A Phase 3, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Efgartigimod (ARGX 113) 10 mg/kg Intravenous in Adult Patients With Primary Immune Thrombocytopenia
Phase: PHASE3
Conditions: Primary Immune Thrombocytopenia
Sponsor: argenx

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Clinical Trial Protocol 
 
Protocol Title: 
A Phase 3, Multicenter, Randomized, Double-Blinded, 
Placebo-Controlled Trial to Evaluate the Efficacy and 
Safety of Efgartigimod (ARGX-113) 10 mg/kg Intravenous 
in Adult Patients With Primary Immune 
Thrombocytopenia 
Protocol Number: 
ARGX-113-1801 (ADVANCE) 
Date of Protocol: 
15 July 2021, Version 6.0, Final 
IND No: 
 
EudraCT No: 
2019-002100-41 
Investigational Product: 
ARGX-113 
Indication 
Primary immune thrombocytopenia 
Trial Phase: 
3 
Sponsor: 
argenx BVBA 
Industriepark Zwijnaarde 7 
9052 Zwijnaarde (Ghent) 
BELGIUM 
Phone: +32 (0)9 310 34 00 
Medical Director: 
, MD 
argenx BVBA 
Industriepark Zwijnaarde 7 
9052 Zwijnaarde (Ghent) 
BELGIUM 
Phone: office 
 
Email: 
 

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Contract Research 
Organization (CRO): 
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 below email address 
Safety Mailbox/Fax: 
Email: safety@argenx.com 
Fax: + 1 833 874 7325 
Confidentiality Statement 
The information in this document is confidential. It contains proprietary information of argenx (the sponsor). It is 
provided to you as an investigator or consultant for review by you, your staff, and the applicable Institutional 
Review Board/Independent Ethics Committee (IRB/IEC). Your acceptance of this document constitutes the 
agreement that you will not disclose the information contained herein to others without written authorization 
from the sponsor. 
 
 

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SIGNATURE OF INVESTIGATOR 
PROTOCOL TITLE: 
A Phase 3, Multicenter, Randomized, Double-Blinded, 
Placebo-Controlled Trial to Evaluate the Efficacy and Safety of 
Efgartigimod (ARGX-113) 10 mg/kg Intravenous in Adult Patients 
With Primary Immune Thrombocytopenia 
PROTOCOL NO: 
ARGX-113-1801 (ADVANCE) 
This protocol is a confidential document of argenx BVBA. 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 BVBA. 
 
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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DOCUMENT HISTORY 
Previous Version Number 
Effective Date 
1.0 
23 May 2019 
2.0 
09 September 2019 
3.0 
18 September 2019 
4.0 
27 May 2020 
5.0 
16 November 2020 
6.0 
15 July 2021 

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SUMMARY OF CHANGES 
The major changes from Protocol Version 5.0 compared to Protocol Version 6.0 are summarized 
below. 
The protocol amendment Summary of Changes table for the previous amendments can be found in 
Appendix 5. 
A strikethrough font is used to indicate deleted text and a bold font to indicate added text. Minor 
administrative editorial changes are not summarized in the following table: 
Summary of Changes Between Protocol Version 5.0 and Protocol Version 6.0 
Section(s) 
Change 
Rationale 
x Front Page 
Safety Mailbox/Fax: 
Email: 248700ADR@parexel.com safety@argenx.com 
Fax: (+1) 833 644 0806 874 7325 
As per argenx safety 
requirements. 
x Synopsis 
x 4.1. Summary of Trial 
Design 
x 6.8.4. 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 patients 
Clarification upon 
request of the German 
competent authorities. 
x Synopsis 
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 AESI in this trial. 
Due to the nature of underlying disease (ie, ITP), any 
occurrence of bleeding will also be considered an 
adverse event of special interest (AESI).Any bleeding or 
infection will be considered as adverse event of special 
interest (AESI). 
Clarification. 
x Synopsis 
x 4.3.1. Inclusion 
Criteria 
7. 
Women of childbearing potential … . Follicle-
stimulating hormone can be used to confirm 
postmenopausal status in amenorrheic patients not 
on hormonal replacement therapy. 
Correction. 

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Section(s) 
Change 
Rationale 
x Synopsis 
x 4.3.2. Exclusion 
Criteria 
16. Patients with known serum positivity or who test 
pPositive serum test at screening for an active viral 
infection at screening 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/Ser
ologicChartv8.pdf)(except patients who are anti 
HBs Ab positive because of HBV vaccination), 
Hepatitis C Virus, HIV 
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. 
x Synopsis 
x 8.4.1. Primary 
Endpoint Analysis 
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 two-sided p-value. 
In addition, an adjusted difference of the proportions 
with its 95% CI will be provided tested by means of 
exact logistic regression, also known exact conditional 
logistic regression.15 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.14 
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.16 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(s) 
Change 
Rationale 
x Synopsis 
x 8.4.2. Key Secondary 
Endpoint Analysis 
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). 
 
It will haveThe model will consist of 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. 
x Definition of Terms 
Childbearing potential: 
… 
Determination of FSH levels can be used to confirm 
postmenopausal status in amenorrheic patients not on 
hormonal replacement therapy. 
Correction. 
x 5.4.2. Rollover to the 
Open-Label 
Extension Trial 
(ARGX-113-1803) 
- For patients on a q2w dosing regimen, the baseline visit 
including first IMP dose administration of the 
ARGX-113-1803 trial will be done 7 days after the 
End-of-Treatment visit of the current trial if visit 24 of 
the ARGX-113-1801 trial was a dosing visit. If 
visit 24 of the ARGX-113-1801 trial was a non-dosing 
visit, the End-of-Treatment visit will coincide with 
visit 1 of the ARGX-113-1803 trial. 
Clarification. 
x 7.2.1. Platelet Count 
The assessment of platelet count can be performed within 
1 day prior to any other trial-specific assessment (except at 
screening, where the informed consent should be obtained 
and weight assessed first, and at randomization) at each 
visit as specified in the SoA (Table 1). 
Correction. 
x 7.3.1. Adverse Events 
Definition of AE 
The following events will NOT be collected as AEs: 
• 
The disease/disorder being studied or expected 
progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than 
expected for the patient’s condition. 
Note: Except for any occurrence of bleeding, which 
will be considered as an AESI as per section 7.3.1.1. 
Clarification. 
 
Definition of SAE 
• 
Requires inpatient hospitalization or prolongation of 
existing hospitalization. In general, hospitalization 
signifies that the patient has been admitted (usually 
involving at least an overnight stay) at the hospital or 
emergency ward for observation and/or treatment that 
To clarify the term 
“hospitalization” in the 
definition of SAE. 

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Section(s) 
Change 
Rationale 
would not have been appropriate in the physician’s 
office or outpatient setting. 
x 7.3.1. Adverse Events 
Definition of SAE 
• 
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). 
 
Definition of SAE 
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. 
x 7.3.1.1. Adverse 
Events of Special 
Interest 
Due to the nature of underlying disease (ie, ITP), any AE 
occurrence of bleeding will also be treated considered an 
AESI. 
Clarification. 
x 7.3.2. Clinical 
Laboratory 
Evaluations 
The actual sample collection date and time must be entered 
in the patient’s source documents and on the central/local 
lab assessment eCRF page. For urinalysis samples, only 
the date of collection is to be entered. 
Correction. 
x 8.2. Analysis 
Populations 
The full analysis set (FAS) consists of all randomized 
patients who have a baseline efficacy observation. 
As per FDA 
recommendations. 
x 8.4.1. Primary 
Endpoint Analysis 
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. 
 
x 8.4.2. Key Secondary 
Endpoint Analysis 
Subject to Alpha 
Control 
When 1 of the main intercurrent events described in 
Section 8.4.1occurs, 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. 
x 12. References 
15. Cox D, Snell E. Analysis of Binary Data. New York: 
Chapman & Hall; 1970. 
16. Agresti A. Categorical Data Analysis. Second Edition. 
New York: John Wiley & Sons. 2002. 
Update 
 
15. International Committee of Medical Journal 
Editors. Defining the role of authors and 
contributors. ICMJE website, 
http://www icmje.org/recommendations/browse/rol
es-and-responsibilities/defining-the-role-of-authors-
and-contributors.html.200699388, argenx BVBA. 
Tissue Cross reactivity of ARGX 113 with Human and 
Correction. 

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Section(s) 
Change 
Rationale 
Cynomolgus Monkey Tissues In Vitro. Final Report. 
Testing Facility Study No. 200699388. 2016. 
x 13. Appendices 
Appendix 2: 
Administrative 
Structure 
Analysis of Pharmacokinetics, IgG Subtypes,
Pharmacodynamics and Anti-Drug Antibodies 
LGC 
Administrative change 
 
Analysis of Total IgG 
PPD Laboratories - US 
2 Tesseneer Road 
Highland Heights, KY 41076 
United States 
 
 
Home Care Vendor: 
Accellacare In-Home Services (previously known as 
Symphony Clinical Research) (an ICON company) 
 
 
 
 

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SYNOPSIS 
Name of Sponsor: 
argenx BVBA 
Name of Investigational Medicinal 
Product (IMP): 
ARGX-113 
Active Ingredient: 
Efgartigimod 
Indication: 
Primary immune thrombocytopenia 
Title of Trial: 
A Phase 3, Multicenter, Randomized, Double-Blinded, 
Placebo-Controlled Trial to Evaluate the Efficacy and Safety of 
Efgartigimod (ARGX-113) 10 mg/kg Intravenous in Adult Patients 
With Primary Immune Thrombocytopenia 
Protocol No: 
ARGX-113-1801 (ADVANCE) 
Trial Sites: 
This is a global, multicenter trial 
Trial Duration: The total maximum trial 
duration per patient is up to 31 weeks: 
- 
Up to 2 weeks of screening 
- 
24 weeks treatment period 
- 
End-of-Treatment visit 1 week after 
visit 24 
- 
4 weeks of follow-up 
Phase: 3 
Objectives: 
Primary Objective: 
x 
To evaluate the efficacy of efgartigimod compared to placebo in achieving a sustained platelet count response 
in patients with chronic primary immune thrombocytopenia (ITP), with a sustained platelet count response 
defined as platelet counts of at least 50×109/L for at least 4 of the 6 visits between week 19 and 24 of the trial*. 
Secondary Objectives: 
x 
To evaluate the efficacy of efgartigimod compared to placebo in overall platelet count response. 
x 
To evaluate the safety and tolerability of efgartigimod administered intravenously (IV) weekly or every other 
week (q2w). 
x 
To evaluate the incidence and severity of bleeding events while receiving treatment with efgartigimod 
compared to placebo. 
x 
To evaluate the use of rescue treatment and changes in concurrent ITP therapy while receiving treatment with 
efgartigimod compared to placebo. 
x 
To evaluate the effects of efgartigimod treatment on quality-of-life (QoL) measures and patient-reported 
outcomes (PRO) compared to placebo. 
x 
To assess the immunogenicity of efgartigimod. 
x 
To assess the pharmacokinetics (PK) of efgartigimod. 
 
 “week” instead of “visits” are 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). 

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x 
To assess the pharmacodynamic (PD) effects of efgartigimod. 
Exploratory Objective: 
x 
 
Trial Design: 
DESCRIPTION 
This is a phase 3, multicenter, randomized, double-blinded, placebo-controlled, parallel-group, up to 31-week trial 
to evaluate the efficacy, safety, and impact on QoL of efgartigimod 10 mg/kg IV treatment in adult patients with 
primary ITP. 
The target population are adult patients with persistent or chronic primary ITP, having an average platelet count of 
<30×109/L, and at the start of the trial being on concurrent ITP treatment(s) and having received at least 1 prior 
therapy for ITP in the past, or not being on treatment for ITP but having received at least 2 prior treatments for ITP. 
If patients are receiving concurrent ITP therapies at baseline, these therapies should have been maintained at a 
stable dose and dosing frequency for 4 weeks prior to randomization. As of week 12, the start or an increase in the 
dose and/or schedule of permitted concurrent ITP therapy is allowed for patients who have an “insufficient 
response” (ie, no platelet count of ≥30×109/L in any of the visits during the last 4 weeks). These patients will be 
considered as “non-responders” for the primary endpoint analysis. 
After confirmation of eligibility, the patients enter a 24-week treatment period and will be randomized to receive 
efgartigimod 10 mg/kg IV or placebo, weekly from visits 1 to 4 and then from visits 5 to 16 either weekly or q2w, 
adjusted according to their platelet counts. From visits 17 to 24, patients will be fixed on the dosing schedule they 
were receiving at visit 16 or at the last visit at which IMP was administered (ie, either weekly or q2w). 
Patients completing the 24-week randomized trial period will perform the End-of-Treatment visit and can enter the 
open-label extension trial (ARGX-113-1803) to receive efgartigimod 10 mg/kg IV. The platelet counts from the 
ARGX-113-1801 trial will be taken into account to assess the dosing frequency in ARGX-113-1803. 
Patients who complete the 24-week trial period but who do not enter the open-label extension trial 
ARGX-113-1803, or patients who discontinue the trial early, with the exception of patients who withdraw their 
consent, will be followed for 4 weeks for ongoing safety and efficacy monitoring. 
For patients who discontinue the trial early, all the assessments listed for the Early Discontinuation visit as 
specified in the schedule of assessments (SoA, Table 1), will be performed. 
SAMPLE SIZE AND STRATIFICATION 
Approximately 117 patients with chronic ITP and up to 39 patients with persistent ITP will be randomized in a 
2:1 ratio to receive efgartigimod or placebo, respectively. Recruitment will end when 117 patients with chronic ITP 
have been randomized. 
Patients will be stratified according to the following factors: 
x 
History of splenectomy (yes vs. no) 
x 
Receiving concurrent ITP therapies at baseline (yes vs. no) 

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SCREENING AND TREATMENT 
During the screening period (up to 2 weeks) the patient’s eligibility for trial participation will be evaluated. 
All eligible patients will be randomized to receive IV infusions of either efgartigimod 10 mg/kg body weight or 
matching placebo throughout the trial. 
All patients will initially receive weekly IV infusions from visits 1 to 4. Based on the platelet counts as of visit 2, 
the dosing frequency can be altered from visits 5 to 16 according to following rules (the change in dosing frequency 
will occur at the current visit): 
x 
Reduce from weekly to q2w in patients achieving 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 – 
3 consecutive visits. 
x 
Increase from q2w to weekly in patients whose platelet counts drop below 100×109/L on 2 consecutive 
visits 
– OR – 
<30×109/L at 1 visit 
– OR –  
in patients who receive rescue therapy (see Section 6.8.4) 
x 
Temporary withholding treatment: 
o 
for reasons described in Section 4.5, IMP should be reintroduced once the investigator considers 
the undue risk to the patient has passed 
o 
in patients with platelet counts greater than 400×109/L, IMP should be resumed at the 10 mg/kg 
q2w dose when the platelet count falls to fewer than 150×109/L 
x 
Post-baseline platelet count can be performed within 1 day of the next procedure as the SoA (both dosing 
and non-dosing visit), allowing the results to be incorporated into the criteria above. 
From visits 17 to 24, the dosing frequency is fixed for each individual patient (ie, either the weekly or q2w 
regimen), based on the regimen the patient was receiving at visit 16 or at the last visit at which IMP was 
administered. 
Exceptions to the fixed dosing frequency are: 
1. Continued weekly dosing for patients requiring rescue therapy. 
2. Continued q2w dosing for patients resuming IMP when the platelet count falls to fewer than 150×109/L after 
having had platelet counts greater than 400×109/L. 

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CONCURRENT ITP THERAPY 
Patients 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 oral corticosteroids, oral immunosuppressants, dapsone/danazol, fostamatinib and/or oral thrombopoietin 
receptor agonists (TPO-RAs; inclusion criterion n°6, Section 4.3.1). 
Dose and frequency of permitted concurrent ITP therapies should remain unchanged during the trial. 
Exceptions are patients who are receiving concurrent treatment with oral TPO-RAs in whom dose changes are 
permitted at label-defined platelet thresholds, and patients 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 patients who have an “insufficient response” (ie, no platelet count of ≥30×109/L in any of the visits during the 
last 4 weeks). These patients will be considered as “non-responders” 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. 
Patients not receiving concurrent ITP therapy are also eligible for the trial. 
RESCUE THERAPY 
“Rescue therapy” is defined as an occurrence where the patient 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 patient. The start date/time of the occurrence is the start of the 
administration of the first rescue treatment. 
Rescue therapy is allowed post-baseline during the 24-week trial period for patients with a platelet count of 
<30×109/L and 1 of the following: 
x 
an immediate risk of bleeding or a clinically significant bleeding or wet purpura 
x 
requirement for urgent or emergent surgery (elective surgeries must be postponed until trial completion) 
The following rescue therapies are permitted: 
x 
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 
x 
immunoglobulins given IV (IVIg): up to 1 g/kg/day × 1-2 days 
x 
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 patients 
x 
platelet transfusions 
It is encouraged to inform the sponsor’s designated Contract Research Organization (CRO) medical monitor prior 
to initiating rescue therapy. 
In the event of rescue with IVIg or IV anti-D: 
x 
If given at a visit where the IMP was due to be administered, the IMP should be withheld and administered 
at the next visit. 
For rescue therapy with methylprednisolone, dexamethasone, prednisone, or platelet transfusions: 
x 
Administration of the IMP continues during rescue therapy. 
Patients who were receiving q2w dosing at the time of rescue therapy will have the IMP administration frequency 
increased to weekly. 
For patients who receive rescue therapy, the platelet counts for 4 weeks after the first day of rescue treatment will 
not be used (ie, are censored) to assess whether or not the patient can transition to q2w treatment. 

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Patients requiring more than 3 occurrences of rescue therapy will discontinue from IMP.  
SAFETY 
The administration of IMP may be temporarily withheld if, in the opinion of the investigator, it could put the 
patient at undue risk in the following circumstances: 
x 
clinically significant disease, including evidence of infection 
x 
severe bleeding, grade 3 or 4 on the WHO bleeding scale, requiring urgent medical and/or surgical 
intervention 
x 
thrombosis 
If the IMP is being withheld, it can be reintroduced once the investigator considers the undue risk to the patient has 
passed. 
The administration of IMP must be temporary withheld from patients with platelet counts greater than 400×109/L, 
IMP should be resumed at the 10 mg/kg q2w dose when the platelet count falls to fewer than 150×109/L. 
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 AESI in this trial. 
Due to the nature of underlying disease (ie, ITP), any occurrence of bleeding will also be considered an adverse 
event of special interest (AESI). 
ASSESSMENT OF BLEEDING 
Signs and symptoms of bleeding are the predominant clinical manifestation of ITP and are typically related to 
platelet counts. 
The occurrence and severity of any bleeding symptoms will be assessed and recorded at every visit using the World 
Health Organization (WHO) bleeding scale as specified in the SoA (Table 1). 
EARLY DISCONTINUATION FROM THE TRIAL 
Any patient prematurely discontinuing the trial should perform the assessments listed for the Early Discontinuation 
visit. 
TRIAL END 
End-of-Trial is defined as last patient last visit in the ARGX-113-1801 trial. 
Planned Number of Patients: 
Approximately 117 patients with chronic ITP and up to 39 patients 
with persistent ITP will be randomized. 
Planned Number of Sites: 
Approximately 125 sites 
Planned Countries: 
This trial 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 who, at the start of the trial, 
are on concurrent ITP treatment(s) and have received at least 1 prior 
therapy for ITP in the past, or are not on treatment for ITP but have 
received at least 2 prior treatments for ITP. 

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Criteria for Inclusion and Exclusion: 
Inclusion Criteria: 
1. Ability to understand the requirements of the trial, to provide 
written informed consent (including consent for the use and 
disclosure of research-related health information), and to comply 
with the trial protocol procedures (including required trial visits). 
2. Male or female patient aged ≥18 years. 
3. Confirmed ITP diagnosis, at least 3 months before randomization 
and according to the American Society of Hematology Criteria, 
and no known other etiology for thrombocytopenia. 
4. Diagnosis supported by a response to a prior ITP therapy (other 
than thrombopoietin receptor agonists [TPO-RAs]), in the 
opinion of the investigator. 
5. Mean platelet count of <30×109/L from 2 counts: 1 platelet count 
collected during the screening period and the predose platelet 
count on the day of randomization (visit 1). 
6. At the start of the trial, the patient is either on concurrent ITP 
treatment(s) and has received at least 1 prior therapy for ITP in 
the past, or the patient is not on treatment for ITP but has 
received at least 2 prior treatments for ITP. Patients receiving 
permitted concurrent ITP treatment(s) at baseline, must have 
been stable in dose and frequency for at least 4 weeks prior to 
randomization. 
Permitted concurrent ITP medications include oral 
corticosteroids, oral immunosuppressants, dapsone/danazol, 
fostamatinib, and/or oral TPO-RAs. 
Patients not receiving concurrent ITP therapy are also eligible for 
the trial if they have not received prior ITP therapy for at least 
4 weeks prior to baseline, and 6 months in case of prior ITP 
therapy with an anti-CD20 therapy (eg, rituximab). 
7. Women of childbearing potential must have a negative serum 
pregnancy test at the screening visit and a negative urine 
pregnancy test at baseline before trial medication (infusion) can 
be administered. Women are considered of childbearing potential 
unless they are postmenopausal (defined by continuous 
amenorrhea) for at least 1 year with a follicle-stimulating 
hormone (FSH) of >40 IU/L or are surgically sterilized (ie, 
women who had a hysterectomy, a bilateral salpingectomy, both 
ovaries surgically removed, or have a documented permanent 
female sterilization procedure including tubal ligation). Follicle-
stimulating hormone can be used to confirm postmenopausal 
status in amenorrheic patients not on hormonal replacement 
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8. Women of childbearing potential should use a highly effective or 
acceptable method of contraception during the trial and for 
90 days after the last administration of the IMP. They must be on 
a stable regimen, for at least 1 month: 
x 
combined (estrogen and progestogen containing) hormonal 
contraception associated with inhibition of ovulation 
o 
oral 
o 
intravaginal 
o 
transdermal 
x 
progestogen-only hormonal contraception associated with 
inhibition of ovulation: 
o 
oral 
o 
injectable 
o 
implantable 
x 
intrauterine device (IUD) 
x 
intrauterine hormone-releasing system 
x 
bilateral tubal occlusion 
x 
vasectomized partner (provided that the partner is the sole 
sexual partner of the trial participant and documented 
aspermia post procedure) 
x 
continuous abstinence from heterosexual sexual contact. 
Sexual abstinence is only allowable if it is the preferred and 
usual lifestyle of the patient. Periodic abstinence (calendar, 
symptothermal, post-ovulation methods) is not acceptable 
x 
male or female condom with or without spermicide 
x 
cap, diaphragm, or sponge with spermicide 
9. Non-sterilized male patients who are sexually active with a 
female partner of childbearing potential must use an acceptable 
method of contraception, ie, a condom. Male patients practicing 
true sexual abstinence (when this is in line with the preferred and 
usual lifestyle of the participant) can be included. Sterilized male 
patients who have had a vasectomy with documented aspermia 
post procedure can be included. In addition, male patients are not 
allowed to donate sperm during this period from signing of ICF, 
throughout the duration of the trial, and for 90 days after the last 
administration of IMP. 
 
Exclusion Criteria: 
1. ITP/thrombocytopenia associated with another condition, eg, 
lymphoma, chronic lymphocytic leukemia, viral infection, 
hepatitis, induced or alloimmune thrombocytopenia, or 
thrombocytopenia associated with myeloid dysplasia. 
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, subcutaneous, or intramuscular route) or 
plasmapheresis (PLEX), 4 weeks prior to randomization. 

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5. Use of anti-CD20 therapy (eg, rituximab) within 6 months prior 
to randomization. 
6. Use of romiplostim within 4 weeks prior to randomization. 
7. Undergone splenectomy less than 4 weeks prior to 
randomization. 
8. Use of any other investigational drug within 3 months or 
5 half lives of the drug (whichever is longer) prior to 
randomization. 
9. Use of monoclonal antibodies or crystallized fragment (Fc) 
fusion proteins, other than those previously indicated, within 
3 months prior to randomization. 
10. At the screening visit, clinically significant laboratory 
abnormalities as below: 
x 
Hemoglobin ≤9 g/dL. 
- OR - 
x 
International normalized ratio >1.5 or activated partial 
thromboplastin time >1.5×ULN. 
- OR - 
x 
Total IgG level <6 g/L. 
11. Patients who have a history of malignancy, including malignant 
thymoma, or myeloproliferative or lymphoproliferative 
disorders, unless deemed cured by adequate treatment with no 
evidence of recurrence for ≥3 years before screening. Patients 
with completely excised non-melanoma skin cancer (such as 
basal cell carcinoma or squamous cell carcinoma) or cervical 
carcinoma in situ would be permitted at any time. 
12. Uncontrolled hypertension, defined as a repeated elevated blood 
pressure exceeding 160 mmHg (systolic) and/or 100 mmHg 
(diastolic) despite appropriate treatments. 
13. History of any major thrombotic or embolic event (eg, 
myocardial infarction, stroke, pulmonary embolism, deep venous 
thrombosis) within 12 months prior to randomization. 
14. History of coagulopathy or hereditary thrombocytopenia or a 
family history of thrombocytopenia. 
15. History of a recent or planned major surgery (that involves major 
organs eg, brain, heart, lung, liver, bladder, or gastrointestinal 
tract) within 4 weeks of randomization. 
16. 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) 

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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 
17. 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 
patient at undue risk. 
18. Patients with known medical history of hypersensitivity to any of 
the ingredients of the IMP. 
19. Patients who previously participated in a clinical trial with 
efgartigimod and have received at least 1 administration of the 
IMP. 
20. Pregnant or lactating females. 
21. Employees of the investigator or trial center, with direct 
involvement in the proposed trial or other trials under the 
direction of that investigator or trial center, as well as family of 
the employees or the investigator. 
22. Patients who received a live/live-attenuated vaccine within 
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. 
Test Product, Dose, and Mode of 
Administration: 
Test product: efgartigimod (ARGX-113), a modified human IgG1 Fc 
fragment 
Dose: 10 mg/kg body weight at infusion visits. The maximum total 
dose per infusion for IMP is 1200 mg for patients with body 
weight ≥120 kg measured at infusion visits 
Mode of Administration: IV infusion over a period of 1 hour 
Comparator, Dose, and Mode of 
Administration: 
Matching placebo with same excipients as the test product but 
without the active substance and will be administered as an IV 
infusion over a period of 1 hour. 
Criteria for Evaluation: 
Primary Endpoint: 
x Proportion of patients with chronic ITP with a sustained platelet count response defined as achieving platelet 
counts of at least 50×109/L for at least 4 of the 6 visits between week 19 and 24 of the trial. 
Patients who discontinue treatment prior to visit 24 due to lack of efficacy (eg, more than 3 occurrences of rescue 
therapy) or due to an AE, and who have not achieved sustained platelet count response between week 19 and 24, 
are considered non-responders. Patients 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, are also considered non-responders. 

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Secondary Endpoints: 
Key Secondary Efficacy Endpoints Subject to Alpha Control: 
x 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. 
x Proportion of patients in the overall population (chronic and persistent ITP) with a sustained platelet count 
response defined as achieving platelet counts of at least 50×109/L for at least 4 of the 6 visits between week 19 
and 24 of the trial. 
x Incidence and severity of the WHO-classified bleeding events in the overall population. 
x Proportion of patients in the overall population achieving platelet counts of at least 50×109/L for at least 6 of the 
8 visits between week 17 and 24 of the trial. 
Other Secondary Endpoints Not Subject to Alpha Control: 
x Percentage of patients 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. 
x Extent of disease control defined as the number of cumulative weeks until week 12, with platelet counts of 
≥50×109/L. 
x Percentage of patients 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. 
x Mean change from baseline in platelet count at each visit. 
x Time to response defined as the time to achieve 2 consecutive platelet counts of ≥50×109/L. 
x Rate of receipt of rescue therapy (rescue per patient per month). 
x Proportion of patients for whom dose and/or frequency of concurrent ITP therapies have increased at week 12 
or later. 
x The number of cumulative weeks over the planned 24-week treatment period with platelet counts of ≥30×109/L 
and at least 20×109/L above baseline. 
x 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 at least 20×109/L above baseline. 
x Change from baseline in PRO (FACIT-Fatigue, Fact-Th6) and QoL (SF-36) at planned visits. 
x Incidence of anti-drug antibodies (ADA) to efgartigimod. 
x Pharmacokinetic parameters of efgartigimod: maximum observed serum concentration (Cmax) and serum 
concentration observed predose (Ctrough). 
x Pharmacodynamics markers: total IgG, IgG isotypes (IgG1, IgG2, IgG3, IgG4), antiplatelet antibody levels. 
Safety Evaluation 
x Evaluate the incidence and severity of AEs, AESIs, and serious AEs (SAEs). 
x Evaluate vital signs, electrocardiogram (ECG), and laboratory assessments. 
Exploratory Endpoint 
x 
. 
Statistical Methods and Plan 
All patients starting at least 1 infusion of efgartigimod or placebo will be assessed for safety according to their 
actual treatment. 
The efficacy analysis will be performed on the full analysis set (FAS) or the subset of patients in the FAS with 
chronic ITP; supportive analyses will be conducted in the per protocol population. The safety analysis will be 
performed on the safety analysis set. 

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The PK analysis set will include all patients from the safety analysis set who have at least 1 serum post-dose PK 
measurement. 
Efficacy: 
The efficacy analysis will be performed on the FAS or the subset of patients in the FAS with chronic ITP (baseline 
primary efficacy observation) and analyzed with intent-to-treat principle (ie, patients will be analyzed according to 
their planned treatment irrespective of the treatment actually received). 
Sample Size 
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 patients with chronic 
ITP receiving placebo and for patients with chronic ITP receiving efgartigimod, respectively. 
The response rate of placebo patients with chronic ITP reaching the primary endpoint is expected to be 
%, while 
for efgartigimod patients with chronic ITP a response rate of 
% is expected (ie, π1 = 
and π2 = 
). Given 
these assumptions, a total of N = 117 patients with chronic ITP randomized will ensure a power of at least 90% to 
reject the null hypothesis at a 1-sided significance level α of 0.025. 
Primary Endpoint 
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 two-sided p-value. In addition, an adjusted 
difference of the proportions with its 95% CI will be provided. 
Key Secondary Endpoints 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 patient this 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 2-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 α=0.05. An 
estimate of the location shift will be provided, along with the associated 95% confidence interval. 
The key secondary endpoints on proportion of patients in the overall population with a sustained platelet count 
response and on proportion of patients in the overall population achieving platelet counts of at least 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 patient (assessed using the WHO bleeding scale; where WHO scale ≥1 at any visit 
is considered a new bleeding event) will be analyzed using a zero-inflated negative binomial model. This model will 
account for the large expected number of patients with zero bleeding events. It is a mixture model consisting of 
2 components: a negative binomial count model and a binary model for predicting excess zeros. The model will 
consist of the number of events as the dependent variable and of randomized treatment, the stratification variables 
(history of splenectomy; receiving concurrent ITP therapies at baseline), and baseline platelet count as independent 
variables. An offset term will be used to allow for patient exposure. Both the count model, using the log link, and 
the binary model, using the logit link, will contain the same independent variables. The probability of no bleeding 
will be estimated for each randomized treatment group. A Wald test will be used to test the null hypothesis that the 
log of the bleeding rate ratio on placebo and efgartigimod is equal to zero against the alternative that it is different 
from zero. The rate of bleeding over 24 weeks on placebo and efgartigimod will be provided, along with the rate 

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ratio, 95% 2-sided CI, and 2-sided p-value. 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 pre-
defined hierarchy resulted in a p-value <0.05. The order in the testing hierarchy of the key secondary endpoints is 
as follows: 
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 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 of the trial. 
3. The incidence and severity of the WHO-classified bleeding events in the overall population. 
4. The proportion of patients 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. 
Other Secondary Endpoints Not Subject to Alpha Control 
The mean changes from baseline in platelet count levels at planned time points and the mean changes from baseline 
in PRO 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, history of 
splenectomy (yes vs. no), and receiving concurrent ITP therapies at baseline (yes vs. no). Least square (LS) means 
for placebo and efgartigimod will be provided, along with the difference in LS means, 95% 2-sided CI, and 2-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 vs. placebo will be provided, along with the associated 
95% 2-sided CI and 2-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 at least 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 at least 20×109/L 
above baseline within the group of patients with a baseline platelet count of <15×109/L will also be analyzed as 
described for the key secondary endpoint. 
Pharmacodynamics, Pharmacokinetics, and Immunogenicity 
Descriptive statistics will be provided for PD parameters (total IgG and subtypes, and antiplatelet antibodies), and 
ADA. Efgartigimod serum concentration data will be summarized. 
Safety 
Incidence and severity of AEs, AESIs, and SAEs will be summarized descriptively. Laboratory parameters, vital signs, 
and ECG data will also be analyzed descriptively. 
Exploratory Endpoint 
Descriptive statistics will be presented for 
. The analysis of 
 will be 
performed at a later stage than the analyses of the other endpoints and will be described in a separate report. 

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Figure 1 
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial to Evaluate the Efficacy and Safety of Efgartigimod (ARGX-113) 10 mg/kg IV in Adult 
Patients With Primary Immune Thrombocytopenia 
 
 
 

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TABLE OF CONTENTS 
SIGNATURE OF SPONSOR ............................................................................ 3 
SIGNATURE OF INVESTIGATOR ................................................................ 4 
DOCUMENT HISTORY ................................................................................... 5 
SUMMARY OF CHANGES .............................................................................. 6 
SYNOPSIS ......................................................................................................... 11 
TABLE OF CONTENTS ................................................................................. 26 
LIST OF TABLES ............................................................................................ 30 
LIST OF FIGURES .......................................................................................... 30 
LIST OF APPENDICES .................................................................................. 30 
LIST OF ABBREVIATIONS .......................................................................... 31 
DEFINITION OF TERMS .............................................................................. 33 
1. 
INTRODUCTION .................................................................................... 36 
 
Background Information ....................................................................................36 
 
Benefit-Risk Assessment .....................................................................................37 
 
Trial Rationale.....................................................................................................38 
2. 
TRIAL OBJECTIVES ............................................................................. 40 
 
Primary Objective ...............................................................................................40 
 
Secondary Objectives ..........................................................................................40 
 
Exploratory Objective ........................................................................................40 
3. 
TRIAL ENDPOINTS ............................................................................... 41 
 
Primary Endpoint ...............................................................................................41 
 
Secondary Endpoints ..........................................................................................41 
 
Exploratory Endpoint .........................................................................................42 
4. 
INVESTIGATIONAL PLAN .................................................................. 43 
 
Summary of Trial Design ...................................................................................43 

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Discussion of Trial Design ..................................................................................47 
 
Selection of Trial Population ..............................................................................48 
4.3.1. 
Inclusion Criteria ...................................................................................................... 48 
4.3.2. 
Exclusion Criteria ..................................................................................................... 49 
 
Early Discontinuation .........................................................................................51 
4.4.1. 
Early Discontinuation From Trial ............................................................................ 51 
4.4.2. 
Early Discontinuation From Treatment .................................................................... 52 
 
Temporary Withholding Treatment .................................................................53 
 
Protocol Deviations .............................................................................................53 
 
Screen Failures, Rescreening, and Retesting ....................................................53 
 
Early Termination of Trial or Site ....................................................................54 
 
End-of-Trial Definition .......................................................................................54 
5. 
TRIAL PROCEDURES ........................................................................... 55 
 
Informed Consent ...............................................................................................55 
 
Screening ..............................................................................................................55 
 
Randomization ....................................................................................................56 
 
Treatment Period ................................................................................................56 
5.4.1. 
Screening and Treatment .......................................................................................... 56 
5.4.2. 
Rollover to the Open-Label Extension Trial (ARGX-113-1803)............................. 57 
 
Follow-up Period .................................................................................................58 
 
Unscheduled Visit ................................................................................................58 
6. 
TRIAL TREATMENT ............................................................................. 59 
 
Treatment Administered ....................................................................................59 
 
Identity of Investigational Medicinal Product..................................................59 
 
Packaging and Labeling .....................................................................................60 
 
Storage of Investigational Medicinal Products ................................................60 
 
Method of Assigning Patients to Treatment Group .........................................60 
 
Dosing Administration for Each Patient ...........................................................60 
 
Blinding ................................................................................................................60 
6.7.1. 
Emergency Unblinding ............................................................................................ 61 

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Prior Treatments and Concomitant Medications ............................................61 
6.8.1. 
Concurrent ITP Therapy........................................................................................... 61 
6.8.2. 
Prohibited Medications and Therapy Prior to Randomization ................................. 62 
6.8.3. 
Prohibited Medications and Therapy During the Trial ............................................ 63 
6.8.4. 
Rescue Therapy ........................................................................................................ 63 
 
Medical Care of Patients After End-of-Treatment or Early Discontinuation
 ...............................................................................................................................64 
 
Treatment Compliance .......................................................................................64 
 
Handling Missed Doses of the Investigational Medicinal Product .................65 
 
Accountability of Investigational Medicinal Product ......................................65 
 
Storage of Blood Samples in the Trial ...............................................................65 
7. 
TRIAL ASSESSMENTS .......................................................................... 66 
 
Demography ........................................................................................................66 
 
Efficacy .................................................................................................................66 
7.2.1. 
Platelet Count ........................................................................................................... 66 
7.2.2. 
General Bleeding Assessment .................................................................................. 66 
 
Safety ....................................................................................................................67 
7.3.1. 
Adverse Events ......................................................................................................... 67 
7.3.2. 
Clinical Laboratory Evaluations ............................................................................... 75 
7.3.3. 
Vital Signs, Physical Examination, and Electrocardiogram ..................................... 76 
7.3.4. 
Medical and Surgical History ................................................................................... 76 
7.3.5. 
Data Safety Monitoring Board ................................................................................. 77 
7.3.6. 
Visit Reminder/Patient ID Card ............................................................................... 77 
 
Pharmacokinetics ................................................................................................77 
 
Pharmacodynamics .............................................................................................77 
 
Anti-Drug Antibodies .........................................................................................78 
 
 ..........................................................................................78 
 
Quality-of-Life and Patient-Reported Outcomes .............................................78 
8. 
STATISTICS ............................................................................................. 80 
 
Determinations of Sample Size ..........................................................................80 

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Analysis Populations ...........................................................................................80 
 
Patient Disposition, Characteristics, and Concomitant Medication ..............81 
 
Statistical Methods ..............................................................................................81 
8.4.1. 
Primary Endpoint Analysis ...................................................................................... 82 
8.4.2. 
Key Secondary Endpoint Analyses Subject to Alpha Control ................................. 83 
8.4.3. 
Other Secondary Endpoint Analyses Not Subject to Alpha Control ........................ 85 
8.4.4. 
Pharmacodynamics, Pharmacokinetics, and Immunogenicity ................................. 85 
8.4.5. 
Safety........................................................................................................................ 86 
8.4.6. 
Exploratory Endpoint Analysis ................................................................................ 86 
 
Interim Analyses .................................................................................................86 
9. 
QUALITY CONTROL AND QUALITY ASSURANCE ..................... 87 
 
Investigator’s Responsibility ..............................................................................87 
 
Quality Control ...................................................................................................87 
 
Monitoring ...........................................................................................................88 
 
Data Management ...............................................................................................88 
 
Quality Assurance Audit ....................................................................................89 
10. ETHICS ..................................................................................................... 91 
 
Institutional Review Board or Independent Ethics Committee......................91 
 
Ethical Conduct of the Trial ..............................................................................91 
 
Patient Information and Informed Consent .....................................................91 
 
Patient Data Protection ......................................................................................92 
11. TRIAL ADMINISTRATION .................................................................. 93 
 
Data Handling and Record Keeping .................................................................93 
 
Direct Access to Source Data/Documents .........................................................93 
 
Investigator Information ....................................................................................94 
11.3.1. 
Investigator Obligations ........................................................................................... 94 
11.3.2. 
Protocol Signatures .................................................................................................. 94 
11.3.3. 
Publication Policy .................................................................................................... 94 
11.3.4. 
Financing and Insurance........................................................................................... 95 
12. REFERENCES.......................................................................................... 96 

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13. APPENDICES ........................................................................................... 97 
 
LIST OF TABLES 
Table 1 
Schedule of Assessments ..................................................................................... 23 
Table 2 
Schedule of Assessments ................................................................................... 110 
 
LIST OF FIGURES 
Figure 1 
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial to 
Evaluate the Efficacy and Safety of Efgartigimod (ARGX-113) 10 mg/kg IV in 
Adult Patients With Primary Immune Thrombocytopenia .................................. 25 
Figure 2 
Decision Tree for the Treatment of Patients ...................................................... 104 
 
LIST OF APPENDICES 
Appendix 1 Laboratory Evaluations ........................................................................................ 97 
Appendix 2 Administrative Structure ...................................................................................... 98 
Appendix 3 World Health Organization Bleeding Scale ....................................................... 100 
Appendix 4 Possible Adaptations of Trial Protocol During COVID-19 Pandemic .............. 102 
Appendix 5 Protocol Amendment History ............................................................................ 112 

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LIST OF ABBREVIATIONS 
ADA 
anti-drug antibodies 
ADR 
adverse drug reaction 
AE 
adverse event 
AESI 
adverse event of special interest 
AIDS 
acquired immunodeficiency syndrome 
ALT 
alanine aminotransferase 
ASH 
American Society of Hematology 
CI 
confidence interval 
CIOMS 
Council for International Organizations of Medical Sciences 
CRO 
contract research organization 
CTCAE 
common terminology criteria for adverse events 
CTR 
clinical trial report 
DSMB 
data safety monitoring board 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
FAS 
full analysis set 
Fc 
crystallized fragment 
FcRn 
neonatal crystallized fragment receptor 
FSH 
follicle-stimulating hormone 
GCP 
good clinical practice 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use 
ID 
identification number 
IEC 
Independent Ethics Committee 
Ig 
immunoglobulin 
IMP 
investigational medicinal product 
IND 
investigational new drug 
 
 
 
 
IRB 
Institutional Review Board 
IRT 
interactive response technology 
ITP 
immune thrombocytopenia 
IUD 
intrauterine device 

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IV 
intravenous 
IVIg 
immunoglobulins given intravenously 
LS 
least square 
MG 
myasthenia gravis 
NCI 
National Cancer Institute 
OR 
odds ratio 
PD 
pharmacodynamic 
PK 
pharmacokinetics 
PLEX 
plasmapheresis 
PP 
per protocol 
PRO 
patient-reported outcomes 
q2w 
biweekly/every other week 
QoL 
quality-of-life 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SC 
subcutaneous 
SoA 
schedule of assessments 
SOP 
standard operating procedure 
TEAE 
treatment-emergent adverse event 
TPO-RA 
thrombopoietin receptor agonist 
US 
United States 
WHO 
World Health Organization 
WHO-DD 
World Health Organization Drug Dictionary 

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DEFINITION OF TERMS 
Blinding: 
A procedure in which 1 or more parties to the trial are kept 
unaware of the treatment assignment in order to reduce the 
risk of biased trial outcomes. The level of blinding is 
maintained throughout the conduct of the trial, and only when 
the data are cleaned to an acceptable level of quality will 
appropriate personnel be unblinded or when required in case 
of a (serious) adverse event ([S]AE). In a double-blind trial, 
the patient, the investigator, site staff, and sponsor staff who 
are involved in the treatment or clinical evaluation of the 
patients and the review or analysis of data are all unaware of 
the treatment assignment. 
Childbearing potential: 
Women of childbearing potential are defined as all female 
participants unless they are postmenopausal (defined by 
continuous amenorrhea) for at least 1 year with a follicle-
stimulating hormone (FSH) of >40 IU/L or are surgically 
sterile (ie, who had a hysterectomy, a bilateral salpingectomy, 
a bilateral oophorectomy, or have current documented tubal 
ligation or any other permanent female sterilization 
procedure). Determination of FSH levels can be used to 
confirm postmenopausal status in amenorrheic patients not on 
hormonal replacement therapy. 
Council for International 
Organizations of Medical 
Sciences: 
The Council for International Organizations of Medical 
Sciences (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. 

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Contract Research 
Organization: 
A person, or a group of persons (commercial, academic, or 
other), who as an independent contractor with argenx BVBA, 
assume(s) 1 or more obligations of argenx BVBA, 
eg, development of a protocol, selection and/or monitoring of 
investigators, evaluation of reports, preparation of materials to 
be submitted to regulatory authorities. 
Database lock: 
An action taken to prevent further changes to a trial database. 
A database is locked after review, query resolution, data 
cleaning and determination that it is ready for analysis. 
Data Safety Monitoring 
Board: 
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 
recommendation to the sponsor concerning the continuation, 
modification or termination of the trial. 
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 patients are protected. (International 
Council for Harmonisation of Technical Requirements for 
Human Use [ICH] E6). 
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), 
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 

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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 informed consent form (ICF). 
International Council for 
Harmonisation: 
The ICH is a project that brings together the regulatory 
authorities of Europe, Japan, and the United States (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 in 
order 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 subject. 

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1. INTRODUCTION 
 
Background Information 
Efgartigimod (ARGX-113) is a modified human immunoglobulin (Ig) G1-derived crystallized 
fragment (Fc) of the za allotype 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 the so-called ABDEG™ technology 
(ABDEG™ = antibody that enhances IgG degradation)1 to increase its affinity for FcRn at both 
physiological and acidic pH. The increased affinity for FcRn of efgartigimod at both acidic 
and physiological pH results in a blockage of FcRn-mediated recycling of IgGs. 
Given the essential role of the FcRn receptor 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. 
The safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of intravenous 
(IV) administrations of efgartigimod have been investigated in a first-in-human study in 
healthy adult subjects. A second study in healthy adult subjects investigated the bioavailability, 
safety, tolerability, immunogenicity, PK, and PD of a subcutaneous (SC) administration of 
efgartigimod and evaluated the reduction of the IV infusion time from 2 hours to 1 hour. 
Phase 2 trials in immune thrombocytopenia (ITP) and myasthenia gravis (MG) have indicated 
that efgartigimod administered by IV infusion 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 ITP and MG patients,2 
separately (see Section 1.3). Additionally, the safety and tolerability of efgartigimod is 
currently being evaluated for the treatment of patients with pemphigus in a phase 2 trial. 
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 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 age5. Adult ITP can persist for years. Even with best available care, patients 
rarely achieve long-term remission, and often require multiple treatment options.6 ITP 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 symptoms 
including evidence of bleeding in the skin and mucosa, and risk of serious intracranial and 

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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,6 as well as impaired quality-of-life (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 immunoglobulins given intravenously 
(IVIg) and anti-D. Second-line treatments include broad immunosuppressants and 
thrombopoietin receptor agonists (TPO-RAs). There is limited evidence to guide the use of 
these treatments, as described in the American Society of Hematology (ASH) guidelines.10 
There is no 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 develop 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 seen the central role of IgG 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. 
 
Benefit-Risk Assessment 
Efgartigimod has been shown to effectively reduce IgG antibodies in several clinical trials, 
including healthy volunteers, patients with MG, and with ITP. 
More specifically, a phase 2 trial (ARGX-113-1603) in patients with ITP enrolled a patient 
population who was predominantly refractory to previous lines of ITP therapy, with the 
majority of patients having long-standing disease, prior ITP treatment exposure and 
approximately half with baseline platelet count of <15×109/L. 
Efgartigimod resulted in a rapid and marked reduction of IgG antibodies (maximum mean 
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Treatment with efgartigimod, whether 5 mg/kg or 10 mg/kg, was associated with an increase 
in platelet counts in more patients than occurred in the placebo group, with greater numerical 
separation from placebo as the platelet count threshold stringency was increased. Additional 
post hoc analyses further supported these observations, showing a longer duration of clinically 
meaningful effect and statistically significantly more active-treated patients achieving a 
platelet count of ≥50×109/L for more than 10 cumulative days compared to the placebo group. 
In each of the subgroups of patients based on ITP classification (newly diagnosed, persistent, 
or chronic ITP) or those with or without historical or concomitant use of TPO-RA, there were 
examples of efgartigimod-treated patients with an increase in platelet count. 
In the open-label treatment period patients received 4 weekly infusions of efgartigimod 
10 mg/kg, either as first exposure in patients who previously received placebo or retreatment 
with efgartigimod. In this part of the trial, the majority of patients (58%) had improved platelet 
counts. 
Efgartigimod is under investigation in MG, another disease driven by IgG autoantibodies. In a 
phase 2 trial ARGX-113-1602, 4 weekly IV infusions of 10 mg/kg efgartigimod led to 
statistically significant improvements in clinical scales and were well tolerated. A phase 3 trial 
ARGX-113-1704 and accompanying open-label extension trial ARGX-113-1705 are ongoing 
in this indication. 
In clinical trials to date, efgartigimod has been well tolerated in healthy adult subjects and 
patients with MG and ITP, separately: the majority of treatment-emergent AEs (TEAEs) were 
considered to be mild (grade 1) in severity. In the completed phase 1 trials ARGX-113-1501, 
ARGX-113-1702, and ARGX-113-1901 in healthy volunteers, and in the phase 2 trial 
ARGX-113-1602 in patients with MG, no grade ≥3 TEAEs were reported and no TEAE led to 
discontinuation. In the phase 2 trial ARGX-113-1603 in patients with ITP, 1 TEAE with 
grade 4 was reported (thrombocytopenia), considered unrelated to treatment, and led to 
treatment discontinuation. 
No clinically significant changes in vital signs and/or electrocardiogram (ECG) findings have 
been observed in clinical trials to date. 
Safety for use during pregnancy has not been established. Therefore, efgartigimod should not 
be administered to pregnant or lactating women. 
Please refer to the current Investigator’s Brochure for more information regarding the 
preclinical and clinical trials, and the potential risks and benefits of efgartigimod. In summary, 
the favorable balance between risks and anticipated efficacy/benefits supports the use of 
efgartigimod in clinical development. 
 
Trial Rationale 
The proposed phase 3 trial aims to establish the efficacy, safety, and impact on patient-reported 
outcomes (PRO) of efgartigimod administered as IV infusions in adult patients with primary 

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ITP who have had an insufficient response or who are intolerant to existing ITP treatments, 
evidenced by a platelet count that is below the clinically accepted level for intervention 
(<30×10⁹/L). 
Patients classified as having persistent ITP (between 3 and 12 months since diagnosis) and 
chronic ITP (greater than 12 months since diagnosis) will be recruited. At the start of the trial, 
the patients are either on concurrent ITP treatment(s) and have received at least 1 prior therapy 
for ITP in the past, or the patients are not on treatment for ITP but have received at least 2 prior 
treatments for ITP. 
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, 
patients with and without concurrent ITP therapy will be enrolled. Experience to date of 
efgartigimod treatment in combination with steroids and immunosuppressants in phase 2 ITP 
and MG trials has not raised any safety concerns with these combinations of treatments. 
This trial will utilize an IV dosing schedule aiming to maximize PD effect (ie, reduction of 
autoantibody levels) and seeking to result in an improvement in platelet count. In patients who 
achieve a prespecified threshold of maintained platelet count improvement, the frequency of 
efgartigimod 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 5.4.1 will be applied. The aim is to achieve the maximum possible proportion of 
patients with a platelet count improvement and then assess whether this can be sustained in the 
last 5 weeks of trial treatment. 
Based on the results of the phase 1 trial in healthy adult subjects, the phase 2 trial in patients 
with ITP, as well as the PK/PD modeling analysis, a dose of 10 mg/kg efgartigimod was 
selected as it is considered safe and well tolerated, achieved consistently a close to maximal 
IgG reduction (ie, 65-70%), and resulted in a clinical response (eg, increase in platelet count) 
in a significant proportion of patients. This dose is also being utilized in the ongoing 
phase 3 trials in MG (see Section 1.2). 
A continuous dosing regimen of weekly or biweekly (q2w) IV infusions of 10 mg/kg 
efgartigimod is anticipated to be safe. In a long-term toxicity trial (26-weeks with 8-weeks 
recovery period), cynomolgus monkeys were dosed with weekly efgartigimod infusions of up 
to 100 mg/kg. The no observed adverse effect level was set at the highest administered dose of 
100 mg/kg. The exposures achieved in this toxicity study were between 35.5 (female animals) 
and 40.8 (male animals) times the simulated area under the curve values in ITP patients using 
the clinical dose of 10 mg/kg. 

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2. TRIAL OBJECTIVES 
 
Primary Objective 
x 
To evaluate the efficacy of efgartigimod compared to placebo in achieving a sustained 
platelet count response in patients with primary chronic ITP, with a sustained platelet 
count response defined as platelet counts of at least 50×109/L for at least 4 of the 6 visits 
between week 19 and 24 of the trial*. 
 
Secondary Objectives 
x 
To evaluate the efficacy of efgartigimod compared to placebo in overall platelet count 
response. 
x 
To evaluate the safety and tolerability of efgartigimod administered IV weekly or q2w. 
x 
To evaluate the incidence and severity of bleeding events while receiving treatment with 
efgartigimod compared to placebo. 
x 
To evaluate the use of rescue treatment and changes in concurrent ITP therapy while 
receiving treatment with efgartigimod compared to placebo. 
x 
To evaluate the effects of efgartigimod treatment on QoL measures and PRO compared to 
placebo. 
x 
To assess the immunogenicity of efgartigimod. 
x 
To assess the PK of efgartigimod. 
x 
To assess the PD effects of efgartigimod. 
 
Exploratory Objective 
x 
. 
 
 “week” instead of “visits” are used in the endpoints, ensuring that the platelet count of the EoT visit is 
regarded as week 24 platelet count. (eg, platelet count after 19 weeks of treatment corresponds with platelet 
count of visit 20). 

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3. TRIAL ENDPOINTS 
 
Primary Endpoint 
x 
Proportion of patients with chronic ITP with a sustained platelet count response defined 
as achieving platelet counts of at least 50×109/L for at least 4 of the 6 visits between 
week 19 and 24 of the trial. 
Patients who discontinue treatment prior to visit 24 due to lack of efficacy (eg, more than 
3 occurrences of rescue therapy) or due to an AE, and who have not achieved sustained platelet 
count response between week 19 and 24, are considered non-responders. Patients 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, are also considered non-responders. 
 
Secondary Endpoints 
Key Secondary Efficacy Endpoints Subject to Alpha Control: 
x 
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. 
x 
Proportion of patients in the overall population (chronic and persistent ITP) with a 
sustained platelet count response defined as achieving platelet counts of at least 50×109/L 
for at least 4 of the 6 visits between week 19 and 24 of the trial. 
x 
Incidence and severity of the WHO-classified bleeding events in the overall population. 
x 
Proportion of patients in the overall population achieving platelet counts of at least 
50×109/L for at least 6 of the 8 visits between week 17 and 24 of the trial. 
Other Secondary Endpoints Not Subject to Alpha Control: 
x 
Percentage of patients 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. 
x 
Extent of disease control defined as the number of cumulative weeks until week 12, with 
platelet counts of ≥50×109/L. 
x 
Percentage of patients 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. 
x 
Mean change from baseline in platelet count at each visit. 
x 
Time to response defined as the time to achieve 2 consecutive platelet counts of 
≥50×109/L. 
x 
Rate of receipt of rescue therapy (rescue per patient per month). 

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x 
Proportion of patients for whom dose and/or frequency of concurrent ITP therapies have 
increased at week 12 or later. 
x 
The number of cumulative weeks over the planned 24-week treatment period with 
platelet counts ≥30×109/L and at least 20×109/L above baseline. 
x 
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 at least 
20×109/L above baseline. 
x 
Change from baseline in PRO (FACIT-Fatigue, Fact-Th6) and QoL (SF-36) at planned 
visits. 
x 
Incidence of anti-drug antibodies (ADA) to efgartigimod. 
x 
Pharmacokinetic parameters of efgartigimod: maximum observed serum concentration 
(Cmax) and serum concentration observed predose (Ctrough). 
x 
Pharmacodynamics markers: Total IgG, IgG isotypes (IgG1, IgG2, IgG3, IgG4), 
antiplatelet antibody levels. 
Safety Evaluation 
x 
Evaluate the incidence and severity of AEs, AESIs, and SAEs. 
x 
Evaluate vital signs, ECG, and laboratory assessments. 
 
Exploratory Endpoint 
x 
 

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4. INVESTIGATIONAL PLAN 
 
Summary of Trial Design 
DESCRIPTION 
This is a phase 3, multicenter, randomized, double-blinded, placebo-controlled, parallel-
group, up to 31-week trial to evaluate the efficacy, safety, and impact on QoL of 
efgartigimod 10 mg/kg IV treatment in adult patients with primary ITP. 
The total maximum trial duration per patient is up to 31 weeks: 
x 
a screening period of up to 2 weeks 
x 
a treatment period of 24 weeks where all patients will receive IV infusions of 
efgartigimod 10 mg/kg or placebo 
x 
End-of-Treatment visit 1 week after visit 24 
x 
a follow-up period of 4 weeks 
The target population are adult patients with persistent or chronic primary ITP, having an 
average platelet count of <30×109/L, and at the start of the trial being on concurrent ITP 
treatment(s) and having received at least 1 prior therapy for ITP in the past or not being on 
treatment for ITP but having received at least 2 prior treatments for ITP. If patients are 
receiving concurrent ITP therapies at baseline, these therapies should have been maintained 
at a stable dose and dosing frequency for 4 weeks prior to randomization. As of week 12, the 
start or an increase in the dose and/or schedule of permitted concurrent ITP therapy is 
allowed for patients who have an “insufficient response” (ie, no platelet count of ≥30×109/L 
in any of the visits during the last 4 weeks). These patients will be considered as “non-
responders” for the primary endpoint analysis. 
After confirmation of eligibility, the patients enter a 24-week treatment period and will be 
randomized to receive 10 mg/kg IV of efgartigimod or placebo, weekly from visits 1 to 4 and 
then from visits 5 to 16 either weekly or q2w, adjusted according to their platelet counts. 
From visits 17 to 24, patients will be fixed on the dosing schedule they were receiving at 
visit 16 or at the last visit at which IMP was administered (ie, either weekly or q2w). 
Assessment of the dosing regimen as described in Section 5.4.1 will be applied. 
Patients completing the 24-week trial period will perform the End-of-Treatment visit and can 
enter the open-label extension trial (ARGX-113-1803) to receive efgartigimod 10 mg/kg IV. 
The platelet counts from the ARGX-113-1801 trial will be taken into account to assess the 
dosing frequency in ARGX-113-1803. 
Patients who complete the 24-week trial period but who do not enter the open-label extension 
trial ARGX-113-1803, or patients who discontinue the trial early, with the exception of 

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patients who withdraw their consent, will be followed for 4 weeks for ongoing safety and 
efficacy monitoring. 
For patients who discontinue the trial early, all the assessments listed for the 
Early Discontinuation visit as specified in the schedule of assessments (SoA, Table 1), will 
be performed. 
SAMPLE SIZE AND STRATIFICATION 
Approximately 117 patients with chronic ITP and up to 39 patients with persistent ITP will 
be randomized in a 2:1 ratio to receive efgartigimod or placebo, respectively. Recruitment 
will end when 117 patients with chronic ITP have been randomized. 
Patients will be stratified according to the following factors: 
x 
History of splenectomy (yes vs. no) 
x 
Receiving concurrent ITP therapies at baseline (yes vs. no) 
SCREENING AND TREATMENT 
During the screening period (up to 2 weeks) the patient’s eligibility for trial participation will 
be evaluated. 
All eligible patients will be randomized to receive IV infusions of either efgartigimod 
10 mg/kg body weight or matching placebo throughout the trial. 
All patients will initially receive weekly IV infusions from visits 1 to 4. 
Based on the platelet counts as of visit 2, the dosing frequency can be altered from 
visits 5 to 16 according to the following rules (the change in dosing frequency will occur at 
the current visit): 
x Reduce from weekly to q2w in patients achieving platelet counts of ≥100×10⁹/L for 3 
out of 4 consecutive visits (the fourth visit being the current visit), and have a platelet 
count of ≥100×10⁹/L at the last of these 4 visits 
– OR – 
3 consecutive visits 
x Increase from q2w to weekly in patients whose platelet counts drop below 100×10⁹/L 
on 2 consecutive visits 
– OR – 
<30×10⁹/L at 1 visit 
– OR – 
in patients who receive rescue therapy (see Section 6.8.4) 

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x Temporary withholding treatment 
o for the reasons described in Section 4.5, IMP should be reintroduced once the 
investigator considers the undue risk to the patient has passed 
o in patients with platelet counts greater than 400×109/L, IMP should be 
resumed at the 10 mg/kg q2w dose when the platelet count falls to fewer than 
150×109/L 
x Post-baseline platelet count can be performed within 1 day of the next procedure as 
per the SoA (both dosing and non-dosing visit), allowing the results to be 
incorporated into the criteria above. 
From visits 17 to 24, the dosing frequency is fixed for each individual patient (ie, either 
weekly or q2w regimen), based on the regimen the patient was receiving at visit 16 or at the 
last visit at which IMP was administered. 
Exceptions to the fixed dosing frequency are: 
- 
Continued weekly dosing for patients requiring rescue therapy. 
- 
Continued q2w dosing for patients resuming IMP when the platelet count falls to 
fewer than 150×109/L after having had platelet counts greater than 400×109/L. 
ROLLOVER TO THE OPEN-LABEL EXTENSION TRIAL (ARGX-113-1803) 
Patients who complete the 24-week trial period have the possibility to enter the open-label 
extension trial (ARGX-113-1803) to receive efgartigimod 10 mg/kg IV. The platelet counts 
from the ARGX-113-1801 trial will be taken into account to assess the dosing frequency in 
ARGX-113-1803. 
CONCURRENT ITP THERAPY 
Patients 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 oral corticosteroids, oral 
immunosuppressants, dapsone/danazol, fostamatinib and/or oral TPO-RAs (inclusion 
criterion n°6, Section 4.3.1). Dose and frequency of permitted concurrent ITP therapies 
should remain unchanged during the trial. 
As of week 12, the start or an increase in the dose and/or schedule of permitted concurrent 
ITP therapy is allowed for patients who have an “insufficient response” (ie, no platelet count 
of ≥30×109/L in any of the visits during the last 4 weeks). These patients will be considered 
as “non-responders” 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. 
Exceptions are patients who are receiving concurrent treatment with oral TPO-RAs in whom 
dose changes are permitted at label-defined platelet thresholds, and patients who are 
receiving concurrent treatment with fostamatinib, in whom dose changes or stopping of 
treatment is allowed in label-defined conditions. 

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All changes or discontinuations in concurrent ITP therapy (type, dose, frequency, date of 
discontinuation and resumption) should be appropriately indicated in the electronic case 
report form (eCRF). The patient does not need to be discontinued from the trial. 
Patients not receiving concurrent ITP therapy are also eligible for the trial. 
RESCUE THERAPY 
“Rescue therapy” is defined as an occurrence where the patient 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 
patient. The start date/time of the occurrence is the start of the administration of the first 
rescue treatment. 
Rescue therapy is allowed post-baseline during the 24-week trial period for patients with a 
platelet count of <30×10⁹/L and 1 of the following: 
x 
an immediate risk of bleeding or a clinically significant bleeding or wet purpura 
x 
requirement for urgent or emergent surgery (elective surgeries must be postponed until 
trial completion) 
The following rescue therapies are permitted: 
x 
IV methylprednisolone up to 1 g/day×1-3 days, or oral dexamethasone up to 
40 mg/day×1-3 days, or oral prednisone up to 1 mg/kg/day×1-2 days 
x 
IVIg: up to 1 g/kg/day×1-2 days 
x 
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 patients 
x 
platelet transfusions 
It is encouraged to inform the sponsor’s designated contract research organization (CRO) 
medical monitor prior to initiating any rescue therapy. 
In the event of rescue with IVIg or IV anti-D: 
x 
If given at a visit where the investigational medicinal product (IMP) was due to be 
administered, the IMP should be withheld and administered at the next visit. 
For rescue therapy with methylprednisolone, dexamethasone, prednisone, or platelet 
transfusions: 
x 
Administration of the IMP continues during rescue therapy. 
Patients who were receiving q2w dosing at the time of rescue therapy will have the IMP 
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For patients who receive rescue therapy, the platelet counts for 4 weeks after the first day of 
rescue treatment will not be used (ie, are censored) to assess whether or not the patient can 
transition to q2w treatment. 
Patients requiring more than 3 occurrences of rescue therapy will discontinue from IMP. 
EARLY DISCONTINUATION FROM THE TRIAL 
Any patient prematurely discontinuing the trial should perform the assessments listed for the 
Early Discontinuation visit as mentioned in the SoA (Table 1). 
TRIAL END 
End-of-Trial is defined as last patient last visit in the ARGX-113-1801 trial. 
 
Discussion of Trial Design 
In the current trial, efgartigimod or placebo will be administered in patients with primary 
ITP, with the aim to evaluate the efficacy, safety, and impact on QoL of efgartigimod versus 
placebo. 
This trial is designed as a randomized, double-blinded trial to evaluate the effect of 
efgartigimod and placebo administered as an IV infusion. The trial consists of a treatment 
period where all patients will initially receive weekly IV infusions from visits 1 to 4. From 
visits 5 to 16, the dosing frequency can be altered (ie, increased or decreased) according to 
specified rules. 
The primary endpoint in this trial is the proportion of patients with chronic ITP that have a 
sustained platelet count response defined as achieving platelet counts of at least 50×109/L for 
at least 4 of the 6 visits between week 19 and 24 of the trial. Patients who discontinue 
treatment prior to visit 24 due to lack of efficacy (eg, more than 3 occurrences of rescue 
therapy) or due to an AE, and who have not achieved sustained platelet count response 
between week 19 and 24, are considered non-responders. Patients 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, are also considered non-responders. 
The key secondary endpoints assess the efficacy of efgartigimod focusing on measures of 
response derived from platelet counts, and the incidence and severity of bleeding. 
The choice of a 10-mg/kg IV dose of efgartigimod was made because it has been shown to be 
well tolerated, to consistently achieve close to maximal PD effect, and to be associated with a 
clinical meaningful effect on platelet counts (see Section 1.3). Based on the transient clinical 
responses observed following short term 4-week treatment in the phase 2 trial, a personalized 
chronic dosing regimen guided by treatment response is proposed in line with the chronic 
nature of the disease: a continuous weekly or q2w dosing regimen of 10 mg/kg. 
Platelet count is an objective measure and is the accepted marker of treatment effect in ITP. 

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Selection of Trial Population 
Approximately 117 patients with chronic ITP and up to 39 patients with persistent ITP will 
be randomized. Recruitment will end when 117 patients with chronic ITP have been 
randomized. 
Patients who do not meet all of the inclusion criteria or who meet any of the exclusion 
criteria will not be eligible to receive any trial medication. 
4.3.1. Inclusion Criteria 
Patients will be randomized in this trial only if they meet all of the following criteria: 
1. Ability to understand the requirements of the trial, to provide written informed consent 
(including consent for the use and disclosure of research-related health information), and 
to comply with the trial protocol procedures (including required trial visits). 
2. Male or female patient aged ≥18 years. 
3. Confirmed ITP diagnosis, at least 3 months before randomization and according to the 
ASH Criteria, and no known other 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 2  counts: 1 platelet count collected during the 
screening period and the predose platelet count on the day of randomization (visit 1). 
6. At the start of the trial, the patient is either on concurrent ITP treatment(s) and has 
received at least 1 prior therapy for ITP in the past, or the patient is not on treatment for 
ITP but has received at least 2 prior treatments for ITP. Patients receiving permitted 
concurrent ITP treatment(s) at baseline, must have been stable in dose and frequency for 
at least 4 weeks prior to randomization. 
Permitted concurrent ITP medications include oral corticosteroids, oral 
immunosuppressants, dapsone/danazol, fostamatinib and/or oral TPO-RAs. 
Patients not receiving concurrent ITP therapy are also eligible for the trial if they have 
not received prior ITP therapy for at least 4 weeks prior to baseline, and 6 months in case 
of prior ITP therapy with an anti-CD20 therapy (eg, rituximab). 
7. Women of childbearing potential (see DEFINITION OF TERMS) must have a negative 
serum pregnancy test at the screening visit and a negative urine pregnancy test at baseline 
before trial medication (infusion) can be administered. Women are considered of 
childbearing potential unless they are postmenopausal (defined by continuous 
amenorrhea) for at least 1 year with an FSH of >40 IU/L or are surgically sterilized (ie, 
women who had a hysterectomy, a bilateral salpingectomy, both ovaries surgically 
removed, or have a documented permanent female sterilization procedure including tubal 

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ligation). Follicle-stimulating hormone can be used to confirm postmenopausal status in 
amenorrheic patients not on hormonal replacement therapy. 
8. Women of childbearing potential should use a highly effective or acceptable method of 
contraception during the trial and for 90 days after the last administration of the IMP. 
They must be on a stable regimen, for at least 1 month, of: 
x combined (estrogen and progestogen containing) hormonal contraception associated 
with inhibition of ovulation: 
o oral 
o intravaginal 
o transdermal 
x progestogen-only hormonal contraception associated with inhibition of ovulation: 
o oral 
o injectable 
o implantable 
x intrauterine device (IUD) 
x intrauterine hormone-releasing system 
x bilateral tubal occlusion 
x vasectomized partner (provided that the partner is the sole sexual partner of the trial 
participant and documented aspermia post procedure) 
x continuous abstinence from heterosexual sexual contact. Sexual abstinence is only 
allowable if it is the preferred and usual lifestyle of the patient. Periodic abstinence 
(calendar, symptothermal, post-ovulation methods) is not acceptable 
x male or female condom with or without spermicide 
x cap, diaphragm, or sponge with spermicide. 
9. Non-sterilized male patients who are sexually active with a female partner of 
childbearing potential must use an acceptable method of contraception, ie, a condom. 
Male patients practicing true sexual abstinence (when this is in line with the preferred and 
usual lifestyle of the participant) can be included. Sterilized male patients who have had a 
vasectomy with documented aspermia post procedure can be included. In addition, male 
patients are not allowed to donate sperm during this period from signing of ICF, 
throughout the duration of the trial, and for 90 days after the last administration of IMP. 
4.3.2. Exclusion Criteria 
Patients will not be enrolled in this trial if they meet any of the following criteria: 

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1. ITP/thrombocytopenia associated with another condition, eg, lymphoma, chronic 
lymphocytic leukemia, viral infection, hepatitis, induced or alloimmune 
thrombocytopenia, or thrombocytopenia associated with myeloid dysplasia. 
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), 4 weeks prior to 
randomization. 
5. Use of anti-CD20 therapy (eg, rituximab) within 6 months prior to randomization. 
6. Use of romiplostim within 4 weeks prior to randomization. 
7. Undergone splenectomy less than 4 weeks prior to randomization. 
8. Use of any other investigational drug within 3 months or 5 half-lives of the drug 
(whichever is longer) prior to randomization. 
9. Use of monoclonal antibodies or Fc fusion proteins, other than those previously 
indicated, within 3 months prior to randomization. 
10. At the screening visit, clinically significant laboratory abnormalities as below:  
x Hemoglobin ≤9 g/dL 
- OR - 
x International normalized ratio >1.5 or activated partial thromboplastin time 
>1.5×ULN 
- OR - 
x Total IgG level <6 g/L 
11. Patients who have a history of malignancy, including malignant thymoma, or 
myeloproliferative or lymphoproliferative disorders, unless deemed cured by adequate 
treatment with no evidence of recurrence for ≥3 years before screening. Patients with 
completely excised non-melanoma skin cancer (such as basal cell carcinoma or 
squamous cell carcinoma) or cervical carcinoma in situ would be permitted at any time. 
12. Uncontrolled hypertension, defined as a repeated elevated blood pressure exceeding 
160 mmHg (systolic) and/or 100 mmHg (diastolic) despite appropriate treatments. 
13. History of any major thrombotic or embolic event (eg, myocardial infarction, stroke, 
pulmonary embolism, deep venous thrombosis) within 12 months prior to 
randomization. 
14. History of coagulopathy or hereditary thrombocytopenia or a family history of 
thrombocytopenia. 
15. History of a recent or planned major surgery (that involves major organs eg, brain, heart, 
lung, liver, bladder, or gastrointestinal tract) within 4 weeks of randomization. 
16. Positive serum test at screening for an active viral infection with any of the following 
conditions: 

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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 
17. 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 patient at undue risk. 
18. Patients with known medical history of hypersensitivity to any of the ingredients of the 
IMP. 
19. Patients who previously participated in a clinical trial with efgartigimod and have 
received at least 1 administration of the IMP. 
20. Pregnant or lactating females. 
21. Employees of the investigator or trial center, with direct involvement in the proposed 
trial or other trials under the direction of that investigator or trial center, as well as 
family of the employees or the investigator. 
22. Patients who received a live/live-attenuated vaccine within 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. 
 
Early Discontinuation 
The criteria for screening and enrollment are to be followed explicitly. If it is noted that a 
patient who does not meet 1 or more of the inclusion criteria and/or meets 1 or more of the 
exclusion criteria is inadvertently enrolled and dosed, the sponsor’s designated CRO monitor 
and the sponsor’s medical director must be contacted immediately. 
4.4.1. Early Discontinuation From Trial 
Early discontinuation from the trial is defined as the permanent cessation of further 
participation in the trial prior to its planned completion and without the possibility to roll 
over to the open-label extension trial (ARGX-113-1803). 
The reason for early discontinuation from the trial will be clearly documented by the 
investigator. 
- 
Patients must be discontinued early from the trial and complete the Early 
Discontinuation visit as specified in the SoA (Table 1) if: 

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x 
they withdraw their consent 
All patients 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. Prior to actual withdrawal of consent, an effort should be made to 
perform a final set of assessments as per Early Discontinuation visit. 
Investigators will make and document all efforts made to contact those patients 
who do not return for scheduled visits. 
- 
Patients must be discontinued early from the trial, complete the Early 
Discontinuation visit as specified in the SoA (Table 1), and have to be followed-up 
for 4 weeks (2 q2w visits) for ongoing safety and efficacy monitoring if: 
x 
it is in the patient’s best interest, discussion with the sponsor’s medical 
director is encouraged prior to discontinuation 
x 
unblinding occurred 
x 
prohibited medication is taken (see Section 6.8.2) 
x 
a severe hypersensitivity reaction to IMP occurs 
x 
the patient became pregnant 
4.4.2. Early Discontinuation From Treatment 
Early discontinuation from treatment means that the patient stops receiving the ongoing IMP 
treatment and does not restart IMP treatment, however, informed consent is not withdrawn. 
These patients will continue the weekly trial visits as specified in the SoA (Table 1) without 
IMP-related assessments. 
Patients must be discontinued early from treatment in the following circumstances: 
x 
on the request of the sponsor (eg, following data safety monitoring board [DSMB] 
advice, see Section 7.3.5) 
x 
patient has missed more than 2 consecutive scheduled doses of IMP treatment 
x 
patient has received more than 3 occurrences of rescue therapy  
Patients who complete the 24-week trial period but who do not enter the open-label extension 
trial ARGX-113-1803, or patients who discontinue the trial early, with the exception of 
patients who withdraw their consent, will be followed for 4 weeks for ongoing safety and 
efficacy monitoring. 

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Temporary Withholding Treatment 
- 
The administration of IMP may be temporary withheld if, in the opinion of the 
investigator, it could put the patient at undue risk in the following circumstances: 
x clinically significant disease, including evidence of infection 
x severe bleeding, grade 3 or 4 on the WHO bleeding scale, requiring urgent medical 
and/or surgical intervention 
x thrombosis 
If the IMP is being withheld, it can be reintroduced once the investigator considers the 
undue risk to the patient has passed. 
- 
The administration of IMP must be temporary withheld from patients with platelet 
counts greater than 400×109/L. IMP should be resumed at the 10 mg/kg q2w dose when 
the platelet count falls to fewer than 150×109/L. 
 
Protocol Deviations 
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 patients, 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. 
Planned protocol exemptions or waivers will not be approved by the sponsor. 
 
Screen Failures, Rescreening, and Retesting 
Evaluations at screening and confirmation at baseline (visit 1) will be used to determine the 
eligibility of each patient for randomization at visit 1. Patients who fail to meet the eligibility 
criteria by visit 1 will be considered screen failures. 
Patients may be retested once (ie, redoing 1 test) if still within the screening period. 
Retesting may be considered in the following case: 
x 
A patient who has clinical laboratory tests values meeting 1 or more exclusion criteria 
which are not in line with the medical history and clinical evaluation of the patient, 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 patient should be rescreened. 
Examples of conditions under which rescreening may be considered include the following: 

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x 
Patients who required treatment for an acute illness (eg, a urinary tract infection) or have 
a chronic medical problem (eg, uncontrolled hypertension) may be rescreened once the 
illness has resolved or the medical problem is stabilized. 
The decision to rescreen patients may be optional, based on the clinical state of the patient 
and the decision to rescreen will solely be made per the investigator’s discretion on a case-
by-case basis. For the purpose of rescreening, a new ICF should be completed, and a new 
patient identification number (ID) generated. 
 
Early Termination of Trial or Site 
The trial may be terminated at any time by the sponsor for safety concerns as recommended 
by the DSMB, inability to achieve the recruitment target within a reasonable time, or if in the 
sponsor's judgment there are no further benefits to be expected from the trial. In such a case, 
the sponsor or designee will inform the trial investigators, institutions, and all regulatory 
authorities. 
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 patients. 
 
End-of-Trial Definition 
The End-of-Trial is defined as last patient last visit in the ARGX-113-1801 trial. 

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5. TRIAL PROCEDURES 
Every effort should be made to ensure that the protocol-required tests and procedures are 
completed as described. 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. 
Each patient should attend each trial visit, whether he/she is on a weekly or q2w IMP 
administration regimen, on the designated days. There is a permissible visit window of 
+2 days during the treatment phase as well as the follow-up period. Every effort should be 
made to schedule every visit on the exact day (which is relative to baseline randomization 
[visit 1]) as described in the SoA (Table 1). 
The treatment phase consists of a 24-week IV treatment period with either efgartigimod 
10 mg/kg or matching placebo, administered weekly from visits 1 to 4 and either weekly or 
q2w from visits 5 to 16, adjusted according to the patient’s platelet count. From 
visits 17 to 24, patients will be fixed on the dosing schedule they were receiving at visit 16 or 
at the last visit at which IMP was administered (ie, either weekly or q2w). Assessment of the 
dosing regimen as described in Section 5.4.1 will be applied. 
At screening, all eligibility assessments should be performed after obtaining informed 
consent as well as the weight assessment. 
The platelet count needs to be performed within 1 day prior to any other assessment. 
As from the signature of informed consent until the last trial-related activity, all AEs that 
occur and all concomitant medications, whether allowed or not, that are taken during the trial 
are to be recorded on the appropriate pages in the eCRF. 
 
Informed Consent 
The patient must sign the ICF prior to any trial-related assessment. 
Prior to signing the ICF, the trial patients will be instructed not to participate in any other 
clinical trial that involves an intervention or collection of data until the completion of the 
current trial. 
Any patient who provides informed consent is being assigned a unique patient ID via the 
interactive response technology (IRT) system. 
 
Screening 
After the informed consent has been obtained, the patient will be screened at the site for 
eligibility based on the inclusion and exclusion criteria defined in Section 4.3.1 and 
Section 4.3.2, respectively. 

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The assessments as specified in the SoA (Table 1) will be performed during screening. 
Patients being screened will be registered in the IRT system. The IMP treatment can be 
started upon confirmation of eligibility at visit 1. 
 
Randomization 
The results of all screening procedures have to be available prior to randomization (visit 1) to 
determine the eligibility for randomization into the trial. Randomization should be performed 
as soon as possible after screening with a maximum of 2 weeks, however only after 
confirmation of eligibility of the patient. If a patient meets all the eligibility criteria and after 
approval from the sponsor, he/she will be randomized via IRT. If a patient is not eligible, the 
patient should be recorded as a screen failure in the IRT system. 
 
Treatment Period 
The assessments as specified in the SoA (Table 1) will be performed during the IMP 
treatment period. 
During the IMP treatment period, all assessments and procedures have to be performed 
before the start of the IMP administration, except for: 
x 
Pharmacokinetic sampling, which will be performed both pre- and post-dose (within 
2 hours prior to the start of the IMP infusion and within 30 minutes after the end of IMP 
infusion, respectively) 
x 
the continuous assessment of AEs and the recording of concomitant therapy 
If the IMP is being withheld, it can be reintroduced once the investigator considers the undue 
risk to the patient has passed (see also Section 4.5). If a patient misses more than 
2 consecutive scheduled doses, then he/she will be discontinued early from further IMP 
treatment as defined in Section 4.4.2. 
The End-of-Treatment/Early Discontinuation visit should be completed for all patients, 
whether they roll over to the open-label extension trial (ARGX-113-1803), discontinue the 
trial early, or complete the 24-week trial period. 
5.4.1. Screening and Treatment 
During the screening period (up to 2 weeks) the patient’s eligibility for trial participation will 
be evaluated. 
All eligible patients will be randomized to receive IV infusions of either efgartigimod 
10 mg/kg body weight or matching placebo throughout the trial. 
All patients will initially receive weekly IV infusions from visits 1 to 4. 

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Based on the platelet counts as of visit 2, the dosing frequency can be altered from 
visits 5 to 16 according to the following rules (the change in dosing frequency will occur at 
the current visit): 
x Reduce from weekly to q2w in patients achieving platelet counts of ≥100×10⁹/L for 
3 out of 4 consecutive visits (the fourth visit being the current visit), and have a 
platelet count of ≥100×10⁹/L at the last of these 4 visits 
– OR – 
3 consecutive visits 
x Increase from q2w to weekly in patients whose platelet counts drop below 100×10⁹/L 
on 2 consecutive visits 
– OR – 
<30×10⁹/L at 1 visit 
– OR – 
in patients who receive rescue therapy (see Section 6.8.4) 
x Temporary withholding treatment 
o for reasons described in Section 4.5, IMP should be reintroduced once the 
investigator considers the undue risk to the patient has passed 
o in patients with platelet counts greater than 400×109/L, IMP should be 
resumed at the 10 mg/kg q2w dose when the platelet count falls to fewer than 
150×109/L 
x Post-baseline platelet count can be performed within 1 day of the next procedure as 
per the SoA (both dosing and non-dosing visit), allowing the results to be 
incorporated into the criteria above. 
From visits 17 to 24, the dosing frequency is fixed for each individual patient (ie, either 
weekly or q2w regimen), based on the regimen the patient was receiving at visit 16 or at the 
last visit at which IMP was administered. 
Exceptions to the fixed dosing frequency are: 
- 
Continued weekly dosing for patients requiring rescue therapy  
- 
Continued q2w dosing for patients resuming IMP when the platelet count falls to 
fewer than 150×109/L after having had platelet counts greater than 400×109/L 
5.4.2. Rollover to the Open-Label Extension Trial (ARGX-113-1803) 
Patients who complete the 24-week trial period have the possibility to enter the open-label 
extension trial (ARGX-113-1803) to receive efgartigimod 10 mg/kg IV. The platelet counts 
from the ARGX-113-1801 trial will be taken into account to assess the dosing frequency in 
ARGX-113-1803. 
Eligible patients who consent to roll over into the open-label extension trial ARGX-113-1803 
should complete the End-of-Treatment visit of the current trial. 

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- 
For patients on a weekly dosing regimen, the baseline visit including first IMP dose 
administration of the ARGX-113-1803 trial will be done on the same day. 
- 
For patients on a q2w dosing regimen, the baseline visit including first IMP dose 
administration of the ARGX-113-1803 trial will be done 7 days after the 
End-of-Treatment visit of the current trial if visit 24 of the ARGX-113-1801 trial was 
a dosing visit. If visit 24 of the ARGX-113-1801 trial was a non-dosing visit, the 
End-of-Treatment visit will coincide with visit 1 of the ARGX-113-1803 trial. 
The platelet counts from the ARGX-113-1801 trial will be taken into account to assess the 
dosing frequency in ARGX-113-1803. 
Patients who do not enter the open-label extension trial (ARGX-113-1803) will remain in the 
current trial to be followed for 4 weeks (2 q2w visits). 
 
Follow-up Period 
Patients who complete the 24-week trial period but who do not enter the open-label extension 
trial ARGX-113-1803, or patients who discontinue the trial early, with the exception of 
patients who withdraw their consent, will be followed for 4 weeks for ongoing safety and 
efficacy monitoring. The follow-up period will consist of 2 q2w visits. 
The assessments as specified in the SoA (Table 1) will be performed during the follow-up 
period. 
 
Unscheduled Visit 
It is at the investigator’s discretion or on request of the patient to initiate an unscheduled 
visit, if deemed necessary for the patient’s safety and well-being. All such visits will be 
entered in the eCRF with any additional required documentation based on the nature of the 
unscheduled visit. 
The assessments as specified in the SoA (Table 1) can be performed at the unscheduled visit. 

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6. TRIAL TREATMENT 
 
Treatment Administered 
The IMP infusions (efgartigimod or placebo) will be administered weekly from visits 1 to 4, 
either weekly or q2w from visits 5 to 16, and fixed on the dosing schedule of visit 16 (or the 
last visit at which IMP was administered) from visits 17 to 24 (ie, either weekly or q2w). 
Patients should receive each IV infusion of IMP at a dose of 10 mg/kg over a period of 
approximately 1 hour. 
The maximum total dose per efgartigimod infusion is 1200 mg for patients with a body 
weight ≥120 kg measured at infusion visits. A variation of ± 10% of the amount of 
efgartigimod will not be considered an overdose/underdose. In case of a change in body 
weight, the dose will automatically be recalculated by the IRT system.  
The matching placebo infusion will contain the same excipients as the efgartigimod infusion 
but without the active substance. 
All IMP treatment will be fully blinded. 
Details on infusion rate and time will be given in the IMP management manual (pharmacy 
manual). 
 
Identity of Investigational Medicinal Product 
The IMP (efgartigimod or placebo) will be supplied to the pharmacy at the investigational 
site (and stored at a temperature of 2°C to 8°C or 35°F to 46°F), 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. 
Efgartigimod for IV administration will be provided as a sterile, colorless, clear concentrate 
for solution for IV infusion in glass vials. Appropriate dilutions in a 0.9% saline solution in 
an infusion bag will be prepared on site prior to administration with an IV pump. 
Matching placebo will be provided as a sterile, colorless, clear concentrate solution for 
IV administration in glass vials with the same formulation as the efgartigimod solution, but 
without the active ingredient that is present in efgartigimod. Appropriate dilutions in a 
0.9% saline solution in an infusion bag will be prepared on site prior to administration with 
an IV pump. 
The IMP will be manufactured in accordance with Good Manufacturing Practice regulations. 
Detailed instructions on IMP management on site (including preparation of the IMP) will be 
included in the IMP management manual (pharmacy manual). 

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Packaging and Labeling 
The IMP will be labeled and secondary packed in accordance to local laws and regulatory 
requirements. 
 
Storage of Investigational Medicinal Products 
The investigator (or his/her designee) is responsible for the correct and safe storage of the 
IMP assigned to the clinical site, in a locked, secure storage facility with access limited to 
those individuals authorized to dispense the IMP and maintained within the appropriate 
temperature ranges. 
The IMP must be stored refrigerated (2°C to 8°C or 35°F to 46°F) in its secondary 
packaging, should not be exposed to freezing temperatures, should not be shaken, and should 
be protected from direct sunlight during storage at the clinical site. 
The IMP temperature will be recorded on a continuous basis at the site pharmacy and 
minimum/maximum temperature ranges should be registered. 
Further requirements on temperature logging during storage and information on how to 
handle temperature excursions can be found in the IMP management manual (pharmacy 
manual). 
 
Method of Assigning Patients to Treatment Group 
Once the patient has provided informed consent, the site will enroll the patient and a 
screening number will be allocated through IRT. Upon confirmation of eligibility at baseline 
(visit 1), the patient will be randomized through IRT by generating a unique patient 
randomization ID. 
This randomization ID will be stored in the IRT system. 
Patients will be randomized in a 2:1 ratio to receive efgartigimod (10 mg/kg) or matching 
placebo. No trial team members from the sponsor, nor from the sponsor’s designated CRO, 
or pharmacy personnel will have access to this IMP treatment assigned until after database 
lock. 
 
Dosing Administration for Each Patient 
During the IMP treatment period, the IMP will be administered as an IV infusion over a 
period of approximately 1 hour. Patients will be asked to remain at the site for at least 
30 minutes after the end of the infusion as part of routine safety monitoring. 
 
Blinding 
This is a randomized, double-blinded, placebo-controlled trial with limited access to the IMP 
treatment assigned (see also DEFINITION OF TERMS). 

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An independent unblinded DSMB and statistician will review all unblinded safety data as 
specified in Section 7.3.5. 
6.7.1. 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 patient, 
unless there is a patient safety issue that via knowledge of the IMP treatment assignment 
would change patient management. The investigator is encouraged to discuss with the 
monitor at the sponsor’s designated CRO or the sponsor’s medical expert before utilizing 
IRT to break the blind. If the blind is broken by the investigator it may be broken only for the 
patient concerned, and the IMP treatment assignment should not be revealed to the trial team 
members from the sponsor, nor from the sponsor’s designated CRO, pharmacy personnel, or 
other site staff. Once unblinded, the patient will be discontinued from the trial and will be 
followed for 4 weeks for ongoing safety and efficacy monitoring. 
The sponsor and monitor at the sponsor’s designated CRO must be notified immediately if a 
patient and/or investigator is unblinded during the course of the trial. Pertinent information 
regarding the circumstances of unblinding must be documented in the patient’s source 
documents and eCRF. Once unblinded, the patient will be early discontinued from the trial 
and followed-up for 4 weeks (2 q2w visits). 
 
Prior Treatments and Concomitant Medications 
All prior ITP procedures and therapies received by the patient since diagnosis, before 
baseline must be recorded in the eCRF, including the name, dose/schedule, duration 
(including start and stop dates), and whether patient responded to them. 
The washout periods as specified in exclusion criteria 2 to 9 must be followed. 
The patient’s history of TPO-RA and other ITP therapy response and intolerance will be 
collected separately in the eCRF. 
All vaccinations received by the patient in the 6 months prior to baseline should be recorded. 
All concomitant medications whether allowed or not must be recorded in the eCRF 
(including the name, dose/schedule, start and stop dates). 
6.8.1. Concurrent ITP Therapy 
Patients 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 oral corticosteroids, oral immunosuppressants, 
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Patients not receiving concurrent ITP therapy are also eligible for the trial if they have not 
received prior ITP therapy for at least 4 weeks prior to baseline (inclusion criterion 6). 
Dose and frequency of permitted concurrent ITP therapies should remain unchanged during 
the trial. 
Exceptions are patients who are receiving concurrent treatment with TPO-RAs in whom dose 
changes are permitted at label-defined platelets thresholds, and patients 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 patients who have an “insufficient response” (ie, no platelet count 
of ≥30×109/L in any of the visits during the last 4 weeks). These patients will be considered 
as “non-responders” 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. 
Any change in concurrent ITP therapy should appropriately be recorded in the eCRF. 
6.8.2. Prohibited Medications and Therapy Prior to Randomization 
The following medications or treatments are not permitted within the specified time window 
prior to randomization: 
x 
Use of anticoagulants (eg, vitamin K antagonists, direct oral anticoagulants) within 
4 weeks prior to randomization. 
x 
Use of any transfusions within 4 weeks prior to randomization. 
x 
Use of Ig (IV, SC, or intramuscular route) or PLEX, 4 weeks prior to randomization. 
x 
Use of anti-CD20 therapy (eg, rituximab) within 6 months prior to randomization. 
x 
Use of romiplostim within 4 weeks prior to randomization. 
x 
Undergone splenectomy less than 4 weeks prior to randomization. 
x 
Use of any other investigational drug within 3 months or 5 half-lives of the drug 
(whichever is longer) prior to randomization. 
x 
Use of monoclonal antibodies or Fc fusion proteins, other than those previously 
indicated, within 3 months prior to randomization. 
x 
Live/live-attenuated vaccines within 4 weeks prior to screening. 

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6.8.3. Prohibited Medications and Therapy During the Trial 
The following medications or treatments are not permitted during the trial: 
x 
Anti-CD20 therapy (eg, rituximab) 
x 
Romiplostim 
x 
Any monoclonal antibodies or Fc fusion proteins or investigational drug 
x 
Live/live-attenuated vaccines 
6.8.4. Rescue Therapy 
“Rescue therapy” is defined as an occurrence where the patient 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 
patient. The start date/time of the occurrence is the start of the administration of the first 
rescue treatment. 
Rescue therapy is allowed for patients having protocol-defined ITP clinical deterioration 
AND if in addition the treating physician believes that the patient’s health is in jeopardy if 
rescue therapy is not given. 
Rescue therapy is allowed post-baseline during the 24-week trial period for patients with a 
platelet count of <30×10⁹/L and 1 of the following: 
x 
an immediate risk of bleeding or a clinically significant bleeding, or wet purpura 
x 
requirement for urgent or emergent surgery (elective surgeries must be postponed until 
trial completion) 
The following rescue therapies are permitted: 
x 
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 
x 
IVIg: up to 1 g/kg/day × 1-2 days 
x 
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 patients 
x 
platelet transfusions 
If a patient needs rescue therapy according to the investigator, it is encouraged to inform the 
medical monitor at the sponsor’s designated CRO, whenever possible prior to actual 
implementation of the rescue therapy. 
In the event of rescue with IVIg or IV anti-D: 

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x 
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 4.5 and Section 6.11). 
For rescue therapy with methylprednisolone, dexamethasone, prednisone, or platelet 
transfusions: 
x 
Administration of the IMP continues during rescue therapy 
Patients who were receiving q2w dosing at the time of rescue therapy will have the 
IMP administration frequency increased to weekly. 
For patients 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 patient 
can transition to q2w treatment. 
Patients requiring more than 3 occurrences of rescue therapy will discontinue from IMP. 
 
Medical Care of Patients After End-of-Treatment or Early 
Discontinuation 
After a patient has completed the trial, has withdrawn/discontinued early, or does not roll 
over to the open-label extension trial (ARGX-113-1803) 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 patient’s individual needs. 
 Treatment Compliance 
The investigator should promote treatment compliance by stating that compliance is 
necessary for the patient’s safety and the validity of the trial. The prescribed dose, timing, 
and mode of administration cannot be changed. All dates, start and end time of IMP 
administration, and any deviations from the intended regimen must be recorded in the eCRF. 
A sponsor’s designated CRO monitor will review the pharmacy records at each site including 
the drug accountability and dispensing records on which the pharmacist or designated person 
should record all IMP released for patient use. The sponsor’s designated CRO monitor will 
compare the dispensing record and vials with the individual patient’s identifiers, kit number, 
and visit schedule to confirm that the patient received the correct treatment and dose, and that 
the dosing schedule is correct. 
Errors that are identified will be communicated to the site personnel to ensure that the errors 
are not repeated. The sponsor’s designated CRO monitor’s report will include details of any 
missed doses, errors in dose, treatment or scheduling errors, and the associated explanations. 
It will be evaluated if these dosing errors will be reported as protocol deviations in the 
clinical database. All supplies and pharmacy documentation must be made available 
throughout the trial for the sponsor’s designated CRO monitor to review. 

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 Handling Missed Doses of the Investigational Medicinal Product 
All efforts will be made to ensure that the patient receives all administrations of IMP within 
the allowed visit windows. However, if a patient misses more than 2 consecutive scheduled 
doses, then he/she will be discontinued early from further IMP treatment (see Section 4.4.2). 
 Accountability of Investigational Medicinal Product 
Detailed instructions on accountability of the IMP will be included in the IMP management 
manual (pharmacy manual). 
 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 for future additional 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 patient would not agree. 
In addition, blood samples may be used to validate methods to measure efgartigimod, 
antibodies, and biomarkers. 

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7. TRIAL ASSESSMENTS 
 
Demography 
Demographic characteristics comprise age, year of birth, gender, race, and ethnicity 
(per local regulations). 
 
Efficacy 
Procedures assessing the efficacy of efgartigimod will mainly focus on measures of response 
derived from platelet counts. These assessments will be performed at the weekly visits 
predose on all IMP administration days, and at the unscheduled visits (if needed), as 
specified in the SoA (Table 1). 
7.2.1. Platelet Count 
The assessment of platelet count can be performed within 1 day prior to any other trial-
specific assessment (except at screening, where the informed consent should be obtained and 
weight assessed first, and at randomization) at each visit as specified in the SoA (Table 1). 
The samples will be analyzed locally. For a single patient, baseline and post-baseline platelet 
count assessments need to be performed at the same facility throughout the trial. 
In addition, the absolute 
 and the 
 
 will be measured locally in facilities equipped 
with a hematology analyzer which can determine this 
. 
7.2.2. General Bleeding Assessment 
Signs and symptoms of bleeding are the predominant clinical manifestation of ITP and are 
typically related to low 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 each visit using the WHO bleeding scale (Appendix 3) as specified 
in the SoA (Table 1). The WHO bleeding scale was originally developed to assess bleeding 
in patients undergoing treatment for cancer and has been used extensively.11 
The wide use of the scale and incorporation into the common terminology criteria for AEs 
(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 

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Safety 
Safety assessments will consist of monitoring and recording all safety information including 
pregnancies, safety laboratory testing, measurement of vital signs, ECG, physical 
examination, and other tests that are deemed critical to the safety evaluation of the trial 
treatment in all patients. As discussed in Section 7.3.1.5, any pregnancy in a female patient 
(or partner of a male patient) that occurs while the patient is enrolled in the trial will also be 
monitored and reported according to the appropriate regulations. Although a pregnancy is not 
considered as an (S)AE, any adverse pregnancy outcome, complication, or elective 
termination of a pregnancy for medical reasons will be recorded and reported as an (S)AE. 
An independent unblinded DSMB will periodically review the safety data as described in the 
DSMB charter (Section 7.3.5). 
The investigator is responsible for recording all AE(SI)s observed during the trial from the 
time the patient signs the ICF until the last contact with the patient. 
7.3.1. Adverse Events 
Definition of AE 
An AE is any untoward medical occurrence in a clinical trial patient, temporally associated 
with the use of IMP, whether or not considered related to the medicinal product or IMP. 
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 IMP, whether or not considered related to the medicinal product or IMP. 
The following events will be collected as AEs: 
x Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (eg, ECG, radiological scans, vital signs measurements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the investigator (ie, not related to progression of 
underlying disease). 
x Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
x New conditions detected or diagnosed after IMP administration even though it may 
have been present before the start of the study. 
x Signs, symptoms, or the clinical sequelae of a suspected intervention-intervention 
interaction. 
x Signs, symptoms, or the clinical sequelae of a suspected overdose of either IMP or a 
concomitant medication. Overdose per se will not be reported as an AE/SAE unless it 
is an intentional overdose taken with possible suicidal/self-harming intent. Such 
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x “Lack of efficacy” or “failure of expected pharmacological action” per se will not be 
reported as an AE or SAE. Such instances will be captured in the efficacy 
assessments. However, the signs, symptoms, and/or clinical sequelae resulting from 
lack of efficacy will be reported as AE or SAE if they fulfill the definition of an AE 
or SAE. 
The following events will NOT be collected as AEs: 
x 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 patient’s condition. 
x The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
patient’s condition. 
Note: Except for any occurrence of bleeding, which will be considered an AESI 
as per section 7.3.1.1. 
x Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that 
leads to the procedure is the AE. 
x Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
x Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen. 
Death is not considered an AE in itself but a (fatal) outcome of an SAE. 

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Definition of SAE 
An SAE is defined as any untoward medical occurrence that at any dose: 
x 
Results in death 
x 
Is life-threatening (the term “life-threatening” in the definition of “serious” refers to an 
event in which the patient 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 was more severe) 
x 
Requires inpatient hospitalization or prolongation of existing hospitalization. In general, 
hospitalization signifies that the patient 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. 
x 
Results in persistent or significant disability or 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. 
x 
Is a congenital abnormality or birth defect 
x 
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 patient or may require medical or surgical 
intervention to prevent 1 of the other outcomes listed in the above definition. 
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. 
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. 

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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 version 5.0), 
seriousness, and causal relationship to the IMP or trial procedures. The action taken with the 
investigational drug and the outcome of the event must also be recorded. 
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 AE (see Section 6.1). 
An overdose is defined as a deliberate or accidental administration of IMP to a patient, at a 
dose greater than that which was assigned to that patient per the trial protocol. 
A medication error is any preventable incident that may cause or lead to inappropriate IMP 
use or patient harm while the IMP is in the control of health care professionals. Such incident 
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 patient 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 excess dose should be documented in the eCRF 
including the additional AE, if any. 
Severity 
All AEs observed will be graded using the National Cancer Institute (NCI) CTCAE 
version 5.0. The NCI CTCAE is a descriptive terminology, which can be utilized for AE 
reporting. A grading (severity) scale is provided for each AE term. The grade refers to the 
severity of the AE. If a particular AE’s severity is not specifically graded by the guidance 
document, the investigator is to use the general NCI CTCAE definitions of grade 1 through 
grade 5 following his or her best medical judgment. The CTCAE displays grades 1 through 5 
with unique clinical descriptions of severity for each AE based on the following general 
guideline: 
x 
Grade 1: mild; asymptomatic or mild symptoms clinical or diagnostic observations only; 
intervention not indicated 
x 
Grade 2: moderate; minimal, local or noninvasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living 
x 
Grade 3: severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
activities of daily living 

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x 
Grade 4: life-threatening consequences; urgent intervention indicated 
x 
Grade 5: death related to AE 
Note: a semi-colon indicates “or” within the description of the grades. 
Relationship 
The causal relationship between the IMP/trial procedures and the AE has to be characterized 
as unrelated, unlikely, possible, probable, and related. 
x 
Events can be classified as “unrelated” if there is no reasonable possibility that the IMP 
caused the AE. 
x 
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. 
x 
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. 
x 
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. 
x 
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 the patient’s clinical 
state. 
In the final evaluation for reporting, the relationship will be converted into a “binary 
determination” as per CIOMS. Unrelated and unlikely will be clubbed into “unrelated,” and 
related, possible, and probable will be clubbed into “(at least possibly) related” for final 
reporting purpose. 
7.3.1.1. 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 like potential immunosuppression, etc). Further 
characterizing information will be collected in the eCRF. This event could be expected due to 
the natural progression of the underlying disease, disorder, or condition of the patient(s) and 
the patient’s predisposing risk factor profile including concomitant medications (eg, bruising 
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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 AESI in this 
trial. 
Due to the nature of underlying disease (ie, ITP), any occurrence of bleeding will also be 
considered an AESI. 
7.3.1.2. 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 “non-serious”) of 
the eCRF. The investigator should complete all the details requested, including date of onset, 
time of onset, stop date (when applicable), stop time (when applicable), severity, action 
taken, outcome, and relationship to IMP and to trial procedures. Each event should be 
recorded separately in the eCRF. 
Any SAE, including death due to any cause, which occurs during this trial after 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). All SAEs will be recorded on the paper SAE report 
form and the AE form in the eCRF. The investigator or designated site staff should check 
that all entered data is consistent. An alert email for the SAE report in the eCRF will then 
automatically be sent by email to the sponsor’s designated CRO safety mailbox via the 
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). 
The report will contain as much available information concerning the SAE as possible, to 
enable the sponsor (or an authorized representative) to file a report, which satisfies regulatory 
reporting requirements. These timelines apply to initial reports of SAEs and to all follow-up 
reports. 
Criteria for documenting the relationship to IMP as well as severity, outcome, and action 
taken will be the same as those previously described. 
All SAEs that are spontaneously reported within 30 days after the last trial visit are to be 
collected and reported in the safety database, and all efforts should be made to follow-up 
until resolution. 
Additional follow-up information should be completed and entered on a paper SAE report 
form and sent by fax/email to the sponsor’s designated CRO. 

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7.3.1.3. Reporting of Serious Adverse Events to Regulatory Authorities and 
Investigators 
The sponsor’s designee will be responsible for reporting all suspected ADRs that are both 
serious and unexpected, and any other applicable reports to regulatory authorities, IRB/IEC, 
and investigators, in accordance with national regulations in the countries where the trial is 
conducted. Relative to the first awareness of the event by/or further provision to the 
sponsor’s designee, these events will be submitted within 7 days for fatal and life-threatening 
events and 15 days for other events, unless otherwise required by national regulations. The 
sponsor’s designee will also prepare an expedited report for other safety issues where 
applicable. 
The investigational site will also forward a copy of all expedited reports to his or her 
IRB/IEC in accordance with national regulations. 
7.3.1.4. Follow-up of Adverse Events and Serious Adverse Events 
Any AEs observed from signing the ICF to the last trial-related activity will be followed-up 
until resolution, until the patient is lost to follow-up, or until the patient withdraws consent. 
Resolution means that the patient has returned to a baseline state of health or the investigator 
does not expect any further improvement or worsening of the AE. 
Every effort should be made to follow all (S)AEs considered to be related to the IMP or trial 
procedures until an outcome can be reported. If the patient is lost to follow-up, all AEs will 
be categorized based on the investigator’s last assessment. 
During the trial period, resolution of SAEs (with dates) should be documented on the AE 
page of the eCRF and in the patient’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. 
For SAEs, AESI, 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. 
7.3.1.5. Reporting and Follow-up Requirements for Pregnancies 
7.3.1.5.1. 
Pregnancies in Female Patients 
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 SoA (Table 1). 

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If a patient becomes pregnant during the administration of IMP and up to 90 days after the 
patient received the last IMP, the sponsor and/or sponsor’s designee should be informed 
immediately (ie, within 24 hours of the trial site’s knowledge of the event). The following 
actions will be performed: 
x 
The patient should immediately be discontinued from IMP treatment. 
x 
The patient should have the Early Discontinuation assessments and enter the 4-week 
follow-up period. 
x 
All assessments for Early Discontinuation (see Section 4.4.1) must be performed unless 
contraindicated by pregnancy (harmful to fetus) or unless the patient withdraws 
informed consent. 
The investigator must update the patient with information currently known about potential 
risks and available treatment alternatives. The pregnancy should be followed-up to determine 
outcome, including spontaneous or voluntary termination, details of the birth, and the 
presence or absence of any birth defects, congenital abnormalities, or maternal and/or 
newborn complications. 
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. 
7.3.1.5.2. 
Pregnancies in Female Partners of Male Patients 
Male patients will be instructed through the ICF to immediately inform the investigator if 
their partner becomes pregnant during the trial or up to 90 days after they received the last 
IMP. A pregnancy report form should be completed by the investigator within 24 hours after 
learning of the pregnancy and submitted via email or fax (see the Safety Mailbox/Fax details 
on the title page of this protocol). Attempts should be made to collect and report details of the 
course and outcome of any pregnancy in the partner of a male patient exposed to the IMP. 
The pregnant partner will need to sign an ICF to allow for follow-up on her pregnancy, its 
outcome, including if appropriate, the birth and health of the baby. Once the ICF has been 
signed, the investigator will update the pregnancy report form with additional information on 
the course and outcome of the pregnancy. An investigator, who is contacted by the male 
patient or his pregnant partner, may provide information on the risks of the pregnancy and 

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the possible effects on the fetus, to support an informed decision in cooperation with the 
treating physician and/or obstetrician. 
7.3.2. Clinical Laboratory Evaluations 
Blood and urine samples for determination of clinical chemistry, hematology, urinalysis, 
coagulation, thyroid, autoimmune antibody testing, FSH (only for women of non-
childbearing potential), PK, PD, antiplatelet antibodies, viral testing, tuberculosis 
QuantiFERON test, and ADA will be collected and analyzed at a central lab as indicated in 
the SoA (Table 1) and Appendix 1. The blood sample for platelet counts and the urine 
sample for the pregnancy test will be analyzed locally. 
In addition, the IPF# and IPF% will be measured locally in the facilities equipped with a 
hematology analyzer which can determine this platelet subset. 
Patients may be rescreened (ie, redoing the full assessments as per SoA, Table 1) or retested 
once (ie, repeating 1 test, see Section 4.7) if still within the screening period. 
On days that IMP is administered, blood for laboratory assessments should be collected 
before dosing. 
Additional safety samples may be collected if clinically indicated, at the discretion of the 
investigator. 
For all female patients of childbearing potential, a serum pregnancy test will be performed 
centrally at screening (on the samples taken for clinical laboratory tests), and a urine 
pregnancy test will be conducted and analyzed locally at the site at the visits specified in the 
SoA (Table 1). 
The estimated total maximum blood volume needed for a patient during the trial (when 
completing the trial) is approximately 618 mL. 
Clinical laboratory tests will be reviewed for results of potential clinical significance at all 
time points throughout the trial. The investigator will evaluate any change in laboratory 
values. If the investigator determines a laboratory abnormality to be clinically significant, it 
will be considered as a laboratory AE, however, if the abnormal laboratory value is 
consistent with a current diagnosis, it may be documented accordingly without being 
reported as an 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 patient’s source documents and on the central/local lab assessment eCRF page. 
For urinalysis samples, only the date of collection is to be entered. 
Refer to Appendix 2 for the addresses of the laboratories used for sample analyses. 

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7.3.3. Vital Signs, Physical Examination, and Electrocardiogram 
The assessment of vital signs (supine blood pressure, heart rate, and body temperature) 
physical examination, and ECG will be performed at the time points indicated in the SoA 
(Table 1). 
Supine blood pressure and heart rate will be measured using standard equipment after at least 
10 minutes rest. 
It is recommended that the method used to measure body temperature at screening is 
maintained throughout the trial for each patient. 
A physical examination will include at a minimum an assessment of general appearance, 
skin, lymph nodes, musculoskeletal/extremities, abdomen, cardiovascular, respiratory, and 
neurological system. 
Height will be measured at screening only. Weight will be measured at screening and at any 
IMP infusion visit. For the assessment of height and weight, patients will be required to 
remove their shoes and wear light indoor clothing. 
A single 12-lead ECG will be taken post-dose at a paper speed of 25 mm/sec in the supine 
position after the patient 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. If no IMP is administered, the ECG will be assessed preferably after the blood 
sample for platelet counts has been taken. 
Clinically significant abnormalities in physical examination, vital signs, and ECG at 
screening will be reported as medical history in 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. 
7.3.4. 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 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 patient 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 for coagulation disorder will be 
prespecified in the eCRF. 
Information should be provided on medical and surgical history and concomitant medical 
conditions specifying those ongoing at screening. 

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7.3.5. Data Safety Monitoring Board 
The sponsor will appoint an independent DSMB consisting of an independent group of 
clinical experts who are not involved in the trial management. They will be supplemented by 
an independent statistician. The objective of the DSMB will be to review all unblinded safety 
data (including the overall number of patients treated up to that point, rates, and patient-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). 
7.3.6. Visit Reminder/Patient ID Card 
Patients must be provided with the address and telephone number of the main contact for 
information about the clinical trial. The investigator must therefore provide a “Visit 
Reminder/Patient ID Card” to each patient. In an emergency situation this card serves to 
inform the responsible attending physician that the patient is in a clinical trial and that 
relevant information may be obtained by contacting the investigator. Patients must be 
instructed to keep the card in their possession at all times. 
 
Pharmacokinetics 
Blood samples for PK will be collected from each patient as presented in the SoA (Table 1). 
Concentrations of efgartigimod will be determined using a validated assay. The actual date 
and time of collection of the blood sample will be recorded in the relevant section of the 
eCRF, as well as the reason in case no sample was taken. 
The PK samples will be taken predose (within 2 hours prior to start of IMP infusion) and 
post-dose (within 30 minutes after the end of IMP infusion). 
 
Pharmacodynamics 
Blood 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 (Table 1). Sampling will be 
done predose on IMP administration visits. Samples will be analyzed by the central 
laboratory. In order to maintain the blind, the IgG testing cannot be performed locally. 
These PD markers will be determined using validated assays. 

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Additionally, presence, nature, and level of antiplatelet antibodies will be tested as indicated 
in the SoA (see Table 1). 
The actual date and time of collection of the blood sample will be recorded in the relevant 
section of the eCRF, as well as the reason in case no sample was taken. 
 
Anti-Drug Antibodies 
Blood samples to assess ADA will be collected as indicated in the SoA (Table 1). Sampling 
will be done predose on IMP administration visits. 
All samples will be analyzed first in a validated screening assay, followed by an assessment 
of specificity of the measured ADA response in positive samples in a confirmation assay. 
Finally, in samples scoring positive in both abovementioned assays, a titration of the ADA 
response will be performed and samples will be tested for neutralizing ADAs. 
The actual date and time of collection of the blood sample will be recorded in the relevant 
section of the eCRF, as well as the reason in case no sample was taken. 
 
 
The sample to measure the 
 has to be collected as the last sample 
predose as indicated in the SoA (Table 1) in sites participating in the 
 
. 
The actual date and time of collection of the blood sample will be recorded in the relevant 
section of the eCRF, as well as the reason in case no sample was taken. 
The sample will be used for an exploratory endpoint and will be analyzed in a specialty lab. 
 
Quality-of-Life and Patient-Reported Outcomes 
The patient will complete the QoL questionnaire (SF-36 v2.0) and the PRO (FACT-Th6 and 
FACIT-Fatigue Scale) as indicated in the SoA (Table 1). 
FACT-Th6: The FACT-Th6 uses the Likert scale, with patients 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 

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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 their 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.” 

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patients in the FAS with chronic ITP will be used. The analysis will follow the intent-to-treat 
principle, ie, patients will be analyzed according to their randomized treatment, irrespective 
of the treatment they actually received. 
The per protocol (PP) population is a subset of the FAS, ie, all patients from the FAS without 
a major protocol deviation. The PP population will be used for sensitivity analyses for the 
primary and key secondary endpoints. 
The safety analysis set comprises all patients in the randomized population who have 
received at least 1 dose or part of a dose of IMP. Patients will be analyzed according to the 
actual treatment received for safety analyses. 
 
Patient Disposition, Characteristics, and Concomitant Medication 
A tabular presentation of the patient disposition will be provided. It will include the number 
of patients screened, randomized, received IMP treatment, completed the trial, as well as the 
number of early discontinuations from IMP treatment (including rescued patients) and trial, 
with reasons for discontinuation from IMP treatment or trial, and major protocol deviations. 
A listing will be presented to describe dates of screening, screen failure with reason, 
randomization or assigned treatment, completion or early discontinuation, and the reason for 
discontinuation, if applicable, for each patient. 
Patient characteristics will be listed and summarized (by treatment group and overall). 
Summaries will include descriptive statistics for continuous measures (number of 
observations, mean, standard deviation, median, 1st quartile, 3rd quartile, minimum, and 
maximum) and for categorical measures (frequency and percentage). Patient characteristics 
include, but are not limited to, age, sex, race, weight, body mass index, and baseline platelet 
level. 
Use of concomitant medication will be summarized by treatment group with frequency and 
percentage. Separate summaries of concurrent ITP therapies and rescue therapy by treatment 
group will be provided. All concomitant medications used will be listed. 
 
Statistical Methods 
All patients starting at least 1 infusion of efgartigimod or placebo will be assessed for safety 
according to their actual treatment. 
The efficacy analysis will be performed on the FAS or the subset of patients in the FAS with 
chronic ITP, and analyzed with intent-to-treat principle (ie, patients will be analyzed 
according to their planned treatment irrespective of the treatment actually received). 
Supportive analyses will be conducted in the PP population. The safety analysis will be 
performed on the safety analysis set. 

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The PK analysis set will include all patients from the safety analysis set who have at least 
1 serum post-dose PK measurement. 
8.4.1. Primary Endpoint Analysis 
Definition of the estimand for the primary endpoint 
x 
Population: adult patients with chronic ITP, having an average platelet count of 
<30×109/L, and, at the start of the trial, either being on concurrent ITP treatment(s) and 
having received at least 1 prior therapy for ITP in the past, or not being on treatment for 
ITP but having received at least 2 prior treatments for ITP 
x 
Variable: sustained platelet count response defined as achieving platelet counts of at 
least 50×109/L for at least 4 of the 6 visits between week 19 and 24 of the trial 
x 
Main intercurrent events: 
i. 
early discontinuation of treatment (prior to visit 24) due to lack of efficacy (eg, more 
than 3 occurrences of rescue therapy) or due to an AE 
ii. 
initiation of rescue therapy at week 12 or later 
iii. 
increase of dose and/or frequency of concurrent ITP therapies at week 12 or later 
x 
Population-level summary: proportion of patients with sustained platelet count response 
Handling of main intercurrent events 
A composite strategy approach will be taken to address the main intercurrent events 
described above. This implies that patients who discontinue treatment prior to visit 24 due to 
lack of efficacy (eg, more than 3 occurrences of rescue therapy) or due to an AE, as well as 
patients 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 non-
responders for the primary endpoint analysis. 
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 two-sided p-value. In addition, an 
adjusted difference of the proportions with its 95% CI will be provided. 
Handling of missing data 
Missing data for reason of 1 of the main intercurrent events will be handled as described 
above. Details on handling other missing data will be provided in the SAP. 

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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 hypothetical and/or ‘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. 
8.4.2. 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 patient this 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 2-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 α=0.05. An estimate of the location shift will be provided, along with the associated 
95% confidence interval. 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 patients in the overall population with a 
sustained platelet count response and on proportion of patients in the overall population 
achieving platelet counts of at least 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 patient (assessed using the WHO bleeding scale; where 
WHO scale ≥1 at any visit is considered a new bleeding event) will be analyzed using a 
zero-inflated negative binomial model. This model will account for the large expected number 
of patients with zero bleeding events. It is a mixture model consisting of 2 components: a 

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negative binomial count model and a binary model for predicting excess zeros. The model will 
consist of the number of events as the dependent variable and of randomized treatment, the 
stratification variables (history of splenectomy; receiving concurrent ITP therapies at baseline), 
and baseline platelet count as independent variables. An offset term will be used to allow for 
patient exposure. Both the count model, using the log link, and the binary model, using the 
logit link, will contain the same independent variables. The probability of no bleeding will be 
estimated for each randomized treatment group. A Wald test will be used to test the null 
hypothesis that the log of the bleeding rate ratio on placebo and efgartigimod is equal to zero 
against the alternative that it is different from zero. The rate of bleeding over 24 weeks on 
placebo and efgartigimod will be provided, along with the rate ratio, 95% 2-sided Wald-type 
CI, and 2-sided p-value. Missing bleeding assessments for reasons of 1 of the main 
intercurrent events will not be imputed, but the offset term will be adapted accordingly to 
reflect the assessment period until the occurrence or start of the intercurrent event. 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 pre-defined 
hierarchy resulted in a p-value <0.05. The order in the testing hierarchy of the key secondary 
endpoints is as follows: 
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 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 of the trial. 
3. The incidence and severity of the WHO-classified bleeding events in the overall 
population. 
4. Proportion of patients 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. 
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. 

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8.4.3. Other Secondary Endpoint Analyses Not Subject to Alpha Control 
The secondary endpoints on overall platelet count response will be analyzed in the same 
manner as the primary endpoint. The secondary endpoint on extent of disease control will 
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 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, history of splenectomy (yes vs. no), and 
receiving concurrent ITP therapies at baseline (yes vs. no). Least square (LS) means for 
placebo and efgartigimod will be provided, along with the difference in LS means, 95% 
2-sided CI, and 2-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 vs. placebo will be provided, along with the 
associated 95% 2-sided CI and 2-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 at least 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 at least 20×109/L above baseline within the group of patients with a 
baseline platelet count of <15×109/L will also be analyzed as described for the key secondary 
endpoint. 
The number of significant bleeding events per patient (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. 
8.4.4. Pharmacodynamics, Pharmacokinetics, and Immunogenicity 
Descriptive statistics will be provided for PD parameters (total IgG and subtypes, and 
antiplatelet antibodies) and ADA. Efgartigimod serum concentration data will be 
summarized. 

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8.4.5. Safety 
Incidence and severity of AEs, AESIs, and SAEs will be summarized descriptively. 
Laboratory parameters, vital signs, and ECG data will also be analyzed descriptively. 
8.4.6. Exploratory Endpoint Analysis 
Descriptive statistics will be presented for 
. The analysis of 
 
 will be performed at a later stage than the analyses of the other endpoints and 
will be described in a separate report. 
 
Interim Analyses 
Not applicable. 

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9. QUALITY CONTROL AND QUALITY ASSURANCE 
 
Investigator’s Responsibility 
The investigator will comply with the protocol which has been approved/given favorable 
opinion by the IRB/IEC, according to ICH Good Clinical Practice (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. Sub-investigators or other designated site staff are eligible to sign for 
the investigator, except where the investigator’s signature is specifically required. 
 
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: 
x 
investigator meetings 
x 
central laboratories for clinical laboratory parameters 
x 
site initiation visit 
x 
routine site monitoring 
x 
ongoing site communication and training 
x 
ongoing oversight by sponsor’s designated CRO monitors of safety parameters and 
adherence to selection criteria 
x 
data management quality control checks 
x 
continuous data acquisition and cleaning 
x 
quality control check of the CTR 
x 
to avoid inter-observer 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 WHO scale 
In addition, periodic audits can be performed as specified in Section 9.5. 
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. 

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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 SOPs of the CRO. 
Monitoring visits must be conducted according to the applicable ICH GCP guidelines to 
verify that, among others, the: 
x 
data are authentic, accurate, and complete 
x 
safety and rights of patients are being protected 
x 
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. 
The sponsor’s designated CRO monitor will perform an eCRF review, source document 
verification, and source document review. 
The source documentation agreement form describes the source data for the different data in 
the eCRF. This document should be completed and signed by the sponsor’s designated CRO 
monitor and investigator, and should be filed in the investigator’s trial file. Any data item for 
which the eCRF will serve as the source must be identified, agreed, and documented in the 
source documentation agreement form. 
Upon completion or premature discontinuation from the trial, the sponsor’s designated CRO 
monitor will conduct site closure activities with the investigator and site staff as appropriate, 
in accordance with applicable regulations, ICH GCP guidelines, and CRO/sponsor 
procedures. 
 
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 patient in electronic format (ie, eCRF). Data will be 
transcribed by the trial site staff from the source documents onto the eCRF. 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 prior to the trial 
being initiated, and any data being entered into the system for any trial patient at the site. 

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The eCRF is essentially considered a data entry form and should not constitute the original 
(or source) medical records unless otherwise specified. Source documents are all documents 
used by the investigator or hospital that relate to the patient’s medical history, that verify the 
existence of the patient, the inclusion and exclusion criteria, and all records covering the 
patient’s participation in the trial. They can include laboratory notes, ECG results, 
memoranda, pharmacy dispensing records, patient files, etc. The eCRFs should be completed 
by the investigator or a qualified designee from the site as soon as the data are available. 
As a matter of regulation, the investigator is responsible for the accuracy and authenticity of 
all clinical data entered onto eCRFs. Prior to database lock, each completed eCRF must be 
reviewed for accuracy by the investigator, corrected as necessary, and then approved. The 
investigator’s e-signature serves to attest that the information contained in the eCRFs has 
been reviewed by the investigator, and is true and accurate. The investigator will be required 
to electronically sign off the eCRF. 
The data will be verified for 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 EDC 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, and IRT provider. This data will need to be reconciled with the 
data recorded in the eCRF before it can be merged with the eCRF data into the clinical 
database. The CRO will provide a data management plan detailing this reconciliation. 
Adverse events, concomitant diseases, and medical history terms will be assigned to a lowest 
level term and a preferred term, and will be classified by high level term, high level group 
term, and primary system organ class 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. 
 
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 

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discretion. Such audits/inspections can occur at any time during or after completion of the 
trial. 

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10. ETHICS 
 Institutional Review Board or Independent Ethics Committee 
The investigator will provide 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. The investigator will supply 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. 
The investigator will report promptly to the IRB/IEC, any new information that may 
adversely affect the safety of patients or the conduct of the trial. Similarly, the investigator 
will submit written summaries of the trial status to the IRB/IEC annually, or more frequently 
if requested by the IRB/IEC. Upon completion of the trial, the investigator will provide the 
IRB/IEC with a brief report of the outcome of the trial, if required. 
 Ethical Conduct of the Trial 
This trial will be conducted and the informed consent will be obtained according to the 
ethical principles stated in the Declaration of Helsinki (2013), the applicable guidelines for 
GCP, or the applicable drug and data protection laws and regulations of the countries where 
the trial will be conducted. 
To comply with the Declaration of Helsinki (2013), argenx is currently assessing the 
appropriateness and possibility of making the trial drug available for clinical trial participants 
post-trial. 
 Patient Information and Informed Consent 
The investigator must explain to each patient 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 patient’s records. Each patient must be informed that participation in the trial is 
voluntary, that he/she may withdraw from the trial at any time, and that withdrawal of 
consent will not affect his/her subsequent medical treatment or relationship with the treating 
physician. 
The ICF will be used to explain the potential risks and benefits of trial participation to the 
patient in simple terms before the patient is screened. A separate ICF will be given in case of 
pregnancy of a female partner of a male patient. The ICF contains a statement that the 
consent is freely given, that the patient is aware of the risks and benefits of entering the trial, 
and that the patient is free to withdraw from the trial at any time. Written consent must be 
given by the patient, after the receipt of detailed information on the trial. 

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All patient information and ICFs must be available in the local and vernacular languages 
required at the site and include patient information sheets/brochures that outline the trial 
procedures. All ICF(s) must be signed and dated by the patient. 
Confirmation of a patient’s informed consent must also be documented in the patient’s 
medical record prior to any trial-related procedure under this protocol, including screening 
tests and assessments. 
The investigator is responsible for ensuring that the informed consent is obtained from each 
patient and for obtaining the appropriate signatures and dates on the informed consent 
document prior to the performance of any protocol procedures and prior to the administration 
of IMP. The investigator will provide each patient with a copy of the signed and dated 
ICF(s). 
 Patient Data Protection 
The ICF will incorporate (or, in some cases, be accompanied by a separate document 
incorporating) wording that complies with relevant data protection and privacy legislation. 

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11. TRIAL ADMINISTRATION 
 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 patient ICFs, laboratory test results, IMP inventory 
records, source documents, relevant correspondence, AE reports, and all other supporting 
documentation) as required by the applicable national regulatory requirements. The trial site 
should plan on retaining such documents for approximately 25 years after trial completion. 
The trial site should retain such documents until at least 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region, or at least 2 years after the formal discontinuation 
of clinical development of the IMP. The sponsor will notify the principal investigator of 
these events. 
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. Patient identification codes (patient names and corresponding trial 
numbers) will be retained for this same period of time. These documents may be transferred 
to another responsible party, acceptable to the sponsor, who agrees to abide by the retention 
policies. The investigator is required to notify the sponsor (or an authorized representative) in 
writing prior to changing the location or status of any essential clinical trial documents. The 
investigator must contact the sponsor prior to disposing of any trial records. 
No records should be disposed without the written approval of argenx BVBA. 
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. 
 Direct Access to Source Data/Documents 
The sponsor or designee, and auditor may access patient 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 
patient’s chart and eCRF records. Such information must be kept confidential and must have 
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 patient 
enrolled into the trial. 
The investigator is responsible for maintaining source documents. These will be made 
available for verification by the sponsor’s designated CRO monitor at each monitoring visit. 
The investigator must submit a completed eCRF for each patient who receives IMP, 

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regardless of duration. All supportive documentation submitted with the eCRF, such as 
laboratory or hospital records, should be clearly identified with the trial and patient number. 
Any personal information, including patient name, should be removed or rendered illegible to 
preserve individual confidentiality. 
 Investigator Information 
11.3.1. Investigator Obligations 
This trial will be conducted by qualified investigators under the sponsorship of argenx 
BVBA (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 site. 
The investigator is responsible for ensuring that all trial site personnel, including 
sub-investigators, 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. 
11.3.2. Protocol Signatures 
After reading the protocol, each investigator will sign the protocol signature page and send a 
copy of the signed page to the sponsor or representative. By signing the protocol, the 
investigator confirms in writing that he/she has read, understands, and will strictly adhere to 
the trial protocol, and will conduct the trial in accordance with ICH tripartite guidelines for 
GCP and applicable regulatory requirements. The trial will not be able to start at any site 
where the investigator has not signed the protocol. 
11.3.3. 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 
has been analyzed and reported and must be submitted to the sponsor for review and 

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comment prior to submission for publication or presentation. Trial patient identifiers will not 
be used in the publication of results. 
Authorship will be granted according to the International Committee of Medical Journal 
Editors criteria,15 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. 
11.3.4. Financing and Insurance 
The sponsor will fund the trial as outlined in the clinical trial agreement. 
The sponsor will obtain adequate global/local insurance for the trial participants including the 
trial patients 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. 

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12. 
REFERENCES 
1. 
Vaccaro C, Zhou J, Ober RJ, Ward ES. Engineering the Fc region of immunoglobulin 
G to modulate in vivo antibody levels. Nature biotechnology. 2005;23(10):1283. 
2. 
LPT31554. Laboratory of Pharmacology and Toxicology (LPT). 4-Week Subchronic 
Toxicity Study of ARGX-113 by Repeated 2-Hour Intravenous Infusion to 
Cynomolgus Monkeys - Multi Site Study. LPT Report No 31554. 2016:1163. 
3. 
Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, et al. 
Standardization of terminology, definitions and outcome criteria in immune 
thrombocytopenic purpura of adults and children: report from an international working 
group. Blood. 2009;113(11):2386-93. 
4. 
Terrell DR, Beebe LA, Vesely SK, Neas BR, Segal JB, George JN. The incidence of 
immune thrombocytopenic purpura in children and adults: A critical review of 
published reports. American journal of hematology. 2010;85(3):174-80. 
5. 
Fogarty PF, Segal JB. The epidemiology of immune thrombocytopenic purpura. Curr 
Opin Hematol. 2007;14(5):515-9. 
6. 
Kistangari G, McCrae KR. Immune thrombocytopenia. Hematology/oncology clinics 
of North America. 2013;27(3):495-520. 
7. 
Zufferey A, Kapur R, Semple J. Pathogenesis and Therapeutic Mechanisms in Immune 
Thrombocytopenia (ITP). Journal of Clinical Medicine. 2017;6(2):16. 
8. 
Cohen YC, Djulbegovic B, Shamai-Lubovitz O, Mozes B. The bleeding risk and 
natural history of idiopathic thrombocytopenic purpura in patients with persistent low 
platelet counts. Archives of Internal Medicine. 2000;160(11):1630-8. 
9. 
Norgaard M, Cetin K, Maegbaek ML, Kristensen NR, Ghanima W, Bahmanyar S, et 
al. Risk of arterial thrombotic and venous thromboembolic events in patients with 
primary chronic immune thrombocytopenia: a Scandinavian population-based cohort 
study. Br J Haematol. 2016;174(4):639-42. 
10. 
Neunert C, Terrell D, Arnold D, Buchanan G, Cines D, Cooper N, et al. American 
Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 
2019;3(23):3829-66. 
11. 
Miller AB HB, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer. 
1981;47(1):7. 
12. 
Josephson CD GS, Assmann SF, Castillejo MI, Strauss RG, Slichter SJ, Steiner ME, 
Journeycake JM, Thornburg CD, Bussel J, Grabowski EF, Neufeld EJ, Savage W, 
Sloan SR. Bleeding risks are higher in children versus adults given prophylactic platelet 
transfusions for treatment-induced hypoproliferative thrombocytopenia. Blood. 
2012;120(4):12. 
13. 
Signorovitch J BA, Grotzinger KM. Validation of the FACIT-fatigue subscale, selected 
items from FACT-thrombocytopenia, and the SF-36v2 in patients with chronic immune 
thrombocytopenia. Qual Life Res. 2011;20(10):7. 
14. 
O’Brien RG, Castelloe JM. Exploiting the Link between the Wilcoxon-Mann-Whitney 
Test and a Simple Odds Statistic. Proceedings of the Thirty-First Annual SAS Users 
Group International Conference. 2006:209-31. 
15. 
International Committee of Medical Journal Editors. Defining the role of authors and 
contributors. ICMJE website, http://www.icmje.org/recommendations/browse/roles-
and-responsibilities/defining-the-role-of-authors-and-contributors.html. 

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Trial Monitoring/Medical Monitoring 
ICON plc 
South County Business Park 
Leopardstown 
Dublin 18 
Ireland 
Home Care Vendor 
Accellacare In-Home Services (previously known as Symphony Clinical Research) (an ICON company) 
700 Deerpath Drive 
Vernon Hills, IL 60061-1802 
USA 
Clinical Trial Supply Management 
Fisher Clinical Services GmbH 
Steinbühlweg 69 
4123 Allschwil 
Switzerland 
Data Management, Biostatistics, Medical Data Review 
SGS Life Sciences (SGS LS), a division of SGS Belgium NV 
Generaal de Wittelaan 19 – A5 
Mechelen, 2800 
Belgium 
Drug Safety Reporting 
Parexel International 
1 Federal Street 
Billerica, MA 01821 
USA 

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Appendix 4 Possible Adaptations of Trial Protocol During COVID-19 Pandemic 
The aim of the ARGX-113-1801 trial is to evaluate the efficacy and safety of efgartigimod 
(ARGX-113) 10 mg/kg intravenous (IV) in adult patients 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 SoA, Table 2). 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 adverse 
events (AEs) reported during argenx clinical trials. 
Based on this risk/benefit assessment, the clinical trial ARGX-113-1801 can continue. 
However, it may not always be possible to perform all visits at the trial site during the 
pandemic. 
In order to allow patients with ITP to receive treatment with the IMP during the COVID-19 
pandemic, this appendix to the protocol has been developed. Only in case a visit to the trial 
site is absolutely not possible, a home visit or a visit at an alternative convenient location can 
be allowed. 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 patients to attend the trial 
visits at the trial site. As soon as the situation returns to normal, the measures specified here 
will not apply any more. 
It remains at the investigator’s discretion to assess if it is in the best interest of the patient to 
participate/continue in the trial. Note that the home nurse, who will go to the patient in case 
of a home visit, could also be another qualified person to perform all tasks (eg, a trained 
qualified physician). 

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Possible Adaptations in ARGX-113-1801 Trial Protocol During COVID-19 Pandemic 
Permission and Duration to Use the “Updated” Protocol Version 
This appendix to the protocol is intended for countries and/or 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 approval from the sponsor or the 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 in the eCRF for the 
applicable visit. 
Testing for COVID-19 
Additional testing for COVID-19 beyond that mandated by relevant local authorities for the 
patient’s screening and randomization is not required. See also Figure 2. 
Based on the exclusion criterion “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 patient at undue 
risk,” patients 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 should use personal protective equipment as directed by the 
local guidelines. 
Patients 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 as an AESI). The administration of IMP may be 
temporarily withheld if, in the opinion of the investigator, it could put the patient at undue 
risk in circumstances as clinically significant disease, including evidence of infection (see 
Section 4.5). 
During the pandemic, site staff or home nurse should call patients prior to each visit to 
enquire 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 below. In case the patient is 
placed in quarantine and is not able to receive IMP, the investigator can specify in 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 in the eCRF. 

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In case of (suspected) COVID-19, the patient will be treated as guided by the local health 
care system. Patients 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. In case the patient has to 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 patient can remain in the trial. 
The investigator can be contacted by the patient at any time by phone/video call in case of 
concerns. 
Forms completed at the patient’s home have to be taken back to the site for data entry. In 
case the trial site would be closed due to the COVID-19 situation, the completed forms have 
to 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. In case the trial site is closed 
due to the COVID-19 situation, an alternative convenient location considered appropriate by 
the investigator and the patient (and confirmed and approved by the sponsor) can be used (eg, 
an infusion center, local clinic, patient’s home). 
If it is not possible for the patient to go to the trial site and the patient cannot be screened or 
treated at an alternative convenient location due to the COVID-19 situation, the patient 
cannot start screening and has to wait until the situation changes and the patient is able to go 
to the trial site for the screening assessments. 
Please note that prospective protocol waivers remain unacceptable and that patients 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. In case the trial site would be closed 
due to the COVID-19 situation, an alternative convenient location considered appropriate by 
the investigator and the patient (and confirmed and approved by the sponsor) can be used (eg, 
an infusion center, local clinic, patient’s home). 
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 patient’s home (or an 
alternative convenient location) to conduct the visit(s). The investigator will talk to the 
patient via an audio or video interview to elicit AEs, concomitant medications, and the 
general well-being of the patient. The investigator will perform the WHO bleeding 
assessments using a video interview with the patient. This will be mentioned in the source 
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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 in order 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 
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 should be in line with applicable local regulations. 
Scheme for Home Visitsa 
Assessment 
Performed by 
Place/Method of 
Assessmenta 
x Patient eligibility 
Trained qualified physician 
Preferably at the trial site 
x 
Quality-of-life and 
patient-reported outcomes 
Patient 
At patient’s home 
x 
Weight 
x 
Electrocardiogram 
x 
Urinalysis 
x 
Urine pregnancy test 
x 
Blood sample (platelet 
count, hematology, 
chemistry, serum 
pregnancy, viral tests, 
pharmacodynamics, 
antiplatelet antibodies, 
anti-drug antibodies, 
pharmacokinetics) 
x 
IMP infusion 
Trained qualified nurse 
In person at patient’s home 
x 
Vital signs 
x 
Physical examination 
Trained qualified 
nurse/trained qualified 
physician 
In person at patient’s home 
x 
General bleeding 
assessment (WHO) 
Trained qualified physician 
In person at patient’s home or 
video call with investigator 
x 
Concomitant therapies 
x 
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). 

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Platelet Count 
A trained qualified nurse can draw the sample at the patient'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 and weight from the day before or all 
can be done on the day on which IMP should be administered according to the SoA. The 
platelet count should be performed at the same local laboratory throughout the trial. 
Quality-of-Life and Patient-Reported Outcomes 
SF-36, FACT-Th6, and FACIT-Fatigue can be completed at home (or an alternative 
convenient location) by the patient. 
Weight 
Calibrated scales can be provided to the home nurse or the patient. 
Vital Signs 
Vital signs can be performed 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. 
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 lab. 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 lab. The testing 
should preferably be done by the initially appointed central laboratory. 

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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 lab. The testing 
should preferably be done by the initially appointed central laboratory. 
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 lab. 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 lab. The testing 
should be done by the initially appointed central 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 lab. The testing 
should be done by the initially appointed laboratory. 
Anti-Drug 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 lab. 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) (pre- and post-dose) using the laboratory kits/requisition forms supplied by the 
central lab. The testing should be done by the initially appointed laboratory. 
IMP Infusions 
A trained qualified nurse can administer the IMP at the patient’s home (or an alternative 
convenient location). Detailed instructions on IMP management can be found in the Home 
Guide for Preparation and Administration. The patient has to be observed for infusion-related 
reactions by the trained qualified nurse for at least 30 minutes following the end of the 
infusion for safety monitoring based on the patient’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. 

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Adverse Events 
The assessment of adverse events can be performed at home (or an alternative convenient 
location) through a phone/video call with the investigator. 
Schedule of Assessments 
In the SoA below, the assessments preferably performed at the trial site are indicated with a 
solid dot “●”(ie, mandatory). The assessments that can be omitted in case 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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Appendix 5 Protocol Amendment History 
The protocol amendment Summary of Changes table for the current amendment is located 
directly before the Synopsis. The protocol amendment Summary of Changes table for the 
previous amendments can be found in this section. 
The major changes from Protocol Version 4.0 compared to Protocol Version 5.0 are 
summarized below. 
A strikethrough font is used to indicate deleted text and a bold font to indicate added text. 
Minor administrative editorial changes are not summarized in the following table: 
Summary of Changes Between Protocol Version 4.0 and Protocol Version 5.0 
Section(s) 
Change 
Rationale 
x Front page 
Medical Director: 
, MD 
argenx BVBA 
Industriepark Zwijnaarde 7 
B-9052 Zwijnaarde 
BELGIUM 
Phone: office 
 
Email: 
 
Internal restructure. 
 
24-Hour Urgent Medical Helpline Number: 
(+1) 919 674 5468857 957 5013 
Administrative change. 
 
Safety Mailbox/Fax: 
Email: be.life.saefax ma@sgs.com 
248700ADR@parexel.com 
Fax: +32 (0)15 29 93 941 833 644-0806 
Change in safety vendor. 
x Section DEFINITION 
OF TERMS 
Childbearing potential: 
Women of childbearing potential are defined as all female 
participants unless they are postmenopausal (defined by 
continuous amenorrhea) for at least 1 year with a follicle-
stimulating hormone (FSH) of >40 IU/L or are surgically 
sterile (ie, who had a hysterectomy, a bilateral 
salpingectomy, a bilateral oophorectomy, or have current 
documented tubal ligation or any other permanent female 
sterilization procedure). Determination of FSH levels can 
be used to confirm postmenopausal status in amenorrheic 
patients not on hormonal replacement therapy. 
Clarification. 

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x Synopsis 
x Section 4.1. Summary 
of Trial Design 
x Section 6.8.4. Rescue 
Therapy 
“Rescue therapy” is defined as an occurrence where 
the patient 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 patient. The start date/time of the occurrence is 
the start of the administration of the first rescue 
treatment. 
Clarification. 
 
Patients requiring more than 3 occurrences of rescue 
therapy more than 3 times will discontinue from IMP. 
 
x Synopsis 
x Section 3.1. Primary 
Endpoint 
x Section 4.2. 
Discussion of Trial 
Design 
x Section 8.4.1. Primary 
Endpoint Analysis 
Patients who discontinue treatment prior to visit 24 due to 
lack of efficacy (eg, need rescue therapy more than 3 
timesmore than 3 occurrences of rescue therapy) or due 
to an AE, and who have not achieved sustained platelet 
count response between week 19 and 24, are considered 
non-responders. 
 
x Section 4.4.2. Early 
Discontinuation from 
Treatment 
• patient has received more than 3 occurrences of rescue 
therapy more than 3 times 
 
x Section 8.4.1. Primary 
Endpoint Analysis 
• Main intercurrent events: 
i. early discontinuation of treatment (prior to visit 24) 
due to lack of efficacy (eg, need for rescue therapy 
more than 3 timesmore than 3 occurrences of rescue 
therapy) or due to an AE 
 
x Synopsis 
x Section 4.3.1. 
Inclusion Criteria 
5. Mean platelet count of <30×10⁹/L (and no single platelet 
count of >35×10⁹/L) from 23 qualifying counts: 1 platelet 
count collected, 2 during the screening period and the 
predose platelet count aton the day of randomization 
(visit 1). The 3 platelet counts must be over the course of 7 
to 14 days, with at least 2 days between any 2 counts. 
To allow more 
flexibility. 
x Synopsis 
x Section 4.3.1. 
Inclusion Criteria 
7. Women of childbearing potential (see DEFINITION OF 
TERMS) must have a negative serum pregnancy test at the 
screening visit and a negative urine pregnancy test at 
baseline before trial medication (infusion) can be 
administered. Women are considered of childbearing 
potential unless they are postmenopausal (defined by 
continuous amenorrhea) for at least 1 year with a follicle-
stimulating hormone (FSH) of >40 IU/L or are surgically 
sterilized (ie, women who had a hysterectomy, a bilateral 
salpingectomy, both ovaries surgically removed, or have a 
documented permanent female sterilization procedure 
including tubal ligation). Follicle-stimulating hormone can 
be used to confirm postmenopausal status in amenorrheic 
patients not on hormonal replacement therapy. 
Clarification 

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8. Women of childbearing potential should use a highly 
effective or acceptable method of contraception (ie, 
pregnancy rate of less than 1% per year) during the trial 
and for 90 days after the last administration of the IMP. 
They must be on a stable regimen, for at least 1 month: 
… 
• male or female condom with or without spermicide 
• cap, diaphragm, or sponge with spermicide. 
As per results of 
reproductive toxicology 
studies. 
 
9. Non-sterilized male patients who are sexually active 
with a female partner of childbearing potential must use an 
acceptable method of effective double contraception, ie, 
being a condom for male patients and a highly effective 
form of contraception for the female partner of 
childbearing potential (same as for female patients 
described in inclusion criterion 8). Male patients practicing 
true sexual abstinence (when this is in line with the 
preferred and usual lifestyle of the participant) can be 
included. Sterilized male patients who have had a 
vasectomy with documented aspermia post procedure can 
be included. In addition, male patients are not allowed to 
donate sperm during this period from signing of ICF, 
throughout the duration of the trial, and for 90 days after 
the last administration of IMP. 
 
x Synopsis 
22. Patients who received a live/live-attenuated vaccine 
within 4 weeks before randomization screening. The 
receipt of any inactivated, sub-unit, polysaccharide, or 
conjugate vaccine at any time before prior to 
screeningrandomization is not considered an exclusion 
criterion. 
Correction. 
x Section 4.3.2. 
Exclusion Criteria 
22. Patients who received a live/live-attenuated vaccine 
withinless than 4 weeks before screening. The receipt of 
any inactivated, sub-unit, polysaccharide, or conjugate 
vaccine at any time before prior to screening is not 
considered an exclusion criterion. 
 
x Synopsis 
x Section 4.3.2. 
Exclusion Criteria 
19. Patients who previously participated in a clinical trial 
with efgartigimod and have received at least 
1 administration of the IMP. 
Clarification. 
x Synopsis 
x Section 8.4.2. Key 
Secondary Endpoint 
Analyses Subject to 
Alpha Control 
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,If the primary endpoint is met, 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 pre-defined hierarchy resulted in 
a p-value <0.05. The order in the testing hierarchy of the 
key secondary endpoints is as follows: 
Clarification. 

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1. The proportion of patients with chronic ITP with a 
sustained platelet count response defined as achieving 
platelet counts of at least 50×109/L for at least 4 of the 6 
visits between week 19 and 24 of the trial (primary 
endpoint). 
2.1. 
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. 
3.2. 
The proportion of patients in the overall 
population (chronic and persistent ITP) with a sustained 
platelet count response defined as achieving platelet 
counts of ≥at least 50×109/L for at least 4 of the 6 visits 
between visits week 19 and week 24 of the trial. 
4.3. 
The incidence and severity of the WHO-classified 
bleeding events in the overall population. 
5.4. 
The proportion of patients in the overall 
population achieving platelet counts of ≥at least 
50×109/L for at least 6 of the 8 visits between week 17 
and 24 of the trial. 
x Table 1 Schedule of 
Assessments 
x Appendix 4 Possible 
Adaptations of Trial 
Protocol During 
COVID-19 Pandemic  
 
Table 2 Schedule of 
Assessments 
Footnote a: 
Screening Period: maximum 14 days 
 
Physical examination: assessment removed at visits 2, 4, 6, 
8, 10, 12, 14, 16, 18, 20, 22; assessment added at visits 5, 
9, and 17. 
To allow more 
flexibility. 
Urine pregnancy test: assessment removed at visits 2, 3, 4, 
“performed only on visits with an IMP infusion”, and 
Follow-up 1; assessment added at visits 5, 9, 13, 17, 21, 
and End-of-Treatment/Early Discontinuation. 
 

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x Table 1 Schedule of 
Assessments 
Footnote d: 
Platelet count is measured locally. Post-baseline platelet 
count and can be performed within 1 day of the next 
procedure as per the SoAschedule of assessments (both 
dosing and non-dosing visits). Eligible patients should 
have a mean platelet count of <30×109/L (and no single 
platelet count of >35×10⁹/L) from 23 qualifying counts:, of 
which 21 platelet count during the screening period and 
the predose platelet count aton the day of randomization 
(visit 1). The 3 platelet counts must be over the course of 7 
to 14 days, with at least 2 days between any 2 counts. The 
last platelet count is to be collected on the day of the 
randomization. 
To allow more 
flexibility. 
 
Footnote e: 
Patient-reported outcomes and QoL assessments need to 
be performed preferably after the platelet count 
assessment. 
 
 
Footnote g: 
Electrocardiogram will be assessed after the end of the 
IMP infusion, if any. If no IMP is administered, the ECG 
will be assessed preferably after the blood sample for 
platelet counts has been taken. 
 
 
Footnote r: 
Patients will remain at the site for at least 1 
hour30 minutes following the end of the infusion for 
safety monitoring based on the patient’s clinical status. 
To shorten the visit 
duration for the patient, 
based on supporting 
safety data. 
x Section 6.6. Dosing 
Administration for 
Each Patient 
Patients will be asked to remain at the site for at least 
1 hour30 minutes after the end of the infusion as part of 
routine safety monitoring. 
 
x Appendix 4. Possible 
Adaptations of Trial 
Protocol During 
COVID-19 Pandemic 
IMP Infusions 
The patient has to be observed for infusion-related 
reactions by the trained qualified nurse for at least 
1 hour30 minutes following the end of the infusion for 
safety monitoring based on the patient’s clinical status. 
 
x Table 2 Schedule of 
Assessments 
Footnote u: 
Patients will remain at home (or an alternative convenient 
location) for at least 1 hour30 minutes following the end 
of the infusion for safety monitoring based on the patient’s 
clinical status. 
 

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x Table 1 Schedule of 
Assessments 
Footnote i: 
At the screening visit, if the investigator detects 1 or more 
screening laboratory abnormalities, the result(s) should be 
confirmed by the central laboratory if still within the 
screening window. 
Correction. 
 
Footnote j: 
Only for women of childbearing potential. To be done 
at least every 4 weeks. 
Clarification. 
x Figure 1 
From visit 17 to 25 (ie, EoT): 
Fixed weekly or q2w dosing (no dosing at EoT) 
 
x Section 1.1. 
Background 
Information 
Efgartigimod encompasses IgG1 residues D2201-K447 
(EU numbering scheme) and has been modified with … 
Correction. 
 
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. 
 
x Section 1.2. Benefit-
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 reporting phase. 
Update. 
x Section 7.3.1. 
Adverse Events 
Definition of AE: 
An AE is any untoward medical occurrence in a clinical 
trial patient, temporally associated with the use of IMP, 
whether or not a pharmaceutical product is administered 
and which does not necessarily have a causal relationship 
with this treatment. An AE can therefore be any 
unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally 
associated with the use of a medicinal product or IMP, 
whether or not considered related to the medicinal product 
or IMP. 
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 IMP, whether or 
not considered related to the medicinal product or 
IMP. 
The following events will be collected as AEs: 
• Any abnormal laboratory test results (hematology, 
clinical chemistry, or urinalysis) or other safety 
assessments (eg, ECG, radiological scans, vital signs 
measurements), including those that worsen from 
baseline, considered clinically significant in the 
Clarification. 

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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 IMP 
administration even though it may have been present 
before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a 
suspected intervention-intervention interaction. 
• Signs, symptoms, or the clinical sequelae of a 
suspected overdose of either IMP or a concomitant 
medication. Overdose per se will not be reported as 
an AE/SAE unless it is an intentional overdose taken 
with possible suicidal/self-harming intent. Such 
overdoses should be reported regardless of sequelae. 
• “Lack of efficacy” or “failure of expected 
pharmacological action” per se will not be reported 
as an AE or SAE. Such instances will be captured in 
the efficacy assessments. However, the signs, 
symptoms, and/or clinical sequelae resulting from 
lack of efficacy will be reported as AE or SAE if they 
fulfill the definition of an AE or SAE. 
The following events will NOT be collected as AEs: 
• Any clinically significant abnormal laboratory 
findings or other abnormal safety assessments which 
are associated with the underlying disease, unless 
judged by the investigator to be more severe than 
expected for the patient’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 patient’s condition. 
• Medical or surgical procedure (eg, endoscopy, 
appendectomy): the condition that leads to the 
procedure is the AE. 
• Situations in which an untoward medical occurrence 
did not occur (social and/or convenience admission to 
a hospital). 
• Anticipated day-to-day fluctuations of pre-existing 
disease(s) or condition(s) present or detected at the 
start of the study that do not worsen. 
An AE can also be a new disease or exacerbation of an 
existing disease (a worsening in the character, frequency, 
or severity of a known condition), if considered clinically 
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Abnormal laboratory values, or test results, physical 
examination findings, and other abnormal investigational 
findings (ie, ECG) should not be reported as AEs unless 
they are considered clinically significant, eg, require 
therapy (eg, hematologic abnormality that requires 
transfusion or hematological stem cell support) or lead to 
treatment discontinuation. 
Death is not considered an AE in itself but a (fatal) 
outcome of an SAE. 
Definition of SAE 
An SAE, experience or reaction, is defined as any 
untoward medical occurrence (whether considered to be 
related to the IMP or not) that at any dose: 
• Rresults in death 
• Iis life-threatening (the term “life-threatening” in the 
definition of “serious” refers to an event in which the 
patient was at risk of death at the time of the event. It 
does not refer to an event, patient is 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 was more 
severe) 
• rRequires inpatient hospitalization or prolongation of 
existing hospitalization. In general, hospitalization 
signifies that the patient has been admitted (usually 
involving at least an overnight stay) at the hospital or 
emergency ward for observation and/or treatment 
that would not have been appropriate in the 
physician’s office or outpatient setting. 
Complications that occur during hospitalization are 
AEs. If a complication prolongs hospitalization or 
fulfills any other seriousness criteria, the event will 
be considered as serious. When in doubt as to 
whether “hospitalization” occurred or was necessary, 
the AE should be considered serious.However, a 
planned hospitalization related to the administration of 
IMP, is not considered an SAE. 
Hospitalization for elective treatment of a pre-existing 
condition that did not worsen from baseline is not 
collected as an AE.(Hospital admissions and/or surgical 
operations planned before a trial are not considered SAEs 
or if the illness or disease, which caused hospitalization, 
existed before the patient was enrolled in the trial, 
provided that it did not deteriorate in an unexpected way 
during the trial. However, the condition for which the 
surgery is required may be an AE). 
• Rresults in persistent or significant disability or 
incapacity 

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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. 
• Iis a congenital abnormality or birth defect 
• oOther 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 
medically significant events, which do not meet any of 
the criteria above, but may jeopardize the patient and or 
may require medical or surgical intervention to prevent 
1 of the other serious outcomes listed in the above 
definition above.  
Examples of such events include invasive or malignant 
cancers, intensive treatment for allergic 
bronchospasm,are blood dyscrasias (eg, neutropenia or 
anemia requiring blood transfusion, etc.) or, 
convulsions, or development of intervention 
dependency or intervention abuse that do not result in 
inpatient hospitalization. 
An unexpected AE is any adverse drug event, which is not 
listed in the reference safety information in the current IB 
or is not listed at the specificity or intensity that has been 
observed. 
Suspected adverse reaction means any AE for which there 
is a reasonable possibility that the drug caused the AE. 
Each AE is to be evaluated for duration, severity (using 
the CTCAE criteria version 5.0), seriousness, and causal 
relationship to the IMP or trial procedures using the 
CTCAE criteria. The action taken with the investigational 
drug and the outcome of the event must also be recorded. 
 
Severity 
Note: a semi-colon indicates “or” within the description 
of the grades. 

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x Section 7.3.3. Vital 
Signs, Physical 
Examination, and 
Electrocardiogram 
If no IMP is administered, the ECG will be assessed 
preferably after the blood sample for platelet counts has 
been taken. 
To allow more 
flexibility. 
x Section 8.4.3. 
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 above. 
Correction. 
x Appendix 2. 
Administrative 
Structure 
Home Care Vendor 
Symphony Clinical Research (an ICON company) 
700 Deerpath Drive 
Vernon Hills, IL 60061-1802 
Illinois 
USA 
Administrative update. 
 
Data Management, Biostatistics, Drug Safety Reporting, 
Medical Data Review 
Change in safety vendor. 
 
Drug Safety Reporting 
Parexel International 
8 Federal Street 
Billerica, MA 01821 
USA 
 
x Appendix 4 Possible 
Adaptations of Trial 
Protocol During 
COVID-19 Pandemic 
Testing for COVID-19 
Based on the exclusion criterion 18 “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 patient at undue risk,” patients with ongoing 
COVID-19 would be excluded from participation in the 
trial. 
Generalization. 
 
Screening Visit 
The screening assessments should be performed at the trial 
site. In case the trial site is closed due to the COVID-19 
situation, an alternative convenient location considered 
appropriate by the investigator and the patient (and 
confirmed and approved by the sponsor) can be used (eg, 
an infusion center, local clinic, patient’s home). 
Clarification. 

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x Appendix 4 Possible 
Adaptations of Trial 
Protocol During 
COVID-19 Pandemic 
Baseline visit 
The baseline visit should be performed at the trial site. In 
case the trial site would be closed due to the COVID-19 
situation, an alternative convenient location considered 
appropriate by the investigator and the patient (and 
confirmed and approved by the sponsor) can be used (eg, 
an infusion center, local clinic, patient’s home). 
Clarification. 
 
Possible Home Visits/Home Assessments 
The investigator will perform the WHO bleeding 
assessments using a video interview with the patient. 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. 
x Appendix 4 Possible 
Adaptations of Trial 
Protocol During 
COVID-19 Pandemic  
 
Table 2 Schedule of 
Assessments 
Footnote e: 
Platelet count is measured locally. Post-baseline platelet 
count and can be performed within 1 day of the next 
procedure as per the SoAschedule of assessments (both 
dosing and non-dosing visits). Eligible patients should 
have a mean platelet count of <30×109/L (and no single 
platelet count of >35×10⁹/L) from 23 qualifying counts:, of 
which 21 platelet count during the screening period and 
the predose platelet count aton the day of randomization 
(visit 1). The 3 platelet counts must be over the course of 7 
to 14 days, with at least 2 days between any 2 counts. The 
last platelet count is to be collected on the day of the 
randomization. 
To allow more 
flexibility. 
 
Footnote f: 
Patient-reported outcomes and QoL assessments need to 
be performed preferably after the platelet count 
assessment. 
 
 
Footnote g: 
Weight can be measured, together with the platelet 
count, within 1 day before the next procedure. 
 
 
Footnote i: 
Electrocardiogram will be assessed after the end of the 
IMP infusion, if any. If no IMP is administered, the ECG 
will be assessed preferably after the blood sample for 
platelet counts has been taken. 
 

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x Appendix 4 Possible 
Adaptations of Trial 
Protocol During 
COVID-19 Pandemic  
 
Table 2 Schedule of 
Assessments 
Footnote k: 
At the screening visit, if the investigator detects 1 or more 
screening laboratory abnormalities, the result(s) should be 
confirmed by the central laboratory if still within the 
screening window. 
Correction. 
 
Footnote l: 
Only for women of childbearing potential. To be done 
at least every 4 weeks. 
Clarification. 
 
 
 

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x Synopsis 
x Section 3.2. 
Secondary Endpoints 
x Section 8.4.2. Key 
Secondary Endpoint 
Analyses Subject to 
Alpha Control 
Incidence and severity of the WHO-classified bleeding 
events in the overall population. 
Clarification. 
x Synopsis 
x Section 4.1. Summary 
of Trial Design 
x Section 4.3. Selection 
of Trial Population 
Approximately 117 patients with chronic ITP and up to 
39 patients with persistent ITP will be randomized. 
Recruitment will end as from 117 patients with chronic ITP 
have been includedrandomized. 
Correction. 
x Synopsis 
x Section 4.1. Summary 
of Trial Design 
x Section 6.8.4. Rescue 
Therapy 
Rescue therapy is allowed post-baseline during the 24-
week treatment trial period for patients with a platelet 
count of <30×10⁹/L and 1 of the following: 
For consistency. 
x Synopsis 
x Section 4.1. Summary 
of Trial Design 
x Section 5.4.1. 
Screening and 
Treatment 
Post-baseline pPlatelet count can be performedwill be 
assessed within 1 day of the next procedure as per 
schedule of assessments (both dosing and non-dosing 
visits) at the start of each visit  before the administration of 
the IV infusion, allowing the results to be incorporated into 
the criteria above. 
To allow more flexibility. 
Continued weekly dosing for patients requiring rescue 
therapy, unless deemed medically inappropriate by the 
investigator. 
Covered already in the 
protocol by the provision 
that the administration of 
IMP may be temporary 
withheld if, in the opinion 
of the investigator, it 
could put the patient at 
undue risk. 
x Synopsis 
x Section 4.1. Summary 
of Trial Design 
x Section 6.8.1. 
Concurrent ITP 
Therapy 
Permitted concurrent ITP medications include oral 
corticosteroids, oral immunosuppressants, 
dapsone/danazol, fostamatinib, and/or eltrombopag oral 
thrombopoietin receptor agonists (TPO-RAs; inclusion 
criterion n°6, Section 4.3.1). 
The only eExceptions are patients who are receiving 
concurrent treatment with the thrombopoietin receptor 
agonist oral (TPO-RAs) eltrombopag in whom dose 
reduction changes are of eltrombopag is permitted at label-
defined platelet thresholds (see SAFETY section), and 
patients who are receiving concurrent treatment with 
fostamatinib, in whom dose changes or stopping of 
treatment is allowed in label-defined conditions. 
To consider all oral TPO-
RAs. 
Fostamatinib has been 
added upon request of the 
US sites. 
Specifying that 
fostamatinib has label-
specific dosing changes 
to be taken into account. 

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x Synopsis 
x Section 4.1. Summary 
of Trial Design 
x Section 6.8.4. Rescue 
Therapy 
Patients who were receiving biweekly q2w dosing at the 
time of rescue therapy will have the IMP administration 
frequency increased to weekly., unless deemed medically 
inappropriate by the investigator. 
Covered already in the 
protocol by the provision 
that the administration of 
IMP may be temporary 
withheld if, in the opinion 
of the investigator, it 
could put the patient at 
undue risk. 
x Synopsis 
x Section 4.1. Summary 
of Trial Design 
x Section 5.4. Treatment 
Period 
If the platelet count is >250×109/L in a patient receiving 
eltrombopag, the dose of eltrombopag should be reduced in 
line with clinical practice recommendations. 
“Eltrombopag” has been 
replaced with “oral TPO-
RAs” and Section 6.8.1. 
Concurrent ITP Therapy 
describes that the dose 
needs to be adjusted at 
label-specific thresholds, 
which makes this 
statement redundant. 
x Synopsis 
Planned Number of Sites: Approximately 95 125 sites 
Update based on current 
site selection. 
x Synopsis 
x Section 4.3.1. 
Inclusion Criteria 
3. Confirmed ITP diagnosis, at least 3 months before 
randomization and according to the American Society of 
Hematology Criteria 2011, and no known other etiology for 
thrombocytopenia. 
Removed the year of 
release of the American 
Society of Hematology 
Criteria and updated the 
references with the most 
recent publication on the 
American Society of 
Hematology Criteria 
x Synopsis 
x Section 4.3.1. 
Inclusion Criteria 
x Section 4.1. Summary 
of Trial Design 
x Section 6.8.1. 
Concurrent ITP 
Therapy 
Permitted concurrent ITP medications include oral 
corticosteroids, oral immunosuppressants, 
dapsone/danazol, fostamatinib, and/or oral TPO-
RAseltrombopag. 
Regulatory approval of 
fostamatinib as ITP 
therapy. 
x Synopsis 
x Section 4.3.2. 
Exclusion Criteria 
1. ITP/thrombocytopenia associated with another 
condition, eg, lymphoma, chronic lymphocytic leukemia, 
viral infection, autoimmune disorders, thyroid disease, 
human immunodeficiency virus (HIV), hepatitis, induced 
or alloimmune thrombocytopenia, or thrombocytopenia 
associated with myeloid dysplasia. 
Correction. 
History of any major thrombotic or embolic event (eg, 
myocardial infarction, stroke, pulmonary embolism, 
deep venous thrombosis) within 12 months prior to 
randomization. 
 

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Section(s) 
Change 
Rationale 
x Synopsis 
x Section 4.3.2. 
Exclusion Criteria 
x Section 6.8.2. 
Prohibited Medication 
and Therapy prior to 
Randomization 
Use of IVIg, (IV, subcutaneous, or intramuscular route), or 
plasmapheresis (PLEX), 4 weeks prior to randomization. 
Administrative change. 
Use of fostamatinib within 4 weeks prior to randomization. 
Regulatory approval of 
fostamatinib as ITP 
therapy. 
x Synopsis 
x Section 4.3.2. 
Exclusion Criteria 
The following exclusion criterion was added: 
Patients who received a live-attenuated vaccine within 
4 weeks before randomization. The receipt of any 
inactivated, sub-unit, polysaccharide, or conjugate 
vaccine at any time prior to randomization is not 
considered an exclusion criterion. 
Preventive protection 
measure for patients. 
x Synopsis 
(Objectives/Criteria 
for Evaluation/ 
Statistical Methods 
and Plan) 
x Section 2.1. Primary 
Objective 
x Section 3.1. Primary 
Endpoint 
x Section 3.2. 
Secondary Endpoints 
x Section 4.2. 
Discussion of Trial 
Design 
x Section 8.4.1. Primary 
Endpoint Analysis 
x Section 8.4.2. Key 
Secondary Endpoint 
Analyses Subject to 
Alpha Control 
“visit” has been replaced with “week.” 
To take into account the 
effect of the full 24-week 
treatment period for the 
efficacy evaluation. 
x Synopsis 
x Section 3.2. Secondary 
Endpoints 
Pharmacokinetic parameters of efgartigimod: maximum 
observed serum concentration (Cmax) and serum 
concentration observed predose (Ctrough). 
Clarification. 
x Synopsis 
x Section 5.4. Treatment 
Period 
The End-of-Treatment/Early Discontinuation visit should 
be completed for all patients, whether they roll-over to the 
open-label extension trial (ARGX-113-1803), discontinue 
the trial early, or complete the 24-week treatment trial 
period. 
For consistency. 

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x Synopsis 
x Section 8.4.2. Key 
Secondary Endpoint 
Analysis Subject to 
Alpha Control 
Key Secondary Endpoints 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 
patient this 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) and history of splenectomy (yes 
versus no) will be used to compare the extent of disease 
control between both treatment groups. The 2-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 α=0.05. An estimate of the 
location shift will be provided, along with the associated 
95% confidence interval. 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, will be analyzed using Cox regression 
methodology. The 2 treatment groups will be compared 
using a Cox proportional hazards regression model 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. A Wald 
test will be used to test the null hypothesis that the log of 
the hazard ratio on placebo and efgartigimod is equal to 
zero (or, equivalently, that the hazard ratio is equal to one) 
against the alternative that it is different from zero (or, 
equivalently, that the hazard ratio is different from one). 
From the model, the hazard ratio for efgartigimod vs. 
placebo will be provided, along with the associated 95% 2
sided Wald type CI and 2 sided p value. The hazard ratio 
will estimate the relative probability of disease control with 
efgartigimod as compared to placebo. The data will also be 
displayed using Kaplan Meier curves and the median 
length of disease control will be displayed by randomized 
treatment arm. 
To allow patients who are 
in disease control during 
much of the trial, but lose 
it near the end, to 
contribute more to the 
final estimate for length 
of disease control. In the 
original time-to-event 
analysis these patients 
would be censored at the 
time when they lose the 
response. The 
time-to-event analysis is 
still planned as 
complementary analysis. 

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Section(s) 
Change 
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x Table 1 Schedule of 
Assessments 
Table footnote k has been added to the assessment 
“Pharmacodynamics”: 
In order to maintain the blind, the IgG testing cannot 
be performed locally. 
To avoid unintentional 
unblinding. 
x List of Abbreviations 
q2w 
biweekly/every other week 
Administrative change. 
x Definition of Terms 
Blinding: 
… In a double-blind trial, the patient, the investigator, site 
staff, and sponsor staff who are involved in the treatment 
or clinical evaluation of the patients and the review or 
analysis of data are all unaware of the treatment 
assignment. 
Administrative change. 
x Section 1.2. Benefit-
Risk Assessment 
More specifically, a phase 2 trial (ARGX-113-1603) in 
patients with ITP enrolled a patient population who was 
predominantly refractory to previous lines of ITP therapy, 
with the majority of patients having long-standing disease, 
prior ITP treatment exposure and approximately half with 
baseline platelet count of <15×109/L. Thirty seven out of 
38 patients (97.4%) had a history of receiving at least 1 ITP 
therapy, either historical or ongoing at baseline. The 
median number of prior unique treatments for ITP was 2.0 
(range 0 10). Twenty seven out of 38 patients (71.1%) 
were receiving at least 1 concomitant ITP therapy at 
baseline, including corticosteroids, immunosuppressants, 
and TPO RAs. 
… 
In clinical trials to date, efgartigimod has been well 
tolerated in healthy adult subjects and patients with MG 
and ITP, separately: the majority of treatment-emergent 
AEs (TEAEs) were considered to be mild (grade 1) in 
severity. In the completed phase 1 trials ARGX-113-
1501, ARGX-113-1702, and ARGX-113-1901 in healthy 
volunteers, and in the phase 2 trial ARGX-113-1602 in 
patients with MG, no grade ≥3 TEAEs were reported and 
no TEAE led to discontinuation. In the phase 2 trial 
ARGX-113-1603 in patients with ITP, 1 TEAE with 
grade 4 was reported (thrombocytopenia), considered 
unrelated to treatment, and led to treatment discontinuation. 
In the MG trial ARGX 113 1602, the most common TEAE 
was headache, reported in 4 of 12 patients (33%) treated 
with efgartigimod 10 mg/kg and 3 of 12 patients (25%) 
who received placebo. In the ITP trial ARGX 113 1603, 
headache was reported in 1 of 13 patients (7.7%) treated 
with efgartigimod 5 mg/kg and 2 of 12 patients (16.7%) 
who received placebo. In the ITP trial, the most common 
TEAEs were petechiae 2 of 13 patients (15.4%) in the 5 
mg/kg group and 2 of 13 patients (15.4%) in the 
efgartigimod 10 mg/kg groups, hypertension in 2 of 13 
patients (15.4%) treated with efgartigimod 10 mg/kg and 1 
To refer to the latest 
version of the 
Investigator’s Brochure 
to ensure the latest 
information is available. 

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Section(s) 
Change 
Rationale 
of 12 patients (8.3%) with placebo, and vomiting in 2 of 13 
patients (15.4%) treated with efgartigimod 10 mg/kg. 
No deaths have occurred in any efgartigimod trial as of 
data cut off date. There is no evidence of an increased risk 
of infection. 
The only clinically relevant laboratory findings, observed 
after repeated administration of  efgartigimod 10 mg/kg, 
were decreased monocyte count (reported for 1 patient with 
MG) and abnormal differential white blood cell count in 
individual healthy volunteers after administration of a 
single dose of 25 and 50 mg/kg efgartigimod, which was 
associated with decreased CD8, CD3, CD56, CD4, and 
CD19 lymphocyte levels. All events were short lasting and 
resolved within 2 to 4 days. An increase in C reactive 
protein was reported in individual healthy volunteers 
administered 25 and 50 mg/kg efgartigimod. All events 
resolved within 3 to 6 days and were in general not 
associated with signs of fever or serious infections. 
In non clinical toxicology trials repeated administration of 
100 mg/kg (15 infusions, every 2 days) efgartigimod was 
associated with reversible Kupffer cell 
hypertrophy/hyperplasia in rat, as well as hepatic 
cytoplasmic alterations and degeneration, and diffuse 
mixed inflammatory cell infiltrates (correlating with 
alanine aminotransferase [ALT] increase) in cynomolgus 
monkey. No such observations were made in a 6 month 
chronic dosing trial where cynomolgus monkeys were 
treated with 100 mg/kg efgartigimod once every week. In 
healthy volunteers, patients with MG, or with ITP, no 
clinically significant changes were observed in liver 
enzyme levels (including ALT and aspartate 
aminotransferase), serum lipids, or electrolytes (including 
potassium). 
No clinically significant changes in vital signs and/or 
electrocardiogram (ECG) findings have been observed in 
clinical trials to date. 
Safety for use during pregnancy has not been established. 
Therefore, efgartigimod should not be administered to 
pregnant or lactating women. No fertility trials have been 
performed so far Reproductive toxicity trials are 
completed and in reporting phase. 
In summary, taking into account the efficacy and safety 
data collected up to date, the benefit risk assessment allows 
further testing of efgartigimod. 
Please refer to the current Investigator’s Brochure for 
more information regarding the preclinical and clinical 
trials, and the potential risks and benefits of 
efgartigimod. In summary, the favorable balance 
between risks and anticipated efficacy/benefits supports 
the use of efgartigimod in clinical development. 

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Section(s) 
Change 
Rationale 
x Section 1.3. Trial 
Rationale 
The aim is to achieve the maximum possible proportion of 
patients with a platelet count improvement and then assess 
whether this can be sustained in the last 5 weeks (visits 19 
to 24) of trial treatment. 
Correction. 
x Section 4.2. 
Discussion of Trial 
Design 
The chosen primary endpoint in this trial is the proportion 
of patients with chronic ITP that have a sustained platelet 
count response … 
Administrative change. 
x Section 4.4.1. Early 
Discontinuation from 
Trial 
the IMP treatment code is broken unblinding occurred 
Correction. 
x Section 4.7. Screen 
failures, Rescreening, 
and Retesting 
Patients may be rescreened (ie redoing the full assessments 
as per SoA, Table 1) or retested once (ie redoing 1 test) if 
still within the screening period. 
 
 
A patient who has clinical laboratory tests values meeting 
1 or more exclusion criteria which are not in line with the 
medical history and clinical evaluation of the patient, 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 allowed within the screening period. If not feasible, the 
patient should be rescreened. 
 
x Section 5. Trial 
Procedures 
Every effort should be made to schedule every visit on the 
exact day (which is relative to baseline randomization 
[visit 1]) as described in the SoA (Table 1). 
Clarification. 
 
At all visits after screening, tThe platelet count needs to be 
performed within 1 day prior to any other assessment 
followed by the weight assessment (only on IMP dosing 
visits). 
To allow more flexibility. 
x Section 6.2. Identity of 
Investigational 
Medicinal Product 
The IMP (efgartigimod or placebo) will be supplied to the 
pharmacy at the investigational site (and stored at a 
temperature of 2°C to 8°C or 35°F to 46°F), by and under 
the responsibility of the sponsor’s designated IMP supply 
vendor, who will also provide. For each IMP batch at the 
site, the investigator with will receive the certificate of 
analysis, certificate of conformity, and European Union 
qualified person release documents. 
Clarification. 
x Section 6.4. Storage of 
Investigational 
Medicinal Products 
The IMP must be stored refrigerated (2°C to 8°C or 35°F 
to 46°F) in its secondary packaging, … 
Administrative change. 

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Section(s) 
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x Section 6.7. Blinding 
This is a randomized, double-blinded, placebo-controlled 
trial with limited access to the IMP treatment assigned (see 
also DEFINITION OF TERMS). The IMP treatment each 
patient receives will not be disclosed to the blinded site 
staff, including the investigator, trial coordinator, patient, 
sponsor, or sponsor’s designee. The storage and 
preparation of IMP will be at a secured location that is not 
accessible to blinded investigational staff. 
Clarification 
x Section 6.7.1. 
Emergency 
Unblinding 
If the blind is broken by the investigator it may be broken 
only for the patient concerned, and the IMP treatment 
assignment should not be revealed to the trial team 
members from the sponsor, nor from the sponsor’s 
designated CRO, or pharmacy personnel, or other site 
staff. Once unblinded, the patient will be discontinued 
from the trial and will be followed for 4 weeks for ongoing 
safety and efficacy monitoring. The follow up period will 
consist of 2 biweekly visits. 
The sponsor and monitor at the sponsor’s designated CRO 
must be notified immediately if a patient and/or 
investigator is unblinded during the course of the trial. 
Pertinent information regarding the circumstances of 
unblinding of a patient’s IMP treatment code must be 
documented in the patient’s source documents and eCRF. 
Once unblinded, the patient will be early discontinued from 
the trial and followed-up for 4 weeks (2 biweekly q2w 
visits). 
Correction. 
x Section 6.8. Prior 
Treatments and 
Concomitant 
Medications 
“TPO” has been replaced with “TPO-RA.” 
Correction. 
x Section 6.8. Prior 
Treatments and 
Concomitant 
Medications 
x Section 6.8.1. 
Concurrent ITP 
Therapy 
The sentence “The washout periods as specified in 
exclusion criteria 2 to 9 must be followed.” Has been 
moved from Section 6.8.1. to Section 6.8. 
Clarification. 

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Section(s) 
Change 
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x Section 8.1. 
Determinations of 
Sample Size 
For the first key secondary endpoint “extent of disease 
control,” assuming a median 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 of 14 10 weeks for patients receiving 
efgartigimod and 3 weeks for patients receiving placebo, a 
total of N=117 patients will ensure a power of >99.9% (two 
sided α of 0.05) to detect a significant difference between 
both treatment groups. For ensuring a power of at least 
90%, a total number of N=27 54 patients 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 versus placebo. 
To allow patients who are 
in disease control during 
much of the trial, but lose 
it near the end, to 
contribute more to the 
final estimate for length 
of disease control. In the 
original time-to-event 
analysis these patients 
would be censored at the 
time when they lose the 
response. The 
time-to-event analysis is 
still planned as 
complementary analysis. 
x Section 8.4.1. Primary 
Endpoint Analysis 
Handling of missing data 
Missing data for reason of 1 of the main intercurrent events 
will be handled as described above. Missing data for other 
reasons will be imputed by multiple imputation. Details on 
handling other missing data will be provided in the SAP. 
Correction. 

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Section(s) 
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x Section 8.4.2. Key 
Secondary Endpoint 
Analysis Subject to 
Alpha Control 
The main event and censoring rules are as follows, where 
event is defined as “loss of disease control”: 
Situation 
Date of event or 
censoring 
Outcome 
No occurrence of platelet 
count of ≥50×109/L 
throughout 24 week 
treatment period 
Date of baseline 
Event 
Early discontinuation of 
treatment (prior to W24) 
Date of treatment 
discontinuation 
Event 
Rescue therapy started 
Date of initiation 
of rescue therapy 
Event 
Dose and/or frequency of 
concurrent ITP therapy 
increased 
Start date of 
increase 
Event 
Disease control at end of 24-
week treatment period 
Date of last 
assessment 
(analysis visit) 
Censored 
Missing platelet counts for other reasons than those 
mentioned in the final event and censoring rules table (as 
detailed in the SAP) will be imputed by multiple 
imputation. Sensitivity analyses will be conducted to assess 
the robustness of the analysis results to the applied 
imputation method. 
When 1 of the intercurrent events described in 
Section 8.4.1 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. 
Missing bleeding assessments for reasons of 1 of the main 
intercurrent events will not be imputed, but the offset term 
will be adapted accordingly to reflect the assessment period 
until the occurrence or start of the intercurrent event. 
Missing bleeding assessment for other reasons will be 
imputed by multiple imputation. 
To allow patients who are 
in disease control during 
much of the trial, but lose 
it near the end, to 
contribute more to the 
final estimate for length 
of disease control. In the 
original time-to-event 
analysis these patients 
would be censored at the 
time when they lose the 
response. The 
time-to-event analysis is 
still planned as 
complementary analysis. 

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The major change from Protocol Version 2.0 compared to Protocol Version 3.0 is summarized 
below. 
A bold font is used to indicate added text. Minor administrative editorial changes are not 
summarized in the following table: 
Summary of Changes Between Protocol Version 2.0 and Protocol Version 3.0 
Section(s) 
Change 
Rationale 
x Section 7.3.1 
Adverse Events 
A bullet was added to the definition of serious AE: 
x other: medically significant events, which do not meet 
any of the criteria above, but may jeopardize the 
patient and may require medical or surgical 
intervention to prevent 1 of the other serious outcomes 
listed in the definition above. Examples of such events 
are blood dyscrasias (eg, neutropenia or anemia 
requiring blood transfusion, etc.) or convulsions that 
do not result in inpatient hospitalization. 
Alignment of the protocol 
with ICH E2A guidelines 
and the categories of 
seriousness in the SAE 
form. 

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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 administrative changes involving document formatting and renumbering of sections, 
grammar, syntax, punctuation, updating of the list of abbreviations, updating abbreviations in 
the body of the document, updating of cited references, and other editorial changes are not 
summarized in the following table: 
Summary of Changes Between Protocol Version 1.0 and Protocol Version 2.0 
Section(s) 
Change 
Rationale 
SIGNATURE OF 
SPONSOR 
Version 2.0: 
 
Change in the individual 
fulfilling the role of Chief 
Medical Officer 
x Synopsis 
x Section 4.1 
Summary of Trial 
Design 
The total maximum trial duration per patient is up to 30 
31 weeks: 
- 
Up to 2 weeks of screening 
- 
24 weeks treatment period 
- 
End-of-Treatment visit 1 week after visit 24 
- 
4 weeks of follow-up 
Clarified timing of the 
end-of-treatment visit and 
updated the total trial 
duration accordingly. 
Synopsis 
The number of planned sites changed  
Version 2.0: approximately 80 95 sites 
As a result from the trial 
feasibility assessment, the 
number of sites will be 
increased. 
 
Version 2.0: 
Planned Countries: This trial is a global, multicenter trial 
United States, Europe, and Japan (European countries to be 
determined) (this list is not exhaustive) 
 

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Section(s) 
Change 
Rationale 
x Synopsis 
x Section 1.3 Trial 
Rationale 
x Section 4.1 
Summary of Trial 
Design 
x Section 4.3.1 
Inclusion Criteria 
x Section 8.4.1 
Primary Endpoint 
Analysis 
Eligibility criteria changed from 1 prior therapy to 
2 prior therapies: 
Version 2.0: At the start of the trial, the patient is either 
on concurrent ITP treatment(s) and has received Patients 
have previously received at least 1 typical ITP therapyat 
least 1 prior therapy for ITP in the past, or the patient is 
not on treatment for ITP but has received at least 2 prior 
treatments for ITP and are continuing at least 1 concurrent 
therapy while on the study. Patients receiving permitted 
concurrent ITP treatment(s) at baseline, must have been 
stable in dose and frequency for at least 4 weeks prior to 
randomization. 
(The following sentence was also deleted in Section 1.3 Trial 
Rationale: The trial requires patients to have had previous 
exposure to an ITP treatment.) 
Change in eligibility 
criteria implemented at 
the request of the FDA. 
x Synopsis 
x Section 4.3.1 
Inclusion Criteria 
Version 2.0: 
Non-sterilized male patients who are sexually active with a 
female partner of childbearing potential must use effective 
double contraception, of which 1 method must be a barrier 
method and the other another barrier method or being a 
condom for male patients and a highly effective form of 
contraception as described above for the female partner 
women of childbearing potential (same as for female 
patients described in inclusion criterion 8) (eg, condom 
with spermicidal cream or jelly, 1 hormonal plus 1 barrier 
method, IUD plus 1 barrier method, or 2 simultaneous barrier 
methods). Male patients practicing true sexual abstinence 
(when this is in line with the preferred and usual lifestyle of 
the participant) can be included. Sterilized male patients who 
have had vasectomy with documented aspermia post 
procedure can be included. In addition, male patients are not 
allowed to donate sperm during this period from signing of 
ICF, throughout the duration of the trial, and for 90 days 
after the last administration of IMP. 
To align with the CTFG 
recommendations. 

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Section(s) 
Change 
Rationale 
x Synopsis 
x Schedule of 
Assessments 
x Section 4.3.1 
Inclusion Criteria 
Removed Inclusion Criterion 3: For Japanese patients 
enrolled in sites in Japan only: A Japanese patient is defined 
as a patient whose parents and 4 grandparents are Japanese, 
who has the Japanese nationality, was born in Japan, has not 
lived outside of Japan for a total of >10 years, and currently 
lives in Japan. 
A separate region-
specific protocol 
amendment for Japan will 
be prepared. 
x Synopsis 
x Section 4.1 
Summary of Trial 
Design 
Version 2.0: 
Non Japanese patients with chronic ITP will be stratified 
according to the following factors: 
Patients will be stratified according to the following 
factors: 
x History of splenectomy (yes vs. no) 
x Receiving concurrent ITP therapies at baseline (yes vs. no) 
For Japanese patients enrolled in sites in Japan (inclusion 
criterion n°3), there will be no stratification ie, 
randomization will be performed within the full set of 
Japanese patients. For non Japanese patients with persistent 
ITP, there will also be no stratification. 
 
x Synopsis 
x Section 4.3.1 
Inclusion Criteria 
Version 2.0: Male or female patient aged ≥18 years (for 
Japan only, patients aged ≥20 years). 
 
x Synopsis 
x Schedule of 
Assessments 
x Section 4.3.2 
Exclusion Criteria 
Removed Exclusion Criterion 12: For patients enrolled in 
sites in Japan only: positive Helicobacter pylori test at the 
screening visit. 
 

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Section(s) 
Change 
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x Synopsis 
x Definition of Terms 
x Section 4.3.1 
Inclusion Criteria 
Removed that the FSH value must be within the 
postmenopausal range per the laboratory. 
Version 2.0: Women of childbearing potential (see 
DEFINITION OF TERMS) must have a negative serum 
pregnancy test at the screening visit and a negative urine 
pregnancy test at baseline before study trial medication 
prior to (infusion) can be administered. Women are 
considered of childbearing potential are defined as all 
female patients unless they are postmenopausal (defined by 
continuous amenorrhea) for at least 1 year with a follicle-
stimulating hormone (FSH) of >40 IU/L or are surgically 
sterilized (ie, women who had a hysterectomy, both ovaries 
surgically removed, or have a documented tubal ligation or 
any other documented permanent female sterilization 
procedure including tubal ligation). Follicle-stimulating 
hormone can be used to confirm postmenopausal status in 
amenorrheic patients not on hormonal replacement therapy if 
the value is within the postmenopausal range per the 
laboratory. 
FSH testing is done at the 
central lab and an FSH of 
>40 IU/L will be 
considered for assessing 
postmenopausal status. 

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Change 
Rationale 
x Synopsis 
x Section 4.3.1 
Inclusion Criteria 
Version 2.0: Women of childbearing potential should use a 
highly effective method of contraception (ie, pregnancy rate 
of less than 1% per year) during the trial and for 90 days 
after the last administration of the IMP. They must be on a 
stable regimen, for at least 1 month, of: 
x combined (estrogen and progestogen containing) 
hormonal contraception associated with inhibition of 
ovulation: 
o 
oral 
o 
intravaginal 
o 
transdermal 
x progestogen-only hormonal contraception associated with 
inhibition of ovulation 
o 
oral 
o 
injectable 
o 
implantable 
x intrauterine device (IUD) 
x intrauterine hormone-releasing system 
x bilateral tubal occlusion 
x vasectomized partner (provided that the partner is the 
sole sexual partner of the trial participant and 
documented aspermia post procedure) 
x , or agree upon continuous abstinence from heterosexual 
sexual contact. Sexual abstinence is only allowable if it is 
the preferred and usual lifestyle of the patient. Periodic 
abstinence (calendar, symptothermal, post-ovulation 
methods) is not acceptable. 
Clarification on the need 
to have a highly effective 
method of contraception 
and clarifying the highly 
effective methods of 
contraception. 
x Section 4.4.1 Early 
Discontinuation 
from Trial 
Version 2.0: Early discontinuation from the trial is defined 
as the permanent cessation of further participation in the trial 
prior to its planned completion and without the possibility 
to roll-over to the open-label extension trial 
(ARGX-113-1803). 
Any patient prematurely discontinuing the trial should 
perform the assessments listed for the Early Discontinuation 
visit as specified in the SoA (Table 1). 
Definition for early 
discontinuation clarified. 

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x Section 4.4.1 Early 
Discontinuation 
from Trial 
Version 2.0: 
The reason for early discontinuation from the trial will be 
clearly documented by the investigator. 
- Patients must be discontinued early from the trial and 
complete the Early Discontinuation visit as specified in 
the SoA (Table 1) if: 
x they withdraw their consent 
x in the patient’s best interest, discussion with the 
sponsor’s medical director is encouraged prior to 
discontinuation 
x the IMP treatment code is unblinded 
All patients 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. Prior 
to actual withdrawal of consent, an effort should be made to 
perform a final set of assessments as per Early 
Discontinuation visit in the SoA (Table 1). 
Investigators will make and document all efforts made to 
contact those patients who do not return for scheduled visits. 
The reason for early discontinuation from the trial will be 
clearly documented by the investigator. 
Patients who discontinue the current trial early and do not 
wish to roll over into the ARGX 113 1803 trial, will perform 
all the assessments listed for the Early Discontinuation visit 
as mentioned in the SoA (Table 1). These patients will be 
followed up for 4 weeks (2 biweekly visits) for ongoing 
safety and efficacy monitoring. 
Patients who complete the current trial treatment but who do 
not wish to roll over into the ARGX 113 1803 trial will be 
followed up for 4 weeks (2 biweekly visits) for ongoing 
safety and efficacy monitoring. 
- Patients must be discontinued early from the trial, 
complete the Early Discontinuation visit as specified in 
the SoA (Table 1), and have to be followed-up for 
4 weeks (2 biweekly visits) for ongoing safety and 
efficacy monitoring if: 
x it is in the patient’s best interest, discussion with the 
sponsor’s medical director is encouraged prior to 
discontinuation 
x the IMP treatment code is broken 
x prohibited medication is taken (see Section 6.8.1) 
x a severe hypersensitivity reaction to IMP occurs 
x the patient became pregnant 
Differentiate the reasons 
for early discontinuation 
from trial, move the 
prohibited medications 
and pregnancy from 
“early discontinuation 
from treatment” to “early 
discontinuation from 
trial”, and add 
hypersensitivity reaction 
as a new bullet at the 
request of the FDA 
(stopping rule for 
immunogenicity). 

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x Section 4.4.2 Early 
Discontinuation 
from Treatment 
Version 2.0: 
These patients will complete all the procedures listed for the 
Early Discontinuation visit as mentioned continue the 
weekly trial visits as specified in the SoA (Table 1) without 
IMP-related assessments. If a patient discontinues trial 
treatment early, he/she will enter a 4 week follow up period 
(2 biweekly visits). 
Patients must be discontinued early from treatment in the 
following circumstances: 
x 
pregnancy 
x 
on the request of the sponsor (eg, following data safety 
monitoring board [DSMB] advice, see Section 7.3.5) 
x 
prohibited medication is taken (see Section 6.8.1) 
x 
patient has missed more than 2 consecutive scheduled 
doses of IMP treatment 
x 
patient has received rescue therapy more than 3 
times 
The administration of IMP may be withheld if, in the opinion 
of the investigator, it could put the patient at undue risk or 
confound the results of the trial, in the following 
circumstances: 
x 
clinical evidence of bacterial, viral, or fungal disease 
x 
other significant disease 
Rescue therapy (pulse steroids, IVIg, anti D, or platelet 
transfusions) may be administered during the 24 week trial 
treatment period. 
Patients who complete the 24-week trial period but who 
do not enter the open-label extension trial 
ARGX-113-1803, or patients who discontinue the trial 
early, with the exception of patients who withdraw their 
consent, will be followed for 4 weeks for ongoing safety 
and efficacy monitoring. 
Differentiate the reasons 
for early discontinuation 
from trial, move the 
prohibited medications 
and pregnancy from 
“early discontinuation 
from treatment” to “early 
discontinuation from 
trial”, and add 
hypersensitivity reaction 
as a new bullet at the 
request of the FDA 
(stopping rule for 
immunogenicity). 

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Change 
Rationale 
x Synopsis 
x New Section 4.5 
Temporary 
Withholding 
Treatment 
x Section 5.4 
Treatment Period 
Individual stopping rules, reasons for early 
discontinuation from treatment and for temporary 
withholding treatment have been added or clarified. 
Version 2.0: 
- The administration of IMP may be temporary withheld if, 
in the opinion of the investigator, it could put the patient at 
undue risk or confound the results of the trial, in the 
following circumstances: 
x clinical evidence of bacterial, viral, or fungal disease 
x 
other clinically significant disease, including 
evidence of infection  
x 
severe bleeding, grade 3 or 4 on the WHO 
bleeding scale, requiring urgent medical and/or 
surgical intervention 
x thrombosis 
If the IMP is being withheld, it can should be reintroduced 
once the investigator considers the undue risk to the 
patientor trial has passed. However, if a patient misses 
more than 2 consecutive doses, he/she will be 
discontinued early from further IMP treatment, and will 
enter the 4 week follow up period according to the SoA 
(Table 1) without the possibility to roll over to the open
label extension trial (ARGX 113 1803). 
- The administration of IMP must be temporary 
withheld from patients with platelet counts greater 
than 400×109/L, IMP should be resumed at the 10 
mg/kg every other week dose when the platelet count 
falls to fewer than 150×109/L. 
Text added at the request 
of the FDA. 
x Synopsis 
x Section 4.1 
Summary of Trial 
Design 
x New Section 4.5 
Temporary 
Withholding 
Treatment 
x Section 5.4.1 
Screening and 
Treatment 
Version 2.0: 
x Temporary withholding treatment: 
o for reasons described in Section 4.5, IMP should be 
reintroduced once the investigator considers the 
undue risk to the patientor trial has passed 
o in patients with platelet counts greater than 
400×109/L, IMP should be resumed at the 10 mg/kg 
every other week dose when the platelet count falls 
to fewer than 150×109/L 
Individual rules for 
temporary withholding 
treatment have been 
added at the request of 
the FDA. 
x Section 5.3 
Randomization 
Version 2.0: If a patient meets all the eligibility criteria and 
after approval from the sponsor, he/she will be stratified 
randomized via IRT. 
Correction 

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Change 
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x Synopsis 
x Table 1 Schedule of 
Assessments 
x Section 5.4.1 
Screening and 
Treatment 
x Section 6.1 
Treatment 
Administered 
Version 2.0: From visits 17 to 24, the dosing frequency is 
fixed for each individual patient (ie, either weekly or 
biweekly regimen), based on the regimen the patient was 
receiving at visit 16 or at the last visit at which IMP was 
administered. 
Clarification on the visit 
used as reference for the 
fixed dosing period and 
of the exceptions to the 
fixed dosing frequency. 
x Section 4.1 
Summary of Trial 
Design 
x Section 5 Trial 
Procedures 
x Section 6.4 
Treatment 
Administered 
Version 2.0: From visits 17 to 24, patients will be fixed on 
the dosing schedule they were receiving at visit 16 or at the 
last visit at which IMP was administered (ie, either weekly 
or biweekly). Assessment of the dosing regimen as 
described in Section 5.4.1 will be applied. 
 
x Synopsis 
x Section 4.1 
Summary of Trial 
Design 
x Section 5.4.1 
Screening and 
Treatment 
Version 2.0: 
From visits 17 to 24, the dosing frequency is fixed for each 
individual patient (ie, either the weekly or biweekly 
regimen), based on the regimen the patient was receiving at 
visit 16 or at the last visit at which IMP was 
administered. Exceptions to the fixed dosing frequency 
are: 
x Continued weekly dosing for patients requiring rescue 
therapy unless deemed medically inappropriate by the 
investigator. 
x Continued biweekly dosing for patients resuming IMP 
when the platelet count falls to fewer than 150×109/L 
after having had platelet counts greater than 
400×109/L. 
 
x Synopsis 
x Section 4.1 
Summary of Trial 
Design 
x 6.8.4 Rescue 
Therapy 
Version 2.0: Patients requiring rescue therapy beyond visit 
12 will be considered non responders for the primary 
endpoint analysis more than 3 times will discontinue from 
IMP. 
Text updated at the 
request of the FDA. 

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x Section 1.3 Trial 
Rationale 
Removed paragraph: The IV infusions of trial treatment 
will be administered weekly from visits 1 to 4. As from visits 
5 to 16, in patients who achieve a platelet count of 
≥100×10⁹/L for 3 out of 4 consecutive visits (the fourth visit 
being the current visit) and have a platelet count of 
≥100×10⁹/L at the last of these visits, or 3 consecutive visits, 
the frequency will be reduced to biweekly administration. 
Trial treatment will be increased from biweekly to weekly 
administration in patients whose platelet counts drop below 
100×10⁹/L on 2 consecutive visits, or <30×10⁹/L at 1 visit, or 
in patients who receive rescue therapy. From visits 17 to 24, 
the dosing frequency is fixed for each individual patient (ie, 
either weekly or biweekly regimen), based on the regimen 
the patient was receiving at visit 16. 
Paragraph removed due 
to redundancy. Dosing 
and frequency regimen 
are specified in 
Section 4.1 Summary of 
Trial Design 
(SCREENING AND 
TREATMENT) 
x Section 4.1 
Summary of Trial 
Design 
x Section 5.4.2 Roll-
Over to the Open-
Label Extension 
Trial (ARGX-113-
1803) 
Version 2.0: Patients who consent to roll over into the open
label extension trial ARGX 113 1803 should complete the 
End of Treatment visit of the current trial, on the same day 
as the signature of the ICF and the baseline visit/first IMP 
dose administration of the ARGX 113 1803 trial. Patients 
who complete the 24-week treatment trial period have the 
possibility to consent to enter the open-label extension trial 
(ARGX-113-1803) to receive efgartigimod 10 mg/kg IV 
according to the frequency they were receiving at the time of 
leaving the ARGX 113 1801 trial (ie, weekly or biweekly). 
The platelet counts from the ARGX-113-1801 trial will be 
taken into account to assess the dosing frequency in 
ARGX-113-1803. 
Text updated to clarify 
the assessment of the 
dosing frequency in 
ARGX-113-1803. 

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x Section 5.4.2 Roll-
Over to the Open-
Label Extension 
Trial (ARGX-113-
1803) 
Eligible patients who consent to roll-over into the open-
label extension trial ARGX-113-1803 should complete the 
End-of-Treatment visit of the current trial, on the same day 
as the signature of the ICF and the baseline visit/first IMP 
dose administration of the ARGX 113 1803 trial. Patients 
who complete the 24 week treatment period have the 
possibility to consent to enter the open label extension trial 
(ARGX 113 1803) to receive efgartigimod 10 mg/kg IV 
according to the frequency they were receiving at the time of 
leaving the ARGX 113 1801 trial (ie, weekly or biweekly). 
x For patients on a weekly dosing regimen, the baseline 
visit including first IMP dose administration of the 
ARGX-113-1803 trial will be done on the same day. 
x For patients on a biweekly dosing regimen, the 
baseline visit including first IMP dose administration 
of the ARGX-113-1803 trial will be done 7 days after 
the End-of-Treatment visit of the current trial. 
Patients who do not enter the open-label extension trial 
(ARGX-113-1803) will remain in this the current trial to be 
followed for 4 weeks (2 biweekly visits). 
Text updated to clarify 
the assessments done at 
the End-of-Treatment 
visit for patients eligible 
and willing to roll-over to 
ARGX-113-1803. 
x Table 1 Schedule of 
Assessments 
Version 2.0: 
End-of-Treatment/Early Discontinuation: This visit should 
be completed for all patients, whether they discontinue the 
trial early, or complete the 24 week treatment period 
performed 7 days (+2 days) after visit 24 for all patients 
who have completed the 24-week trial period, whether 
they were still on IMP or not. 
Early Discontinuation: This visit should be performed on 
the day of early discontinuation for all patients that 
discontinue the trial early. 
Follow-up Period: For patients discontinuing the trial 
treatment early (with the exception of patients who 
withdraw their consent) or who do not roll-over to the 
open-label extension trial (ARGX-113-1803). The follow-up 
period will consist of 2 biweekly visits (ie, 4 weeks). 
h Laboratory assessments include all parameters mentioned 
in Appendix 1 of the protocol and should be done predose. 
Text updated/added for 
clarification purposes. 
x Table 1 Schedule of 
Assessment 
x Section 1.3 Trial 
Rationale 
Version 2.0: Assessment of the dosing regimen as 
described in Section 5.4.1 will be applied. 
 

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x Section 6.11 
Handling Missed 
Doses of the 
Investigational 
Medicinal Product 
x Section 4.4.3 Missed 
Doses 
x Section 5.4 
Treatment Period 
Version 2.0: All efforts will be done made to ensure that the 
patient receives all administrations of IMP within the 
allowed visit windows. However, if a patient misses more 
than 2 consecutive scheduled doses, then he/she will be 
discontinued early from further IMP treatment, and will enter 
the 4 week follow up period according to the SoA (Table 1) 
without the possibility to roll over to the open label 
extension trial (ARGX 113 1803) (see Section 4.4.2). 
Removed Section 4.4.3 Missed Doses: 
If a patient misses 1 or 2 consecutive doses of IMP, he/she 
can stay in the trial and will follow the assessments as per 
SoA (Table 1). If a patient has missed more than 
2 consecutive doses he/she will be discontinued early from 
IMP treatment and will enter the 4-week follow-up period 
according to the SoA (Table 1) without the possibility to roll-
over to the open-label extension trial (ARGX-113-1803). 
Procedure for patients 
who miss more than 
2 consecutive IMP doses 
clarified. 
x Synopsis 
x Section 4.1 
Summary of Trial 
Design 
x Section 6.8.1 
Concurrent ITP 
Therapy 
Version 2.0: As of week 12, an increase in dose and/or 
schedule of permitted concurrent ITP therapy is allowed for 
the the start or an increase in the dose and/or schedule of 
permitted concurrent ITP therapy is allowed for patients 
who have an “insufficient response” (ie, no platelet count of 
≥30×109/L in any of the visits during the last 4 weeks) can 
start or increase the dose and/or schedule of permitted 
concurrent ITP therapy. These patients will be considered as 
“non responders” for the primary endpoint analysis. 
Text updated/added for 
clarification purposes. 
x Synopsis 
x Section 4.1 
Summary of Trial 
Design 
x Section 6.8.1 
Concurrent ITP 
Therapy 
Version 2.0: Patients 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 oral corticosteroids, oral 
immunosuppressants, dapsone/danazol, and/or eltrombopag 
(inclusion criterion n°76, Section 4.3.1). 
 
x Synopsis 
x Section 3.1 Primary 
Endpoint 
x Section 4.2 
Discussion of Trial 
Design 
x Section 8.4.1 
Primary Endpoint 
Analysis 
Version 2.0: Patients who discontinue treatment prior to visit 
24 due to lack of efficacy (eg, need rescue therapy more 
than 3 times) or due to an AE, and who have not achieved 
sustained platelet count response between visits 19 and 24, 
are considered non responders. 
Text added per request of 
the FDA. 

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x Synopsis 
x Section 4.1 
Summary of Trial 
Design 
x Section 4.4.2 Early 
Discontinuation 
from Treatment 
x Section 5.5 
Follow-up Period 
Version 2.0: Patients who complete the 24-week trial 
treatmentperiod but who do not enter the open-label 
extension trial ARGX-113-1803 will complete all the 
assessments as listed for the End of Treatment/Early 
Discontinuation visit and, or patients who discontinue the 
trial treatment early, with the exception of patients who 
withdraw their consent, will be followed for 4 weeks for 
ongoing safety and efficacy monitoring. 
For patients who discontinue the trial early, all the 
assessments listed for the End of Treatment/Early 
Discontinuation visit as specified in the schedule of 
assessments (SoA, Table 1), will be performed at the 
termination visit. These patients will be followed up for 
4 weeks (2 biweekly visits) for ongoing safety and efficacy 
monitoring. 
Clarified that patients 
who withdraw their 
consent cannot be asked 
to return for further 
follow-up visits. 
x Section 7.3.1.1 
Adverse Events of 
Special Interest 
Version 2.0: Efgartigimod treatment induces 
hypogammaglobulinemia, and there is a potential risk for 
infections caused by the hypogammaglobulinemia. As such, 
infections are considered AE(S)I in this trial. 
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 AESI in 
this trial. 
Any bleeding or infection will be considered as AESI. 
(Section moved from 7.3.2 to 7.3.1.1) 
Clarified the reason for 
risk of infection. 
x Section 7.3.1.2 
Reporting of 
Adverse Events and 
Serious Adverse 
Events 
x Section 7.3.1.4 
Follow-up of 
Adverse Events and 
Serious Adverse 
Events 
Version 2.0: The investigator shall report within 24 hours 
any SAE he/she becomes aware of after a patient’s last visit 
if a causal relationship with the investigational product is 
suspected. Such a serious adverse reaction is to be collected 
and reported as previously described for SAEs. 
All SAEs that are spontaneously reported within 30 days 
after the last study trial visit are to be collected and 
reported as previously described and all efforts should be 
made to follow-up until resolution. 
(This paragraph was moved from Section 7.3.1.4 Follow-up 
of Adverse Events and Serious Adverse Events to 
Section 7.3.1.2 Reporting of Adverse Events and Serious 
Adverse Events) 
Text updated/added with 
a reporting timeframe for 
clarification purposes. 

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x Section 7.3.1.5.1 
Pregnancies in 
Female Patients 
Version 2.0: 
x The patient should have the Early Discontinuation End
of Treatment assessments and enter the 4-week follow-up 
period. 
x All assessments for Early Discontinuation End of
Treatment (see Section 4.4.1) must be performed unless 
contraindicated by pregnancy (harmful to fetus) or unless 
the patient withdraws informed consent. 
Correction 
x Section 7.3.2 
Clinical Laboratory 
Evaluations 
Version 2.0: 
On days that IMP is administered, blood for laboratory 
assessments should be collected before dosing. 
For all female patients of childbearing potential, a serum 
pregnancy test will be performed centrally at screening (on 
the samples taken for clinical laboratory tests), and a urine 
pregnancy test will be conducted and analyzed locally at the 
site (on the urine samples taken for urinalysis) at the visits 
specified in the SoA (Table 1). 
Text updated for 
clarification purposes. 
x Section 8.1 
Determination of 
Sample Size 
Version 2.0: For the first key secondary endpoint “extent 
of disease control”, assuming a median 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 of 14 weeks for 
patients receiving efgartigimod and 3 weeks for patients 
receiving placebo, a total of N=117 patients will ensure a 
power of >99.9% (two sided α of 0.05) to detect a 
significant difference between both treatment groups. 
For ensuring a power of at least 90%, a total number of 
N=27 patients would be needed, given these assumptions. 
Calculations are based on the log-rank test. 
Text added at the request 
of the FDA. 
x Section 8.3 Patient 
Disposition, 
Characteristics, and 
Concomitant 
Medication 
Version 2.0: Patient characteristics will be listed and 
summarized (by treatment group and overall). Overall 
sSummaries will include descriptive statistics for continuous 
measures (number of observations, mean, standard 
deviation, median, 1st quartile, 3rd quartile, minimum, and 
maximum) and for categorical measures (frequency and 
percentage). 
Use of concomitant medication will be summarized by 
treatment group with frequency and percentage. Separate 
summaries of concurrent ITP therapies and rescue 
therapy by treatment group will be provided. All 
concomitant medications used will be listed. 
Text added at the request 
of the FDA. 

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Section(s) 
Change 
Rationale 
x Section 8.4.1 
Primary Endpoint 
Analysis 
Version 2.0: 
Definition of the primary estimand for the primary 
endpoint 
x Population: adult patients with chronic ITP, having an 
average platelet count of <30×109/L, and, at the start of 
the trial, either being on concurrent ITP treatment(s) 
and having previouslyreceived at least 1 prior ITP 
therapy for ITP in the past, or not being on treatment 
for ITP but having received at least 2 prior 
treatments for ITP. 
x Variable: sustained platelet count response defined as 
achieving platelet counts of at least 50×109/L for at least 
4 of the 6 visits between visits 19 and 24 of the trial 
x Main intercurrent events: 
 early discontinuation of treatment (prior to visit 24) 
due to lack of efficacy (eg,, need for rescue therapy 
more than 3 times) or due to an AE 
 initiation of rescue therapy at visit 12 or later 
 increase of dose and/or frequency of concurrent ITP 
therapies at visit 12 or later 
x Population-level summary: proportion of patients with 
sustained platelet count response 
Handling of main intercurrent events 
A composite strategy approach will be taken to address the 
main intercurrent events described above. This implies that 
patients who discontinue treatment prior to visit 24 due to 
lack of efficacy (eg, need rescue therapy more than 
3 times) or due to an AE, as well as patients who receive 
rescue therapy at visit 12 or later, or for whom dose and/or 
frequency of concurrent ITP therapies have increased at visit 
12 or later, will be considered non-responders for the 
primary endpoint analysis. 
Estimation of treatment effect and statistical inference 
The primary endpoint will be tested by means of exact 
logistic regression with, also known as exact conditional 
logistic regression.14 The model will contain fixed effect 
terms for randomized treatment and baseline platelet count 
level. The model and will be stratified by history of 
splenectomy (yes vs. no) and receiving concurrent ITP 
therapies at baseline (yes vs. no), at randomization. 
Parameter estimation and hypothesis testing will be 
performed on I log odds ratio (OR) of a sustained platelet 
count response on placebo and efgartigimod will be 
provided, along with the 95% 2 sided confidence interval 
(CI) and 2 sided p value . Using the Newton-Raphson 
Text updated/added at 
the request of the FDA 
regarding testing strategy 
of the primary endpoint. 

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Section(s) 
Change 
Rationale 
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.15 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.16 The OR (by exponentiating the log OR) will 
be provided, along with the 95% 2-sided confidence 
interval (CI) and 2-sided p-value. 
Complementary analyses 
To facilitate interpretation of the estimated treatment effect 
in the primary analysis, complementary analyses will may 
be conducted where the main intercurrent events are handled 
differently, eg, by using the hypothetical and/or “treatment 
policy” strategy. Details will be provided in the SAP. 
x Synopsis 
x Section 3.2 
Secondary 
Endpoints 
Version 2.0: 
Key Secondary Efficacy Endpoints Subject to Alpha 
Control: 
• 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. 
• Proportion of patients in the overall population (chronic 
and persistent ITP) with a sustained platelet count 
response defined as achieving platelet counts of at least 
50×109/L for at least 4 of the 6 visits between visits 19 
and 24 of the trial. 
• Incidence and severity of the WHO-classified bleeding 
events. 
• Proportion of patients in the overall population 
achieving platelet counts of at least 50×109/L for at 
least 6 of the 8 visits between visits 17 and 24 of the 
trial. 
Key secondary efficacy 
endpoint subject to alpha 
control added. 
x Figure 1 
Version 2.0: The figure has been updated. 
For consistency and 
clarification purposes. 

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Section(s) 
Change 
Rationale 
x Section 8.2 Analysis 
Populations 
Version 2.0: The full analysis set (FAS) consists of all 
randomized patients who have a baseline efficacy 
observation. In general, theThe FAS will be used for the 
main efficacy analyses. For the primary and first key 
secondary endpoint the subset of all patients in the FAS 
with chronic ITP will be used. The analysis will follow the 
intent-to-treat principle, ie, patients will be analyzed 
according to their randomized treatment, irrespective of the 
treatment they actually received. 
The per protocol (PP) population is a subset of the FAS, ie, 
all patients from the FAS without a major protocol deviation 
deemed to influence the efficacy evaluation. The PP 
population will be used for sensitivity analyses for the 
primary and key secondary endpoints. 
Clarification and more 
general definition of PP 
population, as analysis 
for initial, more specific, 
definition will be covered 
by other sensitivity 
analyses where the 
intercurrent events will be 
handled differently than 
for primary analysis. 
x Synopsis 
x Section 8.4 
Statistical Methods 
Version 2.0: The efficacy analysis will be performed on the 
FAS or the subset of patients in the FAS with chronic 
ITP, and analyzed with intent-to-treat principle (ie, patients 
will be analyzed according to their planned treatment 
irrespective of the treatment actually received). 
Text added for 
clarification purposes. 
x Synopsis 
x Section 8.4.2 Key 
Secondary Endpoint 
Analyses Subject to 
Alpha Control 
Version 2.0: 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, will be analyzed 
using Cox regression methodology. In this analysis patients 
with no cumulative weeks of disease controlled well be 
assumed to have reached the event (ie, loss of disease 
control) at zero weeks. The 2 treatment groups will be 
compared using a Cox proportional hazards regression model 
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. A Wald 
test will be used to test the null hypothesis that the log of 
the hazard ratio on placebo and efgartigimod is equal to 
zero (or, equivalently, that the hazard ratio is equal to 1) 
against the alternative that it is different from zero (or, 
equivalently, that the hazard ratio is different from 1). 
From the model, the hazard ratio for efgartigimod vs. 
placebo will be provided, along with the associated 95% 
2 sided Wald-type CI and 2-sided p-value. This will estimate 
the relative probability of disease control with efgartigimod 
as compared to placebo. The hazard ratio will estimate the 
relative probability of disease control with efgartigimod 
as compared to placebo. The data will also be displayed 
using Kaplan-Meier curves and the median length of disease 
control will be displayed by randomized treatment arm. 
Text added/updated at the 
request of the FDA. 

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Missing platelet counts for reason of one of the main 
intercurrent events will be handled as “no disease control” 
(<50x109/L) in case of early discontinuation (prior to visit 
24). In case of initiation of rescue therapy, or increase of 
dose and/or frequency of concurrent ITP therapies, platelet 
counts will be censored as of the corresponding start date.  
The key secondary endpoints on proportion of patients in the 
overall population with a sustained platelet count response 
and on proportion of patients in the overall population 
achieving platelet counts of at least 50×109/L for at least 6 
of the 8 visits between visits 17 and 24 of the trial will be 
analyzed in the same manner as the primary endpoint. 
The number of bleeding events per patient (assessed using 
the WHO Bleeding Scale; where WHO scale ≥1 at any visit 
is considered a new bleeding event) will be analyzed using 
a zero-inflated negative binomial model. This model will 
account for the large expected number of patients with zero 
bleeding events. The model will be stratified by history of 
splenectomy (yes vs. no) and receiving concurrent ITP 
therapies at baseline (yes vs. no), at randomization. It is a 
mixture model consisting of 2 components: a negative 
binomial count model and a binary model for predicting 
excess zeros. It will have the number of events as the 
dependent variable and both randomized treatment and 
the stratification variables (history of splenectomy; 
receiving concurrent ITP therapies at baseline) as factors 
in the model. An offset term will be used to allow for patient 
exposure. Both the count model, using the log link, and 
the binary model, using the logit link, will contain the 
same independent variables. The probability of no bleeding 
will be estimated for each randomized treatment group. A 
Wald test will be used to test the null hypothesis that the 
log of the bleeding rate ratio on placebo and efgartigimod 
is equal to zero against the alternative that it is different 
from zero. The rate of bleeding over 24 weeks on placebo 
and efgartigimod will be provided, along with the rate ratio, 
95% 2-sided Wald-type CI, and 2-sided p value.  
If the primary endpoint is met, the key secondary endpoints 
will be analyzed using a closed test fixed-sequence testing 
procedure, for example Hochberg or Holm, 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 
pre-defined hierarchy resulted in a p-value <0.05. The 
order in the testing hierarchy is as follows: 

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1. The proportion of patients with chronic ITP with a 
sustained platelet count response defined as achieving 
platelet counts of at least 50×109/L for at least 4 of the 6 
visits between visits 19 and 24 of the trial (primary 
endpoint). 
2. 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. 
3. The proportion of patients in the overall population 
(chronic and persistent ITP) with a sustained platelet 
count response defined as achieving platelet counts of 
at least 50×109/L for at least 4 of the 6 visits between 
visits 19 and 24 of the trial. 
4. The incidence and severity of the WHO-classified 
bleeding events. 
5. Proportion of patients in the overall population 
achieving platelet counts of at least 50×109/L for at 
least 6 of the 8 visits between visits 17 and 24 of the 
trial. 

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x Section 8.4.2 Key 
Secondary Endpoint 
Analyses Subject to 
Alpha Control 
Version 2.0: The main event and censoring rules are as 
follows, where event is defined as “loss of disease 
control”: 
Situation 
Date of event or 
censoring 
Outcome 
No occurrence of platelet 
count of ≥50×109/L 
throughout 24-week 
treatment period 
Date of baseline 
Event 
Early discontinuation of 
treatment (prior to W24) 
Date of treatment 
discontinuation 
Event 
Rescue therapy started 
Date of initiation 
of rescue therapy 
Event 
Dose and/or frequency of 
concurrent ITP therapy 
increased 
Start date of 
increase 
Event 
Disease control at end of 
24-week treatment period 
Date of last 
assessment 
(analysis visit) 
Censored 
Missing platelet counts for other reasons of one of the main 
intercurrent events will be handled as “no disease control” 
(<50x109/L) in case of early discontinuation (prior to visit 
24). In case of initiation of rescue therapy, or increase of 
dose and/or frequency of concurrent ITP therapies, platelet 
counts will be censored as of the corresponding start date. 
Missing platelet counts for other reasons will be imputed by 
multiple imputation than those mentioned in the final 
event and censoring rules table (as detailed in the SAP) 
will be imputed by multiple imputation. Sensitivity 
analyses will be conducted to assess the robustness of the 
analysis results to the applied imputation method. 
Text added/updated at 
the request of the FDA. 
x Section 11.3.3 
Publication Policy 
Version 2.0: 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 has been analyzed and reported and 
must be submitted to the sponsor for review and comment 
prior to submission for publication or presentation. 
Authorship will be granted according to the International 
Committee of Medical Journal Editors criteria( 17), based on 
scientific input and recruitment efforts, and will be granted 
upon decision of a publication committee. This committee 
will include among others the coordinating investigator and 
the sponsor. 
Wording “after the trial 
has been analyzed and 
reported” added for 
clarification purposes. As 
there is no publication 
committee at argenx, the 
reference has been 
deleted and the reference 
to the International 
Committee of Medical 
Journal Editors has been 
corrected. 

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x Appendix 1 
Version 2.0: 
Pharmacodynamic markers 
Serum levels of total IgG 
and IgG subtypes (IgG1, IgG2, IgG3, and IgG4). Presence, 
nature, and level of antiplatelet antibodies. 
Specification of the 
antiplatelet antibodies on 
a separate line for 
clarification because 
these samples are to be 
taken at a different time 
point. 
 
Version 2.0: 
Antiplatelet antibodies Presence, nature, and level of 
antiplatelet antibodies 
x Table 1 Schedule of 
Assessments 
x List of abbreviations 
x Section 7.2.1 Platelet 
Count 
x Appendix 1 
Version 2.0: 
 
 
Correction.