months before the first dose of the IMP (eg, anti-CD20) 
9. At the screening visit, clinically significant laboratory abnormalities as follows: 
• Hemoglobin ≤9 g/dL 
– OR – 
• International normalized ratio >1.5 or activated partial thromboplastin 
time >1.5×upper limit of normal 
– OR – 
• total IgG level <6 g/L 
10. History of malignancy unless deemed cured by adequate treatment with no evidence 
of recurrence for ≥3 years before the first administration of IMP. Participants with the 
following cancer can be included at any time: 
a. Adequately treated basal cell or squamous cell skin cancer 
b. Carcinoma in situ of the cervix 
c. Carcinoma in situ of the breast or 
d. Incidental histological finding of prostate cancer (TNM stage T1a or T1b) 
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11. Uncontrolled hypertension, defined as a repeated elevated blood pressure exceeding 
160 mmHg (systolic) and/or 100 mmHg (diastolic) despite appropriate treatments 
12a. History of any major thrombotic or embolic event (eg, myocardial infarction, stroke, 
deep venous thrombosis, or pulmonary embolism) within 5 years before 
randomization 
13. History of coagulopathy or hereditary thrombocytopenia or a family history of 
thrombocytopenia 
14. Evidence of an active clinically significant bleeding of an organ or internal mucosal 
bleeding, other than expected in ITP, that warrants emergent treatment or therapeutic 
procedure based on the investigator’s judgment (eg, intracranial hemorrhage, 
pulmonary hemorrhage, bleeding with ongoing need for packed red blood cell 
transfusion) 
15. Estimated high risk of a clinically significant bleeding of an organ or internal mucosal 
bleeding, other than expected in ITP, that warrants emergent treatment or therapeutic 
procedure according to the investigator’s judgment 
16. Clinical evidence of other significant serious diseases, have had a recent major 
surgery, or who have any other condition in the opinion of the investigator, that could 
confound the results of the trial or put the participant at undue risk 
17. Positive serum test at screening for an active viral infection with any of the following 
conditions: 
a. Hepatitis B virus (HBV) that is indicative of an acute or chronic infection, unless 
associated with a negative HBV DNA test 
(https://www.cdc.gov/hepatitis/HBV/PDFs/SerologicChartv8.pdf) 
b. Hepatitis C virus (HCV) based on HCV-antibody assay (unless associated with a 
negative HCV RNA test) 
c. Human immunodeficiency virus (HIV) based on test results that are associated 
with an acquired immunodeficiency syndrome (AIDS)-defining condition or a 
CD4 count ≤200 cells/mm3 
18. Known hypersensitivity reaction to efgartigimod, rHuPH20, or 1 of its excipients 
19. Previously participated in a clinical trial with efgartigimod and have received at least 
1 administration of the IMP 
20a. Pregnant or lactating or intends to become pregnant during the trial 
21. Clinically significant uncontrolled active or chronic bacterial, viral, or fungal 
infection at screening 
22. Any other known autoimmune disease that, in the opinion of the investigator, would 
interfere with an accurate assessment of clinical symptoms of ITP or put the 
participant at undue risk 
23. Clinical evidence of significant unstable or uncontrolled acute or chronic diseases 
other than ITP (eg, cardiovascular, pulmonary, hematologic, gastrointestinal, 
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endocrine, hepatic, renal, neurological, malignancy, infectious diseases, uncontrolled 
diabetes) despite appropriate treatments which could put the participant at undue risk 
24. Current or history of (ie, within 12 months of screening) alcohol, drug, or medication 
abuse 
25. Received a live/live-attenuated vaccine less than 4 weeks before screening. The 
receipt of any inactivated, sub-unit, polysaccharide, or conjugate vaccine at any time 
before screening is not considered an exclusion criterion 
5.3. 
Lifestyle Considerations 
No lifestyle restrictions are required. 
5.3.1. 
Meals and Dietary Restrictions 
Not applicable. 
5.3.2. 
Caffeine, Alcohol, and Tobacco 
Participants with a current or history of alcohol abuse cannot participate in the trial (see 
exclusion criterion 24). 
5.3.3. 
Activity 
Not applicable. 
5.4. 
Screen Failures, Retesting, and Rescreening 
Evaluations at screening and confirmation at baseline (visit 1) will be used to determine the 
eligibility of each participant. Participants who fail to meet the eligibility criteria by visit 1 
will be considered screen failures. 
Participants may be retested once (ie, redoing 1 test) if still within the screening period. 
Retesting may be considered in the following case: 
• A participant who has clinical laboratory test values meeting 1 or more exclusion 
criteria which are not aligned with the medical history and clinical evaluation of 
the participant, may be retested to confirm the value of the test (to be confirmed 
by the central laboratory, except for the platelet count for which 1 retesting can be 
done at the local laboratory), if still within the screening period. If not feasible, 
the participant should be rescreened (ie, redoing the full assessments as per SoA, 
Section 1.3). Refer to Section 8.3.5. 
Rescreening is allowed as long as the participant has not received any IMP. Examples of 
conditions under which rescreening may be considered include participants who required 
treatment for an acute illness (eg, a urinary tract infection) or have a chronic medical problem 
(eg, uncontrolled hypertension); participants may be rescreened once the illness has resolved 
or the medical problem is stabilized. 
The decision to rescreen participants, based on the clinical state of the participant and the 
decision to rescreen will solely be made per the investigator’s discretion on a case-by-case 
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basis. For the purpose of rescreening, a new ICF should be completed, and a new participant 
identification number (ID) will be generated. 
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6. 
TRIAL INTERVENTION 
Trial intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a trial participant according to 
the trial protocol. Trial intervention is defined as IMP in this trial. 
6.1. 
Trial Intervention(s) Administered 
 
Active Treatment 
Control 
Intervention 
Name 
Efgartigimod PH20 SC 
Placebo PH20 SC 
Type 
Biologic 
Other: placebo 
Dose 
Formulation 
Efgartigimod + 2000 U/mL rHuPH20 
solution for SC injection to be dosed 
at a fixed dose of 1000 mg per 
injection 
Matching placebo + 2000 U/mL 
rHuPH20 solution for SC injection 
Unit Dose 
Strength(s) 
Efgartigimod 180 mg/mL 
Experimental 
Placebo 
Dosage 
Level(s) 
1000 mg, qw or q2w 
Matching SC administration, qw or 
q2w 
Route of 
Administration 
SC injection 
SC injection 
Use 
Investigational 
Placebo comparator 
IMP 
IMP 
IMP 
Sourcing 
Provided by the sponsor to the trial 
site 
Provided by the sponsor to the trial 
site 
Packaging and 
Labeling 
The IMP will be provided in glass 
vials. Each glass vial will be labeled 
as required per country requirement 
The IMP will be provided in glass 
vials. Each glass vial will be labeled 
as required per country requirement 
IMP=investigational medicinal product; qw=every week; q2w=every other week; SC=subcutaneous 
Fixed doses of SC IMP will be administered as SC injections. 
All IMP treatment administered SC will be fully blinded. 
For each injection, the date, initiation and completion times (hour and minute), and details of 
any interruptions or premature discontinuation of injections will be recorded on the eCRF. 
The start will be marked as the moment of start pressing the plunger and the end will be 
marked as the completion time of administration of the total volume of IMP. 
The IMP will be administered as 1 injection. The abdomen is the preferred injection site. 
Optional sites (ie, thighs or arms) may be chosen, eg, if the abdomen is affected by lesions, 
bleedings, or other injection site reactions. The injection site and the reason of using another 
site than the abdomen will be documented on the electronic CRF (eCRF). 
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After the administration of the IMP, the participants will be asked to remain at the 
investigative site for at least 30 minutes after the end of the injection as part of routine safety 
monitoring. 
More details are available in the Pharmacy Manual. 
6.2. 
Preparation/Handling/Storage/Accountability/Packaging 
6.2.1. 
Preparation 
Efgartigimod PH20 SC will be provided as a sterile, clear to opalescent, yellowish solution 
for SC injection in glass vials covered with a blinding shell. 
Placebo PH20 SC will be provided as a sterile, colorless, clear solution for injection in glass 
vials covered with a blinding shell, with the same formulation as the efgartigimod PH20 SC 
solution for injection, but without the active ingredient (efgartigimod). 
The IMP will be manufactured to ensure the blind and in accordance with Good 
Manufacturing Practice regulations. Detailed instructions for IMP management on-site 
(including preparation of the IMP) are included in the Pharmacy Manual. 
6.2.2. 
Handling 
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all IMP received and any discrepancies are reported and 
resolved before use of the IMP. 
Only participants enrolled in the trial may receive IMP and only authorized and trained site 
staff may dispense IMP. The IMP administration must be performed by authorized and 
trained site staff or by an adequately trained and supervised participant or his/her caregiver. 
All IMP must be stored in a secure, environmentally controlled, and monitored (manual or 
automated) area in accordance with the labeled storage conditions, with access limited to the 
investigator and authorized site staff. Detailed instructions are included in the Pharmacy 
Manual. 
6.2.3. 
Storage 
The IMP (efgartigimod PH20 SC and placebo PH20 SC) will be supplied to the pharmacy or 
dedicated site location at the trial site by and under the responsibility of the sponsor’s 
designated IMP supply vendor. For each IMP batch at the site, the investigator will receive 
the certificate of analysis, certificate of conformity, and European Union qualified person 
release documents. 
The IMP must be stored refrigerated (2°C to 8°C or 35°F to 46°F) in its secondary 
packaging, should not be exposed to freezing temperatures, should not be shaken, and should 
be protected from direct sunlight during storage at the investigative site. 
The IMP temperature will be recorded on a continuous basis at the site pharmacy and 
minimum/maximum temperature ranges should be registered as specified in the Pharmacy 
Manual. 
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Further requirements on temperature logging during storage and information on how to 
handle temperature excursions can be found in the Pharmacy Manual. 
The investigator (or designee) is responsible for the correct and safe storage of the IMP 
assigned to the investigative site, in a locked, secure storage facility with access limited to 
those individuals authorized to dispense the IMP and maintained within the appropriate 
temperature ranges. 
Further guidance and information for the final disposition of used and unused IMP are 
provided in the Pharmacy Manual. 
6.2.4. 
Accountability 
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for IMP accountability, reconciliation, and record maintenance (ie, receipt, 
reconciliation, and final disposition records). 
Detailed instructions on accountability of the IMP are included in the Pharmacy Manual. 
6.2.5. 
Packaging and Labeling 
The IMP will be labeled and secondary packed in accordance with local laws and regulatory 
requirements. Detailed instructions are included in the Pharmacy Manual. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
Once the participant has provided informed consent, the investigative site will enroll the 
participant and a screening number will be automatically allocated through interactive 
response technology (IRT). 
Upon confirmation of eligibility at baseline (visit 1), the participant will be randomized 
through IRT. 
Participants will be randomized in a 2:1 ratio to receive efgartigimod PH20 SC or placebo 
PH20 SC, respectively. 
At randomization, participants will be stratified according to whether they underwent a 
splenectomy (yes versus no) and if they are receiving concurrent ITP therapies at baseline 
(yes versus no). 
This is a randomized, double-blinded, placebo-controlled trial with limited access to the IMP 
treatment assigned (see also Section 10.10). 
An independent unblinded data safety monitoring board (DSMB), including an independent 
statistician, will review all unblinded safety data as specified in Section 10.1.5.1. 
6.3.1. 
Emergency Unblinding 
The process of breaking the blind will be handled through the IRT. 
Investigators are strongly discouraged from breaking the blind for an individual participant, 
unless there is a participant safety issue that via knowledge of the IMP treatment assignment 
would change participant management. If the investigator decides that unblinding is 
warranted, the investigator may contact the sponsor before unblinding a participant’s IMP 
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unless this could delay emergency treatment for the participant. If a participant’s intervention 
assignment is unblinded, the sponsor must be notified within 24 hours of this occurrence. If 
the blind is broken by the investigator, it may be broken only for the participant concerned, 
and the IMP treatment assignment should not be revealed to the Sponsor’s trial team 
members, nor to the sponsor’s designated CRO, pharmacy personnel, or other site staff. 
Once unblinded, the participant will be discontinued from the trial and will be followed for 
8 weeks for ongoing safety and efficacy monitoring. The follow-up period will consist of 
2 visits every 4 weeks (q4w). 
Pertinent information regarding the circumstances of unblinding of a participant’s IMP 
treatment code must be documented in the participant’s source documents and eCRF. 
The sponsor and monitor at the sponsor’s designated CRO must be notified immediately if a 
participant and/or investigator is unblinded during the course of the trial. 
6.4. 
Trial Intervention Compliance 
The participants are dosed by qualified approved personnel. Adequately trained participants 
or their caregivers are also allowed to administer the IMP on-site under supervision of the 
authorized site staff. They will receive IMP directly from the investigator or designee, under 
medical supervision. The date and time of each dose administered at the investigative site 
will be recorded in the source documents and recorded 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 times of IMP 
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 investigative 
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 dose schedule is correct. 
Errors that are identified will be communicated to the site personnel to ensure that the errors 
are not repeated. The sponsor’s designated CRO monitor’s report will include details of any 
missed doses, errors in dose, treatment or scheduling errors, and the associated explanations. 
These dosing errors will be evaluated to determine whether they should 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. However, if a participant misses more than 2 consecutive 
scheduled doses, then he/she will be discontinued early from trial treatment (see Section 7.1). 
Withholding IMP as described in Section 6.7 and Section 7.1.1 is not considered a missed 
dose. 
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If a participant misses any dose of IMP, he/she should not make up the missed dose. A dose 
is only considered as missed in case of a missed visit. Other reasons for not administering the 
IMP are not considered as a missed dose. 
6.4.2. 
Protocol Deviations 
Prospective approval of protocol deviations to enrollment criteria, also known as protocol 
waivers or exemptions, is not permitted. 
The investigator should not implement any deviation from, or changes to the approved 
protocol without agreement of the sponsor, and prior review and documented approval of an 
amendment from the Institutional Review Board/Independent Ethics Committee (IRB/IEC) 
and regulatory authority as per local regulation, except where necessary to eliminate an 
immediate hazard to trial participants, or when the change involves only logistical or 
administrative aspects of the trial (eg, change of telephone numbers). The investigator (or 
designee) should document and explain any deviation from the approved protocol. 
6.5. 
Screening and Treatment 
After the informed consent has been obtained, the participant will be screened (screening 
period of maximum 14 days) at the investigative site for eligibility based on the inclusion and 
exclusion criteria defined in Section 5.1 and Section 5.2, respectively. 
The assessments as specified in the SoA, Section 1.3 will be performed during screening. 
All participants will initially receive qw SC injections from visit 1 to 4 (consecutive 
administrations of IMP should be at least 5 days apart). 
Based on the platelet counts as of visit 2, the dosing frequency can be altered from 
visits 5 to 16 (consecutive administrations of IMP should be at least 5 or 12 days apart for the 
qw or q2w administration schedule, respectively) according to the following rules (the 
change in dosing frequency will occur at the current visit): 
• Reduce from qw to q2w in participants having platelet counts of ≥100×10⁹/L for 
3 out of 4 consecutive visits (the fourth visit being the current visit), and having a 
platelet count of ≥100×10⁹/L at the last of these 4 visits 
– OR – 
Reduce from qw to q2w in participants having platelet counts of ≥100×10⁹/L for 
3 consecutive visits 
Note: In this case, no IMP will be administered at the last visit confirming the 
qualifying platelet counts of ≥100×10⁹/L. 
• Increase from q2w to qw in participants whose platelet counts drop to <100×10⁹/L 
on 2 consecutive visits 
– OR – 
<30×10⁹/L at 1 visit 
– OR – 
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in participants who receive rescue therapy (see Section 6.6.4) 
• Postbaseline platelet count can be performed within 1 day of the next procedure 
as per SoA (both dosing and nondosing visit), allowing the results to be 
incorporated into the criteria above. 
From visits 17 to 24, the dosing frequency is fixed for each individual participant (ie, either 
qw or q2w regimen), based on the regimen the participant was receiving at visit 16 or at the 
last visit at which IMP was administered. 
Exceptions to the fixed dosing frequency are: 
• Continued qw dosing for participants requiring rescue therapy  
• Continued q2w dosing for participants resuming IMP when the platelet count falls 
to <150×109/L after having had platelet counts >400×109/L 
6.6. 
Prior and Concomitant Therapy 
All prior ITP procedures and therapies received by the participant since diagnosis, before 
baseline, must be recorded on the eCRF, including the name, dose/schedule, duration 
(including start and stop dates), intolerance, whether the participant responded to them, 
details of platelet counts on prior ITP therapies (ie, supporting the participant’s response), 
and the reason for discontinuation from prior therapies that are documented on the 
participant’s source documents at the current trial site. 
The washout periods as specified in the exclusion criteria must be followed. See also 
Section 10.4. 
All available vaccination history should be recorded as part of the participant’s prior 
medication for vaccinations received in the past, or concomitant medication for vaccinations 
received during the trial as described in the SoA (Section 1.3). Any vaccination information 
that the participant, his/her caregiver, or his/her legally authorized representative can 
remember should be recorded on the eCRF (with the brand name of the vaccine and date of 
vaccination, if possible). 
All concomitant medications and procedures whether allowed or not must be recorded on the 
eCRF (including the name, indication [for use], dose/schedule, and start and stop dates). 
6.6.1. 
Concurrent ITP Therapy 
• Participants receiving at least 1 permitted concurrent ITP therapy are eligible for 
the trial, if the dose and schedule have remained unchanged in the last 4 weeks 
before randomization (ie, visit 1). 
• Permitted concurrent ITP medications include corticosteroids, danazol, vinca 
alkaloids, oral immunosuppressants, dapsone, fostamatinib, and/or oral TPO-RAs 
(see inclusion criterion 7, Section 5.1). 
• Dose and frequency of permitted concurrent ITP therapies should remain 
unchanged during the trial. 
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• Exceptions are participants who are receiving concurrent treatment with oral 
TPO-RAs in whom dose changes are permitted at label-defined platelet 
thresholds, and participants who are receiving concurrent treatment with 
fostamatinib, in whom dose changes or stopping of treatment is allowed in 
label-defined conditions. 
• As of week 12, the start or an increase in the dose and/or schedule of permitted 
concurrent ITP therapy is allowed for participants who have an “insufficient 
response” (ie, no platelet count of ≥30×109/L in any of the visits during the last 
4 weeks). These participants will be considered as “nonresponders” for the 
primary endpoint analysis. At the discretion of the investigator, the dose and/or 
schedule of the concurrent ITP therapy can be returned to the baseline levels. 
• Participants not receiving concurrent ITP therapy are also eligible for the trial (see 
inclusion criterion 7, Section 5.1). The washout periods as specified in exclusion 
criteria 2 to 8 must be followed. See also Section 10.4. 
• Any change in concurrent ITP therapy should appropriately be recorded on the 
eCRF. 
• The medical monitor at the sponsor’s designated CRO should be contacted if there 
are any questions regarding concomitant or prior therapy. 
6.6.2. 
Prohibited Medications and Therapy Before Randomization 
The following medications or treatments are not permitted within the specified time window 
before randomization: 
• Use of anticoagulants (eg, vitamin K antagonists, direct oral anticoagulants) 
within 4 weeks before randomization. 
• Use of any transfusions within 4 weeks before randomization. 
• Use of Ig (IV, SC, or intramuscular route) or PLEX, within 4 weeks before 
randomization. 
• Use of anti-CD20 therapy (eg, rituximab) within 6 months before randomization. 
• Use of romiplostim within 4 weeks before randomization. 
• Undergone splenectomy less than 4 weeks before randomization. 
• Use of any other investigational drug within 3 months or 5 half-lives of the drug 
(whichever is longer) before randomization. 
• Use of any monoclonal antibody within 6 months before randomization. 
• Live/live-attenuated vaccines within 4 weeks before screening. 
6.6.3. 
Prohibited Medications and Therapy During the Trial  
The following medications or treatments are not permitted during the trial: 
• Anti-CD20 therapy (eg, rituximab) 
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• Romiplostim 
• Any monoclonal antibodies, Fc fusion proteins, or other investigational drug 
• Live/live-attenuated vaccines 
6.6.4. 
Rescue Therapy 
“Rescue therapy” is defined as an occurrence where the participant needs treatment with 1 or 
more rescue treatments. An “occurrence” is defined as a period of maximum 5 days where 
1 or more rescue treatments are administered simultaneously or consecutively to the trial 
participant. The start date/time of the occurrence is the start of the administration of the first 
rescue treatment. 
Rescue therapy is allowed for participants having protocol-defined ITP clinical deterioration 
AND if in addition, the treating physician believes that the participant’s health is in jeopardy 
if rescue therapy is not given. 
Rescue therapy is allowed postbaseline during the 24-week trial period for participants with a 
platelet count of <30×10⁹/L and 1 of the following: 
• an immediate risk of bleeding or a clinically significant bleeding or wet purpura 
• requirement for urgent or emergent surgery (elective surgeries must be postponed 
until trial completion) 
The following rescue treatments are permitted: 
• IV methylprednisolone up to 1 g/day × 1–3 days, oral dexamethasone up to 
40 mg/day × 1–3 days, or oral prednisone up to 1 mg/kg/day × 1–2 days 
• IVIg: up to 1 g/kg/day × 1–2 days 
• IV anti-D: up to 50–75 mcg/kg/day × 1–2 days 
Note: Anti-D rescue therapy should not be given to Rh(D)-positive participants 
• platelet transfusions 
In the event of rescue with IVIg or IV anti-D: 
• If given at a visit where the IMP was due to be administered, the IMP should be 
withheld and administered at the next visit (see also Section 6.7 and Section 6.4.1) 
For rescue therapy with methylprednisolone, dexamethasone, prednisone, or platelet 
transfusions: 
• Administration of the IMP continues during rescue therapy 
Participants who were receiving q2w dosing at the time of rescue therapy will have the 
IMP administration frequency increased to qw. 
For participants who receive rescue therapy, the platelet counts for 4 weeks after the first day 
of the rescue treatment will not be used (ie, are censored) to assess whether or not the 
participant can transition to q2w treatment. 
Participants requiring more than 3 occurrences of rescue therapy will discontinue from IMP. 
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6.7. 
Dose Modification 
The administration of IMP will be temporarily withheld if it could put the participant at 
undue risk in any of the following circumstances: 
• Platelet count increases to >400×109/L 
The IMP administration should be resumed at the visit where the platelet count 
falls to <150×109/L, at the q2w dosing frequency. 
• Occurrence of infection grade ≥3 according to the National Cancer Institute (NCI) 
Common Terminology Criteria for Adverse Events (CTCAE) 
• Occurrence of bleeding grade ≥3 according to the WHO bleeding scale 
• Occurrence of a thromboembolic event grade >1 according to the NCI CTCAE 
If the IMP is being withheld, it can be reintroduced once the undue risk to the participant has 
passed. 
Even if the participant rolls over to the open-label extension trial (ARGX-113-2005), the 
IMP will be resumed when: 
• The platelet count decreases to <150×109/L at the q2w dosing frequency 
• The AEs as listed previously are resolved according to the medical assessment of 
the investigator 
6.8. 
Intervention After the End of the Trial 
After a participant has completed the trial, has withdrawn/discontinued early, or has 
completed the 2 follow-up visits, usual treatment will be administered if required, in 
accordance with the trial site’s standard of care and generally accepted medical practice 
depending on the participant’s individual needs. 
Eligible participants who have completed the 24-week randomized trial period can enter the 
open-label extension trial ARGX-113-2005 to receive efgartigimod (see Section 4.1). 
• Participants who are receiving a qw regimen:  
− The baseline visit (including the first dose of IMP) of ARGX-113-2005 will 
occur on the same day as the end-of-treatment visit of ARGX-113-2004. 
Assessments that were performed at the end-of-treatment visit of 
ARGX-113-2004 should not be repeated at visit 1 (baseline) of 
ARGX-113-2005. 
• Participants who are receiving a q2w regimen: 
− If visit 24 of ARGX-113-2004 is a dosing visit, then the baseline visit of 
ARGX-113-2005 (including the first dose of IMP) will occur 7 days after the 
end-of-treatment visit of ARGX-113-2004. 
− If visit 24 of ARGX-113-2004 is a nondosing visit, then the baseline visit 
(including the first dose of IMP) of ARGX-113-2005 will occur on the same 
day as the end-of-treatment visit of ARGX-113-2004. Assessments that were 
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performed at the end-of-treatment visit of ARGX-113-2004 should not be 
repeated at visit 1 (baseline) of ARGX-113-2005. 
• Participants who are receiving a qw regimen who meet the criteria (Section 6.5) to 
switch to a q2w regimen based on their platelet counts at the ARGX-113-2004 
end-of-treatment visit: 
− The baseline visit of ARGX-113-2005 (including the first dose of IMP) will 
occur 7 days after the ARGX-113-2004 end-of-treatment visit. 
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7. 
DISCONTINUATION OF TRIAL INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of Trial Intervention 
• Early discontinuation from treatment means that the participant stops receiving 
the ongoing IMP treatment and does not restart IMP treatment; however, 
informed consent is not withdrawn. These participants will continue the qw trial 
visits as specified in the SoA (Section 1.3) without IMP-related assessments. 
• Participants must be discontinued early from treatment in the following 
circumstances: 
− at the request of the sponsor (eg, following DSMB advice, see 
Section 10.1.5.1) 
− participant has missed more than 2 consecutive scheduled doses of IMP 
treatment 
− participant has received more than 3 occurrences of rescue therapy 
− participant develops a new or recurrent malignancy except for basal cell 
carcinoma of the skin, regardless of relationship 
7.1.1. 
Temporary Discontinuation 
See Section 6.7 for specifications regarding temporary withholding of IMP treatment. 
7.1.2. 
Rechallenge 
Not applicable. 
7.2. 
Participant Discontinuation/Withdrawal From the Trial 
• Early discontinuation from the trial is defined as the permanent cessation of 
further participation in the trial before its planned completion and without the 
possibility to roll over to the open-label extension trial ARGX-113-2005. 
• The reason for early discontinuation from the trial will be clearly documented by 
the investigator. 
• 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. 
• At the time of discontinuing from the trial, if possible, an early discontinuation 
visit should be conducted, as shown in the SoA (Section 1.3). See 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 permanently discontinued both from the IMP and from the 
trial at that time. 
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• If the participant withdraws consent for disclosure of future information, the 
sponsor may retain and continue to use any data collected before such a 
withdrawal of consent. 
• If a participant withdraws from the trial, he/she may request destruction of any 
unused samples, and the investigator must document this in the site trial records 
and inform the sponsor accordingly. Trial information and samples collected, 
including their results, from before the participant decided to leave the trial, may 
still be included in the trial results. 
• Participants must be discontinued early from the trial, and complete the early 
discontinuation visit as specified in the SoA (Section 1.3), if: 
− they withdraw their consent 
All participants are free to withdraw consent from participation in the trial at 
any time, for any reason, specified or unspecified, and without prejudice to 
further treatment. Before actual withdrawal of consent, an effort should be 
made to perform a final set of assessments as per the early discontinuation 
visit. 
Investigators will make and document all efforts made to contact those 
participants who do not return for such scheduled visits. 
• Participants must be discontinued early from the trial, complete the early 
discontinuation visit as specified in the SoA (Section 1.3), and be followed for 
8 weeks (2 visits q4w) for ongoing safety and efficacy monitoring if: 
− it is in the participant’s best interest 
− unblinding occurred 
− prohibited medication is taken (see Section 6.6.2) 
− a severe hypersensitivity reaction to IMP occurs 
− the participant became pregnant 
− at the request of the sponsor (eg, following DSMB advice, see 
Section 10.1.5.1) 
7.3. 
Completion of the Trial 
Participants who complete the 24-week trial period but who do not enter the open-label 
extension trial ARGX-113-2005, or participants who discontinue the trial early, with the 
exception of participants who withdraw their consent, will be followed for 8 weeks for 
ongoing safety and efficacy monitoring. 
7.4. 
Lost to Follow-up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the investigative site (see Section 6.4.1). 
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The following actions must be taken if a participant fails to return to the investigative site for 
a required trial visit: 
• The investigative site must attempt to contact the participant 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 (where 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, it will be considered that 
he/she does not want to continue participating in the trial. He/she will be 
considered as lost to follow-up. 
Discontinuation of specific investigative sites or of the trial as a whole are handled as part of 
Appendix 1 (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 
(Section 1.3), is essential and required for trial conduct. 
• When a protocol-required procedure cannot be performed, the investigator will 
document the reason, and any corrective and preventive actions that he/she has 
taken to ensure that the normal processes are adhered to, in source documents. 
The trial team should be informed of these incidents in a timely manner. This will 
be considered a protocol deviation and will be recorded accordingly. 
• At screening, all eligibility assessments should be performed after obtaining 
informed consent. 
• All screening evaluations must be completed and reviewed to confirm that 
participants meet all eligibility criteria before randomization.  
• The investigator will maintain a screening log to record details of all participants 
screened and confirm eligibility or record reasons for screening failure, as 
applicable. 
• Each participant should attend each trial visit on the designated days. There is a 
permissible visit window of +2 days during the treatment period as well as the 
end-of-treatment visit and follow-up period. Every effort should be made to 
schedule every visit on the exact day (which is relative to baseline [visit 1]) as 
described in the SoA (Section 1.3). 
• From the signature of informed consent 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. 
• During the IMP treatment period, all assessments and procedures must be 
performed before the start of the IMP administration, except for ECG assessment 
and the continuous assessment of AEs and the recording of concomitant therapy 
and procedures. 
8.1. 
Demography 
Demographic characteristics comprise age, year of birth, gender, race, and ethnicity (per 
local regulations). Only if requested as per local regulations, no source data verification will 
be performed on race and ethnicity. 
8.2. 
Efficacy Assessments 
Procedures assessing the efficacy of efgartigimod will mainly focus on measures of response 
derived from platelet counts. These assessments will be performed at the qw visits predose 
on all IMP administration days, and at the unscheduled visits (if needed), as specified in the 
SoA (Section 1.3). 
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8.2.1. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8.2.2. 
General Bleeding Assessment 
• Signs and symptoms of bleeding are the predominant clinical manifestation of 
ITP and are typically related to platelet counts. 
• The WHO bleeding scale is a widely recognized tool to assess bleeding and has 
been used in many previous ITP trials. The occurrence and severity of any 
bleeding symptoms will be assessed and recorded at every visit using the WHO 
bleeding scale (Section 10.8) as specified in the SoA (Section 1.3). The WHO 
bleeding scale was originally developed to assess bleeding in participants 
undergoing treatment for cancer and has been used extensively.11 
• The wide use of the scale and incorporation into the CTCAE suggest that it is 
commonly used by clinicians, is applicable across populations and cultures, and is 
responsive to changes in bleeding severity. While validated for mild-to-moderate 
bleeding in ITP, validation for severe bleeding events in ITP has not yet been 
performed.12 
8.3. 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA (Section 1.3). 
8.3.1. 
Physical Examinations 
• Physical examination 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, lymph nodes, musculoskeletal/extremities, abdomen, 
cardiovascular, respiratory, and neurological system. 
• Investigators should pay special attention to clinical signs related to previous 
serious illnesses. 
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• Clinically significant abnormalities in physical examination at screening will be 
reported as medical history on the eCRF. At all other trial visits, new abnormal or 
worsened pre-existing conditions which are clinically significant as judged by the 
investigator, will be reported as an AE. 
• Injection site reactions observed after SC administration will be reported as an 
AE. 
8.3.2. 
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). 
• Supine blood pressure and heart rate will be measured using standard equipment 
after at least 10 minutes with the participant rested and seated. 
• It is recommended that the method used to measure the body temperature 
(eg, orally, tympanic, rectal, axillary, skin, temporal) at screening is maintained 
throughout the trial for each participant. 
• For the assessment of height and weight, participants will be required to remove 
their shoes and wear light indoor clothing. 
• Height will be measured at screening only. Weight will be measured at screening 
and at the time points indicated in the SoA (Section 1.3). 
• Clinically significant abnormalities in vital signs at screening will be reported as 
medical history on the eCRF. At all other trial visits, new abnormal or worsened 
pre-existing conditions which are clinically significant as judged by the 
investigator, will be reported as an AE. 
8.3.3. 
Electrocardiograms 
• The assessment of ECG will be performed at the time points indicated in the SoA 
(Section 1.3). 
• If IMP is administered, the ECG will be performed after the IMP administration. 
• A single 12-lead ECG will be taken at a paper speed of 25 mm/sec in the supine 
position after the participant has rested in this position for at least 10 minutes. The 
ECG will be analyzed centrally. The assessments on heart rate, PR, QT, and QRS 
intervals will be recorded. 
• Clinically significant abnormalities in ECG at screening will be reported as 
medical history on the eCRF. At all other trial visits, new abnormal or worsened 
pre-existing conditions which are clinically significant as judged by the 
investigator, will be reported as an AE. 
8.3.4. 
Medical and Surgical History 
• All significant findings, surgeries, and pre-existing conditions present at screening 
must be reported on the relevant medical history/current medical conditions page 
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of the eCRF, including start and end dates, if known. The date of ITP diagnosis as 
well as the date of confirmation of the diagnosis according to the ASH criteria10 
will be collected separately. 
• The participant will be asked if he/she has been vaccinated for Streptococcus 
pneumoniae, Neisseria meningitidis, and Hemophilus influenzae. Bleeding events 
such as gastrointestinal bleeding, intracranial hemorrhage, and hemorrhage from 
coagulation disorder will be prespecified on the eCRF. 
• Information should be provided on medical and surgical history and concomitant 
medical conditions, specifying those ongoing at screening. 
• A history of a platelet count of <30×109/L before screening should be 
documented for the determination of the participant’s eligibility. 
8.3.5. 
Clinical Safety Laboratory Assessments 
• Blood and urine samples for determination of clinical chemistry, hematology, 
urinalysis, coagulation, thyroid, autoimmune antibody testing, follicle-stimulating 
hormone (FSH; only for women of non-childbearing potential), viral testing, and 
tuberculosis QuantiFERON test will be collected and analyzed at a central 
laboratory as indicated in the SoA (Section 1.3) and Section 10.2. The blood 
sample for platelet counts and the urine sample for the pregnancy test will be 
analyzed locally. 
• For safety assessments during screening, participants may be rescreened 
(ie, redoing the full assessments as per SoA, Section 1.3) or retested once 
(ie, repeating 1 test, see Section 5.4) if still within the screening period. 
• On days that IMP is administered, samples for laboratory assessments should be 
collected before dosing, unless otherwise requested. 
• Additional safety samples may be collected if clinically indicated, at the 
discretion of the investigator. 
• For all female participants of childbearing potential, a serum pregnancy test will 
be performed centrally at screening (on the samples taken for clinical laboratory 
tests), and a urine pregnancy test will be conducted and analyzed locally at the 
investigative 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, with the exception of albumin 
and urine total protein (quantitative) values. Albumin and urine total protein 
(quantitative) values will remain blinded for the trial site. An alert system will be 
implemented to notify the investigator if there are out-of-range albumin or urine 
total protein (quantitative) values to allow for appropriate safety follow-up. 
• 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 
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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. 
• The actual sample collection date and time must be entered in the participant’s 
source documents and on the central laboratory assessment eCRF page. For 
urinalysis samples only the date of collection is to be entered. 
• Refer to Section 10.7 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 repeated until the values return to 
normal or baseline or are no longer considered clinically significant by the 
investigator. 
− If such values do not return to normal/baseline within a period of time judged 
reasonable by the investigator, 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). 
8.3.5.1. 
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 ITP, unless this would not be allowed according to local 
regulations or the participant would not have agreed. After this period of time, the samples 
will be destroyed. 
In addition, serum or plasma samples may be used to validate methods to support the 
efgartigimod program. These samples may also be used for vaccination antibody testing and 
any other additional research interests linked to the development of efgartigimod. 
8.3.6. 
Suicidal Ideation and Behavior Risk Monitoring 
Not applicable. 
8.3.7. 
Visit Reminder/Participant Identification Card 
Participants must be provided with the address and telephone number of the main 
investigative site contact for information about the clinical trial. The investigator must 
therefore provide a “Visit Reminder/Participant ID Card” to each participant. In an 
emergency situation, this card serves to inform the responsible attending physician that the 
participant is in a clinical trial and that relevant information may be obtained by contacting 
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the investigator. Participants must be instructed to keep the card in their possession at all 
times. 
8.4. 
Adverse Events and Serious Adverse Events 
• Definitions of AE and SAE are provided in Section 10.5 as well as guidelines for 
assessing causality and relationship to IMP. 
• AEs will be reported by the participant. 
• The investigator and any qualified designees are responsible for detecting, 
documenting, and recording events that meet the definition of an AE or SAE and 
remain responsible for following up AEs that are serious, considered related to 
IMP or trial procedures, or that caused the participant to discontinue IMP and/or 
the trial (see Section 7). 
• An unexpected AE is any adverse drug event, which is not listed in the reference 
safety information in the current IB section 7 or is not listed at the specificity or 
intensity that has been observed. The assessment of expectedness will be the 
responsibility of the sponsor. 
• 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 CTCAE criteria), 
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 Adverse Event and Serious 
Adverse Event Information 
• All AEs and SAEs will be collected from the signing of the ICF until the 
end-of-treatment or last follow-up visit at the time points specified in the SoA 
(Section 1.3). 
• All SAEs will be recorded and reported to the sponsor or designee immediately 
and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 3 (Section 10.5). 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 AEs or SAEs after conclusion of 
the trial participation. However, if the investigator learns of any SAE, including a 
death, at any time after a participant has been discharged from the trial, and he/she 
considers the event to be reasonably related to the IMP or trial participation, the 
investigator must promptly notify the sponsor. 
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8.4.2. 
Method of Detecting Adverse Events and Serious Adverse Events 
• The method of recording, evaluating, and assessing causality of AEs and SAEs 
and the procedures for completing and transmitting SAE reports are provided in 
Section 10.5. 
• Care will be taken not to introduce bias when detecting AEs and/or SAEs. 
Open-ended and nonleading verbal questioning of the participant is the preferred 
method to inquire about AE occurrences. 
8.4.3. 
Reporting of Adverse Events and Serious Adverse Events 
• 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 and to trial procedures. Each event should be recorded 
separately on the eCRF. 
• 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 10.5. 
• 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 for AEs. 
• 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 Adverse Events and Serious Adverse Events 
• 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 until resolution, until the participant is lost to follow-up, or until the 
participant withdraws consent (as defined in Section 7.4). 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. 
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• 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. 
• For the duration the participant is in the trial, resolution of SAEs (with dates) 
should be documented on the AE page of the eCRF and in the participant’s 
medical record to facilitate source data verification. If, after follow-up, return to 
the baseline status or stabilization cannot be established, an explanation should be 
recorded on the SAE form. 
• All pregnancies reported during the trial should be followed until pregnancy 
outcome. See Section 10.6. 
• For SAEs, AESIs, non-serious AEs, and pregnancies, the sponsor’s designee may 
follow-up by telephone, fax, electronic mail, and/or a monitoring visit to obtain 
additional case details and outcome information (eg, from hospital discharge 
summaries, consultant reports, or autopsy reports) in order to perform an 
independent medical assessment of the reported case. 
• Further information on follow-up procedures is provided in Section 10.5. 
8.4.5. 
Regulatory Reporting Requirements for Serious Adverse Events 
• Prompt notification by the investigator to the sponsor of an SAE is essential so 
that legal obligations and ethical responsibilities towards the safety of participants 
and the safety of IMP under clinical investigation are met. 
• The sponsor has a legal responsibility to notify both the local regulatory authority 
and other regulatory agencies about the safety of IMP under clinical investigation. 
The sponsor will comply with country-specific regulatory requirements relating to 
safety reporting to the regulatory authority, IRBs/IECs, and investigators. 
• An investigator who receives an investigator safety report describing an SAE or 
other specific safety information (eg, summary or listing of SAEs) from the 
sponsor will review and file it with the IB and notify the IRB/IEC, if appropriate, 
according to local requirements. 
• The sponsor or designee will be responsible for reporting SUSARs to the relevant 
regulatory authorities and IEC/IRB, as per applicable regulatory requirements. 
The sponsor or designee will also be responsible for forwarding SUSAR reports 
to all trial investigators, who will be required to report these SUSARs to their 
respective IECs/IRBs per local regulatory requirements.  
8.4.6. 
Pregnancy 
• If a pregnancy is reported, the investigator should inform the sponsor within 
24 hours of learning of the pregnancy and should follow the procedures outlined 
in Section 10.6. 
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• Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs. 
8.4.7. 
Cardiovascular and Death Events 
See Section 8.4.3. 
8.4.8. 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as 
Reportable Adverse Events or Serious Adverse Events 
Not applicable. 
8.4.9. 
Adverse Events of Special Interest 
• An AESI (serious or non-serious, related or not related) is an event of scientific 
and medical concern specific to the sponsor’s product or program (eg, an 
underlying condition being investigated, a mechanism of action/potential 
immunosuppression). Further characterizing information will be collected 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 
(eg, bruising in participants with ITP). 
• Efgartigimod treatment induces reductions in IgG levels, and there is a potential 
risk for infections associated with low IgG levels. As such, infections are 
considered AESIs in this trial. 
• Due to the nature of the underlying disease (ie, ITP), any occurrence of bleeding 
will also be considered an AESI. 
8.5. 
Treatment of Overdose or Medication Error 
• For this trial, a variation of less than ±10% of the amount of efgartigimod will not 
be considered an overdose/underdose or medication error, while a variation 
greater than ±10% of the intended amount of efgartigimod will be considered a 
medication error and/or overdose without an AE. 
• 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 trial protocol. 
• A medication error is any preventable incident that may cause or lead to 
inappropriate IMP use or participant harm while the IMP is in the control of 
health care professionals. Such incidents may be due to health care professional 
practice, product labeling, packaging and preparation, dispensing, distribution, 
administration, education, monitoring, and use. 
• In case of suspected overdose or medication error, the participant should be 
treated according to standard medical practice based on the investigator’s 
judgment. The suspected overdose or medication error with the quantity of the 
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excess dose should be documented on the eCRF including the additional AE, if 
any. 
• 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. 
8.6. 
Pharmacokinetics 
• Serum samples for PK will be collected from each participant as presented in the 
SoA (Section 1.3). Concentrations of efgartigimod will be determined using a 
validated assay. 
• The date and time of each sample will be recorded. 
• Samples will be analyzed by the designated laboratory. 
• If no sample was taken, the reason will be recorded in the relevant section of the 
eCRF. 
• The PK samples will be taken predose, on the day of IMP administration. 
8.7. 
Pharmacodynamics 
• Serum samples for the determination of the PD marker (total IgG) will be 
collected as indicated in the SoA (Section 1.3). 
• The date and time of each sample will be recorded. 
• The PD samples will be taken predose on IMP administration visits. 
• Samples will be analyzed by the designated laboratory. To maintain the blind, the 
IgG testing cannot be performed locally. 
• The PD marker will be determined using a validated assay. 
• Additionally, presence, nature, and level of antiplatelet antibodies will be tested as 
indicated in the SoA (Section 1.3). 
• If no sample was taken, the reason will be recorded in the relevant section of the 
eCRF. 
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8.8. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8.9. 
Hospitalization for ITP Management 
• In-patient hospitalization for the management of ITP during the current trial, for 
at least an overnight stay, will be recorded separately. 
• The hospitalization date and time of admission and discharge will be entered on 
the eCRF. 
• Hospitalization for the participant’s convenience will not be taken into account. 
8.10. 
Genetics 
Genetics are not evaluated in this trial. 
8.11. 
Biomarkers 
Biomarkers are not evaluated in this trial. 
8.12. 
Immunogenicity Assessments 
• Serum samples to assess antidrug antibodies (ADA) against efgartigimod and 
plasma samples to assess antibodies against rHuPH20 will be collected as 
indicated in the SoA (Section 1.3). 
• Samples will be analyzed by the designated laboratory. 
• Sampling will be done predose on IMP administration visits. 
• All samples will be analyzed in validated immunogenicity assays, where samples 
are first screened for a positive assay response. A titer will be determined in the 
confirmed positive samples. Additionally, these samples will be tested for the 
presence of NAb against efgartigimod and/or rHuPH20, and titers will be 
determined for NAb against rHuPH20 in the overall population. 
• If no sample was taken, the reason will be recorded in the relevant section of the 
eCRF. 
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8.13. 
Health Economics/Medical Resource Utilization 
Not applicable. 
8.14. 
Quality-of-Life and Patient-Reported Outcomes 
The participant will complete the QoL questionnaire (SF-36 v2.0 and ITP-PAQ) and the PRO 
(FACT-Th6 and FACIT-Fatigue Scale) as indicated in the SoA (Section 1.3). 
FACT-Th6: The FACT-Th6 uses the Likert scale, with participants rating their degree of 
concern in the past 7 days. The 6 selected items pertain to ability to do usual activities, worry 
about problems with bleeding or bruising, worry about the possibility of serious bleeding, 
avoidance of physical or social activity because of concern with bleeding or bruising and 
frustration due to the inability to carry out usual activities.13 
SF-36 v2.0: The SF-36 is a 36-item scale constructed to survey health-related QoL on 
8 domains: limitations in physical activities due to health problems; limitations in social 
activities due to physical or emotional problems; limitations in usual role activities due to 
physical health problems; bodily pain; general mental health (psychological distress and 
well-being); limitations in usual role activities due to emotional problems; vitality (energy 
and fatigue); and general health perceptions.13 
FACIT-Fatigue Scale: The FACIT-fatigue scale is a short, 13-item, easy-to-administer tool 
that measures an individual’s level of fatigue during his/her usual daily activities over the 
past week. The level of fatigue is measured by recording item responses on a 4-point Likert 
scale ranging from 0 “not at all” to 4 “very much.” 
ITP-PAQ: The ITP-PAQ is a 44-item questionnaire to assess the health-related QoL in 
adults with ITP. It includes scales on a 0 (worst) to 100 continuum for physical health 
(symptoms, fatigue/sleep, bother, and activity), emotional health (psychological and fear), 
overall QoL, social activity, women's reproductive health, and work. 
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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, United States) version 9.4 or higher, and the 
software package R, if applicable. The standard operating procedures (SOPs) and work 
instructions of the sponsor’s designated CRO will be used as the default methodology if not 
otherwise specified. 
A detailed and comprehensive Statistical Analysis Plan (SAP) will be written and signed-off 
before 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 following paragraphs contain the main 
general features of the statistical analysis. More details will be provided as needed in the 
SAP. 
9.1. 
Statistical Methods 
9.1.1. 
Summary Tables, Figures, and Listings 
• Summary tables will summarize endpoints (outcomes) by treatment group and 
time point (eg, visit). For continuous variables, the number of participants (with 
nonmissing values), mean, standard deviation and/or standard error, median, 
quartiles, minimum and maximum will be presented. For categorical variables, for 
each category, the number of participants (count) and percentage will be 
presented for participants without missing values. 
• All summary tables and figures will be supported by full participant listings. 
9.1.2. 
Hypothesis Testing and Confidence Intervals 
Unless otherwise stated, all statistical tests will be two-sided and will be conducted at a 5% 
significance level. Two-sided 95% confidence intervals (CIs) will be provided. 
9.2. 
Statistical Hypotheses 
The statistical hypothesis was derived from the primary trial objective as stated in Section 3. 
• Null hypothesis: the proportion of participants achieving sustained platelet count 
response while receiving efgartigimod PH20 SC is equal to the proportion of 
participants achieving sustained platelet count response while receiving placebo 
PH20 SC 
• Alternative hypothesis: the proportion of participants achieving sustained platelet 
count response while receiving efgartigimod PH20 SC is different from the 
proportion of participants achieving sustained platelet count response while 
receiving placebo PH20 SC 
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9.3. 
Sample Size Determination 
Approximately 180 participants with chronic ITP and up to 39 participants with persistent 
ITP will be randomized in a 2:1 ratio to receive efgartigimod PH20 SC or placebo PH20 SC, 
respectively. 
The null and alternative hypotheses are defined as H0: π1 = π2 vs HA: π1 ≠ π2, where π1 and 
π2 are the population probabilities to achieve a sustained platelet count response (primary 
efficacy endpoint) for participants with chronic ITP receiving placebo PH20 SC and for 
participants with chronic ITP receiving efgartigimod PH20 SC, respectively. 
In the placebo PH20 SC group, the response rate of participants with chronic ITP who reach 
the primary endpoint is expected to be ≤5%, while the response rate of participants with 
chronic ITP in the efgartigimod PH20 SC group is expected to be 21.8% (ie, π1=0.05 and 
π2=0.218), based on the observed response rates in trial ARGX-113-1801. Given these 
assumptions, a total of N=180 randomized participants with chronic ITP will ensure a power 
of at least 80% to reject the null hypothesis at a 1-sided significance level α of 0.025, based 
on Fisher’s exact test. 
For the first key secondary endpoint “extent of disease control,” assuming distributions for 
cumulative number of weeks of disease control over the planned 24-week treatment period 
with platelet counts of ≥50×109/L in the chronic ITP population similar to those observed in 
ARGX-113-1801, a total of N=180 participants will ensure a power of >99% (2-sided α of 
0.05), conditionally on reaching the primary endpoint, to detect a significant difference 
between both treatment groups. For ensuring a power of at least 90%, a total number of N=75 
participants would be needed, given these assumptions. Calculations are based on the 
Wilcoxon-Mann-Whitney test, where the O’Brien-Castelloe approach14 was taken to 
compute the power, taking into account a 2:1 allocation ratio to receive efgartigimod PH20 
SC versus placebo PH20 SC. 
9.4. 
Populations for Analyses 
The following populations are defined: 
Population 
Description 
Full analysis set (FAS) 
All randomized participants. 
Per protocol analysis set 
(PP) 
All participants in the FAS for whom no major protocol deviation is 
reported. 
Safety analysis set (SAF) 
All participants in the randomized population who have received at 
least 1 dose or part of a dose of IMP. 
PK analysis set 
All participants from the safety analysis set who have at least 
1 serum postbaseline PK measurement 
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 
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summary of the planned statistical analyses of the most important endpoints including 
primary and key secondary endpoints. 
9.5.1. 
General Considerations 
• The baseline value will be the last assessment before the first administration of 
IMP. 
• 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 screened, randomized, received IMP treatment, completed the trial, as well as the 
number of early discontinuations from IMP treatment and trial, with reasons for 
discontinuation from IMP or trial. Summaries will be provided by treatment group. 
9.5.3. 
Analysis Sets and Protocol Deviations 
• The number of participants for each analysis set, as described in Section 9.4, will 
be presented in a table and listing. 
• Major protocol deviations, by treatment group, will be summarized in a table and 
presented in a listing. 
• The efficacy analysis will be performed on the FAS or the subset of participants 
in the FAS with chronic ITP; supportive analyses will be conducted on the per 
protocol analysis set. 
• The efficacy analysis will be analyzed with intent-to-treat principle 
(ie, participants will be analyzed according to their planned treatment irrespective 
of the treatment actually received). 
• The safety analysis will be performed on the safety analysis set. 
9.5.4. 
Demographic and Baseline Characteristics, and Concomitant Medication 
Participant demographic and baseline characteristics data, including prior and concomitant 
therapies will be summarized using standard summary statistics (see Section 9.1.1) and 
listed. 
9.5.5. 
Primary Endpoint 
9.5.5.1. 
Definition of the Estimand for the Primary Endpoint 
• Population: adult participants with chronic ITP, having an average platelet count 
of <30×109/L, and, at the start of the trial, either receiving concurrent ITP 
treatment(s) and having received at least 1 prior therapy for ITP in the past, or not 
receiving treatment for ITP but having received at least 2 prior treatments for ITP. 
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• Variable: sustained platelet count response defined as achieving platelet counts of 
≥50×109/L for at least 4 of the 6 visits between week 19 and week 24 of the trial 
• Main intercurrent events: 
− early discontinuation of treatment (before visit 24) due to lack of efficacy 
(eg, more than 3 occurrences of rescue therapy) or due to an AE 
− initiation of rescue therapy at week 12 or later 
− increase of dose and/or frequency of concurrent ITP therapies at week 12 or 
later 
• Population-level summary: proportion of participants with sustained platelet count 
response 
9.5.5.2. 
Handling of Main Intercurrent Events 
A composite strategy approach will be taken to address the main intercurrent events 
described previously. This implies that participants who discontinue treatment before visit 24 
due to lack of efficacy (eg, more than 3 occurrences of rescue therapy) or due to an AE, as 
well as participants who receive rescue therapy at week 12 or later, or for whom dose and/or 
frequency of concurrent ITP therapies have increased at week 12 or later, will be considered 
nonresponders for the primary endpoint analysis. 
9.5.5.3. 
Estimation of Treatment Effect and Statistical Inference 
The primary endpoint will be analyzed using a Cochran-Mantel-Haenszel statistic test 
stratified for the stratification factors history of splenectomy (yes versus no), receiving 
concurrent ITP therapies at baseline (yes versus no), and for baseline platelet count level 
category (<15×109/L versus ≥15×109/L). The treatment effect will be presented as the odds 
ratio together with its 95% confidence interval (CI) and 2-sided p-value. In addition, an 
adjusted difference of the proportions with its 95% CI will be provided. 
9.5.5.4. 
Handling of Missing Data 
Missing data for reason of 1 of the main intercurrent events will be handled as described 
previously. Details on handling other missing data will be provided in the SAP. 
9.5.5.5. 
Complementary Analyses 
To facilitate interpretation of the estimated treatment effect in the primary analysis, 
complementary analyses will be conducted where the main intercurrent events are handled 
differently, eg, by using the “treatment policy” strategy. Furthermore, an exact logistic 
regression analysis, in which the continuous baseline platelet count level is added as 
covariate instead of the baseline platelet count category, will be conducted as supportive 
analysis. Details will be provided in the SAP. 
9.5.6. 
Key Secondary Endpoint Analyses Subject to Alpha Control 
Extent of disease control is defined as the number of cumulative weeks over the planned 
24-week treatment period with platelet counts of ≥50×109/L. For each participant, this 
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number will be calculated by counting the number of analysis visits from week 1 until 
week 24 (end-of-treatment visit) at which the platelet count level is ≥50×109/L. A Wilcoxon-
Mann-Whitney test stratified by receiving concurrent ITP therapies at baseline (yes versus 
no), history of splenectomy (yes versus no), and baseline platelet count level category 
(<15×109/L versus ≥15×109/L) will be used to compare the extent of disease control between 
both treatment groups. The two-sided p-value resulting from this hypothesis test will inform 
on whether the null hypothesis that the distributions of number of cumulative weeks for both 
treatment groups are identical can be rejected. The test will be conducted at a significance 
level of α=0.05. An estimate of the location shift will be provided, along with the associated 
95% CI. 
When 1 of the main intercurrent events occurs, platelet count levels measured after the 
occurrence will be censored (or they will not be taken into account for the calculation of the 
number of cumulative weeks). In other words, they will be handled as if the platelet count 
level were <50×109/L. Missing platelet counts because of early discontinuation due to lack of 
efficacy or due to an AE will be handled in the same way. 
Sensitivity analyses will be conducted to assess the robustness of the analysis results to the 
proposed handling of intercurrent events and missing platelet counts. 
Furthermore, a complementary analysis will be performed where extent of disease control is 
handled as a time-to-event endpoint (with “loss of disease control” being the event). Cox 
proportional hazards regression methodology will be applied for this complementary 
analysis. Details on the model and the event and censoring scheme for this complementary 
analysis will be provided in the SAP. 
The key secondary endpoints on proportion of participants in the overall population with a 
sustained platelet count response and on proportion of participants in the overall population 
achieving platelet counts of ≥50×109/L for at least 6 of the 8 visits between week 17 and 24 
of the trial will be analyzed in the same manner as the primary endpoint. 
The number of bleeding events per participant (assessed using the WHO Bleeding Scale, 
where WHO scale ≥1 at any visit is considered a new bleeding event) will be analyzed using 
a stratified Wilcoxon-Mann-Whitney test similar to that used to compare the extent of 
disease control between both treatment groups. The test will be conducted at a significance 
level of α=0.05. An estimate of the location shift will be provided, along with the associated 
95% CI. Incidence of bleeding will also be summarized descriptively by visit. Severity of 
bleeding will be summarized descriptively by visit. In addition, a summary of within-subject 
maximum severity will be provided. 
The primary endpoint analysis will act as gatekeeper for the testing of the key secondary 
endpoints. Subject to meeting statistical significance for the primary endpoint, the key 
secondary endpoints will be analyzed using a fixed-sequence testing procedure to maintain 
the overall type I error rate at 5%. The type I error rate of each individual test will be 5%, but 
the test will only be conducted if the analysis for all previous endpoints in the predefined 
hierarchy resulted in a p-value <0.05. The order in the testing hierarchy of the key secondary 
endpoints is as follows: 
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1. The extent of disease control defined as the number of cumulative weeks over the 
planned 24-week treatment period with platelet counts of ≥50×109/L in the population 
with chronic ITP 
2. The proportion of participants in the overall population (chronic and persistent ITP) 
with a sustained platelet count response defined as achieving platelet counts of 
≥50×109/L for at least 4 of the 6 visits between week 19 and week 24 of the trial 
3. Proportion of participants in the overall population achieving platelet counts of 
≥50×109/L for at least 6 of the 8 visits between week 17 and 24 of the trial 
4. The incidence and severity of the WHO-classified bleeding events in the overall 
population 
Complementary analyses for the key secondary endpoints will be conducted. Subgroup 
analyses for the primary and/or the key secondary endpoints may be conducted. Details will 
be provided in the SAP. 
9.5.7. 
Other Secondary Endpoint Analyses Not Subject to Alpha Control 
The secondary endpoints on overall platelet count and IWG response3 will be analyzed in the 
same manner as the primary endpoint. The secondary endpoint on extent of disease control 
will be analyzed in the same manner as the corresponding key secondary endpoint. 
The mean changes from baseline in platelet count levels at planned time points and the mean 
changes from baseline in PRO/QoL at planned time points will be analyzed by means of 
mixed models for repeated measurements. The model will include fixed effect terms for 
randomized treatment, baseline platelet level or baseline PRO/QoL, history of splenectomy 
(yes vs no), and receiving concurrent ITP therapies at baseline (yes vs no). Within-participant 
correlation will be modeled by assuming an unstructured covariance matrix for the error 
terms. Least square (LS) means for placebo PH20 SC and efgartigimod PH20 SC will be 
provided, along with the difference in LS means, 95% two-sided CI, and two-sided p-value. 
Time to response (defined as the time to achieve 2 consecutive platelet counts of ≥50×109/L) 
will be analyzed via Cox proportional hazards regression with fixed effect terms for 
randomized treatment and baseline platelet level. The model will be stratified by history of 
splenectomy (yes vs no) and receiving concurrent ITP therapies at baseline (yes vs no), at 
randomization. The hazard ratio for efgartigimod PH20 SC vs placebo PH20 SC will be 
provided, along with the associated 95% two-sided CI and two-sided p-value. The data will 
also be displayed using Kaplan-Meier curves and the median time to response will be 
displayed by randomized treatment arm. 
The number of cumulative weeks over the planned 24-week treatment period with platelet 
counts of ≥30×109/L and ≥20×109/L above baseline will be analyzed in the same way as 
described for the key secondary endpoint ”extent of disease control.” Assessment of number 
of cumulative weeks over the planned 24-week treatment period with platelet counts of 
≥30×109/L and ≥20×109/L above baseline within the group of participants with a baseline 
platelet count of <15×109/L will also be analyzed as described for the key secondary 
endpoint. 
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The number of significant bleeding events per participant (assessed using the WHO Bleeding 
Scale, where WHO scale ≥2 at any visit is considered a new significant bleeding event) will 
be analyzed in the same manner as the corresponding key secondary endpoint. 
9.5.8. 
Exploratory Endpoints 
• 
 
 
 
 
 
 
 
9.5.9. 
Safety Analyses 
• Incidence and severity of AEs, AESIs, and SAEs will be summarized 
descriptively. 
• Laboratory parameters, vital signs, and ECG data will also be analyzed 
descriptively. 
9.5.10. 
Other Analyses 
9.5.10.1. Pharmacodynamics, Pharmacokinetics, and Immunogenicity 
Descriptive statistics will be provided for PD parameters (total IgG and antiplatelet 
antibodies), the presence of antibodies and neutralizing antibodies, and titers of antibodies 
against efgartigimod and/or rHuPH20. Efgartigimod serum concentration data will be 
summarized. 
A population PK/PD analysis may be performed and will be reported in a separate report. 
9.6. 
Interim Analyses 
Not applicable. 
9.7. 
Data Monitoring Committee 
See Section 10.1.5.1. 
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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, Ethical, and Trial Oversight 
Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
• This trial will be conducted and the informed consent will be obtained 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 applicable drug and data protection laws and regulations of the countries 
where the trial will be conducted 
• Before the start of the trial, approval of regulatory authorities should be obtained 
(if applicable). 
• To comply with the Declaration of Helsinki (2013), the sponsor is currently 
assessing the appropriateness and possibility of making the trial drug available for 
clinical trial participants posttrial. 
• The protocol, protocol amendments, informed consent form (ICF), Investigator’s 
Brochure (IB), and other relevant documents (eg, advertisements) must be 
submitted to an Institutional Review Board/Independent Ethics Committee 
(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 and regulatory authority (if 
applicable) approval before implementation of changes made to the trial design, 
except for changes necessary to eliminate an immediate hazard to trial 
participants.  
• The investigator will be responsible for the following: 
− Providing written summaries of the status of the trial to the IRB/IEC annually 
or more frequently in accordance with the requirements, policies, and 
procedures established by the IRB/IEC 
− Notifying the IRB/IEC of SAEs or other significant safety findings as required 
by IRB/IEC procedures 
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− Providing oversight of the conduct of the trial at the investigative 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 
− Providing the sponsor or designee with documentation of IRB/IEC approval 
of the protocol and informed consent documents before the trial may begin at 
the trial sites. 
− Supplying documentation to the sponsor or designee of the required 
IRB/IEC’s annual renewal of the protocol, and any approvals of revisions to 
the informed consent document or amendments to the protocol. 
− Promptly reporting to the IRB/IEC any new information that may adversely 
affect the safety of participants or the conduct of the trial. 
− Upon completion of the trial, the investigator will provide the IRB/IEC with a 
brief report of the outcome of the trial, if required. 
10.1.2. 
Financial Disclosure 
• The sponsor will fund the trial as outlined in the clinical trial agreement. 
• The sponsor will obtain adequate global/local insurance for the trial participants 
for the required duration of time. 
• The sponsor maintains an insurance coverage for this trial in accordance with the 
laws and regulations of the countries in which the trial is performed. Liability and 
insurance provisions for this trial are specified in the investigator’s contract. The 
terms and conditions will apply as specified in the policy document. 
10.1.3. 
Informed Consent Process 
• Before signing the ICF, the trial participants will be instructed not to participate in 
any other clinical trial that involves an intervention or collection of data until the 
completion of the current trial. If a participant’s caregiver will be trained to 
administer the IMP, he/she will also have to sign an ICF. 
• If the IMP will be administered by the participant’s caregiver at the trial site, 
he/she will have to sign a separate ICF in which he/she agrees to share personal 
data and to be trained by the investigator or designee to administer the SC 
injections of efgartigimod PH20. 
• The participant will sign the caregiver’s ICF to indicate that he/she agrees that 
this person will be his/her caregiver. 
• The investigator needs to confirm that the caregiver is competent to administer the 
IMP. 
• The caregiver’s training will be documented. The investigator will sign and save 
this documentation in the participant’s file. 
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• Any participant who provides informed consent will be assigned a unique 
participant ID via the IRT system. 
• The investigator or his/her representative will explain the following to the 
participant and answer all questions regarding the trial: the nature of the trial, its 
purpose, the procedures involved, the expected duration, any potential discomfort, 
potential alternative procedure(s) or course(s) of treatment available, and the 
extent of maintaining confidentiality of the participant’s records. 
• The investigator or his/her representative will explain the following to the 
caregiver and answer all questions regarding his/her role as a caregiver: the 
purpose of the trial, the purpose of his/her role as a caregiver, the expected 
duration, and the extent to which confidentiality of his/her personal data will be 
maintained. 
• Participants must be informed that their participation is voluntary, that they may 
withdraw from the trial at any time, and that withdrawal of consent will not affect 
their subsequent medical treatment or relationship with the treating physician. 
• Caregivers must also be informed that taking on the role of caregiver is voluntary 
and that they may withdraw at any time. 
• Participants will be required to sign a statement of informed consent, after receipt 
of detailed information on the trial, that meets the requirements of 21 CFR 50, 
local regulations, ICH guidelines, Health Insurance Portability and Accountability 
Act requirements, where applicable, and the IRB/IEC or trial center. 
• Caregivers will also be required to sign an ICF, after receipt of detailed 
information on their role as a caregiver in this trial. 
• The ICF will be used to explain the potential risks and benefits of trial 
participation to the participant in simple terms before the participant is screened. 
• The caregiver ICF will be used to explain, in simple terms, the potential risks and 
disadvantages of taking on the role of caregiver. 
• A separate ICF will be issued in case of pregnancy of a female partner of a male 
participant. 
• The ICF and the caregiver ICF contain 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 investigative site and include participant information 
sheets/brochures that outline the trial procedures. All ICF(s) must be signed and 
dated by the participant. 
• The caregiver ICF must be available in the local and vernacular languages 
required at the investigative site. All caregiver ICF(s) must be signed and dated by 
the caregiver and the participant. 
• Confirmation of a participant’s informed consent must also be documented in the 
participant’s medical record before any trial-related procedure under this protocol, 
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including screening tests and assessments. The authorized person obtaining the 
informed consent must also sign the ICF. 
• Confirmation of a caregiver’s informed consent must also be documented in the 
participant’s medical records before any administration of IMP by the caregiver 
occurs. The authorized person obtaining the informed consent must also sign the 
caregiver 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 document before the performance of any protocol procedures 
and before the administration of investigational medicinal product (IMP). 
• The investigator is responsible for ensuring that the informed consent is obtained 
from the caregiver, including the appropriate signatures and dates on the caregiver 
ICF, before any administration of IMP by the caregiver occurs. 
• Participants must be reconsented to the most current version of the ICF(s) during 
their participation in the trial. 
• If a new version of the caregiver ICF is issued, the participant and his/her 
caregiver must both reconsent. 
• A signed and dated copy of the ICF(s) must be provided to the participant. 
• A signed and dated copy of the caregiver ICF must also be provided to the 
participant and his/her caregiver. 
• Participants may be rescreened (ie, redoing the full assessments as per Schedule 
of Activities [SoA], Section 1.3) or retested once (ie, redoing 1 test) if still within 
the screening period. See Section 5.4. 
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 and his/her caregiver must be informed that his/her personal trial-
related data will be used by the sponsor in accordance with local data protection 
law. The level of disclosure must also be explained to the participant and his/her 
caregiver, who will be required to give consent for their data to be used as 
described in the respective 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. 
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• The ICF and the caregiver ICF will incorporate (or, in some cases, be 
accompanied by a separate document incorporating) wording that complies with 
relevant data protection and privacy legislation. 
• The caregiver must be informed that his/her personal data 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. 
10.1.5. 
Committees Structure 
10.1.5.1. Data Safety Monitoring Board 
• The sponsor will appoint an independent Data Safety Monitoring Board (DSMB) 
consisting of an independent group of clinical experts who are not involved in the 
trial management. They will be supplemented by an independent statistician. The 
objective of the DSMB will be to review all unblinded safety data (including the 
overall number of participants treated up to that point, rates, and participant-level 
details) and the evaluation of IgG. The planning and frequency of the meetings 
will be detailed in a DSMB charter. In addition, ad hoc meetings can be requested 
at any time during the trial by either the sponsor or the DSMB. The DSMB will 
advise the sponsor regarding continuation, modification, or termination of the trial 
after every meeting. 
• Additionally, the composition, objectives, role, and responsibilities of the 
independent DSMB will be described in the DSMB charter, agreed with the 
DSMB members and the sponsor. The DSMB charter will also define and 
document the content of the safety summaries and general procedures (including 
communications). 
10.1.6. 
Dissemination of Clinical Trial Data 
• The sponsor or designee, and auditor may access participant records for the 
purpose of monitoring this trial, auditing, and managing progress details. The 
investigator must be fully aware that the sponsor or designee and auditor can 
inspect or verify documents to verify participant’s chart and electronic case report 
form (eCRF) records. Such information must be kept confidential in locked 
facilities that allow for this. The investigator will prepare and maintain adequate 
and accurate source documents to record all observations and other pertinent data 
for each participant enrolled into the trial. 
• The investigator is responsible for maintaining source documents. These will be 
made available for verification by the sponsor’s designated contract research 
organization (CRO) monitor at each monitoring visit. The investigator must 
submit an eCRF for each participant, regardless of duration of participation or 
administration of IMP (ie, an eCRF must be submitted for screen failures as well). 
All supportive documentation submitted with the eCRF, such as laboratory or 
hospital records, should be clearly identified with the trial and participant number. 
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Any personal information, including participant name, should be removed or 
rendered illegible to preserve data privacy. 
10.1.7. 
Data Quality Assurance 
• All participant data relating to the trial will be recorded on eCRF 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 electronically signing the CRF. 
• The investigator must maintain accurate documentation (source data) that 
supports the information entered in the CRF. 
• The investigator must permit trial-related monitoring, audits, IRB/IEC review, 
and regulatory agency inspections and provide direct access to source data 
documents. 
• Monitoring details describing strategy (eg, risk-based initiatives in operations and 
quality such as Risk Management and Mitigation Strategies and Analytical Risk-
Based Monitoring), methods, responsibilities and requirements, including 
handling of noncompliance issues and monitoring techniques (central, remote, or 
on-site monitoring) are provided in the Monitoring Plan. 
• The sponsor or designee is responsible for the data management of this trial 
including quality checking of the data. 
• The sponsor assumes accountability for actions delegated to other individuals 
(eg, CROs). 
• Trial monitors will perform ongoing source data verification to confirm that data 
entered onto 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 trial is being conducted in accordance with the 
currently approved protocol and any other trial agreements, ICH GCP, and all 
applicable regulatory requirements. Only if not allowed as per local regulations, 
no source data verification will occur for data regarding race and ethnicity since 
the eCRF will serve as the source. 
10.1.7.1. Data Handling and Record Keeping 
• It is the investigator’s responsibility to maintain essential trial documents (records 
and documents pertaining to the conduct of this trial and the distribution of IMP, 
including regulatory documents, eCRFs, signed participant ICFs, laboratory test 
results, IMP inventory records, source documents, relevant correspondence, AE 
reports, and all other supporting documentation) as required by the applicable 
national regulatory requirements. The trial site should plan on retaining such 
documents for approximately 25 years after trial completion. The trial site should 
retain such documents until at least 2 years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region, or at least 2 years after the formal 
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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 trial is being conducted. Participant identification codes (participant 
names and corresponding trial numbers) will be retained for this same period of 
time. These documents may be transferred to another responsible party, 
acceptable to the sponsor, who agrees to abide by the retention policies. The 
investigator is required to notify the sponsor (or an authorized representative) in 
writing before changing the location or status of any essential clinical trial 
documents. The investigator must contact the sponsor before disposing of any 
trial records. 
• No records should be disposed without the written approval of argenx BV. 
• For trials conducted outside the US under a US investigational new drug (IND), 
the principal investigator must comply with US Food and Drug Administration 
IND regulations and with those of the relevant national and local health 
authorities. 
10.1.7.2. Quality Assurance Audit 
Trial processes, trial sites (including, but not limited to site visits, central laboratories, 
vendors), the trial database, and trial documentation may be subject to quality assurance audit 
during the course of the trial by the sponsor or sponsor’s designee (CRO or other vendor) on 
behalf of sponsor. In addition, inspections may be conducted by regulatory bodies at their 
discretion. Such audits/inspections can occur at any time during or after completion of the 
trial. 
10.1.7.3. Quality Control 
Quality control will be applied to each stage of trial-related activities. 
The following steps will be taken to ensure the accuracy, consistency, completeness, and 
reliability of the data: 
• investigator meetings 
• central laboratories for clinical laboratory parameters 
• site initiation visit 
• routine site monitoring 
• ongoing site communication and training 
• ongoing oversight by the sponsor or its designated CRO monitors of safety 
parameters and adherence to selection criteria 
• data management quality control checks 
• continuous data acquisition and cleaning 
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• quality control check of the clinical trial report (CTR) 
• to avoid interobserver variability, every effort should be made to ensure that the 
same individual who made the initial baseline determinations completes all 
efficacy and safety evaluations, eg, for the completion of the World Health 
Organization (WHO) bleeding scale. 
In addition, periodic audits can be performed as specified in Section 10.1.7.2. 
When audits or inspections are conducted, access must be authorized for all trial-related 
documents including medical history and concomitant medication documentation to 
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. 
• Paper quality-of-life (QoL) questionnaires and patient-reported outcome (PRO) 
are part of the source documents and must be transcribed onto the eCRF. 
• 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. 
10.1.9. 
Monitoring 
• The sponsor has engaged the services of a CRO to perform all clinical trial 
monitoring functions within this clinical trial. The sponsor’s designated CRO 
monitors will work in accordance with the standard operating procedures (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 trial is conducted in accordance with the currently approved protocol, any 
other trial 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. 
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• The sponsor’s designated CRO monitor will perform an eCRF review, source 
document verification (wherever allowed as 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 trial file. Any data 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 of the trial, the sponsor’s 
designated CRO monitor will conduct investigative 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 trial 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 trial site staff from the source 
documents onto the eCRF, as per local regulations. Data must be entered in 
English. Guidelines for eCRF completion, including the collection of the 
investigator’s e-signature, will be provided by the CRO. Appropriate training and 
security measures will be completed by the investigator and all designated site 
staff before the trial is initiated, and any data are entered into the system for any 
trial participant at the site. 
• The eCRF is essentially considered a data entry form and should not constitute the 
original (or source) medical records unless otherwise specified. Only if requested 
as per local regulations, no data collection or source data verification will be 
performed on race and ethnicity. Source documents are all documents used by the 
investigator or hospital that relate to the participant’s medical history, that verify 
the existence of the participant and the inclusion and exclusion criteria, and all 
records covering the participant’s participation in the trial. They can include 
laboratory notes, electrocardiogram (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 on the eCRFs has been reviewed by the investigator 
and is true and accurate. The investigator will be required to electronically sign 
the eCRF. 
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• 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 trial site, and the trial 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 procedures, and medical history terms 
will be assigned to a lowest level term and a preferred term (PT), and will be 
classified by high level term, high level group term, and primary system organ 
class (SOC) according to the Medical Dictionary for Regulatory Activities 
thesaurus. 
• Prior and concomitant medications 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. 
10.1.11. 
Trial and Site Start and Closure 
• The trial start date is the date of the first ICF signature. 
• The sponsor or designee reserve the right to close the trial site or terminate the 
trial at any time for any reason at the sole discretion of the sponsor. Trial sites will 
be closed upon trial completion. A trial site is considered closed when all required 
documents and trial supplies have been collected and a trial site closure visit has 
been performed. 
• The investigator may initiate trial 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 trial 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 
− In the sponsor’s judgment there are no further benefits to be expected from the 
trial 
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− 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 trial medication development 
• If the trial 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 trial 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 trial 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 trial sites 
prematurely for reasons such as poor protocol compliance or unsatisfactory 
recruitment of participants. 
10.1.12. 
Investigator Obligations 
• This trial 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 trial file provided to each investigative site. 
• The investigator is responsible for ensuring that all trial site personnel, including 
subinvestigators, adhere to all applicable regulations and guidelines, including 
local laws and regulations, regarding the trial, both during and after trial 
completion. The investigator is responsible for informing the IRB/IEC of the 
progress of the trial and for obtaining annual IRB/IEC renewal. The investigator 
is responsible for informing the IRB/IEC of completion of the trial and will 
provide the IRB/IEC with a summary of the results of the trial. 
• 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 trial at the trial 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 trial 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. 
Sponsor 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 trial protocol, and will conduct the trial in accordance with ICH tripartite guidelines for 
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GCP and applicable regulatory requirements. The trial 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 trial, are considered confidential and 
remain the sole property of the sponsor. The results of the trial will be reported in 
a CTR. 
• The CTR, written in accordance with the ICH E3 guideline, will be submitted in 
accordance with local regulations. 
• Any manuscript, abstract or other publication, presentation of results, or 
information arising in connection with the trial must be prepared in conjunction 
with the sponsor after the trial results have been analyzed and reported and must 
be submitted to the sponsor for review and comment before submission for 
publication or presentation. Trial participant identifiers will not be used in the 
publication of results. 
• The sponsor will comply with the requirements for publication of trial 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 investigative site data. 
• Authorship will be determined by mutual agreement and aligned with 
International Committee of Medical Journal Editors criteria15 authorship 
requirements, based on scientific input and recruitment efforts. 
• The sponsor will register and/or disclose the existence of, and the results of 
clinical trials as required by law. 
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10.2. 
Appendix 2: Clinical Laboratory Tests 
Table 3: 
Protocol-Required Laboratory Assessments 
Hematology 
Hemoglobin, white blood cell (WBC) count with WBC differential 
Coagulation 
Activated partial thromboplastin time (aPTT), prothrombin time 
Clinical chemistry 
Creatinine, creatinine clearance, blood urea nitrogen (BUN), alanine 
aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, 
gamma-glutamyl transferase (GGT), C-reactive protein (CRP), alkaline 
phosphatase (ALP), lactate dehydrogenase (LDH), uric acid, albumina, 
potassium, sodium, calcium, hemoglobin A1c (HbA1c), cholesterol (total 
cholesterol, high density lipoprotein [HDL], low density lipoprotein [LDL]), 
triglycerides, serum levels of total IgGb 
Urinalysis 
Color, clarity/appearance, specific gravity, pH, proteina, glucose, ketones, 
blood, bilirubin, urobilinogen, nitrite, leukocyte esterase, and microscopic 
examination including red blood cell (RBC) count, WBC, casts, crystals, 
bacteria 
Serology 
HIV antibodies (1 and 2), HBV surface antigen (HBsAg), antibodies to the 
surface and core antigens of the HBV (anti-HBs and anti-HBc), HBV DNA, 
hepatitis C virus antibody (HCV-Ab), HCV RNA 
Other 
Serum human chorionic gonadotrophin (ß-HCG), follicle-stimulating 
hormone (FSH) test, autoimmune antibody testing, antinuclear antibody, 
thyroglobulin, thyroid stimulating hormone (TSH), tuberculosis 
QuantiFERON test, thyroid peroxidase antibody, thyroglobulin antibody, 
TSH receptor antibody 
Local evaluations 
 
 urine pregnancy 
Other exploratory 
 
a Albumin and urine total protein (if result is quantitative) will not be reported to the site to maintain the blind, 
and an alert system will be implemented for appropriate communication to the investigator, as necessary. 
b This will be assessed at screening only, to maintain the blind. 
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10.3. 
Appendix 3: Pharmacokinetic, Pharmacodynamic, and 
Immunogenicity Assessments 
Table 4: 
Protocol-Required Pharmacokinetic, Pharmacodynamic, and 
Immunogenicity Assessments 
Pharmacokinetics 
Serum levels of efgartigimod 
Pharmacodynamic 
markers 
Serum levels of total IgG 
Antiplatelet antibodies 
Presence, nature, and level of antiplatelet antibodies 
Immunogenicity 
Serum levels of anti-efgartigimod and plasma levels of anti-rHuPH20 
binding antibodies, neutralizing antibodies (NAb) against 
efgartigimod and rHuPH20, and titers of NAb against rHuPH20 in the 
overall population 
 
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10.4. 
Appendix 4: Washout Requirements Before First IMP 
Administration 
 
Drug/Intervention/Event 
Prohibited Period (from Last Dose of Agent) 
Major thrombotic or embolic event (eg, myocardial 
infarction, stroke, deep venous thrombosis, or 
pulmonary embolism) 
5 years 
Any monoclonal antibody or Fc fusion protein 
6 months 
Investigational drug, Fc-containing biologics, like 
soluble receptors 
3 months or 5 half-lives, whichever is longer 
Anticoagulants (eg, vitamin K antagonist, direct oral 
anticoagulant) 
4 weeks 
Transfusion (blood, platelets, plasma) 
4 weeks 
Ig (IV, SC, or intramuscular) or PLEX 
4 weeks 
Romiplostim (contains Fc fragment)a 
4 weeks 
Splenectomy 
4 weeks 
Live/live-attenuated vaccines 
4 weeks before screening 
Anti-CD20 therapy (eg, rituximab) 
6 months before randomization 
a Binds to FcRn to extend half-life; efgartigimod might interfere with disposition. 
 
 
 
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10.5. 
Appendix 5: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
10.5.1. 
Definition of Adverse Event 
 
Adverse Event Definition 
• 
An adverse event (AE) is any untoward medical occurrence in a clinical trial participant, 
temporally associated with the use of trial intervention, whether or not considered related to 
the trial 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 trial intervention. 
 
Events to be Collected as Adverse Events 
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other 
safety assessments (eg, electrocardiogram [ECG], radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically significant 
in the medical and scientific judgment of the investigator (ie, not related to progression of 
underlying disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an increase 
in frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after trial intervention administration even though it 
may have been present before the start of the trial. 
• 
Signs, symptoms, or the clinical sequelae of a suspected intervention- intervention 
interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either trial intervention 
or a concomitant medication. Overdose per se will not be reported as an AE/serious adverse 
event (SAE) unless it is an intentional overdose taken with possible suicidal/self-harming 
intent. Such overdoses should be reported regardless of sequelae. 
• 
“Lack of efficacy” or “failure of expected pharmacological action” per se will not be 
reported as an AE or SAE. Such instances will be captured in the efficacy assessments. 
However, the signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will 
be reported as an AE or SAE if they fulfill the definition of an AE or SAE. 
 
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Events NOT to be Collected as Adverse Events 
• 
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. 
Note: Except for any occurrence of bleeding which will be considered an AESI as per 
Section 8.4.9. 
• 
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to the 
procedure is the AE. 
• 
Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the trial that do not worsen. 
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10.5.2. 
Definition of Serious Adverse Event 
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 in-patient hospitalization or prolongation of existing hospitalization 
• 
In general, hospitalization signifies that the participant has been admitted at the hospital or 
emergency ward for observation and/or treatment that would not have been appropriate in 
the physician’s office or outpatient setting. Complications that occur during hospitalization 
are AEs. If a complication prolongs hospitalization or fulfills any other seriousness criteria, 
the event will be considered as serious. When in doubt as to whether “hospitalization” 
occurred or was necessary, the AE should be considered serious. 
• 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline is not collected as an AE. 
4. Results in persistent disability/incapacity 
• 
The term disability means a substantial disruption of a person’s ability to conduct normal life 
functions. 
• 
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and 
accidental trauma (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. 
− Suspected transmission of any infectious agent via the IMP will also be treated as an 
SAE. 
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10.5.3. 
Recording and Follow-up of Adverse Events and/or Serious Adverse Events 
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 
trial. 
All AEs observed will be graded using the National Cancer Institute (NCI) Common 
Terminology Criteria for Adverse Events (CTCAE) version 5.0. 
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, using 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 (ADL) (eg, preparing meals, shopping for 
groceries or clothes, using the telephone). 
• 
Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization 
or prolongation of hospitalization indicated; disabling; limiting self-care ADL (ie, bathing, 
dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden). 
• 
Grade 4: Life-threatening consequences or urgent intervention indicated. 
• 
Grade 5: Death related to AE. 
NOTE: 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. 
 
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Assessment of Causality 
• 
The investigator is obligated to assess the relationship between trial intervention and each 
occurrence of each AE/SAE, using 1 of the following categories: 
- 
Not related: events can be classified as “not related” if there is not a reasonable 
possibility that the investigational medicinal product (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 trial intervention administration will be 
considered and investigated. 
• 
The investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment. 
• 
For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
• 
There may be situations in which an SAE has occurred, and the investigator has minimal 
information to include in the initial report to the sponsor. However, it is very important that 
the investigator always make an assessment of causality for every event before the initial 
transmission of the SAE data to the sponsor. 
• 
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. 
• 
In the final evaluation for reporting, the assigned relationship, as per the CIOMS will be 
converted into a “binary determination,” as follows: Events with an assigned relationship of 
“unrelated” and “unlikely” will be grouped into the “unrelated” category. Events with an 
assigned relationship of “related,” “possibly related,” or “probably related” will be grouped 
into the “related” category. 
 
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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 trial or during a recognized follow-up period, 
the investigator will provide a copy of any postmortem 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. 
10.5.4. 
Reporting of Serious Adverse Events 
SAE Reporting via Paper Report Form 
• 
All SAEs will be recorded (within 24 hours) on the paper SAE report form and the AE form 
on the electronic case report form (eCRF). 
• 
The investigator or delegated site staff should check that all entered data are consistent. 
• 
An alert email for the SAE report on the eCRF will then automatically be sent by email to 
the sponsor’s designated contract research organization (CRO) safety mailbox via the 
electronic data capture (EDC) system.  
• 
The paper SAE report form should be faxed or emailed to the sponsor’s designated CRO 
(see the Safety Mailbox/Fax details on the title page of this protocol). 
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10.6. 
Appendix 6: Contraceptive Guidance and Collection of Pregnancy 
Information 
10.6.1. 
Definitions 
10.6.1.1. Woman of Childbearing Potential 
A female is considered a woman of childbearing potential (WOCBP) unless she is either: 
a. Postmenopausal:  
A postmenopausal state is defined by continuous amenorrhea for at least 1 year 
without an alternative medical cause with a follicle-stimulating hormone (FSH) 
measurement of >40 IU/L. If a postmenopausal woman is using hormonal 
therapy, such as hormone replacement therapy or hormonal contraceptives, FSH 
levels might be suppressed and therefore an FSH test to confirm a 
postmenopausal state is not considered valid. In this case, the postmenopausal 
state will need to be assessed by the investigator.  
b. Surgically sterilized: 
Women who have had a documented permanent sterilization procedure 
(eg, hysterectomy, bilateral salpingectomy, or bilateral oophorectomy). 
10.6.2. 
Contraception Guidance 
10.6.2.1. Female Contraception For Women of Childbearing Potential 
WOCBP must use 1 of the following contraception methods from signing the ICF until the 
date of the last dose of IMP.  
• Combined (estrogen- and progestogen-containing) hormonal contraception 
associated with inhibition of ovulation: 
− Oral 
− Intravaginal 
− Transdermal 
• Progestogen-only hormonal contraception associated with the inhibition of 
ovulation: 
− Oral 
− Injectable 
− Implantable 
• Intrauterine device (IUD) 
• Intrauterine hormone-releasing system (IUS) 
• Bilateral tubal occlusion 
• Vasectomized partner 
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• Sexual abstinence: A highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the IMP. 
The reliability of sexual abstinence needs to be evaluated relative to the duration 
of the trial and the preferred and usual lifestyle of the participant. 
• 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 
10.6.3. 
Collection of Pregnancy Information 
10.6.3.1. Male Participants With Partners Who Become Pregnant 
• Male participants will be instructed through the ICF to immediately inform the 
investigator if their partner becomes pregnant during the trial. 
• The investigator will attempt to collect pregnancy information on any male 
participant’s female partner who becomes pregnant while the male participant is 
in this trial. 
• After obtaining the necessary signed informed consent from the pregnant female 
partner directly, the investigator will record pregnancy information on the 
appropriate form and submit it to the sponsor within 24 hours of learning of the 
partner’s pregnancy and submitted via email or fax (see the Safety Mailbox/Fax 
details on the title page 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 treating 
physician and/or obstetrician. 
10.6.3.2. Female Participants Who Become Pregnant 
• A serum pregnancy test will be performed centrally at screening. A urine 
pregnancy test will be conducted and analyzed locally at the visits detailed in the 
Schedule of Activities (SoA) (Section 1.3). 
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• The investigator will collect pregnancy information on any female participant 
who becomes pregnant during the trial until their last dose 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 discontinuation assessments and enter 
the 8-week follow-up period. 
− All assessments for early discontinuation (see Section 7) must be performed 
unless contraindicated by pregnancy (harmful to fetus) or unless the 
participant withdraws informed consent. 
• The participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow-up information on the participant and the neonate, 
and the information will be forwarded to the sponsor. Generally, follow-up will 
not be required for longer than 6 to 8 weeks beyond the estimated delivery date. 
Any termination of pregnancy will be reported, regardless of fetal status (presence 
or absence of anomalies) or indication for the procedure. 
• While pregnancy itself is not considered to be an adverse event (AE) or serious 
adverse event (SAE), any pregnancy complication or elective termination of a 
pregnancy for medical reasons will be reported as an AE or SAE. A spontaneous 
abortion (occurring at <22 weeks gestational age) or still birth (occurring at 
>22 weeks gestational age) is always considered to be an SAE and will be 
reported as such. Any posttrial pregnancy-related SAE considered reasonably 
related to the IMP by the investigator will be reported to the sponsor as described 
in Section 8.4.5. While the investigator is not obligated to actively seek this 
information in former trial participants, he or she may learn of an SAE through 
spontaneous reporting. 
• The investigator must update the participant with information currently known 
about potential risks and available treatment alternatives. 
• If required by local regulations, the female participant will be requested to sign a 
separate pregnancy ICF. 
• Full details will be recorded on a paper pregnancy report form and submitted via 
email or fax (see the Safety Mailbox/Fax details on the title page 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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10.7. 
Appendix 7: Administrative Structure 
Central Laboratories 
Cerba Research NV 
Industriepark Zwijnaarde 3 
9052 Gent 
Belgium 
Analysis of Pharmacokinetics, Anti-Drug Antibodies, and Neutralizing Antibodies Against 
Efgartigimod 
DDS (formerly known as LGC) 
Newmarket Road 
Fordham 
Cambridgeshire 
CB7 5WW 
United Kingdom 
Analysis of Total IgG 
PPD Laboratories - US 
2 Tesseneer Road 
Highland Heights, KY 41076 
United States 
Binding Antibodies and Neutralizing Antibodies Against rHuPH20 
LabCorp Bioanalytical Services, LLC 
8211 SciCor Drive, Suite B 
Indianapolis, IN 46214 
USA 
Antiplatelet Antibodies 
Sanquin Diagnostic Services 
Plesmanlaan 125 
1066 CX 
Amsterdam 
The Netherlands 
Long-Term Storage of Pharmacokinetics-Pharmacodynamics, Anti-Drug Antibodies, Antiplatelet 
Antibodies Samples 
Azenta Life Science (previously known as Brooks Life Science, BioStorage Technologies GmbH) 
Im Leuschnerpark 1B 
64347 Griesheim 
Germany 
 
 
 
 
 
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Central ECG Reading 
Clario 
Peterborough Business Park 
Lynchwood House 
Peterborough 
PE2 6FZ 
United Kingdom 
Trial Monitoring/Medical Monitoring 
ICON plc 
South County Business Park 
Leopardstown 
Dublin 18 
Ireland 
Home Care Vendor 
Accellacare In-Home Services (an ICON company) 
700 Deerpath Drive 
Vernon Hills, IL 
60061-1802 
USA 
Clinical Trial Supply Management 
Trial-specific packaging and labeling, shipment to non-EU trial centers: 
Fisher Clinical Services GmbH 
Steinbühlweg 69 
4123 Allschwil 
Switzerland 
Final EU batch release: 
Fisher Clinical Services GmbH  
Im Woerth 3 
79576 Weil am Rhein 
Germany  
Trial-specific packaging and labeling, shipment to EU and non-EU trial centers: 
Fisher Clinical Services GmbH 
Marie-Curie-Str. 16 
D-79618 Rheinfelden (Baden) 
Germany 
Data Management, Biostatistics, and Medical Data Review 
SGS Life Sciences (SGS LS), a division of SGS Belgium NV 
Generaal de Wittelaan 19A b5 
B-2800 Mechelen 
Belgium 
Drug Safety Reporting 
Parexel International 
1 Federal Street 
Billerica, MA 01821 
USA 
 
 
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10.8. 
Appendix 8: World Health Organization Bleeding Scale 
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10.9. 
Appendix 9: Possible Adaptations of Trial Protocol During 
COVID-19 Pandemic 
The aim of trial ARGX-113-2004 is to evaluate the efficacy and safety of efgartigimod PH20 
SC in adult participants with primary immune thrombocytopenia (ITP). 
During the COVID-19 pandemic, it may not be possible to perform site visits as planned for 
this trial (see Schedule of Activities [SoA], Table 5). The main adaptation presented in this 
appendix is the shift from site visits to home visits. 
Argenx has performed a critical assessment of the use of efgartigimod during the COVID-19 
pandemic. From discussions within the company, the physician community, and patient 
associations it has been concluded that the risk/benefit profile of efgartigimod in ongoing 
clinical trials 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 regarding 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 AEs 
reported during argenx clinical trials. 
Based on this risk/benefit assessment, ARGX-113-2004 can continue during the COVID-19 
pandemic. However, it may not always be possible to perform all visits at the trial site during 
the pandemic. 
To allow participants with ITP to receive treatment with the investigational medicinal 
product (IMP) during the COVID-19 pandemic, this appendix to the protocol has been 
developed. If a visit to the trial site is not possible, a home visit or a visit at an alternative 
convenient location can be allowed, as per local regulations. This proposed flexibility in 
executing the trial will be temporary and will only last as long as the COVID-19 pandemic 
affects the ability of the participants to attend the trial visits at the trial site. As soon as the 
situation returns to normal, the measures specified here will no longer apply. 
If allowed per local regulations, it remains at the investigator’s discretion to assess if it is in 
the best interest of the participant to start/continue in the trial. 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 trained qualified physician). 
Permission and Duration to Use the “Updated” Protocol Version 
This appendix to the protocol is intended for countries and/or investigative sites in 
geographical areas where COVID-19 has affected the trial sites’ workload or travel 
restrictions are imposed. Prior to implementation of this protocol appendix, the trial site first 
needs to inform and obtain written approval from the sponsor or the contract research 
organization (CRO). The initial duration of implementation of the protocol appendix will be 
agreed upon and can potentially be extended (upon written agreement) 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 electronic case report form (eCRF) for the applicable visit. 
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Testing for COVID-19 
Additional testing for COVID-19 beyond that mandated by relevant local authorities for the 
participant’s screening and randomization is not required. However, argenx recommends 
participants who develop symptoms of COVID-19 during the trial to be tested. See also 
Figure 1. 
Based on exclusion criterion 23 “Clinical evidence of significant unstable or uncontrolled 
acute or chronic diseases other than ITP (eg, cardiovascular, pulmonary, hematologic, 
gastrointestinal, endocrine, hepatic, renal, neurological, malignancy, infectious diseases, 
uncontrolled diabetes) despite appropriate treatments, which could put the participant at 
undue risk,” participants with ongoing COVID-19 would be excluded from participation in 
the trial. 
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, should apply appropriate social distancing and use personal protective equipment as 
directed by the local guidelines. 
Participants With COVID-19 (Either a Positive Test or With Symptoms) 
The instructions to manage infections in the main protocol are also applicable in case of 
COVID-19 (ie, it will be considered an adverse event of special interest [AESI]). The 
administration of IMP may be temporarily withheld if it could put the participant at undue 
risk due to clinically significant disease, including evidence of infection (see Section 6.7). 
During the pandemic, site staff or the home nurse should call participants before each visit to 
inquire about COVID-19 symptoms, and to check for exposure and infection with the virus 
before deciding to proceed with the visit using the flow charts that follow. If the participant is 
placed in quarantine and is not able to receive IMP, the investigator can specify on the eCRF 
that there was no intention to administer IMP due to COVID-19. 
For all assessments not performed at the trial site, “COVID-19: home visit” or “COVID-19: 
phone call” will be added as a comment on the eCRF. 
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Figure 1: 
Decision Tree for the Treatment of Participants 
 
 
In case of (suspected) COVID-19, the participant will be treated as guided by the local health 
care system. Participants will be observed for safety follow-up by the trial site by phone or 
by video call, if available and compliant with applicable regulations, eg, 21 CFR part 11, data 
protection regulation. If the participant must be isolated for a period longer than 2 weeks, it 
will be discussed on a case-by-case basis with the medical monitor from the sponsor, and/or 
when appropriate the CRO, whether the participant can remain in the trial. 
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The investigator can be contacted by the participant at any time by phone/video call in case 
of concerns. 
Forms completed at the participant’s home must be taken back to the site for data entry. If the 
trial site is closed due to the COVID-19 situation, the completed forms must be stored in a 
safe location until reopening of the trial site. 
Relevant records should be archived in the investigator site’s Trial Master File. The 
investigator/institution or delegate should maintain adequate and accurate source 
documentation. 
Screening Visit 
The screening assessments should be performed at the trial site. If the trial site is closed due 
to the COVID-19 situation, an alternative convenient location considered appropriate by the 
investigator and the participant (and confirmed and approved by the sponsor) can be used 
(eg, an infusion center, local clinic). 
If it is not possible for the participant to go to the trial site and the participant cannot be 
screened or treated at an alternative convenient location due to the COVID-19 situation, the 
participant cannot start screening and must wait until the situation changes and the 
participant is able to go to the trial site for the screening assessments. 
Please note that prospective protocol waivers remain unacceptable and that participants 
should not be included in trials without proper eligibility assessment, including performance 
of planned tests, and written informed consent according to national laws and regulations. 
The investigator remains ultimately responsible for obtaining informed consent, even when 
delegating this task to another individual knowledgeable about the research. 
Baseline Visit 
The baseline visit should be performed at the trial site. If the trial site is closed due to the 
COVID-19 situation, an alternative convenient location considered appropriate by the 
investigator and the participant (and confirmed and approved by the sponsor) can be used 
(eg, an infusion center, local clinic). 
Possible Home Visits/Home Assessments 
All other trial visits can be performed at home (or at an alternative convenient location) 
during the COVID-19 pandemic. A home nurse will travel to the participant’s home (or an 
alternative convenient location) to conduct the visit(s). The investigator will talk to the 
participant via an audio or video interview to elicit AEs, concomitant medications, and the 
general well-being of the participant. The investigator will perform the World Health 
Organization (WHO) bleeding assessments using a video interview with the participant. This 
will be mentioned in the source documents as such. 
All assessments performed at home, should preferably be performed by the same qualified 
trained nurse or another authorized person. This person will get all materials and equipment 
needed to perform the home assessments. 
Blood and urine samples (except the urine pregnancy test, samples for platelet counts) will 
preferably be shipped to and analyzed by a central laboratory. Only in exceptional cases a 
certified local laboratory can be used; laboratory reports should be reviewed by the 
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investigator, any abnormalities will be evaluated for clinical significance, and any significant 
laboratory findings should be recorded as AEs. The laboratory report should be kept as a 
source document. 
The division of tasks between the trained qualified physician and home nurse are indicated in 
the following scheme and should be aligned with applicable local regulations. 
Scheme for Home Visitsa 
Assessment 
Performed by 
Place/Method of 
Assessmenta 
• 
Participant eligibility 
Trained qualified 
physician 
Preferably at the trial site 
• 
Quality-of-life and 
patient-reported outcomes 
Participant 
At participant’s home 
• 
Weight 
• 
Electrocardiogram 
• 
Urinalysis 
• 
Urine pregnancy test 
• 
Blood sample (platelet count, 
hematology, chemistry, serum 
pregnancy, viral tests, 
pharmacodynamics, antiplatelet 
antibodies, immunogenicity, 
pharmacokinetics) 
• 
IMP injection 
Trained qualified 
nurse 
In person at participant’s 
home 
• 
Vital signs 
• 
Physical examination 
Trained qualified 
nurse/trained qualified 
physician 
In person at participant’s 
home 
• 
General bleeding assessment 
(WHO) 
Trained qualified 
physician 
In person at participant’s 
home or video call with 
investigator 
• 
Concomitant therapies 
• 
Adverse events 
Audio/video call 
a Note that a home visit can also be a visit at an alternative convenient location (eg, an infusion center, local 
clinic). 
Platelet Count 
A trained qualified nurse can take the blood sample at the participant’s home, within 1 day 
before the next procedure as per the SoA. If IMP is to be administered, the IMP can be 
prepared and administered the day after, based on the platelet count from the day before, or 
all can be done on the day in which IMP should be administered according to the SoA. The 
platelet count should be performed at the same local laboratory throughout the trial. 
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Quality-of-Life and Patient-Reported Outcomes 
SF-36, ITP-PAQ, FACT-Th6, and FACIT-Fatigue can be completed at home (or an 
alternative convenient location) by the participant. 
Weight 
Calibrated scales can be provided to the home nurse or the participant. 
Vital Signs 
Vital signs can be performed at home (or an alternative convenient location) by a trained 
qualified nurse or physician. The investigator can be contacted by phone/video call in case of 
concerns. 
Physical Examination 
Physical examination can be performed at home (or an alternative convenient location) by a 
trained qualified nurse or, if not allowed per local regulations, a trained qualified physician. 
The investigator can be contacted by phone/video call in case of concerns. 
Electrocardiogram 
An ECG can be taken at home (or an alternative convenient location) by a trained qualified 
nurse. The investigator can be contacted by phone/video call in case of concerns. 
General Bleeding Assessment (WHO) 
The general bleeding assessment can be performed at home (or an alternative convenient 
location) by a trained qualified physician or by means of a video call with the investigator. 
Urinalysis 
A trained qualified nurse can take a urine sample at home (or an alternative convenient 
location) using the laboratory kits/requisition forms supplied by the central laboratory. The 
testing should preferably be done by the initially appointed laboratory. 
Urine Pregnancy Test 
A trained qualified nurse can perform the urine pregnancy test on a urine sample taken at 
home (or an alternative convenient location). 
Hematology and Chemistry Tests 
A trained qualified nurse can take the blood sample at home (or an alternative convenient 
location) using the laboratory kits/requisition forms supplied by the central laboratory. The 
testing should preferably be done by the initially appointed central laboratory. 
Serum Pregnancy Test 
A trained qualified nurse can take a blood sample at home (or an alternative convenient 
location) using the laboratory kits/requisition forms supplied by the central laboratory. The 
testing should preferably be done by the initially appointed central laboratory. 
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Viral Tests 
A trained qualified nurse can take a blood sample at home (or an alternative convenient 
location) using the laboratory kits/requisition forms supplied by the central laboratory. The 
testing should preferably be done by the initially appointed central laboratory. 
Tuberculosis QuantiFERON Test 
The test for tuberculosis can be omitted if the baseline visit cannot be done at the trial site. 
This sample requires specific processing at a high technical level, which could not be feasible 
outside the trial site. 
Pharmacodynamics 
A trained qualified nurse can take a blood sample at home (or an alternative convenient 
location) using the laboratory kits/requisition forms supplied by the central laboratory. The 
testing should be done by the initially appointed designated laboratory. 
Antiplatelet Antibodies 
A trained qualified nurse can take a blood sample at home (or an alternative convenient 
location) using the laboratory kits/requisition forms supplied by the central laboratory. The 
testing should be done by the initially appointed laboratory. 
Immunogenicity 
A trained qualified nurse can take a blood sample at home (or an alternative convenient 
location) using the laboratory kits/requisition forms supplied by the central laboratory. The 
testing should be done by the initially appointed laboratory. 
Pharmacokinetics 
A trained qualified nurse can take the blood samples at home (or an alternative convenient 
location) using the laboratory kits/requisition forms supplied by the central laboratory. The 
testing should be done by the initially appointed laboratory. 
IMP Injections 
A trained qualified nurse can administer the IMP at the participant’s home (or an alternative 
convenient location). Detailed instructions on IMP management can be found in the Home 
Guide for Preparation and Administration. After the administration of the IMP, the 
participant must be observed for injection-related reactions by the trained qualified nurse for 
at least 30 minutes following the end of the injection for routine safety monitoring based on 
the participant’s clinical status. The investigator can be contacted by phone/video call in case 
of concerns. 
Concomitant Therapies 
The assessment of concomitant therapies can be performed at home (or an alternative 
convenient location) through a phone/video call with the investigator. 
Adverse Events 
The assessment of AEs can be performed at home (or an alternative convenient location) 
through a phone/video call with the investigator. 
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Schedule of Activities 
In the following SoA, the assessments preferably performed at the trial site are indicated with 
a solid dot “●”(ie, mandatory). The assessments that can be omitted if it is not possible to 
perform them, are indicated with a circle “Օ”(ie, optional). The assessments that can be 
performed at home (or an alternative convenient location) are indicated with a triangle “Δ.” 
However, if possible and feasible, it is preferred to perform as many assessments as possible 
on-site. 
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be obtained during the screening period. 
 
. 
f If available at baseline. 
g Height will only be measured at the screening visit. 
h If IMP is administered, the ECG will be performed after the IMP administration. 
i Laboratory assessments include all parameters mentioned in Section 10.2. On days that IMP is administered, samples for laboratory assessments should be 
collected before dosing, unless otherwise requested. 
j At the screening visit, if the investigator detects 1 or more screening laboratory abnormalities which are not aligned with the medical history and clinical 
evaluation of the participant, the result(s) should be confirmed if still within the screening window. For rescreening criteria see Section 5.4. 
k Only for women of childbearing potential. 
l At the screening visit, the total IgG level must be determined by the central laboratory (exclusion criterion 9). 
m Only for women of non-childbearing potential. 
n Optional if the baseline visit is held at an alternative convenient location. 
o To maintain the blind, the IgG testing cannot be performed locally. 
p To be collected predose, on the day of IMP administration. 
q If the visit does not coincide with an IMP administration, then the assessment should be performed at the next IMP visit. 
r If the visit does not coincide with an IMP administration, then the assessment should NOT be performed. 
s  
 
t Randomization to be completed before administration of IMP. 
u The IMP (efgartigimod PH20 SC or placebo PH20 SC) will be administered as an SC injection at each IMP administration visit. Participants will be observed 
for at least 30 minutes following the end of the injection for routine safety monitoring based on the participant’s clinical status. Assessment of the dosing 
regimen as described in Section 6.5 will be applied. 
v Adverse events, procedures, and intake of concomitant medication(s) will be monitored continuously from signing the ICF until the last trial-related activity, 
unless the participant withdraws consent. In case of early discontinuation, any adverse events/serious adverse events should be assessed until the participant has 
ended the trial until satisfactory resolution or stabilization. All available vaccination history will be recorded as part of the participant’s prior medication for 
vaccinations received in the past, or concomitant medication for vaccinations received during the trial. 
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10.10. 
Appendix 10: Definition of Terms 
Blinding: 
A procedure in which 1 or more parties to the trial are kept unaware of the treatment assignment 
to reduce the risk of biased trial outcomes. The level of blinding is maintained throughout the 
conduct of the trial, and only when the data are cleaned to an acceptable level of quality will 
appropriate personnel be unblinded or when required in case of an adverse event (AE) or serious 
adverse event (SAE). In a double-blinded trial, the participant, the investigator, site staff, and 
sponsor staff who are involved in the treatment or clinical evaluation of the participants and the 
review or analysis of data are all unaware of the treatment assignment. 
Council for International Organizations of Medical Sciences: 
• The CIOMS is an international, non-governmental, non-profit organization 
established jointly by the World Health Organization (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, or preparation of 
materials to be submitted to regulatory authorities. 
Database Lock: 
An action taken to prevent further changes to a trial database. A database is locked after review, 
query resolution, data cleaning and determination that it is ready for analysis. 
Data Safety Monitoring Board: 
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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Eligible: 
Qualified for randomization into the trial based upon strict adherence to inclusion/exclusion 
criteria. 
Good Clinical Practice: 
A standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and 
reporting of clinical trials that provides assurance that the data and reported results are credible 
and accurate, and that the rights, integrity, and confidentiality of trial participants are protected 
(ICH E6 [R2]). 
Institutional Review Board/Independent Ethics Committee: 
An independent body (a review board or a committee [institutional, regional, national, or 
supranational]), constituted of medical professionals and non-medical members, whose 
responsibility it is to ensure the protection of the rights, safety and well-being of human subjects 
involved in a trial and to provide public assurance of that protection by, among other things, 
reviewing and approving / providing favorable opinion on, the trial protocol, the suitability of the 
investigator(s), the facilities, and the methods and material to be used in obtaining and 
documenting informed consent of the trial subjects. 
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. 
International Council for Harmonisation: 
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: 
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 subjects to reduce bias of selection. 
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. 
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Caregiver: 
A caregiver is a person of legal age from the participant’s social network (eg, family, relatives, 
friends), chosen by the participant. Once he/she receives the necessary training and is found 
competent by the authorized site staff to perform IMP administration, the caregiver can 
administer SC injections to the participant. 
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10.11. 
Appendix 11: Abbreviations 
ADA 
anti-drug antibodies 
AE 
adverse event 
AESI 
adverse event of special interest 
ASH 
American Society of Hematology 
CI 
confidence interval 
CIDP 
chronic inflammatory demyelinating polyneuropathy 
CIOMS 
Council for International Organizations of Medical Sciences 
CRO 
contract research organization 
CTCAE 
common terminology criteria for adverse events 
CTR 
clinical trial report 
Ctrough 
serum concentration observed predose 
DSMB 
data safety monitoring board 
ECG 
electrocardiogram 
eCRF 
FACIT 
FACT 
electronic case report form 
Functional Assessment of Chronic Illness Therapy 
Functional Assessment of Cancer Therapy 
FAS 
full analysis set 
Fc 
crystallized fragment 
FcRn 
neonatal crystallized fragment receptor 
FSH 
follicle-stimulating hormone 
GCP 
good clinical practice 
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 
Ig 
immunoglobulin 
IMP 
investigational medicinal product 
IND 
investigational new drug 
 
 
 
 
IRB 
Institutional Review Board 
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IRT 
interactive response technology 
ITP 
immune thrombocytopenia 
ITP-PAQ 
ITP-Patient Assessment Questionnaire 
IV 
intravenous 
IVIg 
immunoglobulins given intravenously 
IWG 
International Working Group 
LS 
least square 
MG 
myasthenia gravis 
NAb 
neutralizing antibodies 
NCI 
National Cancer Institute 
OR 
odds ratio 
PD 
pharmacodynamic 
PK 
pharmacokinetics 
PLEX 
plasmapheresis 
PRO 
patient-reported outcomes 
QoL 
quality-of-life 
qw 
every week/weekly 
q2w 
every other week 
q4w 
every 4 weeks 
rHuPH20 
recombinant human hyaluronidase PH20 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SC 
SF-36 
subcutaneous 
Short Form-36 
SoA 
schedule of activities 
SOC 
system organ class 
SOP 
standard operating procedure 
SUSAR 
suspected unexpected serious adverse reaction 
TEAE 
treatment-emergent adverse event 
TPO-RA 
thrombopoietin receptor agonist 
WHO 
World Health Organization 
WHO-DD 
World Health Organization Drug Dictionary 
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10.12. 
Appendix 12: Protocol Amendment History 
Amendment 4 (17 Feb 2023) 
This amendment is considered to be substantial based on the definition in Article 2 §2 (13) of the 
Regulation (EU) No 536/2014 of the European Parliament and the Council of the European 
Union. 
Overall Rationale for This Amendment 
The primary reason for this amendment is to implement recommendations from the data safety 
monitoring board (DSMB) to modify the exclusion criterion regarding medical history of 
thromboembolic events and to require a mandatory discontinuation from trial intervention for 
participants who have an initial or recurrent malignancy. Editorial changes are included to help 
with readability. 
The protocol amendment Summary of Changes table for the previous amendment can be found 
in Section 10.12. 
The major changes from protocol v4.0 to v5.0 are summarized in the following table. Refer to 
Section 10.11 for any undefined abbreviations. 
Section  
Description of change 
Brief rationale 
5.2, Exclusion Criteria, 
Criterion 12 
10.4, Appendix 4: 
Washout Requirements 
Before First IMP 
Administration 
The exclusion criterion and washout 
period for serious thromboembolic 
events was updated. The prohibited 
period for any major thrombotic or 
embolic event (eg, myocardial 
infarction, stroke, deep venous 
thrombosis, or pulmonary embolism) 
was revised from within 12 months 
to within 5 years before 
randomization. 
Exclusion criterion 12 was 
renumbered as 12a. 
The DSMB monitoring the 
ARGX-113 ITP program 
recommended a revision to the 
washout period for the exclusion of 
participants with serious 
thromboembolic events. 
7.1, Discontinuation of 
Trial Intervention 
Language was added to clarify that 
any participant developing a new or 
recurrent malignancy except basal 
cell carcinoma will discontinue trial 
treatment regardless of the 
relationship to IMP. 
The DSMB monitoring the 
ARGX-113 ITP program 
recommended a mandatory 
discontinuation from trial 
intervention for trial participants 
with an initial or recurrent 
malignancy. 
1.3, Schedule of 
Activities, Table 1 
10.9, Appendix 9, 
Table 5, Schedule of 
Activities 
8.6, Pharmacokinetics 
Footnote n regarding when 
PK/PD/ADA samples should be 
collected was revised from within 
2 hours to within the same day, 
before IMP administration. 
Table 4 was renumbered as Table 5. 
The revision allows additional 
flexibility for trial sites. 
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Section  
Description of change 
Brief rationale 
2.3.1, Risk Assessment 
Table 2 of potential risks and 
mitigation strategies was added. 
The table succinctly addresses the 
trial risks and mitigation strategies. 
5.1, Inclusion Criteria, 
Criterion 8b 
10.6.2, Contraception 
Guidance 
The contraception requirement for 
male participants was removed. 
Inclusion criterion 8a was 
renumbered as 8b. 
Section 10.6.2.2 Male Contraception 
was deleted. 
This global change was made to all 
ARGX-113 studies based on 
emerging nonclinical data indicating 
that efgartigimod has a low risk of 
teratogenicity/fetotoxicity. 
3, Objectives and 
Endpoints 
9.5.7, Other Secondary 
Endpoint Analyses Not 
Subject to Alpha 
Control 
An efficacy objective was added to 
compare efgartigimod PH20 SC to 
placebo PH20 SC in IWG response 
and initial response, measuring the 
proportions of participants with an 
IWG response, an IWG complete 
response, and an initial response. 
The revision was made to align with 
the SAP. 
3, Objectives and 
Endpoints 
8.12, Immunogenicity 
Assessments 
10.3, Appendix 3, 
Table 4 
Text reading “and titers of NAb 
against efgartigimod and/or 
rHuPH20 in the overall population” 
was revised to “and titers of NAb 
against rHuPH20 in the overall 
population.” 
Table 3 was renumbered as Table 4. 
The text was not correct. Titers are 
determined for only the PH20 NAb 
assay, not the efgartigimod NAb 
assay. 
8.3.2, Vital Signs 
Instructions for taking blood 
pressure were amended to include 
that participants should be seated and 
rested. 
The updated instructions match site 
practices and prevent protocol 
deviations. 
10.4, Appendix 4: 
Washout Requirements 
Before First IMP 
Administration 
Anti-CD20 therapy (eg, rituximab) 
with a washout of 6 months before 
randomization was added. 
This requirement was added to 
match inclusion criterion 7. 
2.2, Background 
1.1, Synopsis 
ARGX-113-1801 was added to the 
list of sources of clinical history. 
Additional data were available in 
ARGX-113-1801 to support product 
development. 
2.3.2, Benefit 
Assessment 
Lengthy description was replaced 
with language that directs the reader 
to the benefit/risk assessment in the 
current IB. 
The IB is the primary repository for 
updated product data. 
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Section  
Description of change 
Brief rationale 
5.1, Inclusion Criteria, 
Criterion 2 
The age of consent inclusion 
criterion was revised to state that 
participants should be at least the 
local legal age of consent for clinical 
trials when signing the ICF. 
Inclusion criterion 2 was renumbered 
as 2a. 
The revision matches global 
requirements for the legal 
participation age. 
8.3.5, Clinical Safety 
Laboratory 
Assessments 
10.2, Appendix 2: 
Clinical Laboratory 
Tests 
Language was added describing 
blinding of albumin and urine total 
protein (quantitative) values and 
noting that an alert system will 
notify the investigator to ensure 
appropriate safety follow up. 
The DSMB monitoring the 
ARGX-113 ITP program advised 
that serum albumin and total protein 
results should remain blinded for the 
trial sites. 
10.7, Appendix 7: 
Administrative 
Structure 
The vendor name LGC was revised 
to DDS. 
The change was made to reflect the 
legal name of the vendor. 
Amendment 3 (15 Jul 2022) 
This amendment was 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. 
The primary reason for this amendment was to increase the sample size, to change the 
hierarchical order for testing the key secondary endpoints based on the top-line results of trial 
ARGX-113-1801, and to revise contraception requirements based on emerging nonclinical data 
that indicated that efgartigimod has a low risk of teratogenicity/fetotoxicity. 
The major changes from protocol v3.0 to v4.0 are summarized below. Refer to Section 10.11 of 
the protocol for any undefined abbreviations. 
Section  
Description of change 
Brief rationale 
Section 9.3. Sample 
Size Determination 
Section 1.1 Synopsis 
Changed the sample size to approximately 180 
participants with chronic ITP 
Adjusted the sample 
size using suitably 
modified assumptions 
of the treatment effect 
size based on the top-
line results of trial 
ARGX-113-1801 
Section 9.5.6. Key 
Secondary Endpoint 
Analyses Subject to 
Alpha Control 
Changed the hierarchical order for testing the third 
and fourth key secondary endpoints 
Modified based on the 
top-line results of 
ARGX-113-1801 
Section 9.5.6. Key 
Secondary Endpoint 
Analyses Subject to 
Alpha Control 
Modified the statistical method for analysis of the key 
secondary endpoint “incidence and severity of the 
World Health Organization (WHO)-classified 
bleeding events in the overall population”  
Modified based on the 
top-line results of 
ARGX-113-1801 
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Section  
Description of change 
Brief rationale 
Section 10.6.2. 
Contraception 
Guidance 
Section 10.6.1.1. 
Woman of 
Childbearing 
Potential 
Section 5.1. 
Inclusion Criteria 
Section 5.2. 
Exclusion Criteria 
Updated contraception requirements to: 
• 
change the period for contraceptive use by 
male and female participants from 90 days 
after last dose of IMP to the date of the last 
dose of IMP 
• 
remove the restriction on donating sperm 
during the trial 
• 
specify that male participants are subject to 
contraception rules if they are not sterilized 
• 
change the criteria for determining 
postmenopausal status 
Updated to align with 
previous nonclinical 
study results that 
indicate that 
efgartigimod has a low 
risk of teratogenicity/ 
fetotoxicity 
Section 10.6.2. 
Contraception 
Guidance 
Section 5.1. 
Inclusion Criteria 
Instruction on contraception requirements moved to 
Section 10.6.2  
Moved from eligibility 
criteria to Appendix 6: 
Contraceptive 
Guidance and 
Collection of 
Pregnancy 
Information 
Section 10.6.3. 
Collection of 
Pregnancy 
Information 
Changed the time period for collecting pregnancy 
information during the trial from 90 days after the last 
dose of IMP to the date of the last dose of IMP 
Updated to align with 
previous nonclinical 
study results that 
indicate that 
efgartigimod has a low 
risk of teratogenicity/ 
fetotoxicity 
Section 1.1. 
Synopsis 
Section 4.1. Overall 
Design 
Section 6.3.1. 
Emergency 
Unblinding 
Section 6.6.4. 
Rescue Therapy 
Section 8. Trial 
Assessments and 
Procedures 
Section 10.1.7.3. 
Quality Control 
Removed mandatory requirements for the investigator 
to consult the sponsor (or its designee) in decisions to:  
• 
Confirm a participant’s eligibility before 
randomization 
• 
Enroll a participant who had a serious adverse 
event during ARGX-113-2004 in the open-
label extension trial ARGX-113-2005 
• 
Unblind a participant’s treatment assignment 
• 
Discontinue a participant from IMP or the 
trial 
• 
Initiate rescue therapy 
• 
Determine whether an abnormal laboratory 
value is considered clinically significant 
Updated because the 
investigator has sole 
responsibility for 
decisions concerning 
an individual 
participant’s 
enrollment and 
medical care at their 
site. The sponsor 
retains its consultative 
role and its monitoring 
and auditing 
responsibilities. 
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Section  
Description of change 
Brief rationale 
Section 1.1. 
Synopsis 
Section 2.2. 
Background 
Section 2.3. 
Benefit/Risk 
Assessment 
Section 4.3. 
Justification for 
Dose 
Revised to reflect emerging data and to refer to the 
current IB for detailed information 
Updated to refer to the 
IB for a summary of 
contemporaneous data 
Section 6.8. 
Intervention After 
the End of the Trial 
Specified that for ARGX-113-2004 participants who 
meet the criteria to switch to a q2w IMP regimen 
based on their platelet counts at the end-of-treatment 
visit, the baseline visit in ARGX-113-2005 will occur 
7 days after the ARGX-113-2004 end-of-treatment 
visit 
Clarified the timing of 
the baseline visit/first 
dose of IMP for 
participants who are 
eligible to switch to a 
q2w IMP regimen  
when entering 
ARGX-113-2005  
Section 8.4.5. 
Regulatory 
Reporting 
Requirements for 
Serious Adverse 
Events 
Updated the reporting requirements for serious 
adverse events  
Updated safety 
reporting processes to 
align with the 
sponsor’s current 
practices 
Section 10.2. 
Appendix 2: 
Clinical Laboratory 
Tests 
Table 1 and Table 4 
Removed the clinical chemistry parameters 
apoliprotein B (apoB), lipoprotein A, fibrinogen, von 
Willebrand factor, D-dimer, and proprotein convertase 
subtilisin/kexin type 9 (PCSK9) 
Removed because 
efgartigimod does not 
reduce albumin levels 
and has had no 
observed effect on 
cholesterol, HDL, or 
LDL levels 
Sponsor Signatory 
Updated the sponsor signatory to 
, MD, 
PhD 
Updated to reflect the 
sponsor’s current chief 
medical officer 
(effective 01 Apr 
2022) 
Section 10.7. 
Appendix 7: 
Administrative 
Structure 
• 
Replaced vendor for central ECG reading  
• 
Updated the business name of the vendor for 
long-term storage of pharmacokinetics-
pharmacodynamics, antidrug antibodies, and 
antiplatelet antibodies samples 
• 
Updated vendor locations for clinical trial 
supply management  
Updated to reflect new 
vendors/vendor 
information 
 
 
 
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Amendment 2 (16 Jul 2021) 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union. 
Overall Rationale for the Amendment: 
The overall rationale for the changes implemented in the protocol amendment is to make 
clarifications and corrections. 
The major changes from protocol version 2.0 compared to protocol version 3.0 are summarized 
below. A strikethrough font is used to indicate deleted text and a bold font to indicate added text. 
Minor editorial changes and document formatting revisions have not been summarized. 
 
Section 
Description of Change 
Brief Rationale 
Front Page 
Safety Mailbox/Fax: 
Email: 248700ADR@parexel.com safety@argenx.com 
Fax: (+1) 833 644 0806 874 7325 
As per argenx safety 
requirements. 
Section 1.1. 
Synopsis 
Section 4.1. Overall 
Design 
All participants or their caregivers (as defined in 
Section 10.10) will be invited to receive training to 
(self-)administer the IMP while under supervision at least 
4 times in the last 10 weeks, until they are capable of 
and comfortable with the (self-)administration 
([self-]administration without supervision is foreseen 
only in the open-label extension trial ARGX-113-2005, 
not in the current ARGX-113-2004 trial). 
If the participant or his/her caregiver successfully 
completes the training to the satisfaction of the 
authorized staff, as well as the participant or his/her 
caregiver, then the participant or his/her caregiver may 
administer the next injections at the trial site under the 
supervision of the authorized staff. The training must be 
documented in the participant’s source documents and 
eCRF. 
To clarify caregiver-
related requirements. 
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Section 
Description of Change 
Brief Rationale 
Table 1: Schedule of 
Activities 
Caregiver informed consent form 
Footnote: 
To be obtained before initiation of the IMP 
administration training. 
To clarify caregiver-
related requirements. 
 
IMP (self-)administration training 
Footnote s: 
Participants or their caregivers will be invited to receive 
training to (self-)administer the IMP while under 
supervision at least 4 times in the last 10 weeks, until 
they are capable of and comfortable with the 
(self-)administration ([self-]administration without 
supervision is foreseen only in the open-label extension 
trial ARGX-113-2005, not in the current 
ARGX-113-2004 trial). 
 
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Section 
Description of Change 
Brief Rationale 
Section 10.1.3. 
Informed Consent 
Process 
• Before signing the ICF, the trial participants will be 
instructed not to participate in any other clinical trial 
that involves an intervention or collection of data until 
the completion of the current trial. If a participant’s 
caregiver will be trained to administer the IMP, 
he/she will also have to sign an ICF. 
• If the IMP will be administered by the 
participant’s caregiver at the trial site, he/she will 
have to sign a separate ICF in which he/she agrees 
to share personal data and to be trained by the 
investigator or his/her designee to administer the 
SC injections of efgartigimod PH20. 
• The participant will sign the caregiver’s ICF to 
indicate that he/she agrees that this person will be 
his/her caregiver. 
• The investigator needs to confirm that the 
caregiver is competent to administer the IMP. 
• The caregiver’s training will be documented. The 
investigator will sign and save this documentation 
in the participant’s file. 
• The investigator or his/her representative will 
explain the following to the caregiver and answer 
all questions regarding his/her role as a caregiver: 
the purpose of the trial, the purpose of his/her role 
as a caregiver, the expected duration, and the 
extent to which confidentiality of his/her personal 
data will be maintained. 
• Caregivers must also be informed that taking on 
the role of caregiver is voluntary and that they may 
withdraw at any time. 
• Caregivers will also be required to sign an ICF, 
after receipt of detailed information on their role as 
a caregiver in this trial. 
• The caregiver ICF will be used to explain, in simple 
terms, the potential risks and disadvantages of 
taking on the role of caregiver. 
• The ICF and the caregiver ICF contains a statement 
that the consent is freely given. 
• The caregiver ICF must be available in the local 
and vernacular languages required at the 
investigative site. All caregiver ICF(s) must be 
signed and dated by the caregiver and the 
participant. 
To clarify caregiver-
related requirements. 
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Section 
Description of Change 
Brief Rationale 
Section 10.1.3. 
Informed Consent 
Process 
• Confirmation of a caregiver’s informed consent 
must also be documented in the participant’s 
medical records before any administration of IMP 
by the caregiver occurs. The authorized person 
obtaining the informed consent must also sign the 
caregiver ICF. 
• The investigator is responsible for ensuring that the 
informed consent is obtained from the caregiver, 
including the appropriate signatures and dates on 
the caregiver ICF, before any administration of 
IMP by the caregiver occurs. 
• If a new version of the caregiver ICF is issued, the 
participant and his/her caregiver must both 
reconsent. 
• A signed and dated copy of the caregiver ICF must 
also be provided to the participant and his/her 
caregiver. 
To clarify caregiver-
related requirements. 
Section 10.1.4. Data 
Protection 
• The participant and his/her caregiver must be 
informed that his/her personal trial-related data will be 
used by the sponsor in accordance with local data 
protection law. The level of disclosure must also be 
explained to the participant and his/her caregiver 
who will be required to give consent for their data to 
be used as described in the respective informed 
consent. 
• The ICF and the caregiver ICF will incorporate (or, 
in some cases, be accompanied by a separate 
document incorporating) wording that complies with 
relevant data protection and privacy legislation. 
• The caregiver must be informed that his/her 
personal data 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. 
 
Section 10.10. 
Appendix 10: 
Definition of Terms 
Caregiver: 
A caregiver is a person of legal age from the 
participant’s social network (eg, family, relatives, 
friends), chosen by the participant. Once he/she 
receives the necessary training and is found 
competent by the authorized site staff to perform IMP 
administration, the caregiver can administer SC 
injections to the participant. 
 
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Section 
Description of Change 
Brief Rationale 
Section 1.1. 
Synopsis 
Section 4.1. Overall 
Trial Design 
If a participant has had an SAE during the 
ARGX-113-2004 trial, his/her eligibility for the 
ARGX-113-2005 trial should be evaluated by the 
investigator and the sponsor’s trial physician. The 
decision to enroll the participant will be made case by 
case. 
Additional safety 
measure. 
Section 1.1. 
Synopsis 
Section 3. 
Objectives and 
Endpoints 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clarification. 
Section 1.1. 
Synopsis 
Section 3. 
Objectives and 
Endpoints 
 
 
 
 
 
 
 
 
 
Inclusion of a 
disease-specific 
measure of health-
related quality-of-life 
for use in adults with 
ITP. 
Table 1: Schedule of 
Activities 
Table 4: Schedule of 
Activities 
ITP-PAQ 
To be assessed at the following timepoints: 
Baseline, visit 13, end-of-treatment, and early 
discontinuation 
Footnote: 
If available at baseline. 
 
Table 1: Schedule of 
Activities 
Table 4: Schedule of 
Activities 
Hematology and chemistry test: 
Footnote added at baseline and visit 14: 
The following parameters should be tested at baseline 
and visit 14: apoB, lipoprotein A, fibrinogen, von 
Willebrand factor, D-dimer, PCSK9 
For safety purposes. 
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Section 
Description of Change 
Brief Rationale 
Section 8.14. 
Quality-of-Life and 
Patient-Reported 
Outcomes 
The participant will complete the QoL questionnaire 
(SF-36 v2.0 and ITP-PAQ) and the PRO (FACT-Th6 
and FACIT-Fatigue Scale) as indicated in the SoA 
(Section 1.3). 
 
ITP-PAQ: The ITP-PAQ is a 44-item questionnaire to 
assess the health-related QoL in adults with ITP. It 
includes scales on a 0 (worst) to 100 continuum for 
physical health (symptoms, fatigue/sleep, bother, and 
activity), emotional health (psychological and fear), 
overall QoL, social activity, women's reproductive 
health, and work. 
Inclusion of a 
disease-specific 
measure of health-
related quality-of-life 
for use in adults with 
ITP. 
Section 10.9. 
Appendix 9: 
Possible 
Adaptations of Trial 
Protocol During 
COVID 19 
Pandemic 
Quality-of-Life and Patient-Reported Outcomes: 
SF-36, ITP-PAQ, FACT-Th6, and FACIT-Fatigue can 
be completed at home (or an alternative convenient 
location) by the participant. 
 
Table 1: Schedule of 
Activities 
Table 4: Schedule of 
Activities 
Footnote k and l (Table 1 and Table 4, respectively) “At 
the screening visit, the total IgG level must be determined 
by the central laboratory (exclusion criterion 9).” added 
to the screening assessment “Hematology and chemistry 
test” and removed from “Pharmacodynamics” 
Clarification. 
Table 1: Schedule of 
Activities 
Section 8.3.5. 
Clinical Safety 
Laboratory 
Assessments 
Table 4: Schedule of 
Activities 
On days that IMP is administered, blood samples for 
laboratory assessments should be collected before dosing, 
unless otherwise requested. 
To allow urine 
samples as well. 
Section 5.1. 
Inclusion Criteria 
2. Male or female, aged ≥18 years at the time the 
informed consent form (ICF) is signed. 
Exceptions are made for The Republic of 
South Korea and Taiwan where, according to 
local regulatory requirements, legal age is 
reached at 19 years and 20 years, respectively.  
To comply with local 
regulatory 
requirements. 
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Section 
Description of Change 
Brief Rationale 
Section 5.2. 
Exclusion Criteria 
14. Evidence of an active clinically significant 
bleeding of an organ or internal mucosal 
bleeding, other than expected in ITP, that 
warrants emergent treatment or therapeutic 
procedure based on the investigator’s judgment 
(eg, intracranial hemorrhage, pulmonary 
hemorrhage, bleeding with ongoing need for 
packed red blood cell transfusion) 
15. Estimated high risk of a clinically significant 
bleeding of an organ or internal mucosal 
bleeding, other than expected in ITP, that 
warrants emergent treatment or therapeutic 
procedure according to the investigator’s 
judgment 
To increase the 
safety of the selected 
population. 
 
17. Positive serum test at screening for an active viral 
infection with any of the following conditions: 
a. 
Hepatitis B virus (HBV) that is indicative of an 
acute or chronic infection, unless associated 
with a negative HBV DNA test 
(https://www.cdc.gov/hepatitis/HBV/PDFs/Sero
logicChartv8.pdf) 
b. Hepatitis C virus (HCV) based on HCV-
antibody assay (unless associated with a 
negative HCV RNA test) 
c. 
Human immunodeficiency virus (HIV) based on 
test results that are associated with an acquired 
immunodeficiency syndrome (AIDS)-defining 
condition or a CD4 count ≤<200 cells/mm3 
Clarification on the 
allowed test for HBV 
detection. 
Section 6.4. Trial 
Intervention 
Compliance 
The participants are dosed by qualified approved 
personnel. Adequately-trained participants or their 
caregivers are also allowed to administer the IMP 
on-site under supervision of the authorized site staff. 
Clarification. 
Section 6.6.4. 
Rescue Therapy 
• IV anti-D: up to 50–75 mcg/kg/day × 1–2 days 
Note: Anti-D rescue therapy should not be given to 
Rh(D)-positive participants 
Clarification upon 
request of the 
German competent 
authorities. 
Section 6.7. Dose 
Modification 
The administration of IMP will be temporarily withheld 
if it could put the participant at undue risk in any of the 
following circumstances: 
• Platelet count increases to >400×109/L 
The IMP administration should be resumed at the 
q2w dosing frequency when at the visit where the 
platelet count falls to <150×109/L, at the q2w dosing 
frequency. 
Clarification. 
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Section 
Description of Change 
Brief Rationale 
Section 6.8. 
Intervention After 
the End of the Trial 
• For participants on a q2w dosing regimen, the baseline 
visit including the first IMP dose administration in the 
ARGX-113-2005 trial will be done 7 days after the 
end-of-treatment visit in the current trial if visit 24 of 
the ARGX-113-2004 trial was a dosing visit. If 
visit 24 of the ARGX-113-2004 trial was a 
nondosing visit, the end-of-treatment visit will 
coincide with visit 1 of the ARGX-113-2005 trial. 
Clarification. 
Section 8.3.5. 
Clinical Safety 
Laboratory 
Assessments 
• Blood and urine samples for determination of clinical 
chemistry, hematology, urinalysis, coagulation, 
thyroid, autoimmune antibody testing, follicle-
stimulating hormone (FSH; only for women of non-
childbearing potential), PK, PD, antiplatelet 
antibodies, viral testing, and tuberculosis 
QuantiFERON test, and anti-drug antibodies (ADA) 
will be collected and analyzed at a central laboratory 
as indicated in the SoA (Section 1.3) and Section 10.2. 
The blood sample for platelet counts and the urine 
sample for the pregnancy test will be analyzed locally. 
PK, PD, antiplatelet 
antibodies, and ADA 
are not safety 
assessments. 
 
The estimated total maximum blood volume needed for a 
participant during the trial (when completing the trial) is 
approximately526 mL. 
Not required as per 
protocol template. 
Section 8.4. 
Adverse Events and 
Serious Adverse 
Events 
• Adverse events will be reported by the participant (or, 
when appropriate, by a caregiver, surrogate, or the 
participant’s legally authorized representative). 
Only the participant 
should report AEs. 
 
• An unexpected AE is any adverse drug event, which is 
not listed in the reference safety information in the 
current IB section 7 or is not listed at the specificity or 
intensity that has been observed. The assessment of 
expectedness will be the responsibility of the 
sponsor. 
To clarify that the 
assessment of 
expectedness is the 
responsibility of the 
sponsor. 
Section 8.4.9. 
Adverse Events of 
Special Interest 
• Due to the nature of the underlying disease (ie, ITP), 
any AE occurrence of bleeding will also be treated 
considered as an AESI. 
Clarification. 
Section 8.6. 
Pharmacokinetics 
Section 8.12.1. 
Anti-Drug 
Antibodies 
• Samples will be analyzed by the designated 
laboratory. 
 
Section 8.7. 
Pharmacodynamics 
• Samples will be analyzed by the specialty designated 
laboratory. To maintain the blind, the IgG testing 
cannot be performed locally. 
 
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Section 
Description of Change 
Brief Rationale 
Section 8.8. Platelet 
Functionality 
• The sample will be used for an exploratory endpoint 
and will be analyzed in a specialty designated 
laboratory. 
Clarification. 
Section 9.5.6. Key 
Secondary Endpoint 
Analyses Subject to 
Alpha Control 
A Wilcoxon-Mann-Whitney test stratified by receiving 
concurrent ITP therapies at baseline (yes versus no), and 
history of splenectomy (yes versus no), and baseline 
platelet count level category (<15×109/L versus 
≥15×109/L) will be used to compare the extent of disease 
control between both treatment groups. 
Addition of baseline 
platelet count level 
category to the 
analysis model to be 
consistent with the 
primary endpoint 
analysis approach 
(CMH test). 
 
When 1 of the main intercurrent events described in 
Section 9.5.5 occurs, platelet count levels measured after 
the occurrence will be censored (or, they will not be 
taken into account for the calculation of the number of 
cumulative weeks). 
Correction. 
 
The model will consist ofhave the number of events as 
the dependent variable and both of randomized treatment, 
and the stratification variables (history of splenectomy; 
receiving concurrent ITP therapies at baseline), and 
baseline platelet count as independent variables as 
factors in the model. 
Inclusion of baseline 
platelet count in the 
model to have an 
analysis approach 
consistent with the 
primary and other 
key secondary 
endpoints. 
Section 9.5.10.1. 
Pharmacodynamics, 
Pharmacokinetics, 
and Immunogenicity 
Descriptive statistics will be provided for PD parameters 
(total IgG and subtypes, and antiplatelet antibodies), the 
presence of antibodies, and titers of antibodies against 
efgartigimod and/or rHuPH20. 
Correction; subtype 
levels are not 
required for PD 
evaluations. 
Section 10.2. 
Protocol-Required 
Safety Laboratory 
Assessments 
Section 10.3. 
Appendix 3: 
Pharmacokinetic, 
Pharmacodynamic, 
and 
Immunogenicity 
Assessments 
“Table 2: Protocol-Required Safety Laboratory 
Assessments” has been split into “Table 2: Protocol-
Required Safety Laboratory Assessments” and “Table 3: 
Protocol-Required Pharmacokinetic, 
Pharmacodynamic, and Immunogenicity 
Assessments” 
To make a 
distinction with the 
assessments related 
to PK, PD, and 
immunogenicity. 
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Section 
Description of Change 
Brief Rationale 
Table 2: Protocol-
Required Safety 
Laboratory 
Assessments 
Clinical chemistry: 
, hemoglobin A1c (HbA1c)a, cholesterola (total 
cholesterol, high density lipoprotein [HDL], low 
density lipoprotein [LDL]), triglycerides, apoBa, 
lipoprotein Aa, fibrinogena, von Willebrand factora, 
D-dimera, PCSK9a 
Footnote a: 
Parameter to be tested at baseline and at visit 14. 
For safety purposes. 
 
Clinical chemistry: 
…, serum levels of total IgGb 
Footnote b: 
At screening only, to maintain the blind. 
Clarification. 
 
Serology: 
Human immunodeficiency virus (HIV) antibodies 
(1 and 2), hepatitis B HBV surface antigen (HbsAg), 
antibodies to the surface and core antigens of the hepatitis 
B virus HBV (anti-HBs and anti-HBc), hepatitis C virus 
antibody (HCV Ab), HCV RNA 
 
Section 10.5.1. 
Definition of 
Adverse Event 
Events NOT to be Collected as Adverse Events 
• 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. 
Note: Except for any occurrence of bleeding, which 
will be considered an AESI as per Section 8.4.9. 
 
Section 10.5.2. 
Definition of 
Serious Adverse 
Event 
Definition of Serious Adverse Event 
3. Requires in-patient 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. 
To clarify the term 
“hospitalization” in 
the definition of 
SAE. 
 
6. Other situations: 
- Suspected transmission of any infectious 
agent via the IMP will also be treated as an 
SAE. 
To fulfill the 
requirements of 
section VI.C.2.2.5 of 
Module V of EMA’s 
Guideline on good 
pharmacovigilance 
practices (GVP). 
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Section 
Description of Change 
Brief Rationale 
Section 10.6.2.1. 
Female 
Contraception For 
Women of 
Childbearing 
Potential 
Progesteroneogen-only hormonal contraception … 
Correction. 
Section 10.6.3.1. 
Male Participants 
With Partners Who 
become Pregnant 
• Male participants will be instructed through the 
informed consent form (ICF) to immediately inform 
the investigator if their partner becomes pregnant 
during the trial or up to 90 days after they received the 
last investigational medicinal product (IMP). 
 
Section 10.7. 
Appendix 7: 
Administrative 
Structure 
Home Care Vendor: 
Symphony Clinical ResearchAccellacare In-Home 
Services (an ICON company) 
Administrative 
change. 
 
Analysis of Pharmacokinetics Pharmacodynamics, Anti-
Drug Antibodies, and Neutralizing Antibodies Against 
Efgartigimod 
LGC 
 
 
Analysis of Total IgG 
PPD Laboratories - US 
2 Tesseneer Road 
Highland Heights, KY 41076 
United States 
 
 
Antibodies and Neutralizing Antibodies Against 
rHuPH20 
Covance LabCorp Bioanalytical Services, LLC 
 
Section 10.9. 
Appendix 9: 
Possible 
Adaptations of Trial 
Protocol During 
COVID 19 
Pandemic 
To allow patients with ITP to receive treatment with the 
investigational medicinal product (IMP) during the 
COVID 19 pandemic, this appendix to the protocol has 
been developed. If a visit to the trial site is not possible, a 
home visit or a visit at an alternative convenient location 
can be allowed, as per local regulations. … 
If allowed per local regulations, iIt remains at the 
investigator’s discretion to assess if it is in the best 
interest of the participant to start/continue in the trial. … 
Clarification. 
 
Pharmacodynamics: 
The testing should be done by the initially appointed 
central designated laboratory. 
 
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Section 
Description of Change 
Brief Rationale 
Section 10.9. 
Appendix 9: 
Possible 
Adaptations of Trial 
Protocol During 
COVID-19 
Pandemic 
Table 4: Schedule of 
Activities 
IMP self administration trainingu 
Footnote: 
Participants or their caregivers will be invited to receive 
training to self administer the IMP under supervision at 
least 4 times in the last 10 weeks (self administration 
without supervision is foreseen only in the open label 
extension trial ARGX 113 2005, not in the current 
ARGX 113 2004 trial). 
Self-administration 
training is not 
applicable for the 
protocol adaptations 
during the 
COVID-19 
pandemic. 
Section 11. 
References 
12. Recombinant human hyaluronidase PH20 (rHuPH20) 
Investigator’s Brochure. Version 98.0. January 20210. 
Update. 
 
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Amendment 1 (12 Jan 2021) 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union. 
Overall Rationale for the Amendment: 
The overall rationale for the changes implemented in the protocol amendment is to align the 
protocol with the responses to the US FDA comments in IND 152588 and make clarifications 
and corrections. 
The major changes from protocol version 1.0 compared to protocol version 2.0 are summarized 
below. 
A strikethrough font is used to indicate deleted text and a bold font to indicate added text. Minor 
editorial changes and document formatting revisions have not been summarized. 
Summary of Changes Between Protocol Version 1.0 and Protocol Version 2.0 
Section 
Description of Change 
Brief Rationale 
Section 1.1. Synopsis 
Section 3. Objectives and 
Endpoints 
Secondary Endpoints: 
• Incidence and prevalence of anti drug 
antibodies (ADA) antibodies to 
efgartigimod and/or rHuPH20 in the 
overall population 
• Titers of ADA antibodies to efgartigimod 
and/or rHuPH20 in the overall population 
Correction 
 
Secondary Endpoints: 
• Pharmacodynamics markers: total IgG, IgG 
isotypes (IgG1, IgG2, IgG3, and IgG4), 
and antiplatelet antibody levels in the 
overall population 
Subtype levels are not 
required for PD 
evaluations 
 
Exploratory Objectives: 
• To evaluate the competency of 
participants or their caregivers to 
administer efgartigimod PH20 SC 
To assess the 
participants 
self-administration 
performance during 
the supported 
administration training 
 
Exploratory Endpoints: 
• Number and percentage of participants 
or caregivers completing the self-
administration/caregiver-supported 
administration training 
• Number and percentage of participants 
or caregivers determined by the site staff 
to be sufficiently competent to 
administer efgartigimod PH20 SC 
• Number and percentage of participants 
or caregivers that administer 
efgartigimod PH20 SC under site staff 
supervision 
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Section 
Description of Change 
Brief Rationale 
Section 1.1. Synopsis 
All participants or their caregivers will be 
invited to receive traininged to self-
administer the IMP under supervision at 
least 4 times in the last 10 weeks (self-
administration without supervision is 
foreseen only in the open-label extension trial 
ARGX-113-2005, not in the current 
ARGX-113-2004 trial). 
If the participant or his/her caregiver 
successfully completes the training to the 
satisfaction of the authorized staff as well as 
the participant, the participant or his/her 
caregiver may administer the next 
injections at the trial site under the 
supervision of the authorized staff. The 
training must be documented in the 
participant’s source documents and eCRF. 
Clarification 
Section 1.2. Schema 
Schema has been updated 
Administrative change 
for consistency and 
clarification 
Section 1.3. Schedule of 
Activities 
Table 2: Protocol-Required 
Safety Laboratory 
Assessments 
Section 10.8. Appendix 8: 
Possible Adaptations of 
Trial Protocol During 
COVID 19 Pandemic 
 
Table 3: Schedule of 
Activities 
Anti drug antibodiesImmunogenicity 
Sampling is done for 
antibodies against the 
drug and the 
formulation 
 
Section 1.3. Schedule of 
Activities 
Section 10.8. Appendix 8: 
Possible Adaptations of 
Trial Protocol During 
COVID 19 Pandemic 
 
Table 3: Schedule of 
Activities 
End-of-Treatment: This visit should be 
performed on trial day 169 (+2 days) (ie, 
7 days [+2 days] after the last dosing visit) for 
all participants who have completed the 
24-week treatment period and who want to 
roll over to the open label extension trial, 
whether they were still receiving IMP or not. 
Every effort should be made to schedule every 
visit on the exact day (which is relative to 
baseline randomization [visit 1]). 
Correction 
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Section 
Description of Change 
Brief Rationale 
Section 1.3. Schedule of 
Activities 
Footnote d: 
Platelet count is measured locally and can be 
performed within 1 day (for postbaseline 
visits) of the next procedure as per schedule of 
activities (both dosing and non-dosing visits). 
Eligible participants should have a mean 
platelet count of <30×109/L from 2 at least 
3 documented, qualifying counts within the 
3 preceding months where at least 2 of the 
qualifying counts must be taken during the 
screening period: 1 platelet count collected 
during the screening period and the predose 
platelet count on the day of randomization 
(visit 1). If the third count is not available 
from the 3 preceding months, this third 
platelet count can be obtained during the 
screening period. 
As per request from 
the FDA 
Section 1.3. Schedule of 
Activities 
Footnote e: 
Patient reported outcomes and quality of life 
(QoL) assessments will preferably be 
performed after the platelet count assessment. 
Correction 
 
Footnote f: 
Electrocardiogram will be assessed after the 
end of the IMP administration, if any. If IMP 
is administered, the ECG will be performed 
after the IMP administration. 
Clarification 
 
Footnote h: 
At the screening visit, if the investigator 
detects 1 or more screening laboratory 
abnormalities which are not aligned with the 
medical history and clinical evaluation of 
the participant, the result(s) should be 
confirmed if still within the screening 
window. For rescreening criteria see Section 
5.4. 
 
 
Footnote o: 
Samples demonstrating a positive anti drug 
antibodies (ADA) titer will be tested for 
neutralizing ADAs. 
Correction 
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Section 
Description of Change 
Brief Rationale 
Section 1.3. Schedule of 
Activities 
Footnote q: 
Participants or their caregivers will be invited 
to receive traininged to self-administer the 
IMP under supervision at least 4 times in 
the last 10 weeks (self-administration without 
supervision is foreseen only in the open-label 
extension trial ARGX-113-2005;, not in the 
current ARGX-113-2004 trial) at least 4 times 
in the last 10 weeks. 
Clarification 
 
Footnote r: 
The IMP (efgartigimod PH20 SC or placebo 
PH20 SC) will be administered as an SC 
injection at each IMP administration visit. 
Participants will remain at home the trial site 
for at least 15 minutes following the end of the 
injection for routine safety monitoring based 
on the participant’s clinical status. 
Correction 
Section 1.3. Schedule of 
Activities 
Footnote s: 
Adverse events, procedures, and intake of 
concomitant medication(s) will be monitored 
continuously from signing the ICF until the 
last trial-related activity, unless the participant 
withdraws consent. In case of early 
discontinuation, any adverse events/serious 
adverse events should be assessed until the 
participant has ended the trial for 30 days 
following the early discontinuation visit or 
until satisfactory resolution or stabilization. 
All available vaccination history will be 
captured as part of the participant’s prior 
medication for vaccinations received in the 
past, or concomitant medication for 
vaccinations received during the trial. 
Clarification 
Section 2.2. Background 
The prevalence of ITP is estimated at 9.5 per 
100 000 adults, and incidence rates have been 
reported at 3.3 adults per 
100 000 adults/years. 
Correction 
Section 2.3. Benefit/Risk 
Assessment 
Please refer to the current Investigator’s 
Brochure (IB) for more information regarding 
preclinical and clinical trials, and the potential 
risks and benefits of efgartigimod3 and 
rHuPH20,12 respectively. 
Clarification 
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Section 
Description of Change 
Brief Rationale 
Section 2.3.1. Risk 
Assessment 
Safety for use during pregnancy has not been 
established. Therefore, efgartigimod should 
not be administered to pregnant or lactating 
women. Reproductive toxicity trials are 
completed and in the reporting phase. 
As per results of 
reproductive 
toxicology studies 
Section 4.1. Overall Design 
All participants or their caregivers will be 
invited to receive traininged to 
self-administer the IMP under supervision at 
least 4 times in the last 10 weeks 
(self-administration without supervision is 
foreseen only in the open-label extension trial 
ARGX-113-2005, not in the current 
ARGX-113-2004 trial) as specified in the SoA 
in Section 1.3. 
If the participant or his/her caregiver 
successfully completes the training to the 
satisfaction of the authorized staff as well as 
the participant, the participant or his/her 
caregiver may administer the next 
injections at the trial site under the 
supervision of the authorized staff. The 
training must be documented in the 
participant’s source documents and eCRF. 
Clarification 
Section 5.1. Inclusion 
Criteria 
5. Mean platelet count of <30×109/L from 2 
at least 3 documented, qualifying counts 
within the 3 preceding months where at 
least 2 of the qualifying counts must be 
taken during the screening period: 
1 platelet count collected during the 
screening period and the predose platelet 
count on the day of randomization (visit 1). 
If the third count is not available from 
the 3 preceding months, this third 
platelet count can be obtained during 
the screening period. 
As per request from 
the FDA 
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Section 
Description of Change 
Brief Rationale 
Section 5.1. Inclusion 
Criteria 
8. Must be on a stable regimen for at least 
1 month of at least 1 highly effective or 
acceptable method of contraception (ie, 
failure rate of less than 1% per year; see 
Highly Effective Methods of Female 
Contraception) during the trial and for 
90 days after the last administration of IMP 
Final results from 
reproductive toxicity 
studies became 
recently available and 
did not indicate a risk 
to male or female 
fertility or embryo-
fetal developmental 
toxicity 
 
9. Non-sterilized male participants who are 
sexually active with a female partner of 
childbearing potential must use effective 
an acceptable method of contraception, ie, 
a condom (see Male Contraception ) from 
signing the ICF through 90 days after the 
last administration of the IMP. Male 
participants practicing true sexual 
abstinence (as consistent with preferred and 
usual lifestyle) can be included. Sterilized 
male participants who have had a 
vasectomy and with documented absence 
of sperm post-procedure can be included. 
Male participants are also not allowed to 
donate sperm during this time from 
signing the ICF through 90 days after the 
last dose of the IMP. 
Section 5.2. Exclusion 
Criteria 
8. Use of any monoclonal antibody or Fc 
fusion proteins, other than those 
previously indicated, within 6 months 
before the first dose of the IMP (eg, anti-
CD20) 
Clarification 
 
15. b. Hepatitis C virus (HCV) based on 
HCV-antibody assay (unless associated 
with a negative HCV RNA test) 
 
 
23. Received a live/live-attenuated vaccine less 
than 4 weeks before screening. The receipt 
of any inactivated, sub-unit, 
polysaccharide, or conjugate vaccine at any 
time before screening is not considered an 
exclusion criterion. 
 
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Section 
Description of Change 
Brief Rationale 
Section 6.1. Trial 
Intervention(s) 
Administered 
For each injection, the initiation and 
completion times (hour and minute), and 
details of any interruptions or premature 
discontinuation of injections will be 
recorded on the eCRF. The start will be 
marked as the moment of start pressing the 
plunger and the end will be marked as the 
completion time of administration of the 
total volume of IMP. 
Paragraph moved from 
Section 8.10. IMP 
Administration in 
order to group all 
information regarding 
the administration of 
IMP in the same 
section 
Section 6.2.1. Preparation 
Efgartigimod PH20 SC will be provided as a 
sterile, clear to opalescent, colorless to 
yellowish, clear solution for SC injection in 
glass vials covered with a blinding shell. 
Clarification 
Section 6.2.2. Handling 
Only participants enrolled in the trial may 
receive IMP and only authorized and trained 
personnel site staff may dispense supply or 
administer IMP. The IMP administration 
must be performed by authorized and 
trained site staff or by an adequately 
trained and supervised participant or 
his/her caregiver. 
 
Section 6.2.3. Storage 
The IMP (efgartigimod PH20 SC and placebo 
PH20 SC) will be supplied to the pharmacy or 
dedicated site location at the investigative 
trial site by and under the responsibility of the 
sponsor’s designated IMP supply vendor. 
 
Section 6.4.1. Handling 
Missed Doses of the 
Investigational Medicinal 
Product 
However, if a participant misses more than 
2 consecutive scheduled doses, then he/she 
will be discontinued early from the trial 
treatment (see Section 7.1). 
Correction 
Section 6.5. Screening and 
Treatment 
Note: in this case, no IMP will be 
administered at the last visit confirming the 
qualifying platelet counts of ≥100×10⁹/L. 
Clarification 
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Section 
Description of Change 
Brief Rationale 
Section 6.6. Prior and 
Concomitant Therapy 
All prior ITP procedures and therapies 
received by the participant since diagnosis, 
before baseline, must be recorded on the 
eCRF, including the name, dose/schedule, 
duration (including start and stop dates), 
intolerance, and whether the participant 
responded to them, details of platelet counts 
on prior ITP therapies (ie, supporting the 
participant’s response), and the reason for 
discontinuation from prior therapies that 
are documented on the participant’s source 
documents at the current trial site. 
As per request from 
the FDA 
 
All vaccinations received by the participant in 
the 6 months before baseline should be 
recorded. 
All available vaccination history will be 
captured as part of the participant’s prior 
medication for vaccinations received in the 
past, or concomitant medication for 
vaccinations received during the trial as 
described in the SoA (Section 1.3). Any 
vaccination information the participant, 
his/her caregiver, or his/her legally 
authorized representative can remember 
should be recorded on the eCRF (with the 
brand name of the vaccine and date of 
vaccination, if possible). 
To evaluate the impact 
of efgatigimod on 
antibody response to 
vaccines 
Section 6.6.4. Rescue 
Therapy 
If a participant needs rescue therapy according 
to the investigator, it is encouraged to inform 
the medical monitor at the sponsor’s 
designated CRO and the sponsor’s medical 
monitor, whenever possible before actual 
implementation of the rescue therapy. 
Clarification 
Section 8.3.3. 
Electrocardiograms 
• If IMP is administered, the ECG will be 
performed after the IMP administration. 
• A single 12-lead ECG will be taken postdose 
at a paper speed of 25 mm/sec in the supine 
position after the participant has rested in 
this position for at least 10 minutes. 
 
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Section 
Description of Change 
Brief Rationale 
Section 8.3.5. Clinical 
Safety Laboratory 
Assessments 
• The estimated total maximum blood volume 
needed for a participant during the trial 
(when completing the trial) is approximately 
568.5526 mL. 
• The actual sample collection date and time 
must be entered in the participant’s source 
documents and on the central laboratory 
assessment eCRF page. For urinalysis 
samples only the date of collection is to be 
entered. 
Correction 
Section 8.3.5.1. Storage of 
Blood Samples in the Trial 
After this period of time, the samples will 
be destroyed. 
In addition, serum or plasma samples may be 
used to validate methods to support the 
efgartigimod program. These samples may 
also be used for vaccination antibody 
testing and any other additional research 
interests linked to the development of 
efgartigimod. 
Clarification 
Section 8.7. 
Pharmacodynamics 
• Serum samples for the determination of the 
PD markers (total IgG, IgG subtypes [IgG1, 
IgG2, IgG3, and IgG4]) will be collected as 
indicated in the SoA (Section 1.3). 
Subtype levels are not 
required for PD 
evaluations 
Section 8.10. IMP 
Administration 
For each injection, the initiation and 
completion times (hour and minute), and 
details of any interruptions or premature 
discontinuation of injections will be recorded 
and will be transferred to the eCRF. The start 
will be marked as the moment of start pressing 
the plunger and the end will be marked as the 
completion time of administration of the total 
volume of IMP. 
Each participant or his/her caregivers will be 
trained to self administer the IMP (self
administration is foreseen in the open label 
extension trial ARGX 113 2005, not in the 
current ARGX-113-2004 trial). The 
participant will receive a manual on 
preparation, handling, storage and 
administration of the IMP. 
More details are available in the Pharmacy 
Manual. 
This section was 
deleted in order to 
avoid repetition 
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Section 
Description of Change 
Brief Rationale 
Section 8.12.1. Anti-Drug 
Antibodies 
• Serum samples to assess ADA antibodies 
against efgartigimod and plasma samples to 
assess ADA immunogenicity against 
rHuPH20 will be collected as indicated in 
the SoA (Section 1.3). 
Correction 
Section 9.4. Population for 
Analyses 
Full analysis set (FAS) 
All randomized patients who have a baseline 
efficacy observation. 
As per FDA 
recommendations 
Section 9.5.5.3. Estimation 
of Treatment Effect and 
Statistical Interference 
The primary endpoint will be analyzed using 
a Cochran-Mantel-Haenszel statistic test 
stratified for the stratification factors 
history tested by means of splenectomy (yes 
versus no), receiving concurrent ITP 
therapies at baseline (yes versus no), and 
for baseline platelet count level category 
(<15×109/L versus ≥15×109/L). The 
treatment effect will be presentedexact 
logistic regression, also known as the odds 
ratio together with its 95% confidence 
interval (CI) and 2-sided p-value. In 
addition, an adjusted difference of the 
proportions with its 95% CI will be 
providedexact conditional logistic 
regression.18 The model will contain fixed 
effect terms for randomized treatment and 
baseline platelet count level and will be 
stratified by history of splenectomy (yes 
versus no) and receiving concurrent ITP 
therapies at baseline (yes versus no). 
Parameter estimation and hypothesis testing 
will be performed on the log odds ratio (OR) 
of a sustained platelet count response for 
patients receiving efgartigimod PH20 SC 
versus patients receiving placebo PH20 SC. 
Using the Newton Raphson algorithm, a 
maximum exact conditional likelihood 
estimate of the log OR will be obtained. In the 
event the algorithm does not converge, the 
median unbiased estimate will be used.17 A 
likelihood ratio test will be conducted to test 
the null hypothesis that the log OR is equal to 
zero against the alternative that it is different 
from zero.19 The OR (by exponentiating the 
log OR) will be provided, along with the 95% 
two sided CI and two sided p value. 
As per FDA 
recommendations 
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Section 
Description of Change 
Brief Rationale 
Section 9.5.5.5. 
Complementary Analyses 
Furthermore, an exact logistic regression 
analysis in which the continuous baseline 
platelet count level is added as covariate 
instead of the baseline platelet count 
category will be conducted as supportive 
analysis. 
As per FDA 
recommendations 
Section 9.5.7. Other 
Secondary Endpoint 
Analyses Not Subject to 
Alpha Control 
The mean change from baseline for IPF# and 
IPF% will be analyzed by means of mixed 
models for repeated measurements, similar to 
the mean change from platelet count analysis 
described previously. 
Correction 
Section 9.5.8. 
• Descriptive statistics will be presented for 
immature platelet fraction, and the 
incidence and duration of hospitalizations 
related to ITP management, and the 
endpoint related to self-
administration/caregiver-supported 
administration of efgartigimod PH20 SC. 
 
Section 9.5.10.1. 
Pharmacodynamics, 
Pharmacokinetics, and 
Immunogenicity 
Descriptive statistics will be provided for PD 
parameters (total IgG and subtypes, and 
antiplatelet antibodies), the presence of 
ADAantibodies, and titers of ADA 
antibodies against efgartigimod and/or 
rHuPH20. 
 
Section 10.2. Appendix 2: 
Clinical Laboratory Tests 
Pharmacodynamic markers 
Serum levels of total IgG and IgG subtypes 
(IgG1, IgG2, IgG3, and IgG4) 
Subtype levels are not 
required for PD 
evaluations 
 
Anti drug antibodiesImmunogenicity 
Correction 
Section 10.3. Appendix 3: 
Washout Requirements 
Before First IMP 
Administration 
Live/live-attenuated vaccines: 
4 weeks before screening 
 
Section 10.4.3. Recording 
and Follow-up of Adverse 
Events and/or Serious 
Adverse Events 
Assessment of Causality 
• In the final evaluation for reporting, the 
assigned relationship, as per the CIOMS 
will be converted into a “binary 
determination,” as follows: Events with 
an assigned relationship of “unrelated” 
and “unlikely” will be grouped into the 
“unrelated” category. Events with an 
assigned relationship of “related,” 
“possibly related,” or “probably related” 
will be grouped into the “related” 
category. 
Clarification 
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Section 
Description of Change 
Brief Rationale 
Section 10.5. Appendix 5: 
Contraceptive Guidance and 
Collection of Pregnancy 
Information 
Highly Effective Methods of Female 
Contraception: For Women of Childbearing 
Potential 
Women of childbearing potential must use 
aThe following methods are considered highly 
effective or acceptable methods of 
contraception, which should be maintained 
at a minimum until 90 days after the last 
dose of IMP (ie, failure rate of <1% per 
year):. 
The same type of hormonal contraception 
must have been received for at least 1 
month before starting the trial. Hormonal 
contraception can be administered orally 
(the pill), by injection, patch, implant, or 
vaginal ring. 
The following methods are considered 
highly effective methods of contraception: 
1. Combined (contains estrogen- and 
progestogenerone-containing) hormonal 
contraception associated with inhibition of 
ovulation: … 
6. Vasectomized partner: if the partner is the 
sole sexual partner of the trial participant and 
the absence of sperm has been documented 
after the procedure 
7. Sexual abstinence: defined as continuous 
abstinence from heterosexual contact. Sexual 
abstinence is only allowed if it is the 
preferred and usual lifestyle of the 
participant. Periodic abstinence (eg, 
calendar, symptothermal, or postovulation 
methods) is not an acceptable method of 
contraception. 
Final results from 
reproductive toxicity 
studies became 
recently available and 
did not indicate a risk 
to male or female 
fertility or embryo-
fetal developmental 
toxicity 
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Section 
Description of Change 
Brief Rationale 
Section 10.5. Appendix 5: 
Contraceptive Guidance and 
Collection of Pregnancy 
Information 
The following methods are considered 
acceptable methods of contraception: 
1. Progesterone-only hormonal 
contraception associated with the 
inhibition of ovulation: 
− 
Oral 
− 
Injectable 
− 
Implantable 
2. Male or female condom with or without 
spermicide 
3. Cap, diaphragm, or sponge with 
spermicide 
Male Contraception: 
Effective An acceptable methods of 
contraception is ainclude condom for the male 
participants combined with a highly effective 
method of contraception for the female partner 
who is a woman of childbearing potential. 
Final results from 
reproductive toxicity 
studies became 
recently available and 
did not indicate a risk 
to male or female 
fertility or embryo-
fetal developmental 
toxicity 
Section 10.6. Appendix 6: 
Administrative Structure 
Anti Drug Antibodies and Neutralizing 
Antibodies Against rHuPH20 
Correction 
 
Project Management and Clinical Research 
Organization for Georgia 
EastHORN 
Panska 73 Str./804 
00 834 Warsaw 
Poland 
Administrative update 
 
Home Care Vendor 
Symphony Clinical Research (an ICON 
company) 
700 Deerpath Drive 
Vernon Hills, IL 60061-1802 
Illinois 
USA 
 
System Version: 1.0, Status: Approved, Document ID: VV-TMF-95336

Clinical Trial Protocol ARGX-113-2004 v6.0 
 
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Section 
Description of Change 
Brief Rationale 
Section 10.8. Possible 
Adaptations of Trial 
Protocol During COVID-19 
Pandemic 
Possible Home Visits/Home Assessments 
The investigator will perform the World 
Health Organization (WHO) bleeding 
assessments using a video interview with the 
participant. The assessments via an audio or 
video interview will be conducted before the 
home nurse administers the IMP. This will be 
mentioned in the source documents as such. 
Correction 
 
anti drug antibodiesimmunogenicity 
 
Section 10.8. Possible 
Adaptations of Trial 
Protocol During COVID-19 
Pandemic 
 
Table 3: Schedule of 
Activities 
Footnote e: 
Eligible participants should have a mean 
platelet count of <30×109/L from 2at least 
3 documented, qualifying counts within the 
3 preceding months where at least 2 of the 
qualifying counts must be taken during the 
screening period: 1 platelet count collected 
during the screening period and the predose 
platelet count on the day of randomization 
(visit 1). If the third count is not available 
from the 3 preceding months, this third 
platelet count can be obtained during the 
screening period. 
As per request from 
the FDA 
 
Footnote e: 
Patient reported outcomes and quality of life 
(QoL) assessments will preferably be 
performed after the platelet count assessment. 
Correction 
 
Footnote g: 
Electrocardiogram will be assessed after the 
end of the IMP administration, if any. If IMP 
is administered, the ECG will be performed 
after the IMP administration. 
Clarification 
Footnote i: 
At the screening visit, if the investigator 
detects 1 or more screening laboratory 
abnormalities which are not aligned with the 
medical history and clinical evaluation of 
the participant, the result(s) should be 
confirmed if still within the screening 
window. For rescreening criteria see 
Section 5.4. 
 
System Version: 1.0, Status: Approved, Document ID: VV-TMF-95336

Clinical Trial Protocol ARGX-113-2004 v6.0 
 
06 Apr 2023 
Efgartigimod PH20 SC 
argenx BV 
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149 
Section 
Description of Change 
Brief Rationale 
Section 10.8. Possible 
Adaptations of Trial 
Protocol During COVID-19 
Pandemic 
 
Table 3: Schedule of 
Activities 
Footnote q: 
Samples demonstrating a positive anti drug 
antibodies (ADA) titer will be tested for 
neutralizing ADAs. 
Correction 
Footnote s: 
The IMP (efgartigimod PH20 SC or placebo 
PH20 SC) will be administered as an SC 
injection at each IMP administration visit. 
Participants will be observed remain at home 
for at least 15 minutes following the end of the 
injection for routine safety monitoring based 
on the participant’s clinical status. Assessment 
of the dosing regimen as described in 
Section 6.5 will be applied. 
 
Footnote t: 
Participants or their caregivers will be invited 
to receive traininged to self-administer the 
IMP under supervision at least 4 times in 
the last 10 weeks (self-administration 
without supervision is foreseen only in the 
open-label extension trial ARGX-113-2005;, 
not in the current ARGX-113-2004 trial) at 
least 4 times in the last 10 weeks. 
Clarification 
 
Footnote u: 
In case of early discontinuation, any adverse 
events/serious adverse events should be 
assessed for 30 days following the early 
discontinuation visit until the participant has 
ended the trial or until satisfactory resolution 
or stabilization. 
All available vaccination history will be 
captured as part of the participant’s prior 
medication for vaccinations received in the 
past, or concomitant medication for 
vaccinations received during the trial. 
 
System Version: 1.0, Status: Approved, Document ID: VV-TMF-95336

Clinical Trial Protocol ARGX-113-2004 v6.0 
 
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Section 
Description of Change 
Brief Rationale 
Section 11. References 
3. Efgartigimod, ARGX-113 Investigator's 
Brochure. Version 98.0. 
Update 
 
12. Recombinant human hyaluronidase PH20 
(rHuPH20) Investigator’s Brochure. 
Version 78.0. January 20192020. 
 
 
18. Cox D, Snell E. Analysis of Binary Data. 
New York: Chapman & Hall; 1970. 
19. Agresti A. Categorical Data Analysis. 
Second Edition. New York: John Wiley & 
Sons. 2002.  
 
 
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11. 
REFERENCES 
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FcRn antagonist, in adult patients with primary immune thrombocytopenia. Am J 
Hematol. 2020;95(2):178-187. 
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and outcome criteria in immune thrombocytopenic purpura of adults and children: report 
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12. Josephson CD, Granger S, Assmann SF, et al. Bleeding risks are higher in children versus 
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selected items from FACT-thrombocytopenia, and the SF-36v2 in patients with chronic 
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15. International Committee of Medical Journal Editors. Defining the role of authors and 
contributors. ICMJE website, http://www.icmje.org/recommendations/browse/roles-and-
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responsibilities/defining-the-role-of-authors-and-contributors.html. Accessed 04 Feb 
2020. 
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