Clinical trial NCT02965573
Conditions: Myasthenia Gravis
Sponsor: argenx
Start date: 2016-12-30; Completion date: 2017-10-20
Enrollment: 24 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a randomized, double-blind, placebo-controlled, multicenter Phase II study to evaluate the safety, efficacy, and pharmacokinetics of ARGX-113 for the treatment of autoimmune Myasthenia Gravis (MG) with generalized muscle weakness.

Detailed description:
Myasthenia Gravis (MG) is an autoimmune disorder characterized in most cases by T cell and antibody responses to neuromuscular junction proteins such as skeletal muscle nicotinic acetylcholine receptor (AChR). Antibodies against epitopes of the AChR of the neuromuscular junction cause failure of neuromuscular transmission, resulting in the characteristic fatigue and weakness associated with this severe disorder.

The study will evaluate an innovative candidate in MG.

Arms: arm 1: During the Treatment period, eligible patients will be randomized at a 1:1 ratio to receive ARGX-113 arm 2: During the Treatment period, eligible patients will be randomized at a 1:1 ratio to receive placebo
Interventions: intervention 1: ARGX-113 intervention 2: Placebo
Intervention descriptions: intervention 1: None intervention 2: None

Protocol documents:
Prot_002.pdf: 
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Clinical Study Protocol 
Protocol Title: 
A Randomized, Double-blind, Placebo-Controlled Phase II 
Study to Evaluate the Safety, Efficacy, and Pharmacokinetics 
of ARGX-113 in Patients with Myasthenia Gravis who have 
Generalized Muscle Weakness 
Protocol Number: 
ARGX-113-1602 
Date of Protocol: 
 
 
2016-11-28, Version 2.0 
Product: 
ARGX-113 
IND No.: 
 
EudraCT No.: 
2016-002938-73 
Study Phase: 
II 
Sponsor: 
argenx BVBA 
Industriepark Zwijnaarde 7, Building C 
B-9052 Zwijnaarde 
BELGIUM 
Phone: +32(0) 9 310 34 00 
Project Manager: 
, MD 
Central Nervous System, Quintiles Istanbul 
Saglik Hizmetleri Arastirma ve Danismanlik Ltd. Sti. 
Nida Kule, Degirmen Sokak, No: 18, Kat: 11, Kozyatagi 
34742, Istanbul, Turkey 
Phone: 
 
 
argenx BVBA 
Industriepark Zwijnaarde 7, Building C 
B-9052 Zwijnaarde 
BELGIUM 
Phone: 
 
Medical Director: 
, MD, PhD 
argenx BVBA 
Industriepark Zwijnaarde 7, Building C 
B-9052 Zwijnaarde 
BELGIUM 
Phone: 
 
Medical Monitor: 
 MD 
Medical Director 
Central Nervous System 
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Signature of Investigator 
PROTOCOL TITLE: 
A Randomized, Double-blind, Placebo-Controlled 
Phase II Study to Evaluate the Safety, Efficacy, and 
Pharmacokinetics of ARGX-113 in Patients with 
Myasthenia Gravis who have Generalized Muscle 
Weakness 
PROTOCOL NO: 
ARGX-113-1602 
This protocol is a confidential communication of argenx. 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. 
 
Instructions to the Investigator: Please SIGN and DATE this signature page. PRINT 
your name, title, and the name of the site in which the study will be conducted. Return 
the signed original copy to the local representative of your Sponsor’s designated CRO 
(Quintiles). 
A scanned copy of this page should also be e-mailed to 
 
 
I have read this protocol in its entirety and agree to conduct the study accordingly: 
 
Signature of Investigator: 
__________________________  
Date: _______ 
Printed Name: 
___________________________ 
Investigator Title: 
__________________________ 
Name/Address of Site: 
___________________________ 
 
___________________________ 
 
___________________________ 
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SYNOPSIS 
Name of Sponsor: 
argenx 
Name of Investigational 
Medicinal Product: 
ARGX-113 
Name of Active Ingredient: 
A human anti-neonatal Fc receptor IgG1 Fc fragment 
Title of Study: 
A Randomized, Double-blind, Placebo-Controlled Phase II Study to Evaluate the 
Safety, Efficacy, and Pharmacokinetics of ARGX-113 in Patients with Myasthenia 
Gravis who have Generalized Muscle Weakness 
Protocol No: 
ARGX-113-1602 
Study sites: 
This study will be conducted in up to 25 sites. 
Study duration: The study duration for each patient is 13 weeks. It 
consists of a Screening period of 15 days, a 3 week Treatment period, 
and an 8 week Follow-up (FU) period. 
Phase: II 
Objectives: 
Primary Objectives: 
• 
To evaluate the safety and tolerability of ARGX-113. 
Secondary Objectives: 
• 
To evaluate the clinical effect of ARGX-113 using: 
o 
Myasthenia Gravis-Activities of Daily Living (MG-ADL) score. 
o 
Quantitative-Myasthenia Gravis score (QMG). 
o 
Myasthenia Gravis Composite score (MGC). 
• 
To evaluate the impact of ARGX-113 on quality of life using 15-item quality of life scale for 
Myasthenia Gravis (MGQoL15r [revised version]). 
• 
To investigate the pharmacokinetics (PK) of ARGX-113. 
• 
To assess the pharmacodynamic (PD) markers (e.g., total immunoglobulin G (IgG) and subtypes, 
anti-acetylcholine receptor [AChR] antibodies). 
• 
To evaluate the immunogenicity of ARGX-113. 
Methodology: This is a randomized, double-blind, placebo-controlled, multicenter Phase II study to 
evaluate the safety, efficacy, and pharmacokinetics of ARGX-113 for the treatment of autoimmune 
Myasthenia Gravis (MG) with generalized muscle weakness. 
Approximately 24 patients will be randomized. 
The study will include a Screening period of maximum 15 days, a Treatment period of 3 weeks from 
Visit 1 to Visit 7 and a Follow-Up (FU) period of 8 weeks starting after completion of Visit 7 to Visit 16. 
Although the FU period is from Visit 8 to Visit 16, the FU in fact starts immediately after the last 
Investigational Medicinal Product (IMP) infusion at Visit 7. 
During the Screening Period, patients’ eligibility will be evaluated for study participation. 
During the Treatment period, eligible patients will be randomized at a 1:1 ratio to receive ARGX-113 
(10 mg/kg) or placebo in 4 infusions administered one week apart in addition to Standard of Care (SoC). 
The total dose per IMP infusion is capped at 1200 mg for patients with body weight ≥ 120 kg. 
Patients will receive ARGX-113 or placebo according to the following regimen: 
• Patients will receive ARGX-113 or matching placebo via intravenous (IV) infusion over a 
period of 2 hours on Days 1 (Visit 1), 8±1 (Visit 3), 15±1 (Visit 5), and 22±1 (Visit 7). 
• The Treatment period consists of 7 visits (of which the 3 visits between the weekly dosing 
visits are optional). 
At the end of the 3 weeks Treatment period, the patient will enter a FU period for 8 weeks. 
During the FU period, 9 visits (of which 1 visit is optional) will take place as detailed in Table 1. 
Study procedures including endpoint assessments will be performed according to the Schedule of 
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Assessments as detailed in Table 1. 
In this study, SoC for a patient is the stable dose and administration of their MG treatment prior to 
enrollment. Permitted SoC for MG treatment under this protocol include azathioprine (AZA), other 
non-steroidal immunosuppressant drugs (NSIDs: e.g., methotrexate, cyclosporine, tacrolimus, 
mycophenolate mofetil, and cyclophosphamide), steroids, as well as cholinesterase inhibitors. Patients 
should be on a stable dose and frequency of SoC prior to enrollment as detailed in of Section 5.3.1 
(Criterion 5) that should be maintained throughout the study without any increase or decrease. 
Patients receiving cholinesterase inhibitors will be required to be on a stable dose for >2 weeks prior to 
Screening. In addition, cholinesterase inhibitors must be held for at least 12 hours consistent with the 
revised manual for the QMG test as recommended by the Myasthenia Gravis Foundation of America Inc 
[MGFA]1, prior to performing the MGQoL15r, MG-ADL, QMG, and MGC assessments at Screening, 
Visits 1, 3, 5, 7, 9, 10, 11, 12, 14, and 16. 
During the study, no changes in the dose level and frequency of ARGX-113 or the SoC will be allowed. 
However, if necessary, patients may receive rescue therapy if their MG deteriorates as judged by the 
Investigator on the basis of parameters such as changes in MGQoL15r, MG-ADL, QMG, MGC on any 
study day. 
Rescue therapy will be determined by the Investigator based on an overall clinical assessment. Rescue 
therapy may include intravenous immunoglobulin (IVIg), plasma exchange (PE), or any other treatment 
chosen by the Investigator. In case a patient needs rescue therapy according to the treating Investigator, the 
Medical Director at the Sponsor should be informed in addition to the Medical Monitor at the Sponsor’s 
designated contract research organization (CRO, Quintiles); where possible prior to actual implementation 
of the rescue therapy. In case rescue therapy is needed (due to deterioration of MG), patients will be 
discontinued from treatment with IMP, but will be followed up for safety. Any patient who discontinues 
study treatment due to safety concerns will be followed up for safety and wherever possible for efficacy. 
For patients who discontinue the study early, all the procedures listed for Early Discontinuation (ED) visit 
(same procedures as for the End-of-Study [EoS] visit or Visit 16) in the Schedule of Assessments (Table 1) 
are to be performed (early discontinuation). This study is exploratory and not powered to address any pre-
defined hypothesis. The safety and efficacy analysis will be performed on the safety analysis set, which 
includes all patients who received at least one infusion of ARGX-113 or placebo. 
Planned number of Patients: 
Approximately 36 patients will be screened in order to randomize 
approximately 24 patients (12 patients per treatment arm) to get at least 
20 patients who received at least 3 doses of IMP (either ARGX-113 or 
placebo) and who completed at least 2 weeks of follow-up post last dose 
(See Appendix 14.6). Patients may be replaced in certain circumstances 
(See Section 5.3.6 and Table 2). Final decision for replacement of 
patients will be done on a case-by-case basis in consultation with the 
Medical Monitor at the Sponsor’s designated contract research 
organization (CRO, Quintiles) and/or the Medical Director at the 
Sponsor’s end. 
Criteria for inclusion and 
exclusion: 
Inclusion Criteria: 
1. Have the ability to understand the requirements of the study, 
provide written informed consent (including consent for the 
use and disclosure of research-related health information), and 
comply with the study protocol procedures (including required 
study visits). 
2. Male or female patients aged ≥18 years. 
3. Diagnosis of autoimmune MG with generalized muscle 
weakness meeting the clinical criteria for diagnosis of MG as 
defined by the Myasthenia Gravis Foundation of America 
(MGFA) Clinical Classification Class II, III, or IVa, and likely 
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not in need of a respirator for the duration of the study as 
judged by the Investigator. 
The confirmation of the diagnosis should be documented and supported 
by: 
• Positive serologic test for anti-AChR antibodies before 
Screening and 
• at least 1 of the following 3 tests: 
(i) History of abnormal neuromuscular transmission test 
demonstrated by single-fiber electromyography or repetitive 
nerve stimulation or 
(ii) History of positive edrophonium chloride test, or 
(iii) Patient has demonstrated improvement in MG signs on 
oral cholinesterase inhibitors as assessed by the treating 
physician. 
4. A total score of ≥ 5 on the MG-ADL at Screening and Baseline 
with more than 50% of this score attributed to non-ocular 
items. 
5. Patients are required to be on a stable dose of their MG 
treatment prior to randomization. For patients receiving AZA, 
other NSIDs, steroids, and/or cholinesterase inhibitors as 
concomitant medications the following conditions will apply: 
• AZA: treatment initiated at least 12 months ago and no 
dose changes in the last 6 months before Screening. 
• Other NSIDs (e.g., methotrexate, cyclosporine, 
tacrolimus, mycophenolate mofetil, and 
cyclophosphamide) treatment initiated at least 6 months 
ago and no dose changes in the last 3 months before 
Screening. 
• Steroids treatment initiated at least 3 months prior to 
and no dose changes in the last month before 
Screening. 
• Cholinesterase inhibitors: to be on a stable dose for 
>2 weeks before Screening. 
Note: cholinesterase inhibitors must be held for at least 
12 hours consistent with the revised manual for the 
QMG test as recommended by the Myasthenia Gravis 
Foundation of America Inc [MGFA]1, before the 
MGQoL15r, MG-ADL, QMG, and MGC assessments. 
6. Females of childbearing potential must have a negative serum 
pregnancy test at Screening and a negative urine pregnancy test 
at Visit 1 prior to administration of IMP. Female of 
childbearing potential are defined as all female participants 
unless they are postmenopausal (defined by continuous 
amenorrhea) for at least 2 years with a Follicle-stimulating 
hormone (FSH) > 40 IU/L or are surgically sterile (i.e., who 
had a hysterectomy, 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 if the test result is within 
the postmenopausal range per the central laboratory. 
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7. Female participants of childbearing potential must agree to use 
a highly effective method of contraception (i.e., pregnancy rate 
of less than 1% per year) during the study and for 90 days after 
the discontinuation of the IMP. Adequate contraceptive 
methods include combined hormonal contraception associated 
with inhibition of ovulation (oral, intravaginal, transdermal), 
progestogen-only hormonal contraception associated with 
inhibition of ovulation (oral, injectable, implantable), 
intrauterine devices (IUDs), intrauterine hormone-releasing 
system (IUS), true sexual abstinence (when this is in line with 
the preferred and usual lifestyle of the participant), bilateral 
tubal occlusion, or a female participant who is not of 
childbearing potential. Female participants and female partners 
of male study participants using a hormonal contraceptive must 
also use a barrier method (i.e., condom or occlusive cap 
[diaphragm or cervical/vault caps]) and should have been 
stable on their hormonal contraceptive treatment for at least 
4 weeks before Screening. 
8. Sterilized male patients who have had vasectomy with 
documented aspermia post procedure can be included. In 
addition, male patients must be advised not to donate sperm 
during this period from signing of Informed Consent Form 
(ICF), throughout the duration of the study, and for 90 days 
after the last administration of IMP. Non-sterilized male 
patients who are sexually active with a female partner of 
childbearing potential must use effective method of double 
barrier contraception (e.g., condom with spermicidal cream or 
jelly, 1 hormonal 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. 
Exclusion Criteria: 
1. Females who are pregnant or lactating. 
2. MGFA Class I, IVb, and V. 
3. Have an active infection, a recent serious infection (i.e., 
requiring injectable antimicrobial therapy or hospitalization) 
within the 8 weeks prior to Screening; or history of or known 
infection with human immunodeficiency virus (HIV), hepatitis 
B virus (HBV), hepatitis C virus (HCV), or Mycobacterium 
tuberculosis. Patients must have negative test results for HBV 
surface antigen, HBV core antibody, HCV antibody, HIV 1 
and 2 antibodies, and a negative QuantiFERON®-TB Gold test 
at Screening. Patients with an indeterminate QuantiFERON®-
TB Gold test result will be allowed one retest; if not negative 
on retesting, the patient will be excluded. 
4. At Screening, have clinically significant laboratory 
abnormalities or as below: 
• Aspartate aminotransferase (AST) and alanine 
aminotransferase (ALT) > 2 × upper limit of normal 
(ULN). 
• Total serum bilirubin of > 1.5 × ULN (except for 
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Grade 1 hyperbilirubinemia solely due to a medical 
diagnosis of Gilbert’s syndrome). 
• Serum creatinine > 1.5 mg/dL and creatinine clearance 
< 50 ml/min (using the Chronic Kidney Disease 
Epidemiology [CKD-EPI]-Creatinine formula). 
• Clinically Significant proteinuria (i.e., > 3 × ULN). 
• Hemoglobin ≤ 9 g/L. 
• Thyroid stimulating hormone or thyroglobulin outside 
of the central laboratory normal range. 
• International normalized ratio (INR) or activated partial 
thromboplastin time (aPTT) > 1.2 × ULN. 
• Total immunoglobulin G level < 6 g/L. 
5. Body Mass Index (BMI) at Screening ≥ 35 kg/m2. 
6. Use of rituximab, belimumab, eculizumab or any monoclonal 
antibody for immunomodulation within 6 months prior to first 
dosing. Patients with prior exposure to rituximab must have 
CD19 counts within the normal range per the central laboratory 
at Screening. 
7. Use of any biological therapy or investigational drug within 
3 months or 5 half-lives of the drug (whichever is longer) 
before Screening. 
8. Immunoglobulins given by IV (IVIg), or intramuscular route, 
or plasmapheresis/plasma exchange (PE) within 4 weeks 
before Screening. 
9. Have known autoimmune disease other than MG that would 
interfere with the course and conduct of the study (such as 
uncontrolled thyroid disease or severe RA). 
10. Have received vaccinations within 4 weeks before Screening or 
have any vaccinations planned during the study. 
11. Have a history of malignancy, including malignant thymoma, 
or myeloproliferative or lymphoproliferative disorders at any 
time, unless deemed cured by adequate treatment with no 
evidence of recurrence for ≥5 years before Screening. Patients 
with completely excised non-melanoma skin cancers (such as 
basal cell carcinoma or squamous cell carcinoma) or cervical 
carcinoma in situ would be permitted at any time. 
12. Have a history of cerebrovascular accident or myocardial 
infarction within the last 12 months before Screening, or 
current severe/unstable angina, arrhythmia, symptomatic 
congestive heart failure New York Heart Association (NYHA) 
class III or IV, or uncontrolled hypertension. 
13. Have clinical evidence of significant unstable or uncontrolled 
acute or chronic diseases (i.e., cardiovascular, pulmonary, 
hematologic, gastrointestinal, endocrinologic, hepatic, renal, 
neurologic, malignancy, or infectious diseases) which, in the 
opinion of the Investigator, could confound the results of the 
study or put the patient at undue risk. 
14. Major past surgery (e.g., heart valve replacement, hip 
replacement) that, in the opinion of the Investigator, poses a 
risk to patient’s safety or interferes with the study evaluation, 
procedures or completion. 
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15. Thymectomy when performed < 3 months prior to Screening. 
16. History or presence of alcoholism or drug/chemical/substance 
abuse within 2 years before Screening per Investigator’s 
opinion. 
Test product, dose and mode 
of administration: 
In this study, the Investigational Medicinal Product is ARGX-113 which 
is a human anti-neonatal Fc receptor IgG1 Fc fragment with immune 
modulating properties. A dose of 10 mg/kg of body weight of 
ARGX-113 will be administered as an intravenous (IV) infusion over a 
period of 2 hours at Visits 1, 3, 5, and 7. The total dose per IMP 
infusion is capped at 1200 mg for patients with body weight ≥ 120 kg. 
Placebo, dose, and mode of 
administration: 
Matching placebo with same buffer components but without the active 
ingredient will be administered intravenously over a period of 2 hours at 
Visits 1, 3, 5, and 7. 
Criteria for evaluation: 
Primary Endpoint: 
• 
Evaluate the incidence and severity of adverse events (AEs) and serious AEs (SAEs). 
• 
Evaluate vital signs, electrocardiogram (ECG), and laboratory assessments. 
Secondary Endpoints: 
• 
Score change from Baseline (defined as the score immediately prior to first dose at Visit 1) at 
Visits 3, 5, 7, 9, 10, 11, 12, 14, and 16 for the following: 
o MG-ADL 
o QMG 
o MGC 
o MGQoL15r 
• 
Maximum reduction from Baseline across visit days for MG-ADL, QMG, MGC, and MGQoL15r 
score. 
• 
Pharmacokinetic parameters of ARGX-113 including maximum observed concentration (Cmax), 
time of maximum concentration (tmax), concentration prior to dosing (Ctrough), half-life, (t1/2,λz), and 
accumulation ratio (Rac). 
• 
Evaluation of PD markers: total IgG (and subtypes) and anti-AChR antibodies. 
• 
Evaluate the incidence of anti-drug antibodies (ADA) to ARGX-113. 
• 
Exploratory pharmacogenetic assessments in patients who sign a separate pharmacogenetic ICF to 
examine FcRn polymorphisms. 
Statistical methods: For the primary objective of safety and tolerability, AEs, SAEs, vital signs, ECGs 
and clinical laboratory assessments at specific time points will be evaluated. All safety data will be 
summarized descriptively. Baseline will be the last assessment before the first dose of the IMP. Number 
and percentage of AEs will be presented for each treatment by Preferred Term (PT) and System Organ 
Class (SOC) of the current Medical Dictionary for Regulatory Authorities (MedDRA) dictionary. 
Individual listings of all serious AEs and discontinuation from IMP will be summarized using the current 
MedDRA dictionary. 
For the secondary objective of clinical effect, the change from Baseline will be evaluated. Actual and 
change in data from Baseline will be summarized descriptively for each treatment by visits. For change 
from Baseline, analysis of covariance (ANCOVA) will be used for continuous variables; (unless otherwise 
specified) with the terms of treatment as fixed effects and Baseline value as covariate in the model. All 
tests of treatment effects will be conducted at a two-sided alpha level of 0.05 or with 2-sided 95% 
confidence intervals (CI). No inferential hypothesis are tested in these secondary variables and summary 
statistics and CIs for these are not adjusted for multiplicity. The p-value if presented will not be considered 
for any inference. Analysis of Baseline characteristics will be summarized appropriately via descriptive 
statistics or visual presentation. For analysis of categorical data, Fisher’s exact test, Chi-squared test, or 
Cochran-Mantel-Haenszel (CMH) test will be performed. 
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For the secondary objectives for PK, the PK of ARGX-113 will be evaluated by assessment of drug 
concentrations in plasma. These drug concentrations will be listed and summarized for each sampling time 
point using arithmetic mean, standard deviation (SD), minimum, median, maximum, number of 
observations and number of observations ≥lower limit of quantification (LLOQ). The PK parameters 
except for tmax will be summarized using geometric mean (Gmean), geometric coefficient of variation 
(GCV), arithmetic mean, SD, minimum, median, and maximum number of observations. In addition, tmax 
will be summarized using median, minimum, maximum, and number of observations. Observed and 
change from Baseline in PD, ADA biomarkers will be listed, summarized, and presented graphically as 
appropriate. 
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Abbreviations: BMI = Body Mass Index; ECG = Electrocardiogram; ED = Early Discontinuation; EoS = End-of-Study; EoT = End-of-Treatment; FU = Follow-Up; MG-ADL = 
Myasthenia Gravis-Activities of Daily Living; QMG = Quantitative Myasthenia Gravis score; MGC = Myasthenia Gravis Composite score; MGQoL15r = 15-item quality of life scale 
for Myasthenia Gravis [Revised version]; US = Unscheduled; V = Visit. 
*: The allowed window period between visits in Treatment period and Follow-up period is ±1 day provided that 2 consecutive visits are 3 days apart at a minimum. Every effort 
should be made to schedule every visit on the exact Day (which is relative to the Baseline visit or [Visit 1]) as described in above Schedule of Assessments (Table 1) without 
the window. 
**: The Visits 2, 4, 6, and 8 are optional. 
a. 
To take place within 15 days prior to first administration of the Investigational Medicinal Product (IMP) at Visit 1. 
b. 
No study-related assessment is to be carried out before the patient has signed informed consent. 
c. 
A complete physical examination will be performed at Screening, Visit 7, and at Visit 16/EoS/ED. An abbreviated examination will be done at all other visits. On dosing 
days, physical examination including weight measurement should be performed pre-dose. 
d. 
Height should only be measured at Screening (and Body Mass Index [BMI] to be calculated accordingly at Screening only). 
e. 
Randomization to be performed only after confirmation of eligibility of the patient including the MG-ADL score assessed at Visit 1 and prior to dosing at Visit 1. The 
assessments for vital signs, urinalysis, and anti-drug antibodies, must be performed pre-dose at visits when the Investigational Medicinal Product (IMP) is administered 
(Visits 1, 3, 5, and 7). Efficacy assessments scheduled on designated Days should be completed pre-dose on each dosing day and should be performed prior to 
any other study specific assessment, except for obtaining informed consent at Screening. Efficacy assessments should be performed in the following sequence 
(at each study visit including these assessments): MGQoL15r, MG ADL, QMG, and MGC. Cholinesterase inhibitors must be held for at least 12 hours before the 
MGQoL15r, MG-ADL, QMG, and MGC assessments (consistent with the revised manual for the QMG test as recommended by the Myasthenia Gravis Foundation of 
America Inc [MGFA])1. A total score ≥5 on the MG-ADL with more than 50% of this score attributed to non-ocular items should be met at both Screening and Baseline 
(Visit 1) to confirm eligibility. 
f. 
Sampling for clinical laboratory tests is to be performed pre-dose on dosing days and tests will include hematology (hemoglobin, platelet count, white blood cell count 
with differential); blood chemistry (including creatinine, creatinine clearance, blood urea nitrogen [BUN], glucose, alanine aminotransferase [ALT], aspartate 
aminotransferase [AST], total bilirubin, gamma-glutamyl transferase [GGT], C-reactive protein [CRP], alkaline phosphatase [AP], lactate dehydrogenase [LDH], uric acid, 
albumin, potassium, calcium, sodium, thyroglobulin, International normalized ratio or activated partial thromboplastin time [aPTT], CD19 counts). Patients need to be 
fasting for at least 8 hours prior to this sampling. 
g. 
Sampling for pharmacodynamic biomarkers is to be performed pre-dose on dosing days and include anti-AChR antibodies and immunoglobulin G and its sub-types. 
Analysis of anti-AChR antibodies will include anti-AChR binding antibodies and anti-AChR blocking antibodies. IgG measurements include total IgG, IgG subtypes (IgG 
1, IgG 2, IgG 3, and IgG 4). In addition, IgA, IgD, IgE, and IgM will also be assessed. 
h. 
ECG (heart rate, PR, QT, and QRS interval) will be read locally and should be performed pre-dose on dosing days. 
i. 
Pharmacokinetic (PK) assessments should be done both pre- and post-dose (within 30 minutes prior to start of infusion for pre-dose sample and within 30 minutes after 
end of infusion for post-dose sample) on all IMP infusion days. 
j. 
Serum pregnancy test must be performed in women of childbearing potential at Screening from the blood sample collected for clinical laboratory tests at the central 
laboratory. 
k. 
Urine pregnancy test will be performed locally pre-dose at Visits 1, 3, 5, 7, 11, and 16/EoS/ED. 
l. 
Tests to assess HbsAg, anti-HCV antibodies, Follicle stimulating hormone (FSH), HIV antibodies and tuberculosis serology (QuantiFERON®-TB Gold) test will be 
performed at the central laboratory. 
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m. A blood sample for the optional pharmacogenetic testing is to be collected before the first dose of the Investigational Medicinal Product is administered at Visit 1 
(Baseline) after a separate pharmacogenetic ICF has been signed, and will be stored for pharmacogenetic analysis. Only if the blood sample at Visit 1 is missed, the 
sample should be drawn at Visit 3 before the administration of the Investigational Medicinal Product. 
n. 
The Investigational Medicinal Product or placebo will be administered as an IV infusion over a period of 2 hours at Visits 1, 3, 5, and 7. Patients should remain at the site 
for at least 2 hours following the end of the infusion for safety monitoring based on the patient’s clinical status. 
o. 
Suicidal ideation and behavior will be assessed via a targeted question based on the Patient Health Questionnaire item 9 (PHQ-9)2 at each scheduled visit except the 
optional visit. 
p. 
Adverse events and intake of concomitant medication(s) will be monitored continuously from signing of informed consent until the last study-related activity at Visit 16. In 
case of early discontinuation, any AEs/SAEs should be assessed for 30 days following the early discontinuation visit and until satisfactory resolution or stabilization. 
 
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TABLE OF CONTENTS 
SIGNATURES OF SPONSOR AND CRO REPRESENTATIVES ....................................3 
SIGNATURE OF INVESTIGATOR .....................................................................................5 
SYNOPSIS ................................................................................................................................6 
TABLE OF CONTENTS ......................................................................................................16 
1.0 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ........................22 
2.0 
INTRODUCTION......................................................................................................25 
2.1 
Background Information...............................................................................25 
2.2 
Investigational Medicinal Product ...............................................................25 
2.3 
Rationale and Standard of Care ...................................................................27 
2.4 
Risk Assessment .............................................................................................28 
3.0 
STUDY OBJECTIVES ..............................................................................................32 
3.1 
Primary Objectives ........................................................................................32 
3.2 
Secondary Objectives.....................................................................................32 
4.0 
SAFETY, EFFICACY, PHARMACOKINETIC, AND 
PHARMACODYNAMIC ENDPOINTS .................................................................33 
4.1 
Primary Endpoint ..........................................................................................33 
4.2 
Secondary Endpoints .....................................................................................33 
5.0 
INVESTIGATIONAL PLAN ...................................................................................34 
5.1 
Summary of Study Design .............................................................................34 
5.2 
Discussion of Study Design ............................................................................37 
5.3 
Selection of Study Population .......................................................................37 
5.3.1 
Inclusion Criteria ...............................................................................37 
5.3.2 
Exclusion Criteria ..............................................................................40 
5.3.3 
Patient Withdrawal from Study .........................................................42 
5.3.4 
Early Discontinuation from the Study Treatment or Study ...............42 
5.3.5 
Follow-Up after Early Discontinuation Visit ....................................45 
5.3.6 
Replacement of Patients ....................................................................45 
5.3.7 
Protocol Deviations/Violations .........................................................45 
5.3.8 
Screen Failures and Rescreening .......................................................46 
5.3.9 
Early Termination of Study or Site ...................................................46 
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6.0 
STUDY PROCEDURES ...........................................................................................48 
6.1 
Informed Consent and Enrollment ..............................................................48 
6.2 
Screening .........................................................................................................48 
6.3 
Randomization ...............................................................................................49 
6.4 
Treatment Period ...........................................................................................50 
6.4.1 
Visits 1, 3, 5, and 7 ............................................................................50 
6.4.2 
Visits 2, 4, and 6 (Optional) ..............................................................51 
6.5 
Follow-Up Period ...........................................................................................52 
6.5.1 
Visit 8 (Optional) ...............................................................................52 
6.5.2 
Visits 9, 10, 11, 12, 14, and 16 ..........................................................52 
6.5.3 
Visits 13 and 15 .................................................................................53 
6.6 
Early Discontinuation Visit ...........................................................................53 
6.7 
Unscheduled Visit...........................................................................................53 
7.0 
STUDY TREATMENTS ...........................................................................................55 
7.1 
Treatments Administered .............................................................................55 
7.2 
Identity of Investigational Medicinal Products ...........................................55 
7.3 
Packaging and Labelling ...............................................................................56 
7.4 
Storage of Investigational Medicinal Product .............................................56 
7.5 
Method of Assigning Patients to Treatment Group....................................56 
7.6 
Selection of Doses in the Study .....................................................................57 
7.7 
Timing of Dose for Each Patient...................................................................57 
7.8 
Blinding ...........................................................................................................58 
7.8.1 
Emergency Unblinding ......................................................................58 
7.9 
Prior and Concomitant Treatments .............................................................58 
7.9.1 
Prohibited Medications during the Study ..........................................58 
7.9.2 
Rescue Therapy .................................................................................59 
7.10 
Medical Care of Patients after End-of-Study ..............................................59 
7.11 
Treatment Compliance ..................................................................................59 
7.12 
Handling Missed Doses of the Investigational Medicinal 
Product ............................................................................................................60 
7.13 
Accountability of Investigational Medicinal Product .................................60 
7.14 
Storage of Blood Samples in the Study ........................................................60 
8.0 
SAFETY, EFFICACY, PHARMACOKINETIC, AND 
PHARMACODYNAMIC ASSESSMENTS ............................................................62 
8.1 
Safety ...............................................................................................................62 
8.1.1 
Adverse Events ..................................................................................62 
8.1.1.1 
Reporting of Adverse Events and Serious 
Adverse Events ................................................................65 
8.1.1.2 
Reporting of Serious Adverse Events to 
Regulatory Authorities and Investigators ........................66 
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8.1.1.3 
Follow-Up of Adverse Events and Serious 
Adverse Events ................................................................67 
8.1.1.4 
Reporting and Follow-Up Requirements for 
Pregnancies ......................................................................68 
8.1.2 
Clinical Laboratory Evaluations ........................................................69 
8.1.3 
Vital Signs, Physical Examination, and ECGs ..................................70 
8.1.4 
Suicidality assessment .......................................................................70 
8.1.5 
Medical History .................................................................................71 
8.1.6 
Independent Data Monitoring Committee .........................................71 
8.2 
Efficacy............................................................................................................72 
8.2.1 
Appropriateness of Measurements ....................................................72 
8.2.2 
Myasthenia Gravis-Activities of Daily Living ..................................72 
8.2.3 
Quantitative Myasthenia Gravis ........................................................72 
8.2.4 
Myasthenia Gravis Composite ..........................................................72 
8.2.5 
15-Item Quality of Life Scale for Myasthenia Gravis .......................73 
8.3 
Pharmacokinetics ...........................................................................................73 
8.4 
Pharmacodynamics ........................................................................................74 
8.5 
Additional Assessment of Immunoglobulins ...............................................74 
8.6 
Anti-drug Antibodies .....................................................................................74 
8.7 
Pharmacogenetics ..........................................................................................74 
9.0 
QUALITY CONTROL AND QUALITY ASSURANCE .......................................75 
9.1 
Investigator’s Responsibility .........................................................................75 
9.2 
Quality Control of Data .................................................................................75 
9.3 
Monitoring ......................................................................................................76 
9.4 
Data Management and Coding .....................................................................77 
9.5 
Quality Assurance Audit ...............................................................................79 
10.0 
STATISTICS ..............................................................................................................80 
10.1 
Determination of Sample Size .......................................................................80 
10.2 
Analysis Population .......................................................................................80 
10.3 
Patient Disposition, Characteristics and Concomitant 
Medication ......................................................................................................81 
10.4 
Statistical Methods .........................................................................................81 
10.4.1 
Primary Endpoint Analyses ...............................................................82 
10.4.1.1 
Adverse Events ................................................................82 
10.4.1.2 
Vital Signs Measurements, Physical Findings 
and Laboratory assessments ............................................82 
10.4.2 
Secondary Endpoint Analyses ...........................................................82 
10.4.2.1 
Analysis of Scales ............................................................82 
10.4.2.2 
Analysis of Pharmacokinetic Parameters ........................83 
10.4.2.3 
Analysis of Pharmacodynamic Parameters .....................84 
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10.4.2.4 
Anti-Drug Antibodies (ADA) Analyses ..........................84 
10.5 
Interim Analyses ............................................................................................84 
11.0 
ETHICS ......................................................................................................................85 
11.1 
Institutional Review Board or Independent Ethics Committee ................85 
11.2 
Ethical Conduct of the Study ........................................................................85 
11.3 
Patient Information and Informed Consent ................................................85 
11.4 
Patient Data Protection .................................................................................86 
12.0 
STUDY ADMINISTRATION...................................................................................87 
12.1 
Administrative Structure ..............................................................................87 
12.2 
Data Handling and Record Keeping ............................................................87 
12.3 
Direct Access to Source Data/Documents ....................................................88 
12.4 
Investigator Information ...............................................................................88 
12.4.1 
Investigator Obligations ....................................................................88 
12.4.2 
Protocol Signatures ............................................................................89 
12.4.3 
Publication Policy ..............................................................................89 
12.5 
Financing and Insurance ...............................................................................89 
13.0 
REFERENCES ...........................................................................................................91 
14.0 
APPENDICES ............................................................................................................93 
14.1 
Appendix 1: Myasthenia Gravis-Activities of Daily Living .......................93 
14.2 
Appendix 2: Quantitative Myasthenia Gravis score...................................94 
14.3 
Appendix 3: Myasthenia Gravis Composite Score ...................................102 
14.4 
Appendix 4: The 15-Item Quality of Life Scale for Myasthenia 
Gravis ............................................................................................................103 
14.5 
Appendix 5: Clinical Laboratory Evaluations ..........................................104 
14.6 
Appendix 6: Sample Size .............................................................................105 
 
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LIST OF INTEXT TABLES 
Table 1 
Schedule of Assessments .................................................................................13 
Table 2 
Potential Scenarios for Early Discontinuation from Study and 
Treatment .........................................................................................................43 
Table 3 
Investigational Medicinal Products ..................................................................56 
Table 4 
Administrative Structure ..................................................................................87 
 
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LIST OF FIGURES 
Figure 1 
Schematic of Study Design for Protocol ARGX-113-1602 .............................36 
 
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1.0 LIST OF ABBREVIATIONS AND DEFINITIONS OF 
TERMS 
Abbreviation 
Definition 
ACh 
Acetylcholine 
AChE 
Anticholinesterase inhibitors 
AChR 
Acetylcholine receptor 
ADA 
Anti-drug antibodies 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
AZA 
Azathioprine 
b.w. 
Body weight 
BMI 
Body Mass Index 
CI 
Confidence interval 
Cmax 
Maximum observed plasma concentration 
CRO 
Contract research organization 
CRP 
C-reactive protein 
CSR 
Clinical study report 
Ctrough 
Concentration observed prior to dosing 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
EoS 
End-of-Study 
EoT 
End-of-Treatment 
FAS 
Full analysis set 
Fc 
Fragment, crystallized 
FcRn 
Neonatal Fc receptor 
FU 
Follow-Up 
GCP 
Good Clinical Practice 
GCV 
Geometric coefficient of variation 
GGT 
Gamma-glutamyl transferase 
Gmean 
Geometric mean 
HBsAg 
Hepatitis B virus surface antigen 
HBV 
Hepatitis B virus 
HCV 
Hepatitis C virus 
IA 
Immunoadsorption 
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ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
IDMC 
Independent Data Monitoring Committee 
IEC 
Independent Ethics Committee 
IgG 
Immunoglobulin G 
IMP 
Investigational Medicinal Product 
IRB 
Institutional Review Board 
IV 
Intravenous 
IVIg 
Intravenous immunoglobulin 
IxRS 
Interactive Voice/Web response system 
LDH 
Lactate dehydrogenase 
LLOQ 
Lower limit of quantification 
MedDRA 
Medical dictionary for regulatory authorities 
MG 
Myasthenia Gravis 
MG-ADL 
Myasthenia Gravis activities of daily living 
MGC 
Myasthenia Gravis composite score 
MGFA 
Myasthenia Gravis Foundation of America 
MG-QOL 
Myasthenia Gravis Quality of Life scale 
MGQoL15r 
15-item Quality of life scale for Myasthenia Gravis 
[revised version] 
NOAEL 
No Observed Adverse Effect Levels 
NSID 
Non-steroidal immunosuppressant drugs 
PD 
Pharmacodynamics 
PE 
Plasma exchange 
pH 
Potential of hydrogen or concentration of hydrogen ions 
PHQ-9 
Patient Health Questionnaire item 9 
PK 
Pharmacokinetics 
PR interval 
Duration from the start of the T wave to the start of the 
QRS complex, representing the time taken for electrical 
activation (of the cardiac conduction system) to pass 
from the sinus node to the atrium, the atrioventricular 
node and the His-Purkinje system to the ventricle 
PT 
Preferred term 
q4d 
Administered every 4 days 
q7d 
Administered every 7 days 
QMG 
Quantitative Myasthenia Gravis score 
QRS interval 
Pertains to depolarization of ventricles 
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QT interval 
Duration from the start of QRS interval to the end of the 
T wave, representing the time taken for depolarization 
and repolarization of the ventricular myocardium 
Rac 
Accumulation ratio 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SD 
Standard deviation 
SoC 
Standard of care 
SOP 
Standard operating procedures 
SUSAR 
Suspected unexpected serious adverse reaction 
t1/2,λz 
Apparent terminal half-life 
tmax 
The time of occurrence of Cmax 
ULN 
Upper limits of normal 
US 
United States 
WHO-DD 
World Health Organization drug dictionary 
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2.0 INTRODUCTION 
Myasthenia Gravis (MG) is an autoimmune disorder characterized in most cases by T cell 
and antibody responses to neuromuscular junction proteins such as skeletal muscle nicotinic 
acetylcholine receptor (AChR). Antibodies against epitopes of the AChR of the 
neuromuscular junction cause failure of neuromuscular transmission, resulting in the 
characteristic fatigue and weakness associated with this severe disorder. The muscle 
weakness fluctuates with activity, and periods of rest offer only a temporary reprieve.3 
2.1 
Background Information 
Antibodies, especially IgG, play a predominant role in the pathogenesis and the treatment of 
many autoimmune diseases such as MG. In most cases, MG is characterized by antibody 
responses to neuromuscular junction proteins such as skeletal muscle AChR. High-affinity, 
anti-AChR antibodies bind to the muscle endplate leading to AChR dysfunction or loss via 
activation of complement, cross-linking of AChR receptors, or direct blockade of 
acetylcholine (Ach) binding sites, thereby leading to an impaired signal transduction and 
resulting muscle weakness.4, 5 The disease is typically managed with acetylcholinesterase 
inhibitors and immunosuppressive medications. Acute exacerbations are treated using either 
therapeutic plasma exchange (PE), immunoadsorption (IA) or intravenous immunoglobulin 
(IVIg). These therapeutic options, except acetylcholinesterase inhibitors, aim at reducing the 
levels of pathogenic autoantibodies but suffer from severe side effects and/or comorbidities.6 
In order to treat IgG-mediated autoimmunity, it would be beneficial to lower levels of 
pathogenic autoantibodies rapidly and sustainably. Antagonizing the neonatal Fc receptor 
(FcRn) could be a therapeutic approach to achieve this as FcRn is a multifunctional molecule 
primarily involved in IgG transport and homeostasis, that influences immunoglobulin G 
(IgG) serum levels and tissue distribution at all stages of life.7, 8. Following IgG uptake by 
pinocytosis, the Fc part of IgGs binds FcRn with high affinity in early, acidic endosomes 
with pH <6.5. Through its ability to rescue IgG from destruction in the lysosomal 
compartment, FcRn is responsible for the maintenance of high concentrations of IgG in 
circulation and concomitantly for the long half-life of IgG compared to other Ig isotypes. 
Thus, targeting the FcRn-IgG interaction would be a rational therapeutic approach to rapidly 
clear pathogenic autoantibodies in IgG-driven autoimmune diseases such as MG. 
2.2 
Investigational Medicinal Product 
ARGX-113 is a human IgG1-derived Fc fragment of the za allotype that binds with 
nanomolar affinity to human FcRn. ARGX-113 encompasses IgG1 residues D220-K447 (EU 
numbering scheme) and has been modified with the so-called ABDEG™ technology 
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(ABDEG™ = antibody that enhances IgG degradation)9 to increase its affinity for FcRn at 
both physiological and acidic pH. The increased affinity for FcRn of ARGX-113 at both 
acidic and physiological pH results in a constitutively blockage of FcRn-mediated recycling 
of IgGs. 
Given the essential role of the FcRn receptor in IgG homeostasis, inhibiting this FcRn 
function, as achieved by ARGX-113, leads to rapid degradation of endogenous IgGs, which 
is expected to include autoantibodies in IgG-driven autoimmune diseases. 
This concept has been validated in various murine disease models together with 
pharmacokinetic/pharmacodynamic (PK/PD) studies in cynomolgus monkeys, either by 
using ARGX-113 or a full- length mAb analogue (HEL-ABDEG™)10, 11 
In murine in vivo disease models for rheumatoid arthritis and multiple sclerosis a clear 
improvement in disease score was observed after treatment with an ABDEG™-equipped 
molecule. This improvement was accompanied with systemic lowering of autoantibody 
levels. 
Pharmacokinetic and PD studies in cynomolgus monkey confirmed the antibody-clearing 
properties of ARGX-113 in a relevant animal model. A single infusion of ARGX-113 
resulted in a decrease of endogenous IgG up to 55% without altering serum albumin 
concentrations as well as IgM or IgA levels. This PD effect was proven to be more potent 
than IVIg, which is considered a standard of care therapy in MG, both in rapidity of onset as 
in depth of the PD effect. Repeated dosing could improve the PD effect up to a maximum 
IgG reduction of 75%. 
These pre-clinical data validated the further development of ARGX-113 for assessing its 
therapeutic potential in IgG-driven autoimmune indications. 
To this end, a Phase I dose-escalation study in healthy volunteers was initiated. In this study 
ARGX-113 was administered to healthy volunteers in single doses (up to 50 mg/kg) as well 
as multiple doses (up to 25 mg/kg). ARGX-113 was proven to be safe and tolerable in this 
healthy volunteer study and pre-clinical PD parameters could be confirmed in a human 
setting. 
The proposed Phase II study aims to further establish the safety, efficacy, PK and PD of 
ARGX-113 in a patient setting, namely in patients with autoimmune MG with generalized 
muscle weakness, and thereby validating the concept of autoantibody reduction as a 
therapeutic treatment modality in this indication. 
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This study will be performed in compliance with the protocol, International Council for 
Harmonisation, Good Clinical Practice (ICH GCP), Declaration of Helsinki, and other 
applicable regulatory requirements. 
2.3 
Rationale and Standard of Care 
The mainstays of MG treatment are AChE inhibitors, immunosuppressants and 
immunomodulating therapies. In the mild form of the disease, AChE inhibitors are used 
initially. These agents include pyridostigmine, neostigmine, and edrophonium and their 
effectiveness varies widely. Patients with generalized MG are treated with corticosteroids. 
Unfortunately, corticosteroids are typically characterized by delayed onset of effects. 
Because of their multiple side effects, the lowest effective dose of corticosteroids is 
recommended for long-term treatment that is often indicated for chronic conditions such as 
MG. Other non-steroidal immunosuppressive (NSIDs) agents are commonly used and 
include azathioprine (AZA), mycophenolate mofetil, cyclosporine, cyclophosphamide, and 
rituximab. However, the effectiveness of many of these medications varies widely among 
patients, take a long time to take effect and have numerous adverse consequences.12 
Plasma exchange (PE), immunoadsorption and IVIg are used for short-term treatment of MG 
exacerbations and when it is desirable to achieve a rapid clinical response. Plasma exchange 
temporarily reduces the concentrations of circulating anti-AChR antibodies and in most 
patients produces improvement in a matter of days. Typically, one exchange removing one to 
two plasma volumes is done every other day up to a total of four to six times, to improve 
muscle strength or ameliorate a myasthenic crisis. Unfortunately, this treatment is invasive 
and has common side-effects such as hypotension, paresthesia, infections, and thrombotic 
complications. IVIg is widely used for patients with exacerbating MG and data from 
randomized controlled studies show efficacy similar to PE. The mechanisms by which IVIg 
produce improvement are not clear, but two important possibilities are competition with 
autoantibodies (i.e., FcRn binding) and Fc receptor binding. It is important to note that a 
higher degree of auto-antibody reduction, faster onset and better clinical efficacy has been 
observed for PE and immunoadsorption when compared with IVIg. A fast onset is important 
for treatment of patients experiencing exacerbations.13, 14 
In preclinical studies, ARGX-113 demonstrated high potency and rapid onset of action in 
IgG autoantibody reduction. In murine in vivo disease models, ARGX-113 demonstrated a 
high therapeutic potential linked to a rapid clearance of IgG autoantibodies. Studies in 
cynomolgus monkeys confirmed this rapid onset of IgG reduction, and demonstrated 
specificity of this effect as IgA, IgM, and albumin levels were not affected. 
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3.0 STUDY OBJECTIVES 
3.1 
Primary Objectives 
• To evaluate the safety and tolerability of ARGX-113. 
3.2 
Secondary Objectives 
• To evaluate the clinical effect of ARGX-113 using: 
o 
Myasthenia Gravis-Activities of Daily Living (MG-ADL) score 
o 
Quantitative-Myasthenia Gravis score (QMG) 
o 
Myasthenia Gravis Composite score (MGC). 
• To evaluate the impact of ARGX-113 on quality of life using 15-item quality of life 
scale for Myasthenia Gravis (MGQoL15r [revised version]). 
• To investigate the PK of ARGX-113. 
• To assess PD markers (e.g., total immunoglobulin G (IgG) and subtypes, anti-AChR 
antibodies). 
• To evaluate the immunogenicity of ARGX-113. 
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4.0 SAFETY, EFFICACY, PHARMACOKINETIC, AND 
PHARMACODYNAMIC ENDPOINTS 
4.1 
Primary Endpoint 
• 
Evaluate the incidence and severity of adverse events (AEs) and serious AEs (SAEs). 
• 
Evaluate vital signs, ECG, and laboratory assessments. 
4.2 
Secondary Endpoints 
• 
Score change from Baseline (defined as the score immediately prior to first dose at 
Visit 1) at Visits 3, 5, 7, 9, 10, 11, 12, 14, and 16 for the following: 
o MG-ADL 
o QMG 
o MGC 
o MGQoL15r 
• 
Maximum reduction from Baseline across visit days for MG-ADL, QMG, MGC, and 
MGQoL15r score. 
• 
Pharmacokinetic parameters of ARGX-113 including maximum observed concentration 
(Cmax), time of maximum concentration (tmax), concentration prior to dosing (Ctrough), half-
life (t1/2,λz), and accumulation ratio (Rac). 
• 
Evaluation of PD markers: total IgG (and subtypes) and anti-AChR antibodies. 
• 
Evaluate the incidence of anti-drug antibodies (ADA) to ARGX-113. 
• 
Exploratory pharmacogenetic assessments in patients who sign a separate 
pharmacogenetic ICF to examine FcRn polymorphisms. 
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5.0 INVESTIGATIONAL PLAN 
5.1 
Summary of Study Design 
This is a randomized, double-blind, placebo-controlled multicenter Phase II study to evaluate 
the safety, efficacy, and pharmacokinetics (PK) of ARGX-113 for the treatment of 
autoimmune MG with generalized muscle weakness. 
Approximately 24 patients will be randomized. 
The study will include a Screening period of maximum 15 days, a Treatment period of 
3 weeks from Visit 1 to Visit 7 and a Follow-Up (FU) period of 8 weeks starting after 
completion of Visit 7 to Visit 16. Although the FU period is from Visit 8 to Visit 16, the FU 
in fact starts immediately after the last Investigational Medicinal Product (IMP) infusion at 
Visit 7. 
During the Screening Period, patients’ eligibility will be evaluated for study participation. 
During the Treatment period, eligible patients will be randomized at a 1:1 ratio to receive 
ARGX-113 (10 mg/kg) or placebo in 4 infusions administered one week apart in addition to 
Standard of Care (SoC). The total dose per IMP infusion is capped at 1200 mg for patients 
with body weight ≥ 120 kg. 
Patients will receive ARGX-113 or placebo according to the following regimen: 
• Patient will receive ARGX-113 or matching placebo via intravenous (IV) infusion 
over a period of 2 hours on Days 1 (Visit 1), 8±1 (Visit 3), 15±1 (Visit 5), and 
22±1 (Visit 7). 
• The Treatment period consists of 7 visits (of which the 3 visits between the weekly 
dosing visits are optional). 
At the end of the 3 weeks Treatment period, the patient will enter a FU period for 8 weeks. 
During the Follow-Up period, 9 visits (of which 1 visit is optional) will take place as detailed 
in Table 1. 
Study procedures including endpoint assessments will be performed according to the 
Schedule of Assessments as detailed in Table 1. 
In this study, SoC for a patient is the stable dose and administration of their MG treatment 
prior to enrollment. Permitted SoC for MG treatment under this protocol include azathioprine 
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(AZA), other non-steroidal immunosuppressant drugs (NSIDs: e.g., methotrexate, 
cyclosporine, tacrolimus, mycophenolate mofetil, and cyclophosphamide), steroids, as well 
as cholinesterase inhibitors. Patients should be on a stable dose and frequency of SoC prior to 
enrollment as detailed in of Section 5.3.1 (Criterion 5) that should be maintained throughout 
the study without any increase or decrease. 
Patients receiving cholinesterase inhibitors will be required to be on a stable dose for 
>2 weeks prior to Screening. In addition, cholinesterase inhibitors must be held for at least 
12 hours consistent with the revised manual for the QMG test as recommended by the 
Myasthenia Gravis Foundation of America Inc [MGFA]1, prior to performing the 
MGQoL15r, MG-ADL, QMG, and MGC assessments at Screening, Visits 1, 3, 5, 7, 9, 10, 
11, 12, 14, and 16. 
During the study, no changes in the dose level and frequency of ARGX-113 or the SoC will 
be allowed. However, if necessary, patients may receive rescue therapy if their MG 
deteriorates as judged by the Investigator on the basis of parameters such as changes in 
MGQoL15r, MG-ADL, QMG, MGC on any study day. 
Rescue therapy will be determined by the Investigator based on an overall clinical 
assessment. Rescue therapy may include IVIg, PE, or any other treatment chosen by the 
Investigator. In case a patient needs rescue therapy according to the treating Investigator, the 
Medical Director at the Sponsor should be informed in addition to the Medical Monitor at 
Sponsor’s designated contract research organization (CRO, Quintiles); where possible prior 
to actual implementation of the rescue therapy. In case rescue therapy is needed (due to 
deterioration of MG), patients need to be discontinued from the treatment, but will be 
followed up for safety. Any patient who discontinues study treatment due to safety concerns 
will be followed up for safety and wherever possible for efficacy. 
For patients who discontinue the study early, all the procedures listed for the Early 
Discontinuation (ED) visit (same procedures as for the End-of-Study [EoS] visit or Visit 16) 
in the Schedule of Assessments (Table 1) are to be performed (early discontinuation). This 
study is exploratory and not powered to address any pre-defined hypothesis. The safety and 
efficacy analysis will be performed on the safety analysis set, which includes all patients who 
received at least one infusion of ARGX-113 or placebo. 
A schematic of study design is presented in Figure 1. 
 
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5.2 
Discussion of Study Design 
ARGX-113, a novel immunomodulator, has been found to be safe and well tolerated in 
non-clinical studies and a single and multiple dose Phase I study. The safety and tolerability 
assessments in the Phase I study was judged sufficient to fulfill the primary objective of this 
study. Preliminary evidence suggests that ARGX-113 has shown promising effect with 
decreased serum IgG levels. This effect has been well characterized in pre-clinical studies 
and justifies its further development in patients with IgG driven autoimmune diseases such as 
MG. 
In the current study, ARGX-113 will be administered for the first time in patients with MG 
who have generalized muscle weakness, with the aim to evaluate the safety, efficacy, and 
PK-PD of ARGX-113. This study is designed as a randomized, double-blind, and placebo 
controlled study to distinguish the effect of the IMP from other influences such as placebo 
effect or biased observation. Patients will continue to receive their routine SoC during the 
study irrespective of the treatment they receive because of randomization. Furthermore, 
patients randomized to ARGX-113 will receive the IMP as an add-on therapy to the routine 
SoC. Since patients with autoimmune MG eligible for this study continue to have significant 
residual symptoms that affect their quality of life whilst on SoC, this study offers an 
opportunity to receive ARGX-113 (a potential new treatment for MG) that may offer 
additional benefit on top of their routine SoC. It serves as a rational therapeutic approach for 
IgG mediated immune diseases such as MG by targeting the FcRn-IgG interaction and 
alleviating autoimmunity by rapidly clearing pathogenic autoantibodies. 
The efficacy of ARGX-113 versus placebo will be explored using clinical activity tools 
commonly used in MG clinical research and clinical practice. Patients achieving clinically 
meaningful response by studying change from Baseline will be used to explore efficacy data 
in the current study. All efficacy and safety assessments used in this study are standard, i.e., 
widely used and generally recognized as reliable, accurate, and relevant. 
5.3 
Selection of Study Population 
5.3.1 
Inclusion Criteria 
Patients will be enrolled in this study only if they meet all of the following criteria: 
1. Have the ability to understand the requirements of the study, provide written informed 
consent (including consent for the use and disclosure of research-related health 
information), and comply with the study protocol procedures (including required study 
visits). 
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2. Male or female patients aged ≥18 years. 
3. Diagnosis of autoimmune MG with generalized muscle weakness meeting the clinical 
criteria for diagnosis of MG as defined by the Myasthenia Gravis Foundation of America 
(MGFA) Clinical Classification Class II, III, or IVa, and likely not in need of a respirator 
for the duration of the study as judged by the Investigator. 
The confirmation of the diagnosis should be documented and supported by: 
• Positive serologic test for anti-AChR antibodies before Screening and 
• At least 1 of the following 3 tests: 
(i) History of abnormal neuromuscular transmission test demonstrated by single-fiber 
electromyography or repetitive nerve stimulation or 
(ii) History of positive edrophonium chloride test, or 
(iii) Patient has demonstrated improvement in MG signs on oral cholinesterase inhibitors 
as assessed by the treating physician. 
4. A total score of ≥ 5 on the MG-ADL at Screening and Baseline with more than 50% of 
this score attributed to non-ocular items. 
5. Patients are required to be on a stable dose of their MG treatment prior to randomization. 
For patients receiving AZA, other NSIDs, steroids, and/or cholinesterase inhibitors as 
concomitant medications the following conditions will apply: 
• AZA: treatment initiated at least 12 months ago and no dose changes in the last 
6 months before Screening. 
• Other NSIDs (e.g., methotrexate, cyclosporine, tacrolimus, mycophenolate mofetil, 
and cyclophosphamide): treatment initiated at least 6 months ago and no dose 
changes in the last 3 months before Screening. 
• Steroids: treatment initiated at least 3 months prior to and no dose changes in the last 
month before Screening. 
• Cholinesterase inhibitors: to be on a stable dose for >2 weeks before Screening. 
Note: cholinesterase inhibitors must be held for at least 12 hours consistent with the 
revised manual for the QMG test as recommended by the Myasthenia Gravis 
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Foundation of America Inc [MGFA]1, before the MGQoL15r, MG-ADL, QMG, and 
MGC assessments. 
6. Females of childbearing potential must have a negative serum pregnancy test at 
Screening and a negative urine pregnancy test at Visit 1 prior to administration of IMP. 
Female of childbearing potential are defined as all female participants unless they are 
postmenopausal (defined by continuous amenorrhea) for at least 2 years with a 
Follicle-stimulating hormone (FSH) > 40 IU/L or are surgically sterile (i.e., who had a 
hysterectomy, 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 if the test result is within the postmenopausal range per the central laboratory. 
7. Female participants of childbearing potential must agree to use a highly effective method 
of contraception (i.e., pregnancy rate of less than 1% per year) during the study and for 
90 days after the discontinuation of the Investigational Medicinal Product (IMP). 
Adequate contraceptive methods include combined hormonal contraception associated 
with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal 
contraception associated with inhibition of ovulation (oral, injectable, implantable), 
intrauterine devices (IUDs), intrauterine hormone-releasing system (IUS), true sexual 
abstinence (when this is in line with the preferred and usual lifestyle of the participant), 
bilateral tubal occlusion, or a female participant who is not of childbearing potential. 
Female participants and female partners of male study participants using a hormonal 
contraceptive must also use a barrier method (i.e., condom or occlusive cap [diaphragm 
or cervical/vault caps]) and should have been stable on their hormonal contraceptive 
treatment for at least 4 weeks before Screening. 
8. Sterilized male patients who have had vasectomy with documented aspermia post 
procedure can be included. In addition, male patients must be advised not to donate 
sperm during this period from signing of Informed Consent Form (ICF), throughout the 
duration of the study, and for 90 days after the last administration of IMP. Non-sterilized 
male patients who are sexually active with a female partner of childbearing potential 
must use effective method of double barrier contraception (e.g., condom with spermicidal 
cream or jelly, 1 hormonal 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. 
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5.3.2 
Exclusion Criteria 
Patients will not be enrolled in this study if they meet any of the following criteria: 
1. Females who are pregnant or lactating. 
2. MGFA Class I, IVb, and V. 
3. Have an active infection, a recent serious infection (i.e., requiring injectable antimicrobial 
therapy or hospitalization) within the 8 weeks prior to Screening; or history of or known 
infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis 
C virus (HCV), or Mycobacterium tuberculosis. Patients must have negative test results 
for HBV surface antigen, HBV core antibody, HCV antibody, HIV 1 and 2 antibodies, 
and a negative QuantiFERON®-TB Gold test at Screening. Patients with an indeterminate 
QuantiFERON®-TB Gold result will be allowed one retest; if not negative on retesting, 
the patient will be excluded. 
4. At Screening, have clinically significant laboratory abnormalities or as below: 
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 
2 × upper limit of normal (ULN). 
• Total serum bilirubin of > 1.5 × ULN (except for Grade 1 hyperbilirubinemia 
solely due to a medical diagnosis of Gilbert’s syndrome). 
• Serum creatinine > 1.5 mg/dL and creatinine clearance < 50 ml/min (using the 
Chronic Kidney Disease Epidemiology [CKD-EPI]-Creatinine formula). 
• Clinically significant proteinuria (i.e., > 3 × ULN) 
• Hemoglobin ≤ 9 g/L 
• Thyroid stimulating hormone or thyroglobulin outside of the central laboratory 
normal range. 
• International normalized ratio (INR) or activated partial thromboplastin time 
(aPTT) > 1.2 × ULN. 
• Total immunoglobulin G level < 6 g/L. 
5. Body Mass Index (BMI) at Screening ≥ 35 kg/m2. 
6. Use of rituximab, belimumab, eculizumab or any monoclonal antibody for 
immunomodulation within 6 months prior to first dosing. Patients with prior exposure to 
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rituximab must have CD19 counts within the normal range per the central laboratory at 
Screening. 
7. Use of any biological therapy or investigational drug within 3 months or 5 half-lives of 
the drug (whichever is longer) before Screening. 
8. Immunoglobulins given by IV (IVIg), or intramuscular route, or plasmapheresis/plasma 
exchange (PE) within 4 weeks before Screening. 
9. Have known autoimmune disease other than MG that would interfere with the course and 
conduct of the study (such as uncontrolled thyroid disease or severe RA). 
10. Have received vaccinations within 4 weeks before Screening or have any vaccinations 
planned during the study. 
11. Have a history of malignancy, including malignant thymoma, or myeloproliferative or 
lymphoproliferative disorders at any time, unless deemed cured by adequate treatment 
with no evidence of recurrence for ≥5 years before Screening. Patients with completely 
excised non-melanoma skin cancers (such as basal cell carcinoma or squamous cell 
carcinoma) or cervical carcinoma in situ would be permitted at any time. 
12. Have a history of cerebrovascular accident or myocardial infarction within the last 
12 months before Screening, or current severe/unstable angina, arrhythmia, symptomatic 
congestive heart failure New York Heart Association (NYHA) class III or IV, or 
uncontrolled hypertension. 
13. Have clinical evidence of significant unstable or uncontrolled acute or chronic diseases 
(i.e., cardiovascular, pulmonary, hematologic, gastrointestinal, endocrinologic, hepatic, 
renal, neurologic, malignancy, or infectious diseases) which, in the opinion of the 
Investigator, could confound the results of the study or put the patient at undue risk. 
14. Major past surgery (e.g., heart valve replacement, hip replacement) that, in the opinion of 
the Investigator, poses a risk to patient’s safety or interferes with the study evaluation, 
procedures or completion. 
15. Thymectomy when performed < 3 months prior to Screening. 
16. History or presence of alcoholism or drug/chemical/substance abuse within 2 years 
before Screening per Investigator’s opinion. 
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5.3.3 
Patient Withdrawal from Study 
Patient withdrawal in this study only refers to patients withdrawn due to withdrawal of 
consent. Any other circumstances for early dropout of a patient from the study treatment or 
study will be referred to as early discontinuation (see Section 5.3.4). 
All patients are free to withdraw consent from participation in the study 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 Visit 16/EoS/ED visit in the Schedule of assessments (Table 1). 
5.3.4 
Early Discontinuation from the Study Treatment or Study 
The criteria for enrollment and randomization are to be followed explicitly. If it is noted that 
a patient who does not meet the inclusion and exclusion criteria is inadvertently randomized 
and dosed, the Medical Monitor at Sponsor’s designated CRO (Quintiles) and the Sponsor’s 
Medical Director must be contacted immediately for discussion on how to proceed with the 
patient. The patient should be discontinued from the study if there is any compelling safety 
concern for the patient to continue. The various scenarios that may occur leading to 
discontinuation of the patient from study and/or treatment is detailed in Table 2. 
 
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Table 2 Potential Scenarios for Early Discontinuation from Study and Treatment 
Scenario 
Discontinuation from 
Study Treatment 
Discontinuation from Study 
Replacement if 
necessary 
Safety Concern during 
Treatment period: In case of 
a safety concern during 
Treatment period, Medical 
Monitor should be consulted 
and the safety and efficacy 
assessments per Follow-up 
period of Table 1 (Visit 9 to 
Visit 16) must be completed 
wherever possible. 
Discontinue patient from Study 
Treatment. 
Patient does not need to be discontinued 
from the study depending on the severity 
and nature of safety event but 
discontinuation from the study needs to 
be discussed with the Medical Monitor 
and/or Sponsor’s Medical Director. 
Wherever possible and appropriate/safe, 
the patient should continue the schedule 
of assessments for the Follow-up Period 
of Table 1 (Visit 9 to Visit 16). 
Patients will be 
analyzed as part 
of Safety and 
Efficacy analysis 
and such a patient 
will not be 
replaced. 
Safety Concern after 
Treatment period: In case of 
a safety concern after 
Treatment period, the safety 
and efficacy assessments per 
Follow-up period of Table 1 
(Visit 9 to Visit 16) must be 
completed where possible and 
Medical Monitor should be 
consulted. 
Not Applicable. 
Patient does not need to be discontinued 
from the study depending on the severity 
and nature of safety event but 
discontinuation from the study needs to 
be discussed with the Medical Monitor 
and/or Sponsor’s Medical Director. 
Wherever possible and appropriate/safe, 
the patient should continue the schedule 
of assessments in the Follow-up Period of 
Table 1 (Visit 9 to Visit 16). 
Patients will be 
analyzed as part 
of Safety and 
Efficacy analysis 
and such a patient 
will not be 
replaced. 
Disease deterioration during 
Treatment period 
After consultation with the 
Medical Monitor, discontinue 
patient from Study Treatment, 
initiate rescue therapy and 
follow-up for 30 days after the 
early discontinuation visit or 
until satisfactory resolution/ 
stabilization. 
After consultation with Medical Monitor 
and prior to start on rescue therapy, all 
Visit 16 assessments should be 
completed. Patients will be discontinued 
from the study and followed up for safety 
for an additional 30 days or until 
satisfactory resolution/stabilization. 
Patients will be 
analyzed as part 
of Safety and 
Efficacy analysis 
and such a patient 
will not be 
replaced 
Disease deterioration after 
Treatment period: In case of 
disease deterioration after 
Treatment period, the safety 
and efficacy assessments per 
Follow-up period of Table 1 
(Visit 16) must be completed 
along with a follow-up for 
30 days after the early 
discontinuation visit or until 
satisfactory resolution/ 
stabilization where possible 
and Medical Monitor should be 
consulted. 
Not Applicable. 
Patient’s study continuation must be 
assessed by the Investigator, discussed 
with the Medical Monitor and/or Sponsor’s 
Medical Director based on clinical 
examination. Possible examples of 
worsening include:  
• 
Severe deterioration where it 
may not be possible for patient 
to continue in the study. 
• 
The “End of Treatment Effect” 
whereby the patient’s condition 
is worsening after any initial 
improvement while on the 
study. 
Prior to initiating rescue therapy, all Visit 
16 assessments should be completed 
and patient should be followed up for 
safety for an additional 30 days or until 
satisfactory resolution/ stabilization. 
Patients will be 
analyzed as part 
of Safety and 
Efficacy analysis 
and such a patient 
will not be 
replaced 
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Scenario 
Discontinuation 
from Study 
Treatment 
Discontinuation from Study 
Replacement if 
necessary 
Voluntary Discontinuation from 
IMP or Major Protocol 
Deviation(s) possibly leading 
to (Details in a separate 
Manual) discontinuation from 
IMP during Treatment period: 
The Schedule of Assessments for 
dosing and safety and efficacy 
evaluations per Table 1 must be 
performed whenever possible 
and must be discussed with the 
Medical Monitor on a case-by-
case basis. 
In case of voluntary 
discontinuation 
during Treatment 
period or any major 
protocol deviation(s) 
possibly leading to 
discontinuation from 
IMP during treatment 
period, a patient 
should be 
discontinued from 
the study treatment. 
Patient does not need to be 
discontinued from the study but 
discontinuation from the study needs 
to be discussed with the Medical 
Monitor and/or Sponsor’s Medical 
Director. And wherever appropriate, 
patient should continue the schedule 
of assessments. 
Patient will not be replaced if 
he/she receives at least 3 
infusions and completes the 
Follow-up assessments as 
indicated in Table 1 with at 
least 2 weeks of Follow-up 
post last dose. 
Patient may be replaced if 
he/she receives less than 3 
infusions and/or cannot 
complete at least 2 weeks of 
Follow-up post last dose as 
indicated in Table 1. 
Major Protocol Deviation(s) 
(Details in a separate Manual) 
after Treatment period: The 
safety and efficacy assessments 
per Follow-up period of Table 1 
(Visit 8 to Visit 16) must be 
completed where possible and 
Medical Monitor should be 
consulted. 
Not Applicable. 
Patient does not need to be 
discontinued from the study but 
discontinuation from the study needs 
to be discussed with the Medical 
Monitor and/or Sponsor’s Medical 
Director. Wherever appropriate, 
patient should continue the schedule 
of assessments. 
Such patients may only be 
replaced they cannot 
complete at least 2 weeks of 
Follow-up post last dose as 
indicated in Table 1. 
 
During the study, in case of situations that occur apart from the scenarios described above, 
the decision to replace patients must be made on a case-by-case basis in consultation with the 
Medical Monitor at the Sponsor’s designated contract research organization (CRO, Quintiles) 
and/or the Medical Director at the Sponsor’s end. 
In addition, patients must be discontinued early from the study in the following 
circumstances: 
• 
Pregnancy. 
• 
Lack of efficacy as judged by the Investigator. 
• 
Emergency unblinding. 
• 
Physician decision. 
• 
Lost to follow up. 
• 
On request of the Sponsor. 
For patients who discontinue the study early, all the procedures as those listed for the Early 
Discontinuation (ED) visit (same procedures as for the End-of-Study [EoS] visit or Visit 16) 
in the Schedule of Assessments (Table 1) are to be performed (early discontinuation visit). 
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5.3.5 
Follow-Up after Early Discontinuation Visit 
Following the early discontinuation visit, any AEs/SAEs should be assessed for 30 days until 
satisfactory resolution or stabilization. 
5.3.6 
Replacement of Patients 
Patients will not be considered for replacement if they receive a minimum of 3 out of 4 doses 
of the IMP during the Treatment period and are followed up for at least two weeks in the 
Follow-up period. Patients who receive fewer than 3 doses of IMP (for reasons other than 
safety or disease deterioration) and/or cannot complete 2 weeks follow-up post last dose will 
be considered for replacement. Details on when replacement may be allowed is present in 
Table 2 (Section 5.3.4). 
Replacement of patients will be done on a case-by-case basis in consultation with the 
Medical Monitor at the Sponsor’s designated contract research organization (CRO, Quintiles) 
and/or the Medical Director at the Sponsor’s end and is guided by the scenarios listed in 
Table 2. 
5.3.7 
Protocol Deviations/Violations 
A protocol deviation is any change, divergence, or departure from the study design or 
procedure that is under the Investigator’s responsibility and oversight (as defined by 
regulations) without prior written IRB/IEC approval or favorable opinion of an appropriate 
amendment, and that may or will have a major impact on the patient’s rights, safety, or 
well-being, or on the integrity and authenticity of the study data. Information regarding 
definition and classification of protocol deviation is detailed in the Protocol Deviation 
guidance document. 
All deviations from the approved protocol must be documented and notified to the 
Sponsor/Sponsor’s designated CRO (Quintiles) at the earliest. The Investigator should not 
deviate from the protocol, except for patient safety reasons, in which case the deviation must 
be reported to the Sponsor/Sponsor’s designated CRO (Quintiles) immediately. The Sponsor 
will not assume any resulting responsibility or liability from unapproved deviations. The 
Investigator, according to applicable regulations and the Ethics Committee’s established 
procedures, will inform the Ethics Committee of protocol deviations. 
All instances where the requirements of the study protocol are not complied with, will be 
captured in the eCRF and the study monitor will prepare a Protocol Deviation/Violation Log. 
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Corresponding patients may be discontinued from the study at the discretion of the 
Sponsor/designee. Deviations from the study protocol should not be made other than as part 
of a protocol amendment. An amendment must be agreed upon by the Sponsor, but not 
implemented until written IRB/IEC approval is obtained, except where necessary to eliminate 
an immediate hazard to study patients or when the change(s) involves only logistical or 
administrative aspects. Protocol deviations/violations and the reason why they occurred will 
be documented in the Clinical study report (CSR). 
5.3.8 
Screen Failures and Rescreening 
Evaluations at Screening and confirmation at Visit 1 will be used to determine the eligibility 
of each patient for randomization at Baseline (Visit 1). Patients who fail to meet the 
eligibility criteria will be considered screen failures. 
Patients may be rescreened once under the following conditions: 
• 
Patients who required treatment for an acute illness that resolved (e.g., a urinary tract 
infection) or had stabilization of a chronic medical problem (e.g., uncontrolled 
hypertension). 
• 
Patients who are not on a stable dose of a concomitant medication prior to 
randomization as per inclusion and exclusion criteria may be re-screened once the 
stable dose criteria is met. 
• 
Patients with an indeterminate QuantiFERON®-TB Gold test result (for 
tuberculosis). 
The decision to rescreen patients may be optional based on clinical state of the patient and 
the decision to rescreen will solely be made based on Sponsor’s discretion on a case-by-case 
basis. 
5.3.9 
Early Termination of Study or Site 
The study may be terminated at any time by the Sponsor for safety concerns due to serious 
AEs, inability to achieve the recruitment target within reasonable time or if in the Sponsor's 
judgement, there are no further benefits to be expected from the study. In such a case, the 
Sponsor or delegate will inform the study Investigators, institutions, and all Regulatory 
Authorities. 
The study can also be terminated by the Regulatory Authority for any reason or at a site level 
as decided by the Independent Data Monitoring Committee (IDMC), Independent Ethics 
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Committee or Institutional Review Board (IEC/IRB). The Sponsor may close individual 
study sites prematurely for reasons such as poor protocol compliance or unsatisfactory 
recruitment of patients. 
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6.0 STUDY PROCEDURES 
Every effort should be made to ensure that the protocol-required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances outside of the control of the Investigator that may make it unfeasible to 
perform the assessment. In such cases, the Investigator will take all steps necessary to ensure 
the safety and well-being of the patient. 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 study team should be informed of these incidents in a timely manner. 
Patients should be seen for all visits on the designated day or as closely as possible to the 
original planned visit schedule. Visits 2, 4, 6 (in the Treatment period) and Visit 8 (in the 
Follow-Up period) are optional. There is a permissible window of ±1 day both for study 
visits in the Treatment period (Visit 1 to Visit 7) and during the FU period (after Visit 7 to 
Visit 16). Every effort should be made to schedule every visit on the exact Day (which is 
relative to the Baseline visit) as described in the Schedule of Assessments (Table 1). 
The assessments to be performed at each study visit will be conducted respecting the order of 
assessments as follows: 
At all visits, the efficacy assessments should be performed first, prior to any other study 
specific procedure with the only exception of obtaining informed consent at Screening. 
6.1 
Informed Consent and Enrollment 
Any patient who provides informed consent (i.e., signs and dates the ICF) will be considered 
enrolled in the study. A Screening number will be obtained by the site using IxRS. In 
addition, patients will be invited to give informed consent (on a separate ICF) for the 
pharmacogenetic sampling. The pharmacogenetic assessment is optional and patients will not 
be excluded from the study if they do not consent to the sampling for this assessment. 
6.2 
Screening 
After informed consent has been obtained, patients will be screened at the site for eligibility 
based on the inclusion and exclusion criteria defined in Section 5.3.1 and 5.3.2 respectively. 
Screening procedures must be performed within 15 days prior to randomization. 
In addition to obtaining written informed consent, the following assessments will be 
performed at Screening: 
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• Assign patient Screening number via IxRS. 
• Eligibility evaluation (review of inclusion and exclusion criteria). 
• Relevant medical and surgical history, relevant prior medications including all 
previous treatment/therapies for MG including patient’s response and all concomitant 
medications. 
• Complete physical examination including height and weight. 
• Vital signs. 
• Demographic data (date of birth, gender, race, and ethnicity). 
• Efficacy assessments in the order of MGQoL15r, MG-ADL, QMG, and MGC before 
any other assessments (except for obtaining informed consent). 
• Clinical laboratory tests (hematology including hemoglobin, platelet count, white 
blood cell count with differential count; blood chemistry, including creatinine, 
creatinine clearance, blood urea nitrogen [BUN], glucose, alanine aminotransferase 
[ALT], aspartate aminotransferase [AST], total bilirubin, gammaglutamyl transferase 
[GGT], C-reactive protein [CRP], alkaline phosphatase, lactate dehydrogenase, uric 
acid, albumin, potassium, sodium, calcium, thyroglobulin, International normalized 
ratio or activated partial thromboplastin time (aPTT), and CD19 counts. 
• ECG. 
• Urinalysis. 
• Serum Pregnancy test. 
• Viral and bacterial tests (including surface antigen of hepatitis B virus [HbsAg] and 
anti-hepatitis C antibodies, HIV, and tuberculosis serology). 
• Suicidality assessment. 
• Assess AEs if any. 
6.3 
Randomization 
The results of all Screening procedures must be available prior to randomization at Visit 1 to 
determine eligibility for randomization into the study. If a patient meets all the study 
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eligibility criteria, the Investigator will randomize the patient at Visit 1 via IxRS; if the 
patient is not eligible, then the patient should be recorded as a screen failure in the IxRS. 
On completion of Screening and randomization, study patients will be instructed not to 
participate in any other clinical study that involves an intervention or collection of data until 
the completion of the current study. 
6.4 
Treatment Period 
On all dosing days (Visits 1, 3, 5 and 7), the following order of assessments should be 
respected:  
• Complete all pre-dose assessments, including confirmation of eligibility at Visit 1, 
prior to dosing (efficacy assessments, all blood sampling except for PK sample to be 
taken post-dose, urine sampling, vital signs, physical examination, ECG) starting 
with the efficacy assessments in the following order: 
 MGQoL15r, 
 MG-ADL, 
 QMG, 
 MGC. 
• Randomization of patient in IxRS (at Visit 1). 
• Administration of ARGX-113 or placebo. 
• Blood sampling for PK post-dose. 
• Patients to remain at the site for over a period of 2 hours following infusion. 
• Record concomitant medications, suicidality assessment, and assess AEs if any. 
The Treatment period will include assessments starting at Visit 1 to Visit 7 (EoT). 
6.4.1 
Visits 1, 3, 5, and 7 
Prior to administration of the IMP (as an IV infusion) at Visits 1, 3, 5, and 7 the following 
assessments will be performed: 
• After review of eligibility criteria, patient will be randomized at Visit 1. 
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• Efficacy assessments in the order of MGQoL15r, MG-ADL, QMG, and MGC before 
any other assessments. At least MG-ADL should be done prior to randomization at 
Visit 1. 
• Abbreviated physical examination including (evaluation of body weight) at Visits 1, 
3, and 5. Complete physical examination at Visit 7. 
• Vital signs. 
• Clinical laboratory tests and urinalysis. 
• Urine pregnancy test. 
• ECG at Visit 1 and Visit 7. 
• Anti-drug antibodies at Visits 1, 5, and 7. 
• Blood sampling for assessment of PD markers (total IgG, IgG subtypes [IgG 1, IgG 2, 
IgG 3, and IgG 4], and anti-AChR antibodies). 
• Blood sampling (with an allowed window of 30 minutes prior to start of infusion) for 
PK assessments. 
• Collect blood sample for pharmacogenetic testing (to assess FcRn polymorphisms) in 
case the patient agrees to participate in optional pharmacogenetic testing and signs 
separate informed consent at Visit 1. If the blood sample at Baseline is missed, the 
sample should be drawn at Visit 3 (prior to administration of IMP). 
• The IMP (ARGX-113 or placebo) will be administered as an IV infusion over a 
period of 2 hours at Visits 1, 3, 5, and 7. 
• Blood sampling post-dose (with an allowed window of 30 minutes after end of 
infusion) for PK assessments. 
• Review of concomitant medications. 
• Suicidality assessment. 
• Assess AEs if any. 
6.4.2 
Visits 2, 4, and 6 (Optional) 
• Blood sampling for PK and PD (total IgG, IgG subtypes [IgG 1, IgG 2, IgG 3, and 
IgG 4], and anti-AChR antibodies). 
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• Review of concomitant medications. 
• Assess AEs if any. 
6.5 
Follow-Up Period 
The FU period will include assessments starting at Visit 8 to Visit 16 (EoS). 
6.5.1 
Visit 8 (Optional) 
• Blood sampling for PK and PD (total IgG, IgG subtypes [IgG 1, IgG 2, IgG 3, and 
IgG 4], and anti-AChR antibodies). 
• Review of concomitant medications. 
• Assess AEs if any. 
6.5.2 
Visits 9, 10, 11, 12, 14, and 16 
• Efficacy assessments in the order of MGQoL15r, MG-ADL, QMG, and MGC prior to 
any other assessments. 
• Abbreviated physical examination (including weight) at Visits 9, 10, 11, 12, 14. A 
complete physical examination (including weight) to be conducted at Visit 16. 
• Vital signs. 
• Clinical laboratory tests, urinalysis. 
• ECG at Visit 16. 
• Anti-drug antibodies. 
• Blood sampling for PK (not on Visits 14 and 16) and PD (total IgG, IgG subtypes 
[IgG 1, IgG 2, IgG 3, and IgG 4], and anti-AChR antibodies) assessments. 
• Perform urine pregnancy test at Visits 11 and 16. 
• The EoS visit will be at Visit 16. 
• Suicidality assessment. 
• Review of concomitant medications. 
• Assess AEs if any. 
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6.5.3 
Visits 13 and 15 
• Clinical laboratory tests. 
• Blood sampling for PD assessments (total IgG, IgG subtypes [IgG 1, IgG 2, IgG 3, 
and IgG 4], and anti-AChR antibodies). 
• Suicidality assessment. 
• Review of concomitant medications. 
• Assess AEs if any. 
6.6 
Early Discontinuation Visit 
In case of early discontinuation visit, the same assessments as scheduled for (Visit 16 or EoS) 
must be performed where possible as follows: 
• Efficacy assessments in the order of MGQoL15r, MG-ADL, QMG, and MGC prior to 
any other assessments. 
• Complete physical examination (including weight). 
• Vital signs. 
• Clinical laboratory tests, urinalysis. 
• ECG. 
• Anti-drug antibodies. 
• Blood sampling for PD (total IgG, IgG subtypes [IgG 1, IgG 2, IgG 3, and IgG 4], 
and anti-AChR antibodies) assessments. 
• Perform urine pregnancy test. 
• Suicidality assessment. 
• Review of concomitant medications. 
• Assess AEs if any. 
6.7 
Unscheduled Visit 
It is at the Investigator’s discretion to initiate an unscheduled visit, if deemed necessary for 
the patient’s safety and well-being (e.g., for a safety FU after completion or discontinuation 
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to monitor any unresolved AE). All such visits will be documented along with any additional 
required documentation based on the nature of unscheduled visit. 
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7.0 STUDY TREATMENTS 
7.1 
Treatments Administered 
ARGX-113 or matching placebo will be administered intravenously as 4 infusions 
administered one week apart (total volume of 250 mL) at Visits 1, 3, 5, and 7 over a period of 
2 hours. 
7.2 
Identity of Investigational Medicinal Products 
ARGX-113 the IMP and related placebo will be supplied to the Investigator or designated 
site staff at the investigational site, by and under the responsibility of the Sponsor’s 
designated IMP supply vendor 
 who will also provide the 
Investigator with certificate of analysis, certificate of conformity and European Union 
Qualified Person (EU QP) release documents. 
ARGX-113, the IMP will be provided as a sterile, colorless, clear concentrate solution for 
intravenous administration in a formulation of
 
 
. The 
extractable volume from one vial is
 mL. Appropriate dilutions in a 
% Saline solution 
will be made on site prior to administration. 
The placebo will be provided as a sterile colorless, clear concentrate solution for intravenous 
administration (
 mL in 20R vial) with the same formulation as the ARGX-113 solution but 
without the active ingredient that is present in ARGX-113. The extractable volume from one 
vial is 
 mL. 
All IMPs will be manufactured in accordance with Good Manufacturing Practice (GMP) 
regulations. Detailed instructions on IMP management on site (including preparation of the 
IMP) will be included in the IMP management manual (pharmacy manual). 
The dose will be 10 mg/kg (total dose per IMP infusion is capped at 1200 mg for patients 
with body weight ≥ 120 kg) and Table 3 provides an outline of the IMP and the dosage form 
and strength for Study ARGX-113-1602. 
 
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designated CRO (Quintiles) will have access to this randomization code until after final 
database lock. 
7.6 
Selection of Doses in the Study 
Based on the preliminary safety and PK/PD data of the aforementioned Phase I study in 
healthy subjects (ARGX-113-1501), a weekly dose of 10 mg/kg ARGX-113 was selected for 
investigation in this exploratory Phase II study as this dose regimen resulted in a maximum 
PD effect and was considered safe. 
There was a dose-dependent decrease of serum IgG concentrations following a single dose 
administration of ARGX-113. There was a maximum decrease of serum IgG concentrations 
at a dose of approximately 10 mg/kg while a lower dose of 2 mg/kg resulted in less reduction 
of IgG concentrations. Pharmacodynamic data after multiple dosing showed that a dose of 
10 mg/kg either administered every 4 or 7 days resulted in what was anticipated to be a 
maximum effect on serum IgG concentrations in terms of both depth of the PD effect and 
time to reach nadir. 
As a lower drug exposure and a less frequent dose administrations are considered more 
convenient for patients, the dose regimen of 4 weekly doses of 10 mg/kg was selected for 
investigation in Phase II studies. ARGX-113 was found to be safe and well tolerated 
following administration of four weekly 2-hour IV 10 mg/kg infusions to healthy subjects. 
It has been reported that reduction of serum IgG concentrations in MG patients following 
short-term treatment with plasma exchange, immunoadsorption or IVIg results in a clinically 
meaningful effect (i.e., amelioration of signs and symptoms)13, 14. 
The impact of reducing serum IgG concentrations with ARGX-113 on the clinical effect of 
MG patients is currently unknown. Thus, the dose which was found to be safe and resulted in 
a maximum PD effect was selected for investigation in this study. Additional doses and dose 
regimens may be considered for future studies. 
During this study, no changes in the IP dose will be allowed. 
7.7 
Timing of Dose for Each Patient 
ARGX-113 and placebo will be administered intravenously as 4 infusions administered one 
week apart over a period of 2 hours at Visits 1, 3, 5, and 7. Patients will be asked to remain at 
the site for a minimum of 2 hours after the end of infusion as part of routine safety 
monitoring at Visits 1, 3, 5, and 7. 
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7.8 
Blinding 
This is a randomized, double-blind, placebo-controlled study with limited access to the 
randomization code. The IMP and placebo will be identical in physical appearance. The 
treatment each patient receives will not be disclosed to the Investigator, investigational site 
staff, patient, Sponsor, the Sponsor’s designated CRO (Quintiles) The study will only be 
unblinded following the database hard lock. 
7.8.1 
Emergency Unblinding 
The process for breaking the blind will be handled through the IxRS. Investigators are 
strongly discouraged from requesting the blind to be broken for an individual patient, unless 
there is a patient safety issue that requires unblinding and would change patient management. 
If possible, Investigators/Sponsor’s medical expert should discuss with the Medical Monitor 
at Sponsor’s designated CRO (Quintiles) before approaching IxRS to break the blind. If the 
blind is broken, it may be broken for only the patient in question. 
The Sponsor and Sponsor’s designated CRO (Quintiles) Medical Monitor must be notified 
immediately if a patient and/or Investigator is unblinded during the course of the study. 
Pertinent information regarding the circumstances of unblinding of a patient’s treatment code 
must be documented in the patient’s source documents and electronic case report forms 
(eCRFs). Once unblinded, the patient will be discontinued early from the study. 
7.9 
Prior and Concomitant Treatments 
All concomitant medications whether allowed or not must be recorded in the eCRFs. All 
clinically relevant prior medications received by the patient including previous treatment for 
MG with patient’s response at least 12 months before Screening must be recorded in the 
eCRFs. 
7.9.1 
Prohibited Medications during the Study 
The following medications will not be permitted during the study and will result in early 
discontinuation from the study when they need to be started: 
• Any IgG therapy; 
• Introduction of a new immunosuppressant that the patient was not already taking at 
Screening; 
• Dose increase in the immunosuppressant that the patient was taking from Screening; 
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• Rituximab, belimumab, eculizumab, or any monoclonal antibody for 
immunomodulation; 
• Vaccines; 
• Therapeutic PE. 
7.9.2 
Rescue Therapy 
Patients are eligible for rescue therapy as judged by the Investigator on the basis of 
parameters such as changes in MGQoL15r, MG-ADL, QMG, and MGC on any study day. 
Rescue therapy will be determined by the Investigator based on an overall clinical 
assessment and could include IVIg, PE, increase in the dose and frequency of SoC or any 
other treatment chosen by the Investigator. In this study, ARGX-113 may interfere with the 
efficacy or duration of efficacy of IVIg considering the half-life of IVIg. Additional details 
about ARGX-113 is present in Section 2.2. 
In case a patient needs rescue therapy according to the treating Investigator, the Medical 
Director at the Sponsor should be informed in addition to the Medical Monitor at the 
Sponsor’s designated contract research organization (CRO, Quintiles); where possible prior 
to actual implementation of the rescue therapy. 
If rescue therapy is administered, patients need to be discontinued from the study. For 
patients who discontinue the study early, all the procedures listed for the Early 
Discontinuation (ED) visit (same procedures as for the End-of-Study [EoS] visit or Visit 16) 
in the Schedule of Assessments (Table 1) are to be performed (early discontinuation visit) 
prior to starting on rescue therapy wherever possible. 
7.10 
Medical Care of Patients after End-of-Study 
After a patient has completed the study or has withdrawn/discontinued early, usual treatment 
will be administered, if required, in accordance with the study site’s SoC and generally 
accepted medical practice depending on the patient’s individual needs. The Sponsor will not 
provide any additional care to patients after they withdraw/discontinue early or complete the 
study neither will the IMP be provided on a compassionate use program. 
7.11 
Treatment Compliance 
The Investigator should promote compliance by stating that compliance is necessary for the 
patient’s safety and the validity of the study. The prescribed dose, timing, and mode of 
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administration may not be changed. All dates and start and end time of IMP administration 
and any deviations from the intended regimen must be recorded. 
7.12 
Handling Missed Doses of the Investigational Medicinal Product 
If the patient misses more than one dose of the IMP he/she may be replaced although may 
continue in the study and maybe evaluable for safety and efficacy evaluation, for details refer 
to Table 2. 
7.13 
Accountability of Investigational Medicinal Product 
The Investigator or delegated site staff is responsible for ensuring that the IMP received at 
the clinical site is inventoried and accounted for throughout the study. 
Infusion of the IMP must be completed under the supervision of the Investigator, by a 
qualified member of the clinical staff. The Investigator or delegated site staff must maintain 
accurate records, demonstrating date and amount of IMP supplied and by whom. 
The Sponsor’s designated site monitor will periodically check the supplies of IMP held by 
the Investigator or pharmacist to ensure accountability and appropriate storage conditions of 
all IMP used. 
Unused IMP must be accessible for verification by the site monitor during on-site monitoring 
visits. Used IMP should be kept on site and its accountability will be checked by the site 
monitor. Only after appropriate verification and confirmation from the site monitor, used 
IMP (vials) can be discarded/destroyed in accordance with the site procedures. 
After the database lock, any remaining unused IMP will be returned to the Sponsor, or 
destroyed at the clinical site with the Sponsor’s written permission (in this case a certificate 
of destruction will be provided and filed in the Trial Master File). 
Hazardous materials such as used needles, syringes, and infusion bags, containing hazardous 
liquids, should be discarded immediately after use in a safe manner and must not be retained 
for drug accountability purposes or verification by the site monitor. 
7.14 
Storage of Blood Samples in the Study 
The leftover of samples that are left after the analysis per protocol is complete and other 
remaining samples (of all samples except for samples taken for clinical laboratory tests) will 
be stored for up to 15 years for future additional research. Patients will be asked to confirm if 
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they allow additional storage of samples in the study ICF to address any scientific questions 
related to ARGX-113 or MG. 
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8.0 SAFETY, EFFICACY, PHARMACOKINETIC, AND 
PHARMACODYNAMIC ASSESSMENTS 
8.1 
Safety 
Safety assessments will consist of monitoring and recording all AEs, including SAEs, and 
pregnancies; suicidality assessment; safety laboratory testing, measurement of vital signs, 
ECGs, physical examinations; and other tests that are deemed critical to the safety evaluation 
of the study in all patients who receive at least 1 dose of the IMP. As discussed in 
Section 8.1.1.4, any pregnancy that occurs while a patient is enrolled in the study will also be 
monitored and reported according to the appropriate regulations. 
8.1.1 
Adverse Events 
The Investigator is responsible for recording all AEs observed during the study from the time 
the patient signs the ICF until the last contact of the patient. 
Definition of AE: An AE is any untoward medical occurrence in a clinical study patient 
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. 
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). 
Abnormal laboratory values, or test results, physical examination findings, and other 
abnormal investigational findings (i.e., ECG) should not be reported as AEs unless they are 
associated with clinical signs and symptoms that are considered clinically significant, require 
therapy (e.g., hematologic abnormality that requires transfusion or hematological stem cell 
support), or lead to treatment discontinuation. 
Death is not considered an AE but an outcome. 
Disease progression can be considered as a worsening of a patient’s condition attributable to 
the disease for which the IMP is being studied. It may be an increase in the severity of the 
disease under study and/or increase in the symptoms of the disease and should be considered 
as disease progression and not an AE. 
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Adverse Drug Reaction (ADR): Any untoward and unintended response in a subject to an 
IMP which is related to any dose administered to that subject. 
Definition of Serious AE (SAE): An SAE, experience or reaction, is any untoward medical 
occurrence (whether considered to be related to IMP or not) that at any dose: 
• 
Results in death; 
• 
Is life-threatening (the patient is at a risk of death at the time of the event; it does not 
refer to an event which hypothetically might have caused death if it were more severe); 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization: Hospital 
admissions and/or surgical operations planned before a study are not considered SAEs or 
if the illness or disease which caused hospitalization existed before the patient was 
enrolled in the study, provided that it did not deteriorate in an unexpected way during the 
study. However, the condition for which the surgery is required may be an AE. 
• 
Results in persistent or significant disability or incapacity; 
• 
Is a congenital abnormality or birth defect; 
• 
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 one of 
the other serious outcomes listed in the definition above. Examples of such events are 
blood dyscrasias (e.g. neutropenia or anemia requiring blood transfusion, etc.) or 
convulsions that do not result in inpatient hospitalization. 
Suspected Unexpected Serious Adverse Reactions and Unexpected Adverse Reactions 
Any suspected adverse reaction that is serious, unexpected, and considered to be related to 
drug exposure is defined as a suspected unexpected serious adverse reaction (SUSAR). 
An unexpected AE is any adverse drug event, which is not listed in the current Investigator’s 
Brochure 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. The following examples provide types of evidence that would suggest a 
causal relationship between the IMP and the AE: 
• A single occurrence of an event that is uncommon and known to be strongly 
associated with drug exposure (e.g., angioedema, hepatic injury, Stevens-Johnson 
Syndrome) 
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• One or more occurrences of an event that is not commonly associated with drug 
exposure, but is otherwise uncommon in the population exposed to the drug (e.g., 
tendon rupture) 
• An aggregate analysis of specific events observed in a clinical study (such as known 
consequences of the underlying disease or condition under investigation or other 
events that commonly occur in the study population independent of drug therapy) that 
indicates those events occur more frequently in the drug treatment group than in a 
concurrent or historical control group. 
An untoward and unintended post-dosing response to a non-study drug is, by definition, not a 
SUSAR, but is, however, an AE. 
Each AE is to be evaluated for duration, severity, seriousness and causal relationship to the 
IMP or study procedures. The action taken with the investigational drug and the outcome of 
the event must also be recorded. 
Overdose 
For the purposes of this study, exceeding the dosage requirements specified in this protocol 
represents an overdose. In case of suspected overdose, the patient should be treated according 
to standard medical practice based on the Investigator’s judgment. 
Severity 
All AEs observed will be graded using the National Cancer Institute (NCI) Common 
Terminology Criteria for Adverse Events (CTCAE) version 4.03. The NCI CTCAE is a 
descriptive terminology which can be utilized for AE reporting. A grading (severity) scale is 
provided for each AE term. Grade refers to the severity of the AE. If a particular AE’s 
severity is not specifically graded by the guidance document, the Investigator is to use the 
general NCI-CTCAE definitions of Grade 1 through Grade 5 following his or her best 
medical judgment. The CTCAE displays Grades 1 through 5 with unique clinical 
descriptions of severity for each AE based on the following general guideline: 
• 
Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
• 
Grade 2: Moderate; minimal, local or non-invasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living (ADL). 
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• 
Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
activities of daily living (ADL). 
• 
Grade 4: Life-threatening consequences; urgent intervention indicated. 
• 
Grade 5: Death related to AE. 
Relationship 
The causal relationship between the IMP/study procedures and the AE has to be 
characterized as unrelated, unlikely, related, possible, and probable. 
• Events can be classified as “unrelated” if there is not a reasonable possibility that the 
IMP caused the AE. 
• 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. 
• 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 reasonable be explained by known characteristics of patient’s 
clinical state. 
• 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. 
• 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. 
In final evaluation for reporting the relationship will be converted into “Binary 
Determination” as per CIOMS. Unrelated and Unlikely will be clubbed into “Unrelated” and 
Related, Possible and Probable will be clubbed into “Related” for final reporting purpose. 
8.1.1.1 
Reporting of Adverse Events and Serious Adverse Events 
All AEs, that occur during the study from signature of informed consent until EoS (Visit 16), 
are to be recorded on the appropriate AE pages (either ‘serious’ or ‘non-serious’) in the 
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eCRF. The Investigator should complete all the details requested, including dates of onset, 
stop date (when applicable), severity, action taken, outcome, and relationship to IMP, and to 
study procedures. Each event should be recorded separately in the eCRF. 
All AEs spontaneously reported by the patient or reported in response to the open question 
from the study personnel: ‘Have you had any health problems since the previous visit/you 
were last asked?’, or revealed by observation will be collected and recorded in the eCRF. 
When collecting AEs, the recording of diagnoses is preferred (when possible) to recording a 
list of signs and symptoms. However, if a diagnosis is known and there are other signs or 
symptoms that are not generally part of the diagnosis, the diagnosis and each sign or 
symptom will be recorded separately. 
Any SAE, including death due to any cause, which occurs during this study after signature of 
informed consent, whether or not related to the IMP, must be reported immediately (within 
24 hours of the study site’s knowledge of the event). All SAEs will be recorded (within 
24 hours) on the electronic SAE report form and the AE form in the eCRF, the Investigator 
or delegated site staff should check that all entered data is consistent. An alert email for the 
SAE report will then be automatically sent by email to the Sponsor’s designated CRO 
(Quintiles) safety mailbox via the electronic data capture (EDC) system. In case the EDC 
system is not functioning correctly or the system is down, all SAEs should be reported by 
fax/email to Sponsor’s designated CRO (Quintiles) using the SAE paper report form. 
The report will contain as much available information concerning the SAE 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 of a patient's last visit are to be 
collected and reported as previously described. 
Additional follow-up information should be completed and entered on an SAE report form in 
the eCRF with again a copy automatically sent to the Sponsor’s designated CRO (Quintiles) 
by email via the EDC system. 
8.1.1.2 
Reporting of Serious Adverse Events to Regulatory Authorities and 
Investigators 
The Sponsor’s designee will be responsible for reporting all SUSARs and any other 
applicable SAEs to regulatory authorities, ethics committees, and Investigators, in 
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accordance with national regulations in the countries where the study is conducted. Relative 
to the first awareness of the event by/or further provision to the Sponsor’s designee, SUSARs 
will be submitted within 7 days for fatal and life-threatening events and 15 days for other 
SUSARs, 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 
IEC/IRB in accordance with national regulations. 
8.1.1.3 
Follow-Up of Adverse Events and Serious Adverse Events 
Any AEs observed from signing the informed consent to the end of the study will be 
followed up to resolution. 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. 
All AEs that occur after the last dose of the IMP should be (pro-actively) followed-up and 
assessed by the Investigator until (EoS visit or Visit 16) or for 30 days after the early 
discontinuation visit (regardless of discontinuation occurring in Treatment period or FU 
period), and until satisfactory resolution or stabilization. 
Serious AEs will be captured and followed up until resolution (if needed, also after the EoS 
visit). 
All SAEs that are spontaneously reported within 30 days of a patient's last dose of IMP 
and/or last visit (EoS visit or Visit 16) are to be collected and reported as previously 
described (as per Section 8.1.1.1) and will be followed-up regardless of the Investigator’s 
opinion of causality. The Investigator should follow each SAE until the event has resolved to 
the baseline grade or better, the event is assessed as stable by the Investigator, until the 
patient is lost to follow-up, or until the patient withdraws consent. If the patient is lost to 
follow-up, the SAE will be categorized based on the Investigator’s last assessment. Every 
effort should be made to follow all SAEs considered to be related to IMP or study procedures 
until an outcome can be reported. During the study period, resolution of SAEs (with dates) 
should be documented on the SAE 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 page of the 
eCRF. 
All pregnancies reported during the study should be followed until pregnancy outcome. 
For SAEs, nonserious AEs, and pregnancies, the Sponsor’s designee may follow-up by 
telephone, fax, electronic mail, and/or a monitoring visit to obtain additional case details and 
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outcome information (e.g., from hospital discharge summaries, consultant reports, or autopsy 
reports) in order to perform an independent medical assessment of the reported case. 
8.1.1.4 
Reporting and Follow-Up Requirements for Pregnancies 
8.1.1.4.1 
Pregnancies in Female Patients 
A serum pregnancy test will be conducted in all females of childbearing potential at 
Screening, and urine pregnancy tests will be conducted locally thereafter at Visits 1, 3, 5, 7, 
11, and 16 as presented in the Schedule of events (Table 1). 
If a patient becomes pregnant after the administration of IMP and up to 90 days after the 
patient received the last infusion, the Sponsor and/or Sponsor’s designee should be informed 
immediately. The patient should be discontinued early from the study treatment as soon as 
the pregnancy is known and the following should be completed: 
• The patient should immediately discontinue from the study. 
• The patient should have an early discontinuation visit. 
• All assessments for early discontinuation visit (See Section 5.3.4 and 6.6) must be 
performed unless contraindicated by pregnancy (harmful to fetus) or unless the 
patient withdraws informed consent. 
The Investigator must inform the patient of information currently known about potential risks 
and about 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. 
Full details will be recorded on a Pregnancy Report eCRF and submitted via the Electronic 
Data Capture (EDC) system, and reporting details will be detailed in the study manual. The 
Investigator will update the Pregnancy Report eCRF 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 eCRF page. 
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8.1.1.4.2 
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 study and up to 90 days after the patient received 
the last infusion. A Pregnancy Report eCRF should be completed by the Investigator within 
1 working day after learning of the pregnancy and submitted via the EDC system. 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. Once 
the ICF has been signed, the Investigator will update the Pregnancy Report eCRF 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 the possible effects on the fetus, to support an informed decision in 
co-operation with the treating physician and/or obstetrician. 
8.1.2 
Clinical Laboratory Evaluations 
Blood and urine samples for determination of clinical chemistry, hematology, and urinalysis 
will be collected and analyzed at a central lab as indicated in the Schedule of Assessments 
(Table 1). Patients need to be fasting for at least 8 hours prior to the sampling for clinical lab 
tests. 
Urine pregnancy test and ECG will be done at local lab. 
Additional safety samples may be collected if clinically indicated at the discretion of the 
Investigator. 
A serum pregnancy test will be performed (on the samples taken for clinical laboratory tests) 
for all patients of childbearing potential at Screening, and a urine pregnancy test will be 
performed locally at the site (can be done on the urine sample taken for urinalysis) at 
Visits 1, 3, 5, 7, 11, and 16. 
The total volume of blood will not exceed 226 mL for the duration of the study. 
Clinical laboratory tests will be reviewed for results of potential clinical significance at all 
time points throughout the study. 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. 
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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 lab assessment eCRF page. 
8.1.3 
Vital Signs, Physical Examination, and ECGs 
Assessment of vital signs (supine blood pressure, pulse rate, and oral body temperature) will 
be performed at the time points indicated in the Schedule of Assessments (Table 1). 
Supine blood pressure and pulse rate will be measured using standard equipment after 
10 minutes rest on a bed. 
A complete physical examination will be performed at Screening, Visit 7, and at 
Visit 16/EoS/ED visit as indicated in the Schedule of Assessments (Table 1) and will include 
an assessment of general appearance, skin, head and neck (including ears, eyes, nose and 
throat), lymph nodes, thyroid, musculoskeletal/extremities, abdomen, breast, and 
cardiovascular, respiratory, neurological, and genital/rectal systems. An abbreviated 
examination will be done at all other visits. In addition, weight will be assessed at each of 
these time points. 
On IMP infusion days, physical examination, including weight, will be assessed pre-dose. 
Height will be measured at Screening visit only. For assessment of height and weight, 
patients will be required to remove their shoes and wear light indoor clothing for these 
measurements. 
The digital ECG assessments will be performed at the time points indicated in the Schedule 
of Assessments (Table 1). 
A ECG will be recorded in the supine position after the patient has rested in this position for 
at least 10 minutes. The assessment on heart rate, PR, QT, and QRS intervals will be locally 
read by the Investigator or delegate. 
8.1.4 
Suicidality assessment 
As is recommended for studies involving a biological product for a neurological indication, a 
prospective assessment for suicidal ideation and behavior will be included in this clinical 
study. 
This so called suicidality assessment will be conducted by specifically asking the following 
question, derived from the Patient Health Questionnaire item 9 (PHQ-9): 
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• "Over the last 2 weeks, how often have you been bothered by thoughts that you would 
be better off dead, or of hurting yourself in some way?" 
The patient will be asked this question at each scheduled visit, except the optional visits to 
collect PK/PD blood samples, and the response documented. Response options as per the 
PHQ-9 are limited to the following: "not at all", "several days", "more than half the days" or 
"nearly every day". 
This specific question was selected for the reported significant linear relationship between 
the item 9 score of the PHQ-9 and the risk of subsequent suicide attempt.2 
8.1.5 
Medical History 
All significant findings that are present at Screening must be reported on the relevant medical 
history/current medical conditions page of the eCRF. 
As part of medical history details must include and is not limited to all previous 
treatment/therapy taken for MG, patient’s response to each of the previous MG 
treatment/therapy received. 
8.1.6 
Independent Data Monitoring Committee 
An IDMC consisting of members who are independent from the Sponsor will be established. 
The IDMC will be established prior to the enrollment of the first patient in the Treatment 
period. The IDMC membership will have 4 independent members (3 physicians and 
1 unblinded biostatistician), including at least one neurologist with expertise in treatment of 
MG, as appropriate. The IDMC quorum will comprise of 3 independent members with 2 
physicians and 1 unblinded biostatistician. Three data review meetings are planned. The 
IDMC will review the safety data during the first and second data review meeting, and during 
the third data review meeting, efficacy and safety data will be reviewed. 
The IDMC is responsible for reviewing and evaluating unblinded safety data collected after 8 
patients complete treatment period and have had a minimum of 2 weeks follow-up. The 
IDMC will subsequently review unblinded safety data after 16 patients complete treatment 
period and have had a minimum of 2 weeks follow-up and after the final database lock all 
safety and efficacy data will be reviewed for all randomized patients. 
The IDMC may also meet in ad hoc meetings at its discretion as needed in response to events 
occurring in the study. The IDMC will review the unblinded safety data during the Data 
review meetings. The roles and responsibilities of the IDMC, their operational procedures, 
and method of communication with argenx will be described in a separate IDMC charter. 
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Members of IDMC will not be Investigators in the study nor will they have any conflict of 
interest with the Sponsor. 
8.2 
Efficacy 
8.2.1 
Appropriateness of Measurements 
Efficacy assessments will be done using MG-ADL, as QMG, MGC, and quality of life will 
be measured using MGQoL15r. These assessments will be completed at Screening, and have 
to be performed pre-dose on all IMP infusion days i.e., at Visits 1, 3, 5, 7; in addition to 
Visits 9, 10, 11, 12, 14, and 16. 
8.2.2 
Myasthenia Gravis-Activities of Daily Living 
The MG-ADL is an 8-item patient-reported scale to assess MG symptoms and their effects 
on daily activities. It evaluates the capacity to perform different activities of daily living such 
as talking, chewing, swallowing, breathing, brushing the teeth/combing the hair, or arising 
from the chair and it also assesses double vision and eyelid droop. It is a discrete quantitative 
variable in which the 8 items are rated from 0 to 3 and the total score can point from 0 to 24; 
with higher scores indicating more impairment. The assessments to be performed using 
MG-ADL does not require any equipment or training. The assessments that will be 
performed using MG-ADL is included in Appendix 14.1. 
8.2.3 
Quantitative Myasthenia Gravis 
The QMG quantifies disease severity based on impairments of body functions and structures 
as defined by the International Classification of Disability and Health.15 
The QMG consists of 13 items that assess ocular, bulbar, and limb function. Out of the 13 
items, 6 are timed tests of endurance measured in seconds. Each item has a possible score 
from 0-3. The total possible score is 39, where higher scores indicate more severe 
impairments. It is based on quantitative testing of sentinel muscle groups to assess limb 
function. It requires minimal equipment such as spirometer, mouthpieces that fit the 
spirometer, nose clips, stopwatch, cups and water for swallowing tests, goniometer, 
dynamometer, and is based on physician’s examination. The items that will be tested is 
included in Appendix 14.2. 
8.2.4 
Myasthenia Gravis Composite 
The MGC has 10 items combining physician examination and patient reported outcomes. 
The 2 ocular items are derived from QMG. It has 3 items on muscle strength (deltoids, hip 
flexors, and neck flexors or extensors) and 4 items on bulbar function (swallowing, chewing, 
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breathing, and speech functions), based on the clinical history. Each item is scored on an 
ordinal scale with 4 possible categories, but the items are weighted, whereby bulbar 
impairments weigh more than ocular ones. The impairments that need to be examined by the 
Investigator include ptosis or upward gaze, double vision, eye closure, neck flexion, shoulder 
abduction, and hip flexion. The patient reported outcomes under MGC are talking, chewing, 
swallowing, and breathing. The maximum possible score is 50, with higher scores reflecting 
more severe impairments. The items that will be tested is included in Appendix 14.3. 
8.2.5 
15-Item Quality of Life Scale for Myasthenia Gravis 
The 15-item Quality of Life scale for Myasthenia Gravis (MGQoL15r) is a quality of life 
scale or survey of patient’s responses and addresses MG-specific psychological well-being 
and social functioning. It is a brief questionnaire that is to be completed by the patient that 
uses 3 response options. The MGQoL15r is helpful in informing the clinician about the 
patient’s perception of the extent of and dissatisfaction with MG-related dysfunction. Each 
item is scored from 0 to 2 according to its frequency, with a maximum score of 30. The 
questions that patients should provide a response to assess their quality of life is included in 
Appendix 14.4. 
8.3 
Pharmacokinetics 
In order to assess the PK parameters of ARGX-113, blood samples will be collected from 
each patient as presented in Table 1. Concentrations will be determined using a validated 
assay. The actual date and time of collection of blood sample will be recorded in the relevant 
section of the eCRF. 
Pharmacokinetic calculations will be performed by Quintiles using Quintiles SOPs and 
standard non-compartmental and/or compartmental methods, as appropriate. 
The appropriate PK parameters will be calculated after single (Visit 1) and multiple 
administrations (Visits 3, 5, and 7) of ARGX-113 using individual concentration data in 
plasma and actual sampling times: 
Cmax 
maximum observed plasma concentration 
tmax 
the time of occurrence of Cmax 
Ctrough 
plasma concentration observed at pre-dose at Visits 3, 5, and 7 
t1/2,λz 
the apparent terminal half-life, calculated from (ln 2)/λz (Visit 7 only) 
Rac 
accumulation ratio, calculated as Visit 7 Cmax /Visit 1 Cmax 
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8.4 
Pharmacodynamics 
The PD markers (anti-AChR antibodies and immunoglobulin-G and its sub-types) will be 
measured on at the times indicated in Table 1. Results will be determined using a validated 
assay. The actual date and time of collection of blood sample will be recorded in the relevant 
section of the eCRF. 
8.5 
Additional Assessment of Immunoglobulins 
The blood sample used to assess the PD markers, will be used to assess IgA, IgM, IgE, and 
IgD. 
8.6 
Anti-drug Antibodies 
Blood sample to assess ADA will be collected pre-dose at Visits 1, 5, and 7. Subsequently 
ADA will be assessed at Visits 9, 10, 11, 12, 14, and 16 during the Follow-up period. 
8.7 
Pharmacogenetics 
This study includes an optional Pharmacogenetic assessment which requires signature of a 
separate informed consent if the patient agrees to participate. It is required as part of this 
protocol that the Investigator presents this option to the patient. As this is an optional 
assessment, if the patient refuses consent he/she will not be excluded from the study. In this 
study, pharmacogenetic analysis will not be used for making regulatory judgments pertaining 
to the safety or efficacy of the IMP. 
However, these data may be considered for voluntary submission, consistent with applicable 
regulatory guidance on this topic, in order to develop the knowledge base necessary to 
establish the validity of new genomic biomarkers. 
If patients consent for this optional assessment, a blood sample will be collected prior to first 
dosing on (Visit 1) and will be stored for pharmacogenetic analysis (limited to the assessment 
of FcRn polymorphisms). In case the blood draw at Baseline is missed, the sample should be 
taken at Visit 3 prior to the administration of IMP. 
Blood samples taken for this pharmacogenetic analysis will be stored for up to 15 years at 
Quintiles Q2 lab during which the assessment of FcRn polymorphisms may be done on the 
DNA derived from the samples, and these will not be used for additional gene analysis. 
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9.0 QUALITY CONTROL AND QUALITY ASSURANCE 
9.1 
Investigator’s Responsibility 
The Investigator will comply with the protocol (which has been approved/given favorable 
opinion) by the Ethics Committee, ICH GCP, and applicable regulatory requirements as 
described in the Clinical Study Agreement. The Investigator is ultimately responsible for the 
conduct of all aspects of the study at the study site and verifies by signature the integrity of 
all data transmitted to the sponsor. The term “Investigator” as used in this protocol as well as 
in other study documents, refers to the Investigator or authorized study personnel that the 
Investigator has designated to perform certain duties. Sub-Investigators or other authorized 
study personnel are eligible to sign for the Investigator, except where the Investigator’s 
signature is specifically required. 
9.2 
Quality Control of Data 
Quality control will be applied to each stage of data handling. 
The following steps will be taken to ensure the accuracy, consistency, completeness, and 
reliability of the data: 
• 
Investigator meetings. 
• 
Central laboratories for clinical laboratory parameters and ECGs. 
• 
Site Initiation visit. 
• 
Early site visits post-enrollment. 
• 
Routine site monitoring. 
• 
Ongoing site communication and training. 
• 
Data management quality control checks. 
• 
Continuous data acquisition and cleaning. 
• 
Internal review of data. 
• 
Quality control check of the CSR. 
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In addition, Sponsor and/or Sponsor’s designated CRO (Quintiles) Clinical Quality 
Assurance (CQA) Department may conduct periodic audits of the study processes, including, 
but not limited to study site, or site visits, central laboratories, vendors, clinical database, and 
final CSR. When audits are conducted, access must be authorized for all study related 
documents including medical history and concomitant medication documentation to 
authorized Sponsor’s representatives and regulatory authorities. 
9.3 
Monitoring 
The Sponsor has engaged the services of a CRO, named Quintiles, to perform all monitoring 
functions within this clinical study. Sponsor’s designated CRO (Quintiles’) monitors will 
work in accordance with Quintiles’ standard operating procedures (SOPs) and have the same 
rights and responsibilities as monitors from the Sponsor organization. Monitors will establish 
and maintain regular contact between the Investigator and the Sponsor. 
Monitors will evaluate the competence of each study site, informing the Sponsor about any 
problems relating to facilities, technical equipment, or medical staff. During the study, 
monitors will check that written informed consent has been obtained from all patients 
correctly prior to any study related procedures performed and that data are recorded correctly 
and completely. Monitors are also entitled to compare entries in eCRFs with corresponding 
source data and to inform the Investigator of any errors or omissions. Monitors will also 
control adherence to the protocol at the study site. They will arrange for the supply of IMP 
and ensure appropriate storage conditions are maintained. 
Monitoring visits will be conducted according to all applicable regulatory requirements and 
standards. The Investigator must permit study related monitoring by providing direct access 
to source data and to the patients’ medical histories. The Clinical Monitors will perform 
monitoring visits at each site at regular intervals during the study and after the study has 
completed, as appropriate. The monitor will make written reports to the Sponsor on each 
occasion when contact with the Investigator is made, regardless of whether it is by phone or 
in person. 
Monitoring visits must be conducted according to the applicable ICH-GCP guidelines to 
ensure protocol adherence, quality of data, study treatment accountability, compliance with 
regulatory requirements, and continued adequacy of the investigational site and its facilities. 
During monitoring visits, entries in the eCRFs will be compared with the original source 
documents (source data verification). For this study, the data will be 100% checked and 
verified. 
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9.4 
Data Management and Coding 
Data generated within this clinical study will be handled according to the SOPs of the Data 
Management and Biostatistics departments of the Sponsor’s designated CRO (Quintiles). 
Data for this study will be recorded via InForm 5.5 EDC system using eCRFs. It will be 
transcribed by the site from the paper source documents onto the eCRF. The information 
collected on eCRFs must be identical to the corresponding information appearing in original 
source documents. There are no exceptions to this rule. Appropriate training and security 
measures will be completed with the Investigator and all authorized study site staff prior to 
the study being initiated and any data being entered into the system for any study patients at 
the site. 
All data must be entered in English. The eCRFs should always reflect the latest observations 
on the patients participating in the study. Therefore, the eCRFs are to be completed as soon 
as possible during or after the patient’s visit. 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. The Investigator must verify 
that all data entries in the eCRFs are accurate and correct. 
As a matter of regulation, the Investigator is responsible for the accuracy and authenticity of 
all clinical and laboratory data entered onto eCRFs. The Investigator should also ensure that 
patient submits completed and correct questionnaires. Prior to submission, each completed 
eCRF must be reviewed for accuracy by the Investigator, corrected as necessary and then 
approved. The Investigator’s e-signature serves to attest that the information contained on the 
eCRFs has been reviewed by the Investigator and is true and accurate. The Investigator will 
be required to electronically sign off on the eCRF and SAE data. 
The monitor will review the eCRFs and evaluate them for completeness and consistency. The 
eCRF will be compared with the source documents to ensure that there are no discrepancies 
between critical data. All entries, corrections and alterations are to be made by the 
responsible Investigator or his/her designee. The monitor cannot enter data in the eCRFs. 
Once clinical data of the eCRF have been submitted to the central server, corrections to the 
data fields will be audit trailed, meaning that the reason for change, the name of the person 
who performed the change, together with time and date will be logged. Roles and rights of 
the site staff responsible for entering the clinical data into the eCRF will be determined in 
advance. If additional corrections are needed, the responsible monitor or Data Manager will 
raise a query in the EDC application. The appropriate study site staff will answer queries sent 
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to the Investigator. This will be audit trailed by the EDC application meaning that the name 
of investigational staff, time, and date stamp are captured. 
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 study. They 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. 
Instructions for the completion of eCRFs will be provided. 
The eCRFs will be considered complete when all missing, incorrect and/or inconsistent data 
have been accounted for. If some assessments are not done, or if certain information is not 
available or not applicable or unknown, the Investigator should indicate this in the eCRF 
using appropriate item or form level comments. 
The Investigator is responsible for maintaining source documents. These will be made 
available for inspection by the study monitor at each monitoring visit. The Investigator must 
submit a completed eCRF for each patient who receives IMP, regardless of duration. All 
supportive documentation submitted with the eCRF, such as laboratory or hospital records, 
should be clearly identified with the study and patient number. Any personal information, 
including patient name, should be removed or rendered illegible to preserve individual 
confidentiality. 
The eCRF records will be automatically appended with the identification of the creator, by 
means of their unique User Identification (ID). Specified records will be electronically signed 
by the Investigator to document his/her review of the data and acknowledge that the data are 
accurate. This will be facilitated by means of the Investigator’s unique User ID and 
password; date and time stamps will be added automatically at time of electronic signature. If 
an entry on an eCRF requires change, the correction should be made in accordance with the 
relevant software procedures. All changes will be fully recorded in a protected audit trail, and 
a reason for the change will be required. 
Adverse events, concomitant diseases/medical history terms will be assigned to a lowest 
level term (LLT) and a preferred term (PT) and will be classified by high level term (HLT), 
high level group term, and primary system organ class (SOC) according to the Medical 
Dictionary for Regulatory Activities (MedDRA) thesaurus. 
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Concomitant medications will be classified according to active drug substance using the 
World Health Organization Drug Dictionary (WHO-DD). The generic name, the preferred 
name, and the WHO name will be assigned using WHO-DD thesaurus. 
The Anatomical Therapeutic Chemical (ATC) classes will be assigned to the concomitant 
medications. 
9.5 
Quality Assurance Audit 
Study sites, the study database and study documentation may be subject to Quality Assurance 
audit during the course of the study by the Sponsor or Sponsor’s designated CRO (Quintiles) 
on behalf of Sponsor. In addition, inspections may be conducted by regulatory bodies at their 
discretion. 
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10.0 STATISTICS 
The statistical analyses will be performed by Sponsor’s designated CRO (Quintiles) using 
statistical analysis system (SAS®), (SAS Institute, Cary, NC, USA) version 9.2 or higher. 
The SOPs and work instructions of Sponsor’s designated CRO (Quintiles’) will be used as 
the default methodology if not otherwise specified. 
Any change to the data analysis methods will be mentioned in the statistical analysis plan 
(SAP). Any additional analysis, and the justification for making the change, will be described 
in the CSR. Additional exploratory analyses of the data will be conducted as deemed 
appropriate. 
10.1 Determination of Sample Size 
Approximately 36 patients will be screened in order to randomize approximately 24 patients 
(12 patients per treatment arm) to get at least 20 patients who have received at least 3 doses 
of IMP (either ARGX-113 or placebo) and who completed at least 2 weeks of follow-up 
period post last dose (See Appendix 14.6). Patients may be replaced in certain circumstances. 
Possible scenarios in which a patient may be replaced is mentioned in Table 2. Final decision 
for replacement of patients will be done on a case-by-case basis in consultation with the 
Medical Monitor at the Sponsor’s designated contract research organization (CRO, Quintiles) 
and/or the Medical Director at the Sponsor’s end. 
10.2 Analysis Population 
The analysis of data will be based on different analysis sets according to the purpose of 
analysis. The decision regarding validity of data for each of the analysis sets will be based on 
a blinded review of data, which will occur prior to declaring database-lock and before 
unblinding of data for analysis. 
• Randomized Population: Any patients who have been allocated to a randomized 
treatment arm, regardless of whether they received the planned treatment or not. 
• Full Analysis Set (FAS): Patients will be considered under planned treatment for 
analyses based on FAS. The secondary endpoints analysis will be on the FAS, 
defined as all randomized patients who had an evaluable efficacy endpoint. 
The efficacy endpoint will be considered evaluable when the following condition is met: 
• At least one MG-ADL, QMG, MGC, MGQoL15r scores are available within one of 
the post-baseline assessment up to Visit 16 with the corresponding Baseline value. 
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• 
Safety Population: The safety population considered for safety analyses will be the 
randomized population who received at least one dose or part of a dose. The safety 
population will be analyzed according to the treatment actually received. 
• 
PK analysis set: PK analysis population considered for PK analysis will be the 
randomized population who have at least one plasma concentration data value 
available for ARGX 113. 
10.3 Patient Disposition, Characteristics and Concomitant Medication 
A tabular presentation of the patient disposition will be provided. It will include the number 
of patients screened, enrolled, randomized, completed, as well as the number of dropouts, 
with reasons for discontinuation and major protocol deviations or violations. 
A listing will be presented to describe dates of Screening, randomization or assigned 
treatment, screen failure with reason, completion or early discontinuation/withdrawal and the 
reason for early discontinuation, if applicable, for each patient. 
A list of protocol violations will be identified and discussed with the Investigator to 
categorize as major or minor and the same will be reported. 
Patient characteristics will be recorded prior to randomization and will be listed and 
summarized by treatment. Overall summaries will include descriptive statistics for 
continuous measures (number of observation [n], mean, standard deviation (SD), median, 
minimum and maximum) and for categorical measures (sample size, frequency, and percent). 
Treatments will be compared by using t-tests for quantitative measures and the Fisher’s exact 
test or the Chi-squared test for categorical measures. Patient characteristics include but are 
not limited to age, gender, race, weight, and BMI. 
Categorical use of concomitant medication will be summarized by treatment with frequency 
and percentage. All concomitant medications used will be listed. Exposure to the IMP, i.e., 
total amount of IMP received, will be summarized and listed for all patients. 
10.4 Statistical Methods 
Safety, tolerability, efficacy, PK, and PD data will be listed and summarized by treatment 
group using descriptive statistics. Graphical representations of data will be presented as 
deemed appropriate. No formal hypothesis testing will be conducted in this study, p-values if 
presented are to be interpreted descriptively. Continuous variables will be summarized by 
descriptive statistics ([n], mean, SD, median, minimum, and maximum). Categorical 
variables will be summarized in frequency tables (frequencies and percentages). 
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Details of statistical analysis methods will be provided in the SAP that will be prepared and 
signed off prior to unblinding and database lock. 
10.4.1 
Primary Endpoint Analyses 
10.4.1.1 
Adverse Events 
Treatment-emergent AEs are defined as AEs that first occurred or worsened in severity after 
the first administration of the IMP. 
Summaries over SOC, PT and listings of AEs leading to death, SAEs, AEs, and AEs that led 
to discontinuation of study treatment will be presented. Summaries will also be presented by 
relationship to IMP and severity of the AE. 
10.4.1.2 
Vital Signs Measurements, Physical Findings and Laboratory assessments 
Summaries and listings of data for vital signs, hematology, clinical chemistry and urinalysis 
laboratory tests, ECGs, suicidality assessments, and physical examination findings will be 
presented. Appropriate data will be summarized for the observed value at each scheduled 
assessment and for the corresponding change from Baseline. 
For hematology and clinical chemistry tests, listings of patient data will also flag up any 
abnormal or out-of-range values. Clinically significant changes in the laboratory test 
parameters will be summarized and listed. Hematology and clinical laboratory data will be 
reported in System International (SI) units. 
For ECG variables, the QT correction factor will be based on both the Bazett and Fridericia 
formulae (QTcB and QTcF). Categorical summaries of absolute QT, QTcB and QTcF values 
and change from (Baseline) values in QT, QTcB and QTcF values will be presented by 
treatment and visit. 
10.4.2 
Secondary Endpoint Analyses 
10.4.2.1 
Analysis of Scales 
Analyses of data derived from scales (MG-ADL, QMG, MGC, and MGQoL15r) will be 
based on FAS. Actual score, change from Baseline and maximum reduction from Baseline 
will be summarized descriptively. 
Analyses of the change from Baseline in efficacy rating scales will be performed using a 
mixed- model repeated measures (MMRM) analysis from Visit 1 to Visit 16. The models 
included the fixed treatment, baseline score and patient as a random effect. Appropriate 
covariance structure will be used. At each visit day, IMP will be compared with placebo and 
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model-based Least Squares Means for the treatment effects, 95% CIs and p-values will be 
calculated for within and between treatment comparisons. 
Figure for change from Baseline in total score (last observation carried forward) in patients 
will be presented. Number and percentage of patients by levels of point reduction will be 
presented by horizontal bars for IMP and placebo. 
10.4.2.2 
Analysis of Pharmacokinetic Parameters 
Pharmacokinetic analyses will be performed based on the PK population. Plasma 
concentrations at each sampling time point will be summarized for ARGX-113 by the 
following summary statistics: 
• Arithmetic mean calculated using untransformed data 
• SD calculated using untransformed data 
• Minimum 
• Median 
• Maximum 
• Number of observations 
• Number of observations ≥lower limit of quantification (LLOQ) 
Geometric mean plasma concentrations against protocol time will be shown by patient in 
both linear and log scales, respectively. Note that the values of geometric mean (Gmean) ± SD 
will also be shown in this graph using vertical lines. 
The following summary statistics will be presented for all the PK parameters except for tmax 
• Gmean 
• GCV 
• Arithmetic mean calculated using untransformed data 
• SD calculated using untransformed data 
• Minimum 
• Median 
• Maximum 
• Number of observations 
The following summary statistics will be presented for the PK parameters tmax 
• Number of observations 
• Median 
• Minimum 
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• Maximum 
10.4.2.3 
Analysis of Pharmacodynamic Parameters 
Continuous PD parameters summarized with descriptive statistics including geometric mean. 
Pharmacodynamic parameters include total IgG, IgG subtypes, anti AChR antibodies. 
Further details will be described in the SAP. 
10.4.2.4 
Anti-Drug Antibodies (ADA) Analyses 
Frequency and percentage of ADA response will be presented and listed. ADA response data 
will also be summarized as proportions along with their 95% CIs using exact test separately 
for each treatment. Further detail analyses will be presented in the SAP. 
10.5 Interim Analyses 
Not applicable. 
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11.0 ETHICS 
11.1 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 study may begin at the 
study 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 study. Similarly, the Investigator 
will submit written summaries of the study status to the IRB/IEC annually, or more 
frequently if requested by the IRB/IEC. Upon completion of the study, the Investigator will 
provide the IRB/IEC with a brief report of the outcome of the study, if required. 
11.2 Ethical Conduct of the Study 
This study will be conducted and the informed consent will be obtained according to the 
ethical principles stated in the Declaration of Helsinki (2008), the applicable guidelines for 
GCP, or the applicable drug and data protection laws and regulations of the countries where 
the study will be conducted. 
11.3 Patient Information and Informed Consent 
The informed consent form (ICF) will be used to explain the risks and benefits of study 
participation to the patient in simple terms before the patient is enrolled into the study. A 
separate ICF will be given in case a patient consents for Pharmacogenetic analysis and for 
Pregnancy in case of a female partner of 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 
study, and that the patient is free to withdraw from the study at any time. Written consent 
must be given by the patient and/or legal representative, after the receipt of detailed 
information on the study. 
All ICFs must be available in the local and vernacular languages required at the site and 
include patient information sheets/brochures that outline the study procedures. All ICF(s) 
must be signed and dated by the patient or a legally acceptable representative. 
For patients who are unable to read and write, the patient information sheet and ICF(s) 
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should be read to the patient in his/her native language in the presence of an impartial witness 
who is literate and not affiliated with the study. The patient having understood the 
information given to him/her in the presence of an impartial witness will thumbprint the 
ICF(s) and the same will be countersigned by the impartial witness. If the patient or legally 
acceptable representative cannot read, then an impartial witness will witness and attest the 
entire consent process and will be required to sign the consent form. 
Confirmation of a patient’s informed consent must also be documented in the patient’s 
medical record prior to any testing under this protocol, including Screening tests and 
assessments. 
The Investigator is responsible for ensuring that informed consent is obtained from each 
patient or legal representative 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 consent form. 
11.4 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. 
Sponsor or representative will not provide individual genotype results to patients, any 
insurance company, any employer, their family members, general physician, or any other 
third party, unless required to do so by law. 
Extra precautions are taken to preserve confidentiality and prevent genetic data being linked 
to the identity of the patient. In exceptional circumstances, however, certain individuals 
might see both the genetic data and the personal identifiers of a patient. For example, in the 
case of a medical emergency, a Sponsor or representative physician or an Investigator might 
know a patient’s identity and also have access to his or her genetic data. Also regulatory 
authorities may require access to the relevant files. 
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12.0 STUDY ADMINISTRATION 
12.1 Administrative Structure 
     Table 4 
Administrative Structure 
Clinical Trial Supply Management 
B & C Group 
Watson & Crick Hill 
Rue Granbonpré 11 
B-1435 Mont-Saint-Guibert 
Belgium 
Clinical Laboratory 
Q2 Lab Solutions 
The Alba Campus, Rosebank 
Livingston, West Lothian 
EH54 7EG, United Kingdom 
And 
Q2 Lab Solutions 
27027 Tourney Road 
Valencia, CA 91355 
USA 
Analysis of PK-PD, Anti-drug antibodies 
SGS Cephac Europe SAS 
90 Avenue des Hauts de la Chaume BP. 28 
86281 Saint-Benoit Cedex 
France 
Study Monitoring 
Quintiles 
Parque Empresarial Cristalia 
Vía de los Poblados, 3 
Edificio 7/8, 5 Planta 
28033 Madrid - Spain 
Drug Safety Reporting 
Quintiles Ireland Limited 
Estuary House, East point Business Park, 
Alfie Byrne Road, 
Dublin 3 - Ireland 
Data Management 
Quintiles, India 
3rd Floor, Etamin Block, 
Prestige Technology Park II, Sarjapur-Marathahalli Outer Ring 
Road 
Bengaluru-560103, Karnataka - India 
Biostatistics 
Quintiles Research ( India ) Pvt Ltd 
12 Floor , G.Corp Tech Park 
Thane-Ghodbunder Road 
Kasarvadavali , Thane (West )-400615, Maharashtra - India 
Medical Monitoring 
Quintiles, 500 Brook Drive, Green Park 
Reading, Berkshire, RG2 6 UU, UK 
Telephone number +
 
Study Report Preparation 
Quintiles, India 
Quintiles, I Floor, 'A' wing 
Salarpuria Supreme 
#92/5, Outer Ring Road, Munnekolala Village, Marathalli 
Bengaluru -560037, Karnataka - India 
 
12.2 Data Handling and Record Keeping 
It is the Investigator’s responsibility to maintain essential study documents (including 
regulatory documents, eCRFs, signed patient ICFs, source documents, relevant 
correspondence, AE reports, and all other supporting documentation) as required by the 
applicable national regulatory requirements. The study site should plan on retaining such 
documents for approximately 15 years after study completion. The study site should retain 
such documents until at least 2 years after the last approval of a marketing application in an 
ICH region and until there are no pending or contemplated marketing applications in an ICH 
region or at least 2 years after the formal discontinuation of clinical development of the IMP. 
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These documents should be retained for a longer period if required by the applicable 
regulatory requirements or the hospital, institution, or private practice in which the study is 
being conducted. Patient identification codes (patient names and corresponding study 
numbers) will be retained for this same period of time. These documents may be transferred 
to another responsible party, acceptable to 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 study documents. 
The Investigator must contact Sponsor prior to disposing of any study records. 
The United States (U.S) Food and Drug Administration (FDA) regulations (21 CFR 
§312.62[c]) and the ICH Guideline for GCP (see Section 4.9 of the guideline) require that 
records and documents pertaining to the conduct of this study and the distribution of IMP, 
including eCRFs, consent forms, laboratory test results, and medication inventory records, 
must be retained by the Principal Investigator for 15 years after the last marketing application 
approval in an ICH region or after at least 15 years have elapsed since formal discontinuation 
of clinical development of the IMP will notify the PI of these events. 
No records should be disposed of without the written approval of argenx. 
For studies conducted outside the U.S. under a U.S. Investigational New Drug (IND), the 
Principal Investigator must comply with U.S. FDA IND regulations and with those of the 
relevant national and local health authorities. 
12.3 Direct Access to Source Data/Documents 
The Sponsor or designee and auditor may access patient records for the purpose of 
monitoring this study, auditing, and managing progress details. The Investigator must be 
fully aware that the Sponsor or designee and auditor can inspect, verify, or copy documents 
to verify patient chart and eCRF records. Such information must be kept confidential and 
must have locked facilities that allow for this. Patient identification number and not the 
patient’s name will be recorded on all documents related to the study. The Investigator will 
prepare and maintain adequate and accurate source documents to record all observations and 
other pertinent data for each patient randomized into the study. 
12.4 Investigator Information 
12.4.1 
Investigator Obligations 
The Investigator is responsible for ensuring that all study site personnel, including 
Sub-Investigators, adhere to all applicable regulations and guidelines, including local laws 
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and regulations, regarding the study, both during and after study completion. The 
Investigator is responsible for informing the IRB/IEC of the progress of the study and for 
obtaining annual IRB/IEC renewal. The Investigator is responsible for informing the 
IRB/IEC of completion of the study and will provide the IRB/IEC with a summary of the 
results of the study. 
12.4.2 
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 study protocol and will conduct the study in accordance with ICH Tripartite Guidelines 
for GCP and applicable regulatory requirements. The study will not be able to start at any site 
where the Investigator has not signed the protocol. 
12.4.3 
Publication Policy 
All information regarding ARGX-113 supplied by the Sponsor to the Investigator and all 
data generated as a result of this study, are considered confidential and remain the sole 
property of the Sponsor. The results of the study will be reported in a CSR. 
The CSR written in accordance with the ICH E3 Guideline, will be submitted in accordance 
with local regulations. 
Any manuscript, abstract or other publication or presentation of results or information arising 
in connection with the study must be prepared in conjunction with the Sponsor and must be 
submitted to the Sponsor for review and comment prior to submission for publication or 
presentation. Study subject identifiers will not be used in publication of results. 
Authorship will be granted based on scientific input, recruitment efforts, and will be granted 
upon decision of a publication committee. This committee will include among others the 
coordinating Investigator and the Sponsor. 
The Sponsor will register and/or disclose the existence of and the results of clinical studies as 
required by law. 
12.5 Financing and Insurance 
Sponsor will fund the study as outlined in the Clinical Trial Agreement. All direct costs 
associated with the conduct of the study and laboratory investigations will be paid for by the 
Sponsor. 
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Sponsor will obtain adequate global/local insurance for the study participants including the 
study patients for the required duration of time. 
Sponsor will provide insurance coverage with respect to any liability caused by the IMP 
and/or study-related procedures in connection with this clinical study. Liability and insurance 
provisions for this study are specified in the Investigator’s contract. The terms and conditions 
will apply as specified in the policy document. 
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13.0 REFERENCES 
1. Barohn R, Herbelin L. The Quantitative Myasthenia Gravis Test Manual, Myasthenia 
Gravis Foundation of America, Inc. Revised March 25, 2000. University of Texas, 
Southwestern Medical Center, Dallas, Texas. 
2. Simon, G.E., Rutter, C.M., Peterson, D. et al. Does response on the PHQ-9 depression 
questionnaire predict Subsequent suicide attempt or suicide death? Psychiatr Serv. 
2013; 64:1195–1202. 
3. Howard JF, Barohn RJ, Cutter GR, Freimer M, Juel VC et al. A Randomized, 
Double-Blind, Placebo-Controlled Phase II Study of Eculizumab in Patients with 
Refractory Generalized Myasthenia Gravis. Muscle & Nerve. 2013 Jul; 48 (1): 76-84 
4. Conti-Fine BM, Milani M, Kaminski HJ. Myasthenia gravis: past, present, and future. 
J Clin Invest. 2006; 116:2843–54. [PubMed: 17080188]. 
5. Meriggioli MN, Sanders DB. Autoimmune myasthenia gravis: emerging clinical and 
biological heterogeneity. Lancet Neurol. 2009; 8:475–90. [PubMed: 19375665] 
6. Zinman L, Ng E, Bril V. IV immunoglobulin in patients with myasthenia gravis: a 
randomized controlled trial. Neurology. 2007; 68:837–41. [PubMed: 17353471] 
7. Challa, D.K., et al., Autoantibody depletion ameliorates disease in murine 
experimental autoimmune encephalomyelitis. MAbs, 2013. 5 (5): p. 655-9. 
8. Roopenian DC, Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nat Rev 
Immunol. 2007; 7:715–25. [PubMed: 17703228] 
9. Vaccaro, C., et al., Engineering the Fc region of immunoglobulin G to modulate in 
vivo antibody levels. Nat Biotechnol, 2005. 23 (10): p. 1283-8. 
10. Challa, D.K., et al., Autoantibody depletion ameliorates disease in murine 
experimental autoimmune encephalomyelitis. MAbs, 2013. 5 (5): p. 655-9. 
11. Patel, D.A., et al., Neonatal Fc receptor blockade by Fc engineering ameliorates 
arthritis in a murine model. J Immunol, 2011. 187 (2): p. 1015-22. 
12. Gilhus NE et al., Myasthenia gravis: a review of available treatment approaches, 
Autoimmune Dis 2011: 847393. 
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13. Liu J, Wang W, Zhao C, et al. Comparing the autoantibody levels and clinical 
efficacy of double filtration plasmapheresis, immunoadsorption and intravenous 
immunoglobulin for the treatment of late-onset myasthenia gravis. Ther Apher Dial. 
2009; 14(2):153-160. PMID 20438536. 
14. Meriggioli, M. N., & Sanders, D. B. (2009). Autoimmune myasthenia gravis: 
emerging clinical and biological heterogeneity. Lancet Neurol, Vol. 8, No. 5, pp. 475-
490, ISSN: 1474-4422 
15. World Health Organization. International Classification of Functioning, Disability, 
and Health (ICF). 1st edition. World Health Organization 2001: Available: 
http://www.who.int/classifications/icf/en/. Accessed: Aug 20th 2013. 
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14.2 Appendix 2: Quantitative Myasthenia Gravis score 
QUANTITATIVE MYASTHENIA GRAVIS TESTING FORM 
Patient Name: 
Patient #: 
Date: 
MR#: 
 
DOB:  
Sex: 
 
Ht.(in)  
 
Wt.(kg):  
 
Evaluator: 
Handedness: 
Leggedness: 
 
Time of Exam:  
 
Anticholinesterase Medication: 
 
Comments: 
 
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TOTAL QMG SCORE:  
 
 
 
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GENERAL INSTRUCTIONS 
 
1. Patients must be off pyridostigmine (or any acetylcholinesterase inhibitor medication) for twelve (12) hours prior  to testing, 
(if medically safe to do so). 
 
2. Perform the tests in the order given in this Manual and shown on the Videotape. 
 
3. Calibrate the respiratory equipment on the day of the test, per manufacturers’ instruction, before the test begins. Place the calibration 
record in folder in an accessible place. 
 
4. For all measurements, record actual numbers as well as grade, i.e., if it takes 30 seconds before a patient sees double, record on the 
far right box 30/1 for 30 seconds and a grade of 1. 
 
5. Patients must remain seated for the respiratory test. 
 
6. At the end of the scoring sheet, add up the grade for that patient and that becomes the Total 
QMG Score. 
 
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QUANTITATIVE MG SCORE 
I. DOUBLE VISION: 
Patients' preparation: Patient is sitting. Ask if the patient is experiencing double vision looking straight ahead. If yes, record 0/3 
(actual time/grade) on the scoring sheet. If no, ask the patient to look to the right for just an instant and then to the left without moving 
their head. If the patient sees double in only one direction, record side and record result as 0/3. If there is no eye movement, record as 
0/3. If the patient does not see double, or sees double in both directions, have them perform the test as described below gazing to the 
right. 
 
Explanation to patient: "I need for you to face forward. When I ask, look over to your right (left) side without turning your head. If or 
when you start to see double, please let me know." 
 
Notes to examiner: Patient's head will usually start to turn in the direction of the gaze. Try to maintain the head in a forward position. 
Record the time and grade. Example: double vision is evident at 15 sec. In the scoring section, record 15/1. 
 
 
 
II. PTOSIS (upward gaze): 
Patients' preparation: Patient is sitting. Ask the patient to look straight ahead. If the upper lid is touching the pupil, record as 
0/3. Ask the patient to look up at the ceiling without moving the head. 
 
Explanation to patient: "I need you to face forward. When I ask, look up at the ceiling without moving your head. Keep looking up 
until I tell you to relax." 
 
Notes to examiner: Patient's head will usually start to move up. Try to maintain the head in a forward position. Record time and grade 
when you see either eyelid (lashes) start to droop. Ex: Right eyelid starts to droop at 9 sec., record 9/2. If neither eyelid touches the 
pupil, record 60/0. 
 
 
 
 
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III. FACIAL MUSCLES: 
Patients' preparation: Patient is sitting facing forward. 
 
Explanation to patient: "Squeeze your eyes shut. Do not allow me to open your eyes." 
 
Notes to examiner: If the patient cannot fully close either eye shut, record the grade as 3. No time score is needed on this test. Record 
grade of the weaker eye. 
 
 
 
IV. SWALLOWING: 
Patient's preparation: Patient is sitting. Four ounces of water (no ice) is poured into a cup. The water should be no cooler than water 
fountain cool. 
Explanation to patient: "I need for you to drink this water as you normally would." 
 
Notes to examiner: Listen for coughing and/or throat clearing during the test and immediately post test. 
Don't ask patients to drink faster than what they feel comfortable doing. 
 
 
 
V. SPEECH: 
Patient's preparation: Patient is sitting. 
 
Explanation to patient: "Count out loud from 1 to 50 at a comfortable pace." 
 
Notes to examiner: This is one of the most difficult tests to score because of varying accents. Record number when you notice a nasal 
or slurring of the speech. 
 
 
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VI. RIGHT & LEFT ARM OUTSTRETCHED: 
Patient's preparation: The patient needs to be sitting in a chair with both feet on the floor. They must be seated without leaning 
against the back of a chair. Test both arms at the same time. Arms need to be out to the side at 90o, palms down. (Demonstrate this 
position). If the patient cannot raise an arm out to 
90o due to a shoulder problem, do not test that arm. The elbows are extended through full mechanical range. 
 
Explanation to patient: "I need for you to hold both arms out to the side like this. Keep the arms out as long as possible. If one arm 
tires more than the other, you may lower that arm and keep the other arm up." 
 
Notes to examiner: It is not uncommon that the arms start to droop. If the arms drop more than 10o from starting position, remind the 
patient to pull the arms up. If the patient can pull the arms up but cannot maintain that position for longer than two seconds, stop the 
test. If one arm is lowered, be careful that the patient does not start to lean to the side that the arm was lowered to give the appearance 
that he/she is maintaining a 90o angle. Record time/grade (ex: 45 sec for right arm is 45/2; whereas 100 sec for left arm is 100/1). 
 
 
 
VII: FORCED VITAL CAPACITY: 
Patient preparation: Patients must remain seated for this test. 
 
Explanation to patient: "I am testing total lung capacity. I am going to ask you to hold this mouthpiece away from your face. I will then 
place the nose-clips on your nose. I will tell you to take a deep breath in, and then place the mouthpiece in your mouth. You will blow 
out as hard and as fast as you can. Keep blowing until I tell you to stop. 
Notes to examiner: We are only testing FVC. A minimum of three trials and a maximum of five trials will be performed. The goal is 
to get the best two trials within 5% of each other. Give a lot of encouragement. Record best FVC (liters and percentage) and grade 
on sheet, (ex: 2.55 - 60% / 2). 
 
The “normal” FVC values, and therefore the percent  predicted calculations  can vary with the spirometer that  is used. Some 
spirometers come with specified normal  values. That  is why the same spirometer should be used each time you test a subject. 
For multi-site studies, parameters and normal  values should be decided so that all sites are using the same information. 
 
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VIII: RIGHT & LEFT HAND GRIP: 
Patient preparation: Patient is sitting in a chair. The elbow should be at 90o. Support should be under the medial aspect of the 
forearm and under the dynamometer. 
 
Explanation to patient: "I am testing grip strength. I need for you to squeeze as hard as you can. Nothing will move, but it is 
measuring how hard you are squeezing." 
 
Notes to examiner: Give vocal encouragement. Record the two trials (kgs) in column and score (ex: if testing a female and results are 
10 and 8 kgs, record as 10/1.) 
 
 
 
IX. HEAD LIFTED: 
Patient preparation: The patient will lie down without a pillow under the head. A pillow may be placed under the knees or the knees 
bent so that the feet are flat on the bed. 
 
Explanation to patient: "I need for you to lift your head off of the table. Keep it up as long as possible." 
 
Notes to examiner: Place your hand under their head (without touching) to provide some cushion if the head drops back. The head 
should come up and forward, not just up to the ceiling. If the head drops within 10o of neutral, stop the test. 
 
 
 
X. RIGHT & LEFT LEG OUTSTRETCHED: 
Patient preparation: Patient is supine with a pillow under the head. Both legs must be out straight and shoes off. 
 
Explanation to patient: "I need for you to hold your right leg up. Hold the leg up in this position as long as possible." 
 
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Notes to examiner:  Leg must be maintained at 45-50% of hip flexion. If the leg start to droop, ask the patient to lift the leg up. If the 
patient lifts the leg up, but cannot maintain that position for 2 seconds, stop the test. Watch for hands under the hips and/or rotation of 
the leg. 
Myasthenia Gravis Foundation of America, Inc. 
 
1821 University Ave W, Ste S256 
St Paul, MN  55104 
 
Phone: (651) 917-6256 or (800) 541-5454 
Fax: (651) 917-1835 
Email: mgfa@myasthenia.org 
Website: www.myasthenia.org 
 
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14.3 Appendix 3: Myasthenia Gravis Composite Score 
 
Please note that “moderate weakness” for neck and limb items should be construed as weakness that equals roughly 50% +/- 15% 
of expected normal strength. Any weakness milder than that would be “mild” and any weakness more severe than that would be 
classified as “severe”. 
 
Total Score 
 
 
 
 
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14.5 Appendix 5: Clinical Laboratory Evaluations 
Hematology 
Complete blood count (CBC), [hemoglobin, hematocrit, red blood cells (RBCs), white 
blood cells (WBCs), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin 
concentration (MCHC), mean corpuscular volume (MCV), platelet count, and differential 
blood cell counts (neutrophils, lymphocytes, monocytes, eosinophils, basophils)] and 
erythrocyte sedimentation rate (ESR). 
Clinical Chemistry 
Creatinine, creatinine clearance, blood urea nitrogen (BUN), glucose, alanine 
aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, 
gamma-glutamyl transferase (GGT), C-reactive protein (CRP), alkaline phosphatase, 
lactate dehydrogenase (LDH), uric acid, albumin, potassium, sodium, calcium. 
thyroglobulin, International normalized ratio or activated partial thromboplastin time 
(aPTT), CD19 counts. 
Urinalysis 
Color, clarity/appearance, specific gravity, pH, protein, glucose, ketones, blood, bilirubin, 
urobilinogen, nitrite, leukocyte esterase, and microscopic examination including RBC, 
WBC, cast crystals, bacteria. 
Serology 
Hepatitis B virus (HBV) Hepatitis B surface antigen (HBsAg)], HBV core antibody, 
[hepatitis C virus (HCV), hepatitis C virus antibody (HCV-Ab)], human immunodeficiency 
virus (HIV) antibodies (1 and 2), and tuberculosis serology 
Other 
Serum and urine human chorionic gonadotrophin (ß-HCG), Follicle-stimulating hormone 
(FSH) test, and QuantiFERON®-TB Gold test. 
Other 
Immunoglobulins* 
IgA, IgD, IgE, and IgM. 
Pharmacodynamic 
Parameters and PK 
Analysis* 
Total IgG and IgG subtypes (IgG 1, IgG 2, IgG 3, and IgG 4) and anti-AChR antibodies 
that include anti-AChR binding antibodies and anti-AChR blocking antibodies. 
Anti-drug antibodies 
(ADA) 
Levels of anti-ARGX113 antibodies 
*PK sample analysis, sample analysis for PD (assessing total IgG, IgG subtypes and other Immunoglobulins and Anti-AChR 
antibodies) and analysis for anti-drug antibodies (ADA) will be performed at SGS Cephac Europe SAS, and Q2 Solutions will 
manage the PK-PD-ADA samples and ship them for testing at SGS Cephac Europe SAS. All other laboratory tests such as 
hematology, clinical chemistry, urinalysis, and serology will be performed by Q2 Solutions. 
 
 
 
 
 
 
 
 
 
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14.6 Appendix 6: Sample Size 
Assuming MG-ADL scores as a key indicator for efficacy. To detect the difference of 4 
points between MG-ADL scores of Active and Placebo with variability (1) SD=1.80 for 
active and SD=3.72 for placebo, a sample size of 10 subjects per group would be 
sufficient to achieve 80% power. Approximately 36 patients will be screened in order to 
randomize approximately 24 patients (12 patients per treatment arm) to get at least 20 
patients who received at least 3 doses of IMP (either ARGX-113 or placebo) and who 
completed at least 2 weeks of follow-up post last dose. Based on below calculation data 
of 10 to 12 subjects per group would be sufficient to produce clinically meaningful data 
for further exploratory analysis. Although this study is exploratory and not statistically 
powered, descriptive efficacy assessments will be analyzed to assist in designing future 
studies. 
nQuery output: 
 
Two group Satterthwaite t-test of equal means (unequal variances) (equal n's) 
1 
2 
Test significance level, α 
0.050 
0.050 
1 or 2 sided test? 
2 
2 
Group 1 mean, µ1 
4.300 
4.000 
Group 2 mean, µ2 
7.900 
8.000 
Difference in means, µ1 - µ2 
-3.600 
-4.000 
Group 1 standard deviation, σ1 
1.800 
1.800 
Group 2 standard deviation, σ2 
3.720 
3.720 
Power ( % ) 
80 
80 
n per group 
12 
10 
 
Reference: Howard JF, Barohn RJ, Cutter GR, Freimer M, Juel VC et al. A Randomized, 
Double-Blind, Placebo-Controlled Phase II Study of Eculizumab in Patients with 
Refractory Generalized Myasthenia Gravis. Muscle & Nerve. 2013 Jul; 48 (1): 76-84. 
System Version: 1.0, Status: Approved, Document ID: VV-TMF-48138

SAP_001.pdf: 
 
 
Statistical Analysis Plan 
 
 
 
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reproduction is strictly prohibited. 
 
 
STATISTICAL ANALYSIS PLAN  
 
 
ARGX-113-1602 
A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE II STUDY TO 
EVALUATE THE SAFETY, EFFICACY, AND PHARMACOKINETICS OF ARGX-113 IN 
PATIENTS WITH MYASTHENIA GRAVIS WHO HAVE GENERALIZED MUSCLE WEAKNESS 
 
 
 
 
 
AUTHOR: 
 
VERSION NUMBER AND DATE: V1.0, 06 OCT 2017 
 
 
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reproduction is strictly prohibited. 
MODIFICATION HISTORY 
 
Unique 
Identifier 
for 
this Version 
Date of the 
Document 
Version 
Author 
Significant 
Changes 
from 
Previous 
Authorized Version 
1.0 
06 Oct 2017 
 
Initial version after first draft review. 
 
 
 
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reproduction is strictly prohibited. 
TABLE OF CONTENTS 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ..................................................................... 7 
1. 
INTRODUCTION ........................................................................................................................ 9 
2. 
STUDY OBJECTIVES ................................................................................................................... 9 
2.1. 
Primary Objective ................................................................................................................................9 
2.2. 
Secondary Objectives ..........................................................................................................................9 
3. 
STUDY DESIGN ........................................................................................................................ 10 
3.1. 
General Description .......................................................................................................................... 10 
3.2. 
Schedule of Events ............................................................................................................................ 11 
3.3. 
Changes to Analysis from Protocol..................................................................................................... 11 
4. 
PLANNED ANALYSES .............................................................................................................. 11 
4.1. 
Independent Data Monitoring Committee (IDMC) ............................................................................. 11 
4.2. 
Interim Analysis................................................................................................................................. 11 
4.3. 
Final Analysis..................................................................................................................................... 11 
5. 
ANALYSIS SETS AND PRESENTATION OF DATA .................................................................... 12 
6. 
GENERAL CONSIDERATIONS .................................................................................................. 12 
6.1. 
Reference Start Date and Study Day .................................................................................................. 13 
6.2. 
Precision ........................................................................................................................................... 13 
6.3. 
Baseline ............................................................................................................................................ 14 
6.4. 
Unscheduled Visits and Early Termination Data ................................................................................. 14 
6.5. 
Windowing Conventions ................................................................................................................... 14 
6.6. 
Statistical Tests ................................................................................................................................. 14 
6.7. 
Common Calculations ........................................................................................................................ 14 
6.8. 
Software Version ............................................................................................................................... 15 
7. 
STATISTICAL CONSIDERATIONS ............................................................................................. 15 
7.1. 
Adjustments for Covariates and Factors to be Included in Analyses.................................................... 15 
7.2. 
Multicenter Studies ........................................................................................................................... 15 
7.3. 
Missing data ...................................................................................................................................... 15 
7.4. 
Multiple Comparisons/ Multiplicity.................................................................................................... 15 
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7.5. 
Examination of Subgroups ................................................................................................................. 15 
8. 
OUTPUT PRESENTATIONS ...................................................................................................... 16 
9. 
DISPOSITION AND WITHDRAWALS ....................................................................................... 16 
10. 
PROTOCOL DEVIATION .......................................................................................................... 16 
11. 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS ................................................. 17 
12. 
MEDICAL HISTORY .................................................................................................................. 17 
13. 
CONCOMITANT MEDICATIONS ............................................................................................. 17 
14. 
STUDY MEDICATION EXPOSURE ........................................................................................... 18 
15. 
EFFICACY OUTCOMES ............................................................................................................ 18 
16. 
SAFETY OUTCOMES ................................................................................................................ 19 
16.1. 
Adverse Events.................................................................................................................................. 19 
16.2. 
Suicidality Assessment ...................................................................................................................... 20 
16.3. 
Laboratory Evaluations ...................................................................................................................... 20 
16.4. 
ECG Evaluations ................................................................................................................................ 20 
16.5. 
Vital Signs ......................................................................................................................................... 21 
16.6. 
Physical Examination ......................................................................................................................... 21 
17. 
PHARMACOKINETIC ANALYSIS .............................................................................................. 21 
17.1. 
Pharmacokinetic Concentrations ....................................................................................................... 21 
17.2. 
Pharmacokinetic Parameters ............................................................................................................. 22 
18. 
PHARMACODYNAMIC OUTCOMES ....................................................................................... 24 
19. 
ADDITIONAL ASSESSMENT OF IMMUNOGLOBULINS .......................................................... 24 
20. 
ANTI-DRUG ANTIBODIES (ADA) ANALYSES ........................................................................... 25 
21. 
PHARMACOGENETIC OUTCOMES ......................................................................................... 25 
APPENDIX 1. PARTIAL DATE CONVENTIONS ..................................................................................... 26 
 
 
 
 
 
 
 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation  
Definition  
ACh  
Acetylcholine  
AChR  
Acetylcholine receptor  
ADA  
Anti-drug antibodies  
AE  
Adverse event  
AUCtau 
Area under the concentration-time curve during the dosing interval 
AUC0-infinity 
Area under the concentration time curve from time 0 extrapolated to infinity over the 
entire course of therapy 
BLQ 
Below the Limit of Quantification 
BMI  
Body Mass Index  
CI  
Confidence interval  
Cmax  
Maximum observed plasma concentration 
CSH 
Compound Symmetry Heterogeneous 
Ctrough  
Concentration observed at the end of the dosing interval  
ECG  
Electrocardiogram  
eCRF  
Electronic case report form  
ED 
Early Discontinuation 
EoS  
End-of-Study  
FAS  
Full analysis set  
Fc  
Fragment, crystallized  
FcRn  
Neonatal Fc receptor  
FU  
Follow-Up  
GCP  
Good Clinical Practice  
GCV  
Geometric coefficient of variation  
Gmean  
Geometric mean  
ICF  
Informed consent form  
ICH  
International Council for Harmonisation  
IDMC  
Independent Data Monitoring Committee  
IgG  
Immunoglobulin G  
IMP  
Investigational Medicinal Product  
IV  
Intravenous  
LLOQ  
Lower limit of quantification  
LS 
Least Squares 
MedDRA  
Medical dictionary for regulatory authorities  
MG  
Myasthenia Gravis  
MG-ADL  
Myasthenia Gravis activities of daily living  
MGC  
Myasthenia Gravis composite score  
MGFA  
Myasthenia Gravis Foundation of America  
MGQoL15r  
15-item Quality of life scale for Myasthenia Gravis [revised version]  
MMRM 
Mixed Model Repeated Measures 
PD  
Pharmacodynamics  
PK  
Pharmacokinetics  
 
 
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Abbreviation  
Definition  
PR interval  
Duration from the start of the T wave to the start of the QRS complex, representing 
the time taken for electrical activation (of the cardiac conduction system) to pass 
from the sinus node to the atrium, the atrioventricular node and the His-Purkinje 
system to the ventricle  
PT  
Preferred term  
QMG  
Quantitative Myasthenia Gravis score  
QRS interval  
Pertains to depolarization of ventricles  
QT interval  
Duration from the start of QRS interval to the end of the T wave, representing the 
time taken for depolarization and repolarization of the ventricular myocardium  
QTcF 
QT interval with Fridericia's correction
Rac  
Accumulation ratio  
Rsq 
Coefficient of determination 
SAE  
Serious adverse event  
SAP  
Statistical Analysis Plan  
SD  
Standard deviation  
SoC  
Standard of care  
SOC 
System Organ Class 
SOP  
Standard operating procedures  
t1/2,λz  
Apparent terminal half-life  
TEAE 
Treatment Emergent Adverse Events 
tmax  
The time of occurrence of Cmax  
UN 
Unstructured 
WHO-DD  
World Health Organization drug dictionary  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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reproduction is strictly prohibited. 
1. INTRODUCTION 
This document describes the statistical analyses to be performed and data presentations to be produced 
for this Randomized, Double-blind, and Placebo-Controlled Phase II Study to evaluate the Safety, Efficacy, 
and Pharmacokinetics of ARGX-113 in subjects with Myasthenia Gravis who have Generalized Muscle 
Weakness. 
The purpose of this statistical analysis plan (SAP) is to ensure the credibility of the study findings by 
specifying the statistical approaches to the analysis of double-blinded data prior to database lock. This 
SAP was developed based on the International Council for Harmonisation (ICH) E3 and E9 Guidelines 
and in reference to the Protocol ARGX-113-1602 v2 dated 28NOV2016. 
Any deviations during the analysis and reporting process from the current SAP will be described and 
justified in the final report. Analysis issues that suggest changes to the principal features stated in the 
protocol will be documented in a protocol amendment. Otherwise, the statistical analysis plan will be 
updated through an amendment with the changes in the analysis documented in the amendment. 
2. STUDY OBJECTIVES 
2.1. PRIMARY OBJECTIVE 
The primary objective is 
• 
To evaluate the safety and tolerability of ARGX-113. 
2.2. SECONDARY OBJECTIVES 
The secondary objectives are 
 
To evaluate the clinical effect of ARGX-113 using: 
o 
Myasthenia Gravis-Activities of Daily Living (MG-ADL) score. 
o 
Quantitative-Myasthenia Gravis score (QMG). 
o 
Myasthenia Gravis Composite score (MGC). 
 
To evaluate the impact of ARGX-113 on quality of life using the 15-item quality of life scale for 
Myasthenia Gravis (MGQoL15r [revised version]). 
 
To investigate the pharmacokinetics (PK) of ARGX-113. 
 
To assess the pharmacodynamic (PD) markers (e.g., total immunoglobulin G (IgG) and subtypes, 
anti-acetylcholine receptor [AChR] antibodies). 
 
To evaluate the immunogenicity of ARGX-113. 
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reproduction is strictly prohibited. 
3. STUDY DESIGN 
3.1. GENERAL DESCRIPTION 
This is a randomized, double-blind, placebo-controlled, multicenter Phase II study to evaluate the safety, 
tolerability, efficacy, pharmacokinetics, pharmacodynamics and immunogenicity of ARGX-113 for the 
treatment of autoimmune Myasthenia Gravis (MG) with generalized muscle weakness. 
Approximately 24 subjects will be randomized in a 1:1 ratio to receive either ARGX-113 (10 mg/kg) or 
matching placebo via intravenous (IV) infusion in addition to Standard of Care (SoC) over a period of 2 
hours during the treatment period, i.e. on Days 1 (Visit 1), 8±1 (Visit 3), 15±1 (Visit 5), and 22±1 (Visit 7). 
The Treatment period consists of 7 visits (of which the 3 visits between the weekly dosing visits are 
optional). 
A schematic of the study design is included as Figure 1. 
Figure 1: Schematic of Study Design 
                     
 
Placebo + Standard of Care* 
 
n=12* 
ARGX -113 (10 mg/Kg) + Standard of care*
n=12*
1 
Study Visit*** 
3 4**
10
8**
11
*Standard of care as defined in Summary of Study Design section of the protocol 
Screening/Baseline 
< 15 Days 
(Day -15 to Day -1) 
9
14
16
Dosing with ARGX-113 or  
Placebo at Visits 1, 3, 5, and 7 
Treatment period
(Visit 1 to Visit 7) 
Follow-Up period (Immediately after last 
Infusion at Visit 7 to Visit 16) 
12
2** 
6** 7
5
13**
15**
 
 
Randomiza
tion       
 
(1:1 ratio) 
 
Visit 1 
(Baseline) 
**Blood Sampling only and Intermediate Blood Sampling at Visits 2, 4, 6, and 8 is Optional 
***The allowed visit window between visits is ±1 day in the Treatment and Follow-Up period 
l
d
li
Stable dose of SoC 
before and during 
Screening Period 
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The study will include a screening period of at most 15 days, a treatment period of 3 weeks (4 infusions 
administered one week apart) from Visit 1 to Visit 7 and a follow-up (FU) period of 8 weeks starting after 
completion of Visit 7 to Visit 16. 
Although the FU period is from Visit 8 to Visit 16, the FU in fact starts immediately after the last 
Investigational Medicinal Product (IMP) infusion at Visit 7. 
The total dose per IMP infusion is capped at 1200 mg for subjects with body weight ≥ 120 kg 
3.2. SCHEDULE OF EVENTS 
Schedule of events can be found in Table 1 of the protocol. 
3.3. CHANGES TO ANALYSIS FROM PROTOCOL 
As per the protocol, the analysis of change from baseline in the efficacy rating scales is to be performed 
using Mixed Model Repeated Measures (MMRM) with fixed treatment, baseline score and subject as a 
random effect. This has been updated in Section 16 of the SAP to use MMRM model including treatment, 
visit and treatment x visit interaction terms as fixed effects, with baseline and baseline x visit terms as 
covariates and subject as random effect. 
4. PLANNED ANALYSES 
This Statistical Analysis Plan describes the methodology for final analysis and reporting. 
4.1. INDEPENDENT DATA MONITORING COMMITTEE (IDMC)  
Separate SAP and Mock shells are provided for the IDMC. 
4.2. INTERIM ANALYSIS  
No interim Analysis is planned for this study. 
4.3. FINAL ANALYSIS  
All final, planned analyses identified in this SAP will be performed by QuintilesIMS Biostatistics following 
Sponsor Authorization of this Statistical Analysis Plan, Database Lock, and Sponsor Authorization of 
Analysis Sets. 
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5. ANALYSIS SETS AND PRESENTATION OF DATA 
The analysis of data will be based on different analysis sets according to the purpose of the analysis in 
question. Data summaries will be presented by treatment and overall as appropriate. Listings will be 
presented for all the subjects available in the data transfer received from data management. 
The following analysis sets will be used. 
All Subjects 
Subjects who have signed the informed consent form and have been screened. 
Randomized Analysis Set 
Subjects who have been allocated to a randomized treatment arm, regardless of whether they received the 
planned treatment or not. 
 
Full Analysis Set (FAS) 
FAS is defined as all randomized subjects with at least one of the MG-ADL, QMG, MGC, and MGQoL15r 
scales available for one of the post-baseline assessments up to Visit 16 along with the corresponding 
baseline value. 
 
Safety Analysis Set 
The safety analysis set used for all safety analyses will comprise all subjects in the randomized population 
who received at least one dose or part of a dose. The safety analysis will be based on the actual treatment 
received. 
 
Pharmacokinetic (PK) Analysis Set 
The PK analysis set considered for PK analysis will comprise all subjects in the randomized population who 
have at least one plasma concentration data value available for ARGX-113 without major protocol deviations 
thought to impact PK. Subjects who did not receive IMP will not be included in the PK Analysis Set. 
 
Pharmacodynamic (PD) Analysis Set 
The PD analysis set considered for all PD analyses will comprise all subjects in the randomized population 
who have at least one non-missing post dose PD measurement available without major protocol deviations 
thought to impact PD. 
 
A listing will be presented to report the number of subjects in each Analysis set under each treatment arm. 
6. GENERAL CONSIDERATIONS 
The following descriptive statistics will be presented in summary tables: 
 
Continuous variables: number (valid cases), mean, median, standard deviation (SD), minimum, 
and maximum 
 
Categorical variables: summarized by treatment group using frequency tables (frequencies and 
percentages). Percentages are routinely based on the total within the group count excluding the 
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missing category if not otherwise mentioned. Missing category with zero count will not be 
presented. 
In general, the number of decimal places displayed for each statistic will be determined as follows: 
o 
Mean and median: 1 more than the number of decimal places allotted in the raw data 
received from data management. 
o 
SD: 2 more than the number of decimal places allotted in the raw data. 
o 
Minimum and maximum: equal to the number of decimal places allotted in the raw data. 
o 
Percentages: All percentages between 0% and 100% will be rounded to one decimal 
unless there is a need to report more than one decimal for percentages. 
o 
Ranges will be reported to the same number of decimal places displayed by the 
laboratory. 
6.1. REFERENCE START DATE AND STUDY DAY 
Reference start date is defined as the day of the first dose of study medication, (Day 1 is the day of the 
first dose of study medication), and will appear in every listing where an assessment date or event date 
appears. If Reference Start Date < Date of randomization, it will be considered as protocol deviation and 
detailed accordingly in the PD Log. 
Study Day will be calculated from the reference start date, and will be used to show start/ stop day of 
assessments and events. 
 
If the date of the event is on or after the reference date then:  
Study Day = (date of event – reference date) + 1. 
 
 
If the date of the event is prior to the reference date then:  
Study Day = (date of event – reference date). 
In the situation where the event date is partial or missing, Study Day, and any corresponding durations 
will appear partial or missing in the listings. 
6.2. PRECISION 
Safety variables (i.e. clinical laboratory values, vital signs, and ECG intervals), including derivations 
thereof will be reported to the same precision as the source data.  
All PK and PD concentrations will be reported and analysed with the same precision as the source data 
provided by the bio-analytical laboratory or clinical laboratory regardless of how many significant figures 
or decimals the data carry.  Time variables for PK/PD will have units of hour and have two decimal places, 
for source data used for calculation of PK/PD parameters, and for reporting in listings.  Derived PK 
parameters will be rounded for reporting purposes in by-subject listings.  The rounded derived PK 
parameter values in listings will be considered the source data for the calculation of descriptive statistics.  
For most derived PK/PD parameters, 3 significant digits will be used as the standard rounding procedure, 
with the following exceptions: 
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• 
Parameters directly derived from source data (e.g. Cmax) will be reported and analysed with 
the same precision as the source data. 
• 
Parameters derived from actual elapsed sample collection times (e.g., tmax) will be reported 
with the same precision as the actual elapsed sampling time value of the source data, 
normally 2 decimal places. 
For the reporting of descriptive statistics, the mean will be presented to one digit more precision than the 
source data.  Standard deviation will be presented to two digits more precision than the source data.   The 
minimum, median, and maximum, will be presented to the same precision as the source data.  Coefficient 
of variation and percentages will always be reported to 1 decimal place.   
6.3. BASELINE 
Unless otherwise specified, baseline is defined as the last non-missing measurement (including 
unscheduled assessments) taken prior to the reference start date and/or time. If the last non-missing 
measurement is recorded on the day of IP administration and is specified to be done pre-dose as per the 
protocol then it will be considered baseline. For Adverse Events/Concomitant Medications if start date 
and/or time of measurement and IP administration coincide, that measurement will be considered as post-
baseline. 
6.4. UNSCHEDULED VISITS AND EARLY TERMINATION DATA 
In general, for by-visit summaries, data recorded at the nominal visit (including optional visits) will be 
presented. Unscheduled measurements will not be included in by-visit summaries and efficacy analyses. 
Early termination data will be mapped to the next available visit number for by-visit summaries. 
Listings will include scheduled, unscheduled, retest and early termination data. 
6.5. WINDOWING CONVENTIONS 
No visit windowing will be performed for this study. 
6.6. STATISTICAL TESTS 
The default significance level will be (5%); confidence intervals will be 95% and all tests will be two-sided, 
unless otherwise specified in the description of the analyses. 
6.7. COMMON CALCULATIONS 
For quantitative measurements, change from baseline will be calculated as: 
 
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 
Test Value at Visit X – Baseline Value 
6.8. SOFTWARE VERSION 
For tables, listings and graphs SAS ® version 9.4 will be used. 
Non-compartmental PK parameter calculations will be performed using Phoenix® WinNonlin® 6.4 or 
higher (Certera, Princeton, New Jersey). 
Figures may be prepared using SAS®, Phoenix® WinNonlin®, or SigmaPlot 12.5 or higher (Systat 
Software, Inc., San Jose, California, United States). 
7. STATISTICAL CONSIDERATIONS 
7.1. ADJUSTMENTS FOR COVARIATES AND FACTORS TO BE INCLUDED IN ANALYSES 
Baseline will be used as covariate in all analyses of change from baseline MG data. Wherever appropriate 
baseline x visit term will be included in the analysis. In case of non-convergence, baseline*visit term will 
be excluded from the model and/or an appropriate covariance matrix will be used. 
7.2. MULTICENTER STUDIES 
This study will be conducted by multiple investigators at multiple sites. However, because of the small 
sample size (12 subjects planned per treatment group) analysis models will not include the factor center. 
7.3. MISSING DATA 
Missing safety and efficacy data will not be imputed. For efficacy data the missing data handling approach 
will be based on MMRM. 
7.4. MULTIPLE COMPARISONS/ MULTIPLICITY 
No adjustment is made for multiplicity since this is an exploratory study and no confirmatory hypothesis 
testing is performed. 
7.5. EXAMINATION OF SUBGROUPS 
No subgroup analyses will be performed for this study. 
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8. OUTPUT PRESENTATIONS 
The Mock Shells provided with this SAP describe the format, layout and content of the summary tables, 
figures and listings to be provided by QuintilesIMS Biostatistics. This document will be a working 
document and updates will be documented in its modification history. 
All visit assessments will be presented according to the nominal visit name. Study populations will be 
summarized and listed as well. 
9. DISPOSITION AND WITHDRAWALS 
All subjects who provide informed consent will be accounted for in this study. 
Data collected on Early Termination (ET) and End of Study (EOS) in the electronic Case Report Form 
(eCRF) will be used to present disposition and withdrawal results. Frequency tables will be provided for: 
- 
number of subjects who provided informed consent 
- 
number of subjects randomized 
- 
number of subjects treated with at least one dose of study medication  
- 
number of subjects who completed the treatment period with minimum of 2 weeks FU 
- 
number of subjects who completed the study 
- 
number of subjects still ongoing in the study 
- 
number of subjects who discontinued the study 
- 
primary reason for discontinuation of the study 
- 
number of subjects who discontinued the treatment 
- 
primary reason for treatment discontinuation 
A listing will be presented of dates of Screening, randomization, screen failure with reason, completion or 
early discontinuation/withdrawal and the reason for early discontinuation, if applicable, for each subject. 
10. PROTOCOL DEVIATION 
All protocol deviations/violations observed during study conduct will be captured in Clinical Trial 
Management System (CTMS). 
QuintilesIMS and sponsor will review the protocol deviation records from CTMS and provide confirmation 
of the categorization of deviations as minor, major or critical. 
A frequency table for major protocol deviations will be provided. The listing of all protocol deviations will 
be presented. 
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11. DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS 
Demographic data and other baseline characteristics will be presented for the Randomized population. 
The Summary statistics will be provided for: 
 
Age (years) 
 
Weight (kg) 
 
Height (cm) 
 
BMI (kg/m2) 
 
Frequency tables will be provided for: 
 
Sex 
 
Ethnicity 
 
Race 
 
A listing for subject demographic data and other baseline characteristics; including Weight, Height and 
BMI will be presented. 
12. MEDICAL HISTORY 
Medical History will be presented for the Safety population and coded using Medical Dictionary for 
Regulatory Activities (MedDRA) coding dictionary version 19.1. Medical History conditions are defined as 
those conditions which stop prior to or at Screening. 
Frequency tables (presented by System Organ Class (SOC) and Preferred Term (PT) and Listings will be 
provided for the Safety Population. Myasthenia Gravis History including information about MGFA 
classification, anti-ACHr antibodies testing, neuromuscular transmission test, edrophonium chloride test and 
improvement on MG signs on oral cholinesterase will be listed and summarized for the Safety Population. 
13. CONCOMITANT MEDICATIONS 
Prior and concomitant medications will be presented for the Safety Analysis Set. A frequency table will be 
provided for all medications by Anatomic, therapeutic and chemical classification (ATC) Level 1 and 3. A 
separate frequency table will be provided for Myasthenia Gravis therapy medications. All medications will 
be coded by the WHO Drug Dictionary version Dec 2016. 
See Appendix 1 for handling of partial dates for medications. If it is not possible to define a medication as 
either prior or concomitant, the medication will be classified by the worst case; i.e. concomitant. 
- 
‘Prior’ medications are medications which started and stopped prior to the first dose of study 
medication. 
- 
‘Concomitant’ medications are medications which: 
o 
started prior to, on or after the first dose of study medication 
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o 
AND ended on or after the date of first dose of study medication or were ongoing at the end 
of the study. 
Listings of medications and of MG therapy given to subjects with all details will be presented. 
14. STUDY MEDICATION EXPOSURE 
Study medication exposure will be presented for the Safety Analysis Set. A listing of exposure to study 
medication in days will be presented along with details of start and end time of infusion, interruptions, total 
volume administered, prematurely stopped and whether subject remained at the site for 2 hours after end 
of infusion. A summary of exposure to report the number of completed infusions and a separate listing to 
show any overdoses will be presented. 
15. EFFICACY OUTCOMES 
All efficacy analysis will be performed using FAS. The following summaries and corresponding listings will 
be provided for the efficacy results: 
• 
Summary of scores and change from baseline by visit, at each post baseline visit for 
- 
Myasthenia Gravis-Activities of Daily Living (MG-ADL) score 
- 
Quantitative-Myasthenia Gravis score (QMG) 
- 
Myasthenia Gravis Composite score (MGC) 
- 
Quality of life using 15-item quality of life scale for Myasthenia Gravis (MGQoL15r [revised 
version]) 
• 
Maximum reduction in score from baseline across visit days for MG-ADL, QMG, MGC, and 
MGQoL15r score. 
The analyses of data derived from the various scales (MG-ADL, QMG, MGC, and MGQoL15r) will be based 
on the FAS. Actual score, change from Baseline and maximum reduction from Baseline will be summarized 
descriptively. 
Analyses of change from baseline by visit will be performed using a mixed-model repeated measures 
(MMRM) analysis from Visit 1 to Visit 16. The model will include treatment, visit and treatment x visit 
interaction terms as fixed effects, with baseline and baseline x visit terms as covariates. If the baseline x 
visit term is found to be not significant then it can be excluded from the model. An unstructured (UN) 
covariance matrix for the repeated measures within subject will be specified for the analysis* and the 
following statistics will be presented for each visit: 
- 
Least Square (LS) Means per treatment group 
- 
Standard error of LS Means 
- 
95% confidence interval (CI) 
- 
LS Mean Difference (ARGX-113 – Placebo) 
- 
Standard error of LS Mean Difference 
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- 
95% confidence interval (CI) for LS Mean Difference 
- 
p-value for testing differences between treatment groups 
*If the model does not converge upon using UN, a simpler covariance matrix like CSH (not restrictive) will 
be used instead. 
 
A box plot for change from baseline of ARGX and Placebo will be presented across visits. A box plot also 
presented for maximum reduction from baseline score. 
 
 Analysis of maximum reduction in scores will be performed using ANCOVA with baseline score as a 
covariate and treatment as fixed factor. 
16. SAFETY OUTCOMES 
All outputs for safety outcomes will be based on the Safety Analysis Set. 
There will be no statistical tests performed for differences between the treatment groups with regards to 
safety data. 
16.1. ADVERSE EVENTS 
Adverse Events (AEs) will be coded using MedDRA central coding dictionary, Version 19.1. 
Treatment-emergent AEs are defined as AEs that first occurred or worsened in severity after the first 
administration of the IMP. Any AEs started after the informed consent form has been signed and before 
the first administration of the IMP will be considered as Non-TEAEs. 
The relationship to study drug will be summarized as related and unrelated. AEs that are recorded as 
‘related’, ’possibly’ or ‘probable’ in the eCRF are categorized as ‘related’ whereas the AEs that are 
recorded as ‘unrelated’ and ‘unlikely’ are categorized as ‘unrelated’. Missing relationship/missing severity 
would be considered by the worst case as "Related" and "Grade 5" respectively. 
Listings will include TEAEs and Non-TEAEs. Separate listing will be provided for AEs leading to 
discontinuation, serious adverse events (SAEs) and deaths. 
For each treatment group, TEAEs, non-TEAEs, drug related AEs, relationship to study drug, AEs leading 
to discontinuation and SAEs will be summarized by primary SOC and PT. Also, summary of National 
Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 4.03) will be 
presented by primary SOC and PT. AE tables include number and percentage of subjects and number of 
events. 
An overall summary of adverse events will be produced including frequency counts of: 
- 
number of subjects with at least one TEAE 
- 
number of subjects with at least one non-TEAE 
- 
number of subjects with at least one serious TEAE 
- 
number of subjects withdrawn from treatment with at least one serious TEAE 
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- 
number of subjects with at least one related serious TEAE 
- 
number of subjects who discontinue from the study due to a TEAE 
- 
number of subjects with at least one TEAE with CTCAE severity grade >=3 
- 
number of subjects with at least one related TEAE 
- 
number of deaths 
16.2. SUICIDALITY ASSESSMENT  
A separate listing for suicidality assessment will also be presented. 
16.3. LABORATORY EVALUATIONS 
Results from both the central and local laboratory will be included in the reporting. Central laboratory 
results will be reported for hematology, clinical chemistry and urinalysis. A list of laboratory assessments 
to be included in the outputs is given in the protocol. 
A summary will be provided for the incidence of abnormal values according to normal range criteria for 
the laboratory data. A listing of subjects with values outside the normal range in question will be presented. 
Urinalysis quantitative results will be summarized with descriptive statistics and qualitative results will be 
presented with frequency and percentages. All the results will be listed as well. 
All parameters will be summarized descriptively and shift tables will be presented for categorical data. 
Hematology, Clinical Chemistry, Urinalysis and other tests with numeric data will be presented graphically. 
16.4. ECG EVALUATIONS 
The following ECG parameters will be summarized descriptively: 
• 
Heart Rate (bpm) 
• 
PR Interval (msec) 
• 
QRS Interval (msec) 
• 
QT Interval (msec) 
• 
QTcF Interval (msec) 
 
The overall assessment of the ECG (Investigator’s judgment) will be summarized with frequency and 
percentage for the following categories: 
o 
Normal 
o 
Abnormal, Not Clinically Significant (ANCS) 
o 
Abnormal, Clinically Significant (ACS) 
 
 
 
 
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Absolute values for QT and QTcF intervals will be classified as: 
- 
>=450 msec 
- 
>=480 msec 
- 
>=500 msec 
 
Change from Baseline for QT and QTcF intervals will be classified as: 
- 
>30 msec 
- 
>60 msec 
A listing for all ECG parameters will also be presented. 
16.5. VITAL SIGNS 
The following Vital Signs measurements will be summarized descriptively: 
- 
Systolic Blood Pressure (mmHg) 
- 
Diastolic Blood Pressure (mmHg) 
- 
Heart Rate (bpm) 
- 
Oral Body Temperature (⁰C) 
- 
Weight (kg) 
Listings will be provided for above vital signs parameters. 
16.6. PHYSICAL EXAMINATION  
The frequency (percentage) table for physical examinations along with a shift table of clinically significant 
findings will be summarized by body system. All the collected data will be listed as well. 
17. PHARMACOKINETIC ANALYSIS 
All PK analysis will be performed using PK Analysis Set. 
17.1. PHARMACOKINETIC CONCENTRATIONS 
A listing of PK blood sample collection times as well as derived sampling time deviations will be provided. 
A subject listing of all concentration-time data will be presented. Individual subject concentration-time data 
will be graphically presented on linear and semi-logarithmic scales. 
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Plasma concentrations of ARGX-113 will be summarized by nominal time point using the following 
statistics: 
 
Number of observations (n)  
 
Number of observations ≥ lower limit of quantification (LLOQ)  
 
Arithmetic mean  
 
SD 
 
Geometric mean 
 
Geometric SD 
 
Minimum  
 
Median 
 
Maximum 
If warranted by the data, concentrations may be further summarized by ADA presence. Concentrations 
of ARGX-113 that are below the limit of quantification (BLQ) will be set to the lower limit of quantification 
(LLOQ) for the computation of descriptive statistics. A figure of geometric mean concentration-time (in 
days) data (±SD, as appropriate; from the start of the first infusion) will be presented on linear and 
semi-logarithmic scales. 
17.2. PHARMACOKINETIC PARAMETERS 
For PK parameter calculations, Visit 1 pre-dose samples that are BLQ or missing will be assigned a 
numerical value of zero.  Any anomalous concentration values observed at pre-dose on Visit 1 will be 
identified in the study report and used for the computation of PK parameters.  Pharmacokinetic 
parameters will be computed if the pre-dose anomalous concentration is not greater than 5% of the 
observed maximum concentration (Cmax).  If a pre-dose concentration value on Visit 1 is greater than 5% 
of Cmax in the profile, PK parameters for the profile shall not be included in the summaries but will be 
calculated and listed. Additionally, these anomalous pre-dose concentrations will be flagged in the 
concentration listings, with different symbols for those greater than or less than 5% of Cmax.  
Following Cmax, BLQ values embedded between 2 quantifiable data points will be treated as missing when 
calculating PK parameters for Visit 7.  If a BLQ value occurs at the end of the collection interval (after the 
last quantifiable concentration), it will be set to zero.  If consecutive BLQ concentrations are followed by 
quantifiable concentrations in the terminal portion of the concentration curve on Visit 7, these quantified 
values will be excluded from the PK analysis by setting them to missing, unless otherwise warranted by 
the concentration-time profile.   
The following PK parameters will be estimated for ARGX-113 by non-compartmental methods using 
actual elapsed time from start of dosing after Visits 1, 3, 5 and 7:  
Cmax 
maximum observed plasma concentration. If the end of infusion sample is collected more 
than one hour post infusion, Cmax will be listed only and not included in summaries.  
tmax 
the time of occurrence of Cmax 
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Ctrough 
plasma concentration observed at the end of the dosing interval at Visits 3, 5 7, and 9. 
These concentrations will be included in summaries regardless of sampling time deviation.  
t1/2,z 
the apparent terminal half-life, calculated from (ln 2)/λz (Visit 7 only) 
Rac 
accumulation ratio, calculated as Visit 7 Cmax /Visit 1 Cmax 
AUCtau 
area under the concentration-time curve during the dosing interval. This parameter will be 
determined for each active subject and dose if there are two quantifiable postdose 
concentrations available. If the end of infusion sample is collected more than one hour 
post infusion, AUCtau will be listed only and not included in summaries. 
AUC0-infinity 
area under the concentration-time curve from time 0 (pre-infusion on Day 1 Visit 1) 
extrapolated to infinity over the entire course of therapy using time elapsed from the start 
of the first infusion. If the extrapolated area is greater than 20% of AUC0-infinity, then 
AUC0-infinity will be listed but not summarized.  
 
Subjects with partial data will be evaluated on a case-by-case basis to determine if sufficient data are 
available for reliable estimation of PK parameters. 
The following summary statistics will be presented for all the PK parameters except for tmax : 
 
Geometric Mean 
 
Geometric Coefficient of Variation (GCV) % (calculated as GCV = 100 * sqrt { exp(s2) – 1 }, where 
‘s’ is the SD of the data on a log scale. 
 
Arithmetic mean  
 
SD  
 
Minimum 
 
Median 
 
Maximum 
 
Number of observations 
For tmax the following summary statistics will be presented: 
 
Number of observations 
 
Median 
 
Minimum 
 
Maximum 
If warranted by the data, PK parameters may be further summarized by ADA presence.  
 
 
 
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The following PK parameters will be calculated for Visit 7 for diagnostic purposes and listed, but will not 
be summarized. 
t1/2, Interval 
The time interval (h) of the log-linear regression to determine z. 
t1/2, N 
Number of data points included in the log-linear regression analysis to determine 
z.   
Rsq 
Coefficient of determination for calculation of z (Regression coefficient).  If Rsq 
< 0.800, then z and related parameters will be listed but not included in summary 
statistics. 
18. PHARMACODYNAMIC OUTCOMES 
Pharmacodynamic analysis will be performed using the PD Analysis Set (unless specified differently 
underneath). Pharmacodynamic endpoints include observed, change from baseline (post baseline value 
– baseline value), and percent change from baseline ((change from baseline/baseline) *100%) total IgG, 
IgG subtypes (IgG 1, IgG 2, IgG 3 and IgG 4), and binding and blocking anti-AChR antibodies. See Section 
6.3 for baseline definition. 
Observed, change from baseline, and percent change from baseline values for all PD endpoints will be 
listed and summarized with descriptive statistics including geometric mean. Frequency table for 
percentage drop in IgG for ARGX-113 below cut-off per visit will be presented. Same table will be 
presented for subjects with QMG and MG-ADL clinical significant improvement. QMG clinical significant 
improvement means a drop of at least 3 points as compared to baseline and MG-ADL clinical significant 
improvement means a drop of at least 2 points as compared to baseline.  For these mentioned frequency 
tables, FAS will be used. 
Plots of geometric mean (±SD) percent change from baseline by treatment will be presented for each PD 
marker. Plot of evolution of percentage drop in IgG from baseline (mean +/- stderr) and delta QMG (mean 
+/- stderr) in function of visit will also presented. Same plot will also be made for evolution of drop in IgG 
from baseline and delta MG-ADL, delta MGC and MGQoL15r in function of visit. For these evolution plots, 
FAS will be used. Plots will be made for ARGX-113 and for Placebo separately. 
19. ADDITIONAL ASSESSMENT OF IMMUNOGLOBULINS 
The observed, change from baseline, and percent change from baseline of IgA, IgM, IgE and IgD will be 
listed and summarized with descriptive statistics, using PD Analysis Set.  
See Section 6.3 for baseline definition. 
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20. ANTI-DRUG ANTIBODIES (ADA) ANALYSES 
ADA will be summarized by frequency and percentages of response, using PD Analysis Set. The following 
statistics will be presented for ADA response for each treatment 
- 
Proportion 
- 
95% Confidence Interval of Proportion (using Clopper-Pearson exact method) 
- 
Difference in proportions (ARGX-113 – Placebo) 
- 
95% CI of Difference 
- 
p-value (using Fisher’s Exact Test) 
21. PHARMACOGENETIC OUTCOMES 
For subjects who signed a separate Pharmacogenetic ICF, FcRn polymorphisms will be examined as a 
part of exploratory assessments. Assessment of FcRn polymorphism will be done to examine the gene 
sequence, gene expression, transcription and polymorphism. No genetic testing or genetic profiling will 
be done. 
Descriptive statistics will be used to study the genetic makeup of these subjects. Any categorical variables 
(if available) will be summarized by frequency (percentage) under each category. A listing of all 
Pharmacogenetic outcomes will be presented. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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APPENDIX 1. PARTIAL DATE CONVENTIONS 
Imputed dates will NOT be presented in the listings. 
Algorithm for Treatment Emergence of Adverse Events: 
 
START DATE 
STOP 
DATE 
ACTION 
Known 
Known 
If start date and time < study med start date and time, 
then not TEAE 
If start date and time >= study med start date and time, 
then TEAE 
 
Partial 
If start date and time < study med start date and time, 
then not TEAE 
If start date and time >= study med start date and time, 
then TEAE 
 
Missing 
If start date and time < study med start date and time, 
then not TEAE 
If start date and time >= study med start date and time, 
then TEAE 
 
 
 
Partial, 
but 
known 
components show that it 
cannot be on or after 
study med start date and 
time 
Known 
Not TEAE 
 
Partial 
Not TEAE 
 
Missing 
Not TEAE 
 
 
 
Partial, could be on or 
after study med start date 
and time 
Known 
If stop date and time < study med start date and time, 
then not TEAE 
If stop date and time >= study med start date and time, 
then TEAE 
 
Partial 
Impute stop date and time as latest possible date and 
time (i.e. last day of month if day unknown or 31st 
December if day and month are unknown), then: 
If stop date and time < study med start date and time, 
PPD
CCI
CCI
CCI


 
 
Statistical Analysis Plan 
 
 
 
ARGX-113-1602 
Page 27 of 28 
 
Document: 
 
Author: 
 
Version Number: 
                                 1.0 
 
 
Version Date: 
                            06 Oct 2017 
Template No:  
 
Reference:  
 
Effective Date: 01Apr2016 
 
Copyright © 2009, 2010, 2012, 2016 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited. 
START DATE 
STOP 
DATE 
ACTION 
then not TEAE 
If stop date and time >= study med start date and time, 
then TEAE 
 
Missing 
Assumed TEAE 
 
 
 
Missing 
Known 
If stop date and time < study med start date and time, 
then not TEAE 
If stop date and time >= study med start date and time, 
then TEAE 
 
Partial 
Impute stop date and time as latest possible date and 
time (i.e. last day of month if day unknown or 31st 
December if day and month are unknown), then: 
If stop date and time < study med start date and time, 
then not TEAE 
If stop date and time >= study med start date and time, 
then TEAE 
 
Missing 
Assumed TEAE 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PPD
CCI
CCI
CCI


 
 
Statistical Analysis Plan 
 
 
 
ARGX-113-1602 
Page 28 of 28 
 
Document: 
 
Author: 
 
Version Number: 
                                 1.0 
 
 
Version Date: 
                            06 Oct 2017 
Template No:  
 
 
Effective Date: 01Apr2016 
 
Copyright © 2009, 2010, 2012, 2016 Quintiles Transnational Corp. All rights reserved. 
The contents of this document are confidential and proprietary to Quintiles Transnational Corp. Unauthorized use, disclosure or 
reproduction is strictly prohibited. 
Algorithm for Prior / Concomitant Medications:  
 
START 
DATE 
STOP 
DATE 
ACTION 
Known 
Known 
If stop date < study med start date, assign as prior  
If stop date >= study med start date, assign as concomitant 
 
Partial 
Impute stop date as latest possible date (i.e. last day of month if day 
unknown or 31st December if day and month are unknown), then: 
If stop date < study med start date, assign as prior 
If stop date >= study med start date, assign as concomitant 
 
Missing 
If stop date is missing could never be assumed a prior medication hence 
assign as concomitant. 
 
 
 
Partial 
Known 
Impute start date as earliest possible date (i.e. first day of month if day 
unknown or 1st January if day and month are unknown), then: 
If stop date < study med start date, assign as prior 
If stop date >= study med start date, assign as concomitant 
 
Partial 
Impute start date as earliest possible date (i.e. first day of month if day 
unknown or 1st January if day and month are unknown) and impute stop 
date as latest possible date (i.e. last day of month if day unknown or 31st 
December if day and month are unknown), then: 
If stop date < study med start date, assign as prior 
If stop date >= study med start date, assign as concomitant 
 
Missing 
Impute start date as earliest possible date (i.e. first day of month if day 
unknown or 1st January if day and month are unknown), then: 
If stop date is missing could never be assumed a prior medication hence 
assign as concomitant. 
 
 
 
Missing 
Known 
If stop date < study med start date, assign as prior 
If stop date >= study med start date, assign as concomitant 
 
Partial 
Impute stop date as latest possible date (i.e. last day of month if day 
unknown or 31st December if day and month are unknown), then: 
If stop date < study med start date, assign as prior 
If stop date >= study med start date, assign as concomitant 
 
Missing 
Assign as concomitant 
 
PPD
CCI
CCI
CCI