A Multicenter, Prospective, Open-label, Non-controlled Clinical Trial to Assess the Efficacy and Safety of Immune Globulin (Human), 10% Caprylate/Chromatography Purified (IGIV-C) in Patients With Myasthenia Gravis Exacerbations
Phase: PHASE3
Conditions: Myasthenia Gravis Exacerbations
Sponsor: Grifols Therapeutics LLC

ClinicalTrials.gov ID: NCT02413580

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Summary of Changes for Amendment 3 
Protocol Version 
Date of Approval 
4.0 
Amendment 3 + Integrated Protocol 
30 Mar 2016 
3.0 
Amendment 2 + Integrated Protocol 
03 Sep 2015 
2.0 
Amendment 1 + Integrated Protocol 
June 19, 2014 
1.0 
Original 
February 27, 2014 
 
Amendment 3 
The protocol for GTI1305 (Protocol Amendment 2, Version 3.0, dated 03 Sep 2015) has 
been amended and reissued as Protocol Amendment 3, Version 4.0, dated 30 Mar 2016. See 
Appendix 8 for a summary of changes for Amendment 3. 

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Investigator Signature Page 
The undersigned confirms that he/she agrees to conduct the study under the conditions 
described in this protocol and comply with International Conference on Harmonization 
Good Clinical Practice (ICH GCP) and all applicable regulatory requirements: 
 
 
___________________________________  
______________________ 
INVESTIGATOR NAME (Please Print)  
 
LOCATION 
 
 
___________________________________  
______________________ 
INVESTIGATOR SIGNATURE  
 
 
 
DATE 
 

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TABLE OF CONTENTS 
GLOSSARY AND ABBREVIATIONS....................................................................................8 
1 
INTRODUCTION ...........................................................................................................10 
1.1 
Myasthenia Gravis Exacerbations ..........................................................................10 
1.2 
Management of MG Exacerbations .......................................................................10 
1.3 
Immune Globulin (Human), 10% Caprylate/Chromatography Purified (IGIV-
C)............................................................................................................................12 
1.4 
Study Rationale and Dose Selection ......................................................................12 
1.4.1 
Study Rationale ............................................................................................12 
1.4.2 
Dose Rationale .............................................................................................12 
2 
STUDY OBJECTIVES ....................................................................................................13 
2.1 
Efficacy Objectives ................................................................................................13 
2.1.1 
Primary Objective ........................................................................................13 
2.1.2 
Secondary Objectives ...................................................................................13 
2.1.3 
Exploratory Objectives ................................................................................13 
2.2 
Safety Objective .....................................................................................................14 
3 
INVESTIGATIONAL PLAN ..........................................................................................14 
3.1 
Study Design and Plan ...........................................................................................14 
3.2 
Selection of Study Population ................................................................................14 
3.2.1 
Inclusion Criteria .........................................................................................15 
3.2.2 
Exclusion Criteria ........................................................................................15 
3.3 
Treatments..............................................................................................................16 
3.3.1 
Treatment to be administered .......................................................................16 
3.3.1.1 
Immune Globulin (Human), 10% Caprylate/Chromatography 
Purified (IGIV-C)...............................................................................16 
3.3.1.2 
Labeling of Investigational Product ...................................................17 
3.3.1.3 
Storage of Investigational Product .....................................................17 
3.3.1.4 
Preparation .........................................................................................17 
3.3.1.5 
Accountability for Investigational Product ........................................17 
3.3.2 
Rationale for Selection of Doses/Timing of Investigational Product in 
the Study ......................................................................................................18 
3.3.2.1 
Selection of IGIV-C Dose and Interval in the Study .........................18 
3.3.3 
Method of Assigning Subjects to Treatment Groups ...................................18 
3.3.3.1 
Subject Numbering ............................................................................18 
3.3.3.2 
Blinding..............................................................................................18 
3.3.3.3 
Administration and Timing of Investigational Products for Each 
Subject................................................................................................18 
3.3.3.4 
Treatment Compliance .......................................................................18 
3.4 
Prior and Concomitant Therapy .............................................................................19 
3.4.1 
Prohibited Medications Prior to Study Participation ...................................19 

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3.4.2 
Prohibited Concomitant Medications during the Study ...............................19 
3.4.3 
Restricted Concomitant Medications during the Study ...............................19 
3.5 
Efficacy Study Variables .......................................................................................20 
3.5.1 
Primary Variable ..........................................................................................20 
3.5.2 
Secondary Variables ....................................................................................20 
3.5.3 
Exploratory Variables ..................................................................................20 
3.5.4 
Quantitative Myasthenia Gravis Scale (QMG) ............................................20 
3.5.5 
MG Composite Scale ...................................................................................21 
3.5.6 
MG-ADL......................................................................................................21 
3.6 
Safety Study Variables ...........................................................................................21 
3.6.1 
Thromboembolic Events Risk......................................................................22 
3.6.2 
Hemolysis Detection ....................................................................................22 
3.7 
Assessments ...........................................................................................................22 
3.7.1 
Assessment Periods ......................................................................................22 
3.7.2 
Observations and Measurements .................................................................22 
3.7.2.1 
Treatment and Post-infusion Follow-up Phase ..................................23 
3.7.3 
Description of Laboratory Tests and Procedures .........................................29 
3.7.3.1 
Thromboembolic Events Risk Testing...............................................30 
3.7.3.2 
Hemolysis Testing .............................................................................30 
3.7.3.3 
Virus Safety Testing ..........................................................................30 
3.7.3.4 
AChR Antibody (or MuSK) Testing..................................................30 
3.7.3.5 
IgG Concentration Measurements .....................................................31 
3.7.3.6 
Biomarker Testing .............................................................................31 
3.8 
Screen Failures .......................................................................................................31 
3.9 
Removal of Subjects ..............................................................................................31 
3.10 
Follow-up of Subjects Withdrawn from Study ......................................................32 
3.11 
Premature Termination of Study/Closure of Center ..............................................32 
4 
ADVERSE EVENTS .......................................................................................................32 
4.1 
Warnings/Precautions ............................................................................................32 
4.1.1 
Interaction/Overdose ....................................................................................32 
4.1.2 
Preparation and Handling ............................................................................32 
4.1.3 
Live Viral Vaccines .....................................................................................32 
4.2 
Specification of Safety Parameters ........................................................................33 
4.3 
Methods and Timing for Assessing, Recording and Analyzing Safety 
Parameters ..............................................................................................................33 
4.3.1 
Adverse Events ............................................................................................33 
4.3.2 
Vital Signs ....................................................................................................33 
4.3.3 
Physical Assessment ....................................................................................34 
4.3.4 
Blood Biochemistry and Haematological Parameters .................................34 
4.3.5 
Thromboembolic Events Risk......................................................................34 

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4.3.6 
Hemolysis ....................................................................................................34 
4.4 
Procedures for Eliciting Reports of and for Recording and Reporting Adverse 
Events and Intercurrent Illnesses ...........................................................................34 
4.4.1 
Adverse Event ..............................................................................................34 
4.4.2 
Suspected Adverse Drug Reaction (ADR)/Adverse Reaction (AR) ............35 
4.4.3 
Causality of Adverse Event .........................................................................35 
4.4.4 
Intensity of Adverse Event or Suspected Adverse Drug Reaction ..............36 
4.4.5 
Expectedness of Adverse Event or Suspected Adverse Drug Reaction ......36 
4.4.6 
Seriousness of Adverse Event or Suspected Adverse Drug Reaction; 
Serious Adverse Event .................................................................................37 
4.4.6.1 
Serious Adverse Event Management .................................................37 
4.4.6.2 
Hospitalization or Prolongation of Hospitalization ...........................38 
4.4.7 
Adverse Events of Special Interest ..............................................................38 
4.4.7.1 
Thromboembolic events.....................................................................38 
4.4.7.2 
Hemolysis ..........................................................................................38 
4.4.8 
Procedures for Eliciting Reports of and for Recording and Reporting 
Adverse Events and Suspected Adverse Drug Reactions ............................38 
4.4.9 
Timelines and Reporting of Serious Adverse Events ..................................39 
4.4.10 
Type and Duration of the Follow-Up of Subjects after Adverse Event or 
Suspected ADR ............................................................................................40 
5 
STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE ................40 
5.1 
Statistical and Analytical Plans ..............................................................................40 
5.1.1 
Subject Population(s) for Analysis ..............................................................40 
Safety Population ...............................................................................................................40 
Evaluable Population .........................................................................................................40 
5.1.2 
Demographic and Baseline Characteristics .................................................41 
5.1.3 
Efficacy Analyses ........................................................................................41 
5.1.3.1 
Primary Efficacy Analyses ................................................................41 
5.1.3.2 
Secondary Efficacy Analyses ............................................................41 
5.1.3.3 
Exploratory Efficacy Analyses ..........................................................41 
5.1.4 
Safety Analyses ............................................................................................42 
5.2 
Determination of Sample Size ...............................................................................43 
6 
ADMINISTRATIVE .......................................................................................................44 
6.1 
Investigators, Other Study Personnel and External Committees ...........................44 
6.2 
Data Quality ...........................................................................................................44 
6.3 
Documentation .......................................................................................................44 
6.3.1 
Record Retention .........................................................................................44 
6.3.2 
Access to Information for Monitoring .........................................................45 
6.3.3 
Access to Information for Audits or Inspections .........................................45 
7 
ETHICAL AND LEGAL ASPECTS ...............................................................................45 

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7.1 
Institutional Review Board/Ethics Committee ......................................................45 
7.2 
Ethical Conduct of the Study .................................................................................46 
7.3 
Regulatory Authority Approvals/Authorizations ...................................................46 
7.4 
Subject Information and Informed Consent Form .................................................46 
7.5 
Insurance ................................................................................................................47 
7.6 
Confidentiality .......................................................................................................47 
8 
USE OF DATA AND PUBLICATION ..........................................................................47 
9 
REFERENCES ................................................................................................................49 
10 APPENDICES .................................................................................................................53 
 
LIST OF APPENDICES 
Appendix 1 
Schedule of Study Procedures ...................................................................54 
Appendix 2 
MGFA Clinical Classification ...................................................................56 
Appendix 3 
QMG Test Items ........................................................................................57 
Appendix 4 
MG Composite Scale .................................................................................58 
Appendix 5 
MG Activities of Daily Living (MG-ADL) Profile ...................................59 
Appendix 6 
Monitoring of Thromboembolic Events Risk ............................................60 
Appendix 7 
Hemolysis Detection ..................................................................................64 
Appendix 8 
Summary of Changes for Amendment 2 ...................................................66 
 

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GLOSSARY AND ABBREVIATIONS 
AAN 
American Academy of Neurology 
AChR 
Acetylcholine receptor 
AE 
Adverse event 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
AR 
Adverse reaction 
ARC 
Absolute reticulocyte count  
AST 
Aspartate aminotransferase 
B19V 
Parvovirus B19 
Breg 
Regulatory B cell 
BUN 
Blood urea nitrogen 
CBC 
Complete blood count 
CIDP 
Chronic inflammatory demyelinating polyneuropathy 
CRO 
Clinical research organization 
CS 
Corticosteroid 
DAT 
Direct antiglobulin test 
DBP 
Diastolic blood pressure 
DVT 
Deep venous thrombosis 
ECG 
Electrocardiogram 
eCRF 
electronic case report form  
EFNS 
European Federation of Neurological Societies 
GBS 
Guillain-Barré syndrome 
HAV 
Hepatitis A virus 
HBV 
Hepatitis B virus 
HCG 
Human chorionic gonadotropin 
HCV 
Hepatitis C virus 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HIV 
Human immunodeficiency virus 
HR 
Heart rate 
IB 
Investigator’s Brochure 
ICF 
Informed consent form 
ICH GCP 
International Conference on Harmonization Good Clinical Practice 
ICU 
Intensive Care Unit 
IgA 
Immunoglobulin A 
IgG 
Immunoglobulin G 

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IGIV 
Intravenous immunoglobulin 
IGIV-C 
Immune Globulin (Human), 10% Caprylate/Chromatography Purified 
IgM 
Immunoglobulin M 
IP 
Investigational product 
IRB/EC 
Institutional review board/Ethics committee 
ITP 
Idiopathic thrombocytopenic purpura 
IV 
Intravenous 
LDH 
Lactate dehydrogenase 
MedDRA 
Medical Dictionary for Regulatory Activities 
MG 
Myasthenia gravis 
MG-ADL 
Myasthenia gravis-activities of daily living 
MGFA 
Myasthenia Gravis Foundation of America 
MuSK 
Muscle specific kinase  
NAT 
Nucleic acid testing 
PE 
Pulmonary embolism 
PI 
Primary immunodeficiency 
PLEX 
Plasma exchange 
QMG 
Quantitative myasthenia gravis scale 
RBC 
Red blood count 
RR 
Respiratory rate 
SAE 
Serious adverse event 
SBP 
Systolic blood pressure 
SD 
Standard deviation 
SPC 
Summary of product characteristics 
Suspected ADR 
Suspected adverse drug reaction 
T 
Temperature 
TBL 
Total bilirubin 
TE 
Thromboembolic event 
TEAE 
Treatment emergent adverse event 
Treg 
Regulatory T cell 
ULN 
Upper limit of normal 
 

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1 
INTRODUCTION 
In addition to the information provided below, please also refer to the Immune Globulin 
(Human), 10% Caprylate/Chromatography Purified (IGIV-C) Investigator’s Brochure (IB) 
and any additional data supplied by the Sponsor. 
1.1 
Myasthenia Gravis Exacerbations 
Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction and is 
clinically manifested as variable and fluctuating muscle weakness (1). In most cases, the 
disorder is associated with the production of antibodies against acetylcholine receptors 
leading to the destruction of the postsynaptic motor end plate (2). Clinical symptoms of MG 
include muscle fatigue and weakness that can be localized, such as ocular, or generalized 
across multiple muscle groups (systemic).  
Myasthenic symptoms and signs may worsen or exacerbate. MG exacerbations are 
characterized by worsening muscle weakness resulting in swallowing difficulty, acute 
respiratory failure, or major functional disability responsible for the discontinuation of 
physical activity. These cases fall in the class IVb-V of the disease severity staging proposed 
by the Myasthenia Gravis Foundation of America (MGFA) (3). Particularly, MG crisis is the 
most severe phenotype (class V of MGFA classification) and commonly requires an effective 
and urgent life-saving treatment such as invasive or noninvasive mechanical ventilation due 
to respiratory failure (4). 
The majority of patients have their first MG exacerbation within the first 2 years after disease 
onset (5), and about 20% of the patients develop crisis episodes within the first year (6). 
Infection or changes in medications (such as recent addition of a corticosteroid [CS], a dose 
reduction or overtreatment with acetylcholinesterase inhibitors) are common triggers for 
exacerbations of MG (7,8). Other recognized triggers for exacerbations in refractory MG 
include emotional stress, hot environment, sudden elevation of body temperature and 
hyperthyroidism, with autoimmune thyroid disease being a common association of 
myasthenia gravis (9). However, approximately 33 to 50% of patients with MG do not have 
an obvious cause for an exacerbation (7). Since identified causes can relate to infection or 
medications, physical examination, review of medications, chest X-ray, complete blood 
count (CBC), and blood as well as other cultures, depending on presentation, should be 
obtained (8). 
1.2 
Management of MG Exacerbations 
Management for myasthenic exacerbations should be carried out in an intensive care unit 
(ICU) or general ward staffed with physicians who are experienced in the management of 
MG, respiratory insufficiency, infectious disease, and fluid and electrolyte therapy (1,10). 
After stabilizing the patient and securing the airway, respiration, and haemodynamics, 
options for specific treatment include use of acetylcholinesterase inhibitors, plasma exchange 
(PLEX), intravenous immunoglobulin (IGIV), and immunosuppressive drugs (such as CS), 
(11). Autoantibody activity in MG can be modulated by either removal from plasma by 
PLEX or selective immunoadsorption techniques or by the expansion of the immunoglobulin 

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pool by administering high-dose IGIV that interferes with the autoantibody activity by means 
of several and still poorly understood pathways (12). CS administration results in a gradual 
effect on symptoms, which starts after a few days and is clinically obvious after 
approximately 2 weeks, but maximum benefit may take months (13,14). Initial treatment 
with prednisone may lead to an exacerbation of MG in almost half of the patients attempted 
and it is recommended that initiation of CS should occur in a hospital setting where 
respiratory function can be monitored (15). Additionally, if patients experience an MG 
exacerbation and are already receiving CS, then CS use should not be discontinued while 
treating the exacerbation (15). 
PLEX and IGIV are common treatment modalities for MG exacerbation. Their beneficial and 
symptom-relieving effect is regarded as well proven from several studies and from 
widespread clinical use. In contrast to most other treatment options, the clinical response is 
rapid and often with a dramatic effect (11). PLEX therapy produces its clinical effect by 
removing plasma containing acetylcholine receptor (AChR) antibodies. Although efficacious, 
PLEX has drawbacks, such as increased side-effects as compared to IGIV and the 
haemodynamics of PLEX (16). The mechanism by which IGIV exerts its clinical effect in 
MG is still unknown, but it is believed to improve symptoms by modulating the pathogenic 
autoantibody response. Other mechanisms of action postulated in other diseases include the 
Fc receptor blockade of the reticuloendothelial system, modulation of the idiotypic-anti-
idiotypic network, enhancement of regulatory T cells, inhibition of complement deposition, 
modulation of cytokines, growth factors and adhesion molecules, modulation of apoptosis 
and macrophages, and immune regulation of both B-cell and T-cell immune function (17,18). 
Improvement in MG symptoms typically occurs in about 70% of patients, beginning during 
treatment or within a few days of initiating IGIV treatment and lasting for weeks to months 
(19). 
Several studies comparing PLEX with IGIV have demonstrated equal efficacy, but 
significantly fewer or less severe side effects were noted for the IGIV treatment (20,21). 
These recommendations are also supported by the European Federation of Neurological 
Societies (EFNS) guidelines with IGIV and PLEX both being effective (recommendation 
level A) for the treatment of MG exacerbations (16). The Therapeutics and Technology 
Assessment Subcommittee of American Academy of Neurology (AAN) recently released 
updated evidence-based guidelines that consider IGIV as an effective therapy for moderate-
to-severe cases of MG, but also acknowledges the need for additional clinical trials (22). 
Importantly, IVIG can be used for management of MG exacerbations in patients with 
contraindications or who have experienced a lack of clinical response to PLEX (13,15). 
A recent Cochrane Review (23) identified four trials in acute exacerbation or worsening MG 
in which IGIV was compared to placebo, CS or PLEX in a randomized, controlled manner. 
The placebo controlled trial showed some evidence for a positive effect of IGIV. A trial 
against CS, a commonly used immune modulator in MG, was underpowered and showed no 
difference in treatment effect between IGIV and CS. The two trials comparing IGIV to 
PLEX, both generally accepted therapies, also showed a similar treatment effect. 

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1.3 
Immune Globulin (Human), 10% Caprylate/Chromatography 
Purified (IGIV-C)  
Immune Globulin (Human), 10% Caprylate/Chromatography Purified (IGIV-C) is an 
intravenous (IV) product that is currently available commercially in a number of countries 
for the treatment of primary immunodeficiency (PI), idiopathic thrombocytopenic purpura 
(ITP), and chronic inflammatory demyelinating polyneuropathy (CIDP) as well as other 
indications in some countries.  
In addition to the information provided above, please refer to the IGIV-C IB and any 
additional data supplied by the Sponsor. 
1.4 
Study Rationale and Dose Selection 
1.4.1 
Study Rationale 
The general recommendation is that IGIV concentrates are a safe and effective treatment 
option as a short term treatment for acute exacerbation of MG. Moreover, IGIV-C has 
demonstrated a positive treatment effect in clinical studies of MG exacerbations (24-26), but 
further clinical data are needed to confirm the effectiveness of IGIV-C in the treatment of 
MG exacerbations. The MGFA, Inc. Task Force on clinical research standards recommended 
that the Quantified Myasthenia Gravis Scale (QMG) be used in all prospective clinical trials 
in MG to assess clinical efficacy in MG (3). 
This is a multicenter, prospective, open-label, non-controlled study to assess the efficacy and 
safety of IGIV-C in subjects with MG class IVb-V exacerbations according to the MGFA 
(3). The primary measure of efficacy for this study is the change in the QMG score from 
Baseline to Day 14. 
1.4.2 
Dose Rationale 
The optimal dose of IGIV for MG exacerbation is still unclear, but prior reviews reported a 
usual dose of 2 g/kg, which is administered over 3 to 5 days (13,19). More recent studies in 
MG have evaluated the administration of a total IGIV dose of 2 g/kg over 2 consecutive days 
(1 g/kg daily) with no increase in side effects and a comparable benefit lasting up to 30 to 60 
days post-treatment (24-26).  
Likewise, in a study of subjects with Guillain-Barré syndrome (GBS), a total IGIV dose of 
2 g/kg administered over 2 consecutive days (1 g/kg daily) was compared to the standard 
regimen of 0.4 g/kg daily for 5 days and there were no significant differences in the primary 
or secondary outcome measures (27). 
Based on the above, subjects will receive a single, total IGIV-C dose of 2 g/kg of body 
weight that will be administered on 2 consecutive days (at a dose of 1 g/kg per day).  

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2 
STUDY OBJECTIVES 
2.1 
Efficacy Objectives 
2.1.1 
Primary Objective 
The primary objective of this study is to evaluate the efficacy of an IV infusion of IGIV-C 
(total dose of 2 g/kg administered over 2 consecutive days at a dose of 1 g/kg per day) in 
subjects with MG exacerbations by assessing the change in score of MG symptoms as 
measured by the QMG from Baseline to Day 14. 
2.1.2 
Secondary Objectives 
The secondary objectives of this study are to evaluate the efficacy of an IV infusion of 
IGIV-C (total dose of 2 g/kg administered over 2 days at a dose of 1 g/kg per day) in subjects 
with MG exacerbations by: 
• Percentages of subjects who experience a clinical improvement assessed by QMG from 
Baseline (Day 0) to Day 14 where clinical improvement is defined as at least 3 point 
decrease in QMG 
• Percentages of subjects who experience a clinical improvement assessed by MG – 
Activities of Daily Living (MG-ADL) from Baseline (Day 0) to Day 14 where clinical 
improvement is defined as at least 2-point decrease in MG-ADL 
• Percentages of subjects who experience a clinical improvement assessed by the MG 
Composite from Baseline (Day 0) to Day 14 where clinical improvement is defined as at 
least 3 point decrease in the MG Composite 
 
2.1.3 
Exploratory Objectives  
The exploratory objectives for this study are to evaluate the effect of an IV infusion of 
IGIV-C on:  
• Change in and percentage of subjects who experience a clinical improvement in QMG 
score from Baseline (Day 0) to Days 7, 21 and 28 
• Change in and percentage of subjects who experience a clinical improvement in 
MG-ADL from Baseline (Day 0) to Days 7, 14, 21 and 28 
• Change in and percentage of subjects who experience a clinical improvement in the MG 
Composite from Baseline (Day 0) to Days 7, 14, 21 and 28 
• Change in AChR antibody (or muscle specific kinase [MuSK] antibody) levels from 
Baseline (Day 0) to Days 14 and 28 
• Change in Immunoglobulin G (IgG) levels from Baseline (Day 0) to Day 1 (after 
completion of infusion), Days 7, 14, 21 and 28 
• Length of ICU stay and length of intubation (if applicable) 
 

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2.2 
Safety Objective 
The safety objective of this study is to evaluate the safety and tolerability of an IV infusion of 
IGIV-C (total dose of 2 g/kg administered over 2 consecutive days at a dose of 1 g/kg per 
day) in subjects with MG exacerbations. 
3 
INVESTIGATIONAL PLAN 
3.1 
Study Design and Plan 
This is a multicenter, prospective, open-label, non-controlled study to assess the efficacy and 
safety of an IV dose of 2 g/kg of IGIV-C in subjects with MG exacerbations. The study 
consists of a single dose course of IGIV-C treatment followed by 28-days of post-infusion 
assessments. The total duration of study participation for each subject is up to 28 ± 2 days. 
Approximately 50 subjects, ages 18 or greater, are planned to be enrolled in the study and 
receive a single, total dose of 2 g/kg of IGIV-C over 2 consecutive days (dose of 1 g/kg per 
day) across multiple centers in North America and Europe. 
Informed consent will be obtained from subjects who experience an exacerbation of MG that 
is not attributable to an infection or change in medication. After obtaining informed consent, 
study eligibility will be determined by the Investigator using the protocol inclusion/exclusion 
criteria (See Section 3.2). Subjects must meet all inclusion/exclusion criteria prior to 
receiving IGIV-C at the Baseline Visit (Day 0 and Day 1). Throughout the course of the 
clinical study, assessments will consist of the following: QMG score (See Section 3.5.4), MG 
Composite Scale (See Section 3.5.5), MG-ADL (See Section 3.5.6), physical assessments, 
infusion vital signs monitoring, laboratory tests, recording of adverse events (AEs) and 
concomitant medications. Each MG assessment should be performed by the same clinical 
staff member whenever possible. 
A schematic of the study design and essential activities is shown in Figure 3-1, and a 
schedule of procedures is provided in Appendix 1. 
Baseline Visit
IGIV-C 2 g/kg
(Administered as 
2 consecutive doses of
 1 g/kg on Day 0 and Day 1)
QMG assessed at Day 0
Day 7 Visit
QMG
Day 28 Visit
(Final Study Visit)
QMG
Day 14 Visit
QMG
 
Day 21 Visit
QMG
Day 0  Day 1
 
Figure 3-1 Overall Study Schema 
3.2 
Selection of Study Population 
Study population will be made up of individuals with MG suffering from an exacerbation or 
crisis as defined by difficulty in swallowing, acute respiratory failure or major functional 

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disability responsible for the discontinuation of physical activity that is not attributable to an 
infection or change in medication. 
3.2.1 
Inclusion Criteria 
A subject must meet all the following inclusion criteria to be eligible for participation in this 
study: 
1. Male or female aged ≥18 years. 
2. Subjects must be willing and able to provide written informed consent (if applicable, a 
legally authorized representative may provide informed consent on behalf of the subject). 
3. Subjects who meet the clinical criteria for diagnosis of MG with an exacerbation defined 
as worsening of MG symptoms as defined by an MGFA classification IVb or V 
(Appendix 2). 
4. Subjects on long-term (8 weeks) corticosteroid treatment for MG.  
5. Female subjects of child-bearing potential must have a negative test for pregnancy 
(human chorionic gonadotropin (HCG)-based assay). 
6. Subjects must be willing to comply with all aspects of the clinical trial protocol, 
including blood sampling and long-term storage of extra samples, for the entire duration 
of the study. 
 
3.2.2 
Exclusion Criteria 
A subject meeting any of the following exclusion criteria is NOT eligible for participation in 
the study: 
1. Subjects who have received immune globulin treatment given by IV, subcutaneous or 
intramuscular route within the last 30 days. 
2. Subjects with documentation of a lack of clinical response to IVIG therapy for MG. 
3. Subjects documented positive for antibodies directed against MuSK. 
4. Subjects with CS treatment initiated within the last 8 weeks or modified within the last 2 
weeks. 
5. Subjects with PLEX within the last 30 days. 
6. Subjects with MG exacerbation attributable to change in medication or evident infection 
as defined by, but not limited to, the presence of at least one of the following diagnostic 
features: 1) axillary temperature ≥38°C, 2) positive blood culture of infective 
microorganism, 3) white blood cell count >12×109/L and differential white blood cell 
count of >10% band neutrophils (>1.2×109/L), and 4) pulmonary infiltrate with 
consolidation on chest X-ray. Alternatively, other signs and symptoms may be considered 
for the diagnosis of evident infection according to the Investigator’s judgement. 
7. Subjects with inadequate venous access. 
8. Subjects with a history of anaphylactic reactions or severe reactions to any blood-derived 
product. 
9. Subjects with a history of intolerance to any component of the investigational products 
(IPs).   
10. Subjects with a documented diagnosis of thrombotic complications to polyclonal IVIG 
therapy in the past. 

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11. Subjects with a history of recent (within the last year) myocardial infarction, stroke or 
uncontrolled hypertension. 
12. Subjects who suffer from uncontrolled congestive heart failure, embolism or documented 
electrocardiogram (ECG) changes indicative of myocardial ischemia or atrial fibrillation.   
13. Subjects with current known hyperviscosity or hypercoagulable state. 
14. Subjects currently receiving anti-coagulation therapy. 
15. Subjects with a history of chronic alcoholism or illicit drug abuse (addiction) in the 12 
months preceding the Baseline Visit. 
16. Subjects with active psychiatric illness that interferes with compliance or communication 
with health care personnel. 
17. Females who are pregnant, breastfeeding, or of child-bearing potential and unwilling to 
practice a highly effective method of contraception (oral, injectable or implanted 
hormonal methods of contraception, placement of an intrauterine device or intrauterine 
system, condom or occlusive cap with spermicidal foam/gel/film/cream/suppository, 
male sterilization, or true abstinence*) throughout the study.   
*  True abstinence: When this is in line with the preferred and usual lifestyle of the 
subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation 
methods], declaration of abstinence for the duration of a trial, and withdrawal are not 
acceptable methods of contraception.) 
18. Subjects with any medical condition which makes the clinical trial participation 
unadvisable or which is likely to interfere with the evaluation of the study treatment 
and/or the satisfactory conduct of the clinical trial according to the Investigator’s 
judgment. 
19. Subjects currently receiving, or having received within 3 months prior to the Baseline 
Visit, any investigational medicinal product or device. 
20. Subjects who are unlikely to adhere to the protocol requirements or are likely to be 
uncooperative or unable to provide a storage serum/plasma sample prior to the first IP 
infusion. 
21. Subjects with a known Immunoglobulin A (IgA) deficiency and anti-IgA serum 
antibodies. 
22. Subjects with renal impairment (i.e., serum creatinine exceeds more than 1.5 times the 
upper limit of normal [ULN] for the expected normal range for the testing laboratory). 
23. Subjects with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels 
exceeding more than 2.5 times the ULN for the expected normal range for the testing 
laboratory. 
24. Subjects with haemoglobin levels <9 g/dL. 
 
3.3 
Treatments 
3.3.1 
Treatment to be administered 
3.3.1.1 
Immune Globulin (Human), 10% Caprylate/Chromatography Purified (IGIV-C) 
The IP provided by Grifols Therapeutics Inc. is marketed IGIV-C in glass vials. Detailed 
information regarding IGIV-C can be found in the IGIV-C IB. 

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3.3.1.2 
Labeling of Investigational Product 
IPs will be labeled according to the requirements of local law and legislation. Label text will 
be approved according to agreed Grifols Therapeutics Inc. procedures, and a copy of the 
labels will be made available to the study site upon request. 
3.3.1.3 
Storage of Investigational Product 
IP must be stored in a secure area accessible to study personnel authorized by the 
Investigator, such as the study staff responsible for the preparation and dispensing of 
investigative product. 
IP must be stored at temperatures of 2°C to 8°C (36°F to 46°F). Do not freeze. Investigators, 
or designees, are responsible for maintaining storage temperature records and for 
immediately reporting deviations in temperature to the study monitor. 
3.3.1.4 
Preparation 
The volume (i.e., total infusion dose administered) of IP to be prepared for each IV infusion 
will be individualized for each subject based on body weight, and the protocol specified total 
2 g/kg dosage to be administered over 2 consecutive days at a dose of 1 g/kg per day. The IP 
will be prepared by the study site pharmacist or designee. 
IP must be inspected visually before being prepared for administration to subjects. The 
solution must not be used if turbid or if it contains visible particles. Solution which has been 
frozen should not be used. The Investigator, or designee, is responsible for immediately 
reporting any discrepancies noted with IP to the study monitor. 
Reference the Pharmacy Manual for detailed IP preparation and administration instructions. 
3.3.1.5 
Accountability for Investigational Product 
IP is to be used only for the study in accordance with the directions given in this protocol. 
The Investigator, or designee such as the study pharmacist, is responsible for the distribution 
of the IP in accordance with directions given in the protocol and Pharmacy Manual. 
The Investigator, or designee such as the study pharmacist, is responsible for maintaining 
accurate records of the IP for his/her site. IP inventory/dispensing documentation verifying 
the receipt, dispensing, destruction or return must be maintained and kept current by the 
Investigator or designee. The inventory must be made available for inspection by the 
monitor. IP supplies must be accounted for by the monitor and inventory/dispensing logs 
must be verified by the monitor prior to IP return or destruction. Written documentation of 
any used and unused inventory is required. At the end of the study, a copy of the 
inventory/dispensing log(s) will be retrieved by the monitor and returned to Grifols 
Therapeutics Inc. 
IGIV-C vials may be supplied in the following vial sizes 10, 25, 50, 100, and 200 mL. 

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3.3.2 
Rationale for Selection of Doses/Timing of Investigational Product in the 
Study 
3.3.2.1 
Selection of IGIV-C Dose and Interval in the Study 
The optimal dose of IGIV for MG exacerbation is still unclear; however, recent studies have 
divided the total dose of 2 g/kg into two, consecutive daily doses of 1 g/kg each with no 
increase in side effects as compared to the longer dosing period of 3 to 5 days (24-26).   
Based on the above, subjects will receive a single, total IGIV-C dose of 2 g/kg of body 
weight that will be administered on 2 consecutive days at a dose of 1 g/kg per day.  
3.3.3 
Method of Assigning Subjects to Treatment Groups 
This is an open-label, uncontrolled study; all subjects will receive the same IP (IGIV-C) via 
IV administration. Each subject’s IGIV-C dose will be individualized based on the subject’s 
weight and the protocol specified dose of 2 g/kg over 2 consecutive days. Therefore, each 
subject’s infusion volume and duration of the infusion will vary from subject to subject. 
 
3.3.3.1 
Subject Numbering 
Within each study site, subjects in the study will receive a consecutive subject number. 
Subject numbers are generated beginning with the study center number (3 digits, assigned by 
the Sponsor) followed consecutively with a unique number for each subject (4 digits, 
including leading zeros). For example, if the Investigator’s center number is 301, subject 
number will be 3010001, 3010002, 3010003, etc., in consecutive order. Subject numbers, 
once assigned, will not be reused at any center. 
3.3.3.2 
Blinding 
This is an open-label study with no blinding. 
3.3.3.3 
 Administration and Timing of Investigational Products for Each Subject 
IGIV-C will be administered as a total dose of 2 g/kg given in two divided, daily doses of 
1 g/kg over 2 consecutive days. The initial infusion will be on Day 0 followed by a second 
infusion on Day 1. All subjects will receive this single total dose of IGIV-C. Infusion 
administration, including infusion rate, is provided in the Pharmacy Manual. 
Details regarding infusion preparation are located in the Pharmacy Manual. In the event that 
the subject is not able to tolerate the set infusion rate, the rate may be decreased for better 
tolerability. The initial and final infusion rates will be recorded. 
3.3.3.4 
Treatment Compliance 
Reasons for any deviation from the administration of less than 100% of the IP dose as 
prepared by the pharmacist, or designee, must be recorded in the electronic case report form 
(eCRF) and in the subject’s medical records. 

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All IV infusions will be administered at the study site under the supervision of the treating 
Investigator or designee. 
3.4 
Prior and Concomitant Therapy 
Concomitant medications must be recorded in the eCRF, including the trade or generic 
names of the medication, the dose, the route of administration, and the duration of the 
medication (frequency). 
3.4.1 
Prohibited Medications Prior to Study Participation 
The following medications are prohibited for the specified timeframe prior to study 
participation. 
• Immune globulin treatment given by IV, subcutaneous or intramuscular route within the 
last 30 days 
• CS treatment newly initiated within the last 8 weeks or modified within the last 2 weeks  
• Subjects with PLEX within the last 30 days 
• Any IP(s) within 3 months 
 
3.4.2 
Prohibited Concomitant Medications during the Study 
Use of the following medications is prohibited during the study or during the specified 
timeframe: 
• Any IgG therapy other than IGIV-C provided for this study 
• Any IP(s) which are not part of this study 
• Live viral vaccines (e.g., measles, mumps, rubella) 
• PLEX 
• Anti-coagulant therapy except when administered during hospitalization as prophylactic 
treatment as part of standard of care for deep venous thrombosis (DVT) prevention  
• Systemic antibiotic therapy  
- 
Note: antibiotics are allowed for treatment of AEs where medically necessary 
according to the Investigator’s opinion and for safety reasons. 
 
3.4.3 
Restricted Concomitant Medications during the Study 
This section describes medications that are restricted but not prohibited during the study 
participation: 
• Changes to routine therapy (such as CS, cholinesterase inhibitors or other 
immunosuppressants) to treat symptoms of MG, as described in the medical history prior 
to exacerbation, will not be permitted until Day 14 (after primary efficacy assessment) 
unless necessary according to the Investigator’s opinion and for safety reasons. 
• Except for the baseline visit, subjects receiving cholinesterase inhibitors will be 
instructed not to take medication 12 hours prior to assessment and for those receiving 

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slow-release cholinesterase inhibitors, the medication will be held 24 hours before the 
assessment.  
 
3.5 
Efficacy Study Variables  
3.5.1 
Primary Variable 
The primary variable to assess efficacy in this study is the change in QMG score from 
Baseline (Day 0) to Day 14. 
3.5.2 
Secondary Variables 
Secondary efficacy variables assessed in this study are: 
• Percentages of subjects who experience a clinical improvement assessed by QMG from 
Baseline (Day 0) to Day 14 where clinical improvement is defined as at least 3 point 
decrease in QMG 
• Percentages of subjects who experience a clinical improvement assessed by MG-ADL 
from Baseline (Day 0) to Day 14 where clinical improvement is defined as at least 2 point 
decrease in MG-ADL 
• Percentages of subjects who experience a clinical improvement assessed by the MG 
Composite from Baseline (Day 0) to Day 14 where clinical improvement is defined as at 
least 3 point decrease in the MG Composite  
 
3.5.3 
Exploratory Variables 
Exploratory efficacy variables that will be evaluated in this study include the following: 
• Change and percentage of subjects who experience a clinical improvement in QMG score 
from Baseline (Day 0) to Day 7, Day 21 and Day 28  
• Change and percentage of subjects who experience a clinical improvement in MG-ADL 
from Baseline (Day 0) to Day 7, Day 14, Day 21 and Day 28 
• Change and percentage of subjects who experience a clinical improvement in the MG 
Composite from Baseline (Day 0) to Day 7, Day 14, Day 21 and Day 28 
• Change in AChR antibodies (or MuSK antibodies) from Baseline (Day 0) to Day 14 and 
Day 28 
• Change in IgG levels from Baseline (Day 0) to Day 1 (after completion of infusion), 
Day 7, Day 14, Day 21 and Day 28 
• Length of ICU stay and length of intubation (if applicable) 
 
3.5.4 
Quantitative Myasthenia Gravis Scale (QMG) 
The MGFA, Inc. Task Force on Clinical Research Standards recommends that the QMG be 
used in all prospective clinical trials in MG (3). The QMG is easy to administer by clinical 
evaluators and/or physicians in approximately 30 minutes with minimal equipment to 
measure spirometry and muscle strength testing. The QMG should be performed by the same 

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clinical staff member whenever possible. An average 3.5-point improvement in QMG score 
indicates clinical improvement (24). 
QMG Test Items are attached in Appendix 3. 
Since this study exclusively enrolls subjects with MGFA classification of IVb or V severity, 
a proportion of subjects may be intubated and otherwise compromised so that the QMG score 
may need to be performed in extenuating circumstances. Assessments may not be feasible in 
standard format, although still obtainable with minor modifications. As such, it is necessary 
to standardize the methodology employed so that consistent scoring is obtained across study 
centers for subjects in these extenuating circumstances. 
A guideline for the QMG test for subjects in extenuating circumstances is available for these 
specific situations, which is located in the MG assessment binder provided to each site. 
3.5.5 
MG Composite Scale 
The MG Composite scale takes less than five minutes to complete, is made up of three 
ocular, three bulbar, one respiratory, one neck, and two limb items (29,30). The MG 
Composite scale should be performed by the same clinical staff member whenever possible. 
The task force on MG study design of the medical scientific advisory board of the MGFA 
recommends using the MG Composite as the quantitative measure for determining 
improvement and worsening for patients with generalized MG disease. A 3-point 
improvement in MG Composite score reliably indicates clinical improvement. A 3-point 
improvement in the MG Composite score also appears to be meaningful to the patient (28). 
A guideline for administering the MG Composite Scale is available in the MG assessment 
binder provided to each site. The MG Composite items are listed in Appendix 4. 
3.5.6 
MG-ADL 
The MG-ADL is an 8-item, patient reported questionnaire that is completed to assess the 
symptoms and activities in MG (31). A 2-point improvement in the MG-ADL indicates 
clinical improvement (31). The MG-ADL should be performed by the same clinical staff 
member whenever possible. 
The questionnaire and scoring is provided in Appendix 5. 
3.6 
Safety Study Variables 
The following safety variables will be assessed in this study: 
• AEs, Suspected adverse drug reactions (Suspected ADRs), adverse reactions (ARs), 
serious AEs (SAEs), and discontinuations due to AEs and SAEs. 
• Vital Signs. Abnormal findings judged as clinically relevant by the Investigator will be 
considered AEs. Clinically relevant changes as determined by the Investigator in vital 
signs (temperature [T], respiratory rate [RR], heart rate [HR], systolic blood pressure 

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[SBP] and diastolic blood pressure [DBP]) during infusions will be considered AEs 
temporally associated to the infusion. 
• Physical Assessments. Physical exams, excluding the breast and genitourinary areas, will 
be recorded as normal or abnormal, according to the physician’s judgment criteria. 
Abnormal findings judged by the Investigator as clinically relevant will be considered 
AEs. 
• Blood biochemistry and Haematology. Laboratory results out of the normal range that are 
judged by the Investigator as clinically relevant will be considered AEs. 
• Thromboembolic events (TEs) risk. 
• Hemolysis detection. 
 
3.6.1 
Thromboembolic Events Risk 
During the clinical trial, TE risk will be determined by the Investigator or study staff using 
the measurement of D-dimer blood levels, the Wells clinical prediction rule for both DVT 
and for pulmonary embolism (PE), and evaluation of clinical signs and symptoms of TEs 
(such as pain, dyspnea, discoloration -paleness or redness- in lower extremities). Monitoring 
will be performed at Day 0 (prior infusion), Day 1 (after the infusion), Day 7 ± 1 and Day 28 
± 2. 
Procedures for the monitoring of TEs risk are provided in Appendix 6. 
3.6.2 
Hemolysis Detection 
Blood assessments including whole blood hemoglobin, serum or plasma free hemoglobin, 
haptoglobin, lactate dehydrogenase (LDH), direct antiglobulin test (DAT), absolute 
reticulocyte count (ARC), red blood count (RBC), hematocrit, total bilirubin (TBL), indirect 
bilirubin, blood smear, and urinalysis including urinary sediment and hemoglobinuria will be 
conducted at Day 0 (prior infusion), Day 1 (after the infusion), Day 7 ± 1 and Day 28 ± 2 for 
hemolysis detection. In addition, clinical parameters including red/dark urine, jaundice, as 
well as other signs and symptoms of anemia (such as pallor or tachycardia) will be assessed 
at Day 0 (prior infusion) and Day 1 (after the infusion), Day 7 ± 1 and Day 28 ± 2. 
Procedures for hemolysis detection are provided in Appendix 7. 
3.7 
Assessments 
3.7.1 
Assessment Periods 
The study consists of a single treatment with a 28 ± 2 days assessment period. The expected 
duration of a study subject’s participation will be approximately 28 ± 2 days. 
3.7.2 
Observations and Measurements 
The following is a description of the procedures/assessments to take place at each study visit. 
Each MG assessment should be performed by the same clinical staff member whenever 

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possible. See the Overall Study Schema (Figure 3-1) and Schedule of Procedures in 
Appendix 1 for a summary of study visits and the procedures conducted at each visit. 
3.7.2.1 
Treatment and Post-infusion Follow-up Phase 
All subjects will start their participation in the study upon the signing of the ICF. If 
applicable, a legally authorized representative may provide informed consent on behalf of the 
patient (see Section 7.4). 
Eligible subjects will complete the Baseline (Day 0) visit, thereby initiating the Treatment. 
Subjects will continue with assessments for 28 days, with scheduled visits and assessments at 
Days 7, 14, 21, and 28. Visits/procedures and assessments should be scheduled at the 
protocol specified study day ± 1 day from Day 7 to Day 14, ± 2 days for visits at Day 21 and 
Day 28.   
BASELINE VISIT 
The Baseline Visit will occur after the subject is stabilized according to the Investigator’s 
judgment. Local laboratory results and assessments related to the inclusion and exclusion 
criteria must be available prior to the investigational product infusion at Day 0.  
For eligible subjects, IGIV-C will be administered as a total dose of 2 g/kg (20 mL/kg) given 
in divided doses of 1 g/kg per day over two days. The initial infusion will be on Baseline 
(Day 0) followed by a second infusion on Day 1. 
The following procedures and assessments will be conducted during the Baseline (Day 0) 
Visit. 
Prior to the investigational product infusion (Day 0) 
• Informed consent prior to the initiation of screening procedures 
• Subject number assigned 
• Medical history including demographics and concomitant diseases 
• AE, concomitant medication  
• Physical exam (excluding breast and genitourinary areas) 
• Vital signs including T, RR, HR, SBP, and DBP 
• Inclusion/exclusion criteria review 
• Height 
• Weight (Note: The recorded weight will be used to calculate the IP infusion dose) 
• Laboratory assessments (see Section 3.7.3): 
- 
Urine collection (within 8 hours prior to the IP infusion on Day 0) 
◦ 
Urine Pregnancy Test (potential child-bearing females only; results must be 
negative for the subject to continue in the study) 
◦ 
Hemolysis (urine sediment and measuring of hemoglobinuria). Note: Local 
laboratory is to be utilized for testing and reporting. If the local laboratory is 
unable to perform any of the assessments, the central laboratory may be 
utilized.   

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- 
Blood collection (within 8 hours prior to IP infusion on Day 0) 
◦ 
Biochemistry  
◦ 
Haematology 
◦ 
D-dimer   
◦ 
Hemolysis (whole blood hemoglobin, serum or plasma free hemoglobin, 
haptoglobin, LDH, DAT, ARC, RBC, hematocrit, TBL, indirect bilirubin, and 
blood smear). Note: Local laboratory is to be utilized for testing and reporting. 
If the local laboratory is unable to perform any of the assessments, the central 
laboratory may be utilized. 
◦ 
AChR antibodies (or MuSK antibodies, if negative for AChR antibodies; See 
Section 3.7.3.4) 
◦ 
IgG levels 
◦ 
Retain samples for future biomarker testing (These samples will be collected 
and retained for future biomarker testing only for subjects who provide 
consent for this portion of the study) 
◦ 
Retain samples for virus safety testing as detailed in Table 3-1 (These 
retention samples will be tested only if the subject exhibits clinical signs and 
symptoms consistent with hepatitis A, hepatitis B, hepatitis C, HIV, or 
parvovirus B19 infection while participating in the study. These samples will 
be retained until all analyses in support of the study are complete.) 
• Thromboembolic events risk monitoring (Appendix 6) (prior to IP infusion on 
Day 0) 
• Hemolysis detection assessment (Appendix 7) (prior to IP infusion on Day 0) 
• QMG score 
• MG Composite 
• MG-ADL 
 
During and Post-completion of the IP infusion (Day 0) 
• Pharmacist, or designee, to prepare and dispense the IP per Pharmacy Manual 
• Administer the infusion (Per Pharmacy Manual) 
• During the infusion, vital signs (including T, RR, HR, SBP, and DBP) will be 
monitored and recorded 1) within 15 ± 5 minutes before the beginning of each 
infusion; 2) every 30 ± 10 minutes during the first hour of each infusion; and 3) at 30 
± 10 minutes post-completion of each infusion. Note: Any clinically significant vital 
sign will be recorded as an AE in the eCRF. 
• Documentation of total infusion volume prepared (as received from pharmacist or 
designee), total time to infuse, total volume infused, and, if necessary, any infusion 
interruption with explanation 
• AE, concomitant medication 
 

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STUDY VISIT AT DAY 1 
• Pharmacist, or designee, to prepare and dispense the IP per Pharmacy Manual 
• Administer the infusion (Per Pharmacy Manual) 
• During the infusion, vital signs (including T, RR, HR, SBP, and DBP) will be 
monitored and recorded 1) within 15 ± 5 minutes before the beginning of each 
infusion; 2) every 30 ± 10 minutes during the first hour of each infusion; and 3) at 30 
± 10 minutes post-completion of each infusion. Note: Any clinically significant vital 
sign will be recorded as an AE in the eCRF. 
• Laboratory assessments (see Section 3.7.3): 
- 
Urine collection (between 8 and 24 hours post-completion of the IP infusion 
on Day 1) 
◦ 
Hemolysis (urine sediment and measuring of hemoglobinuria). Note: Local 
laboratory is to be utilized for testing and reporting. If the local laboratory is 
unable to perform any of the assessments, the central laboratory may be 
utilized. 
- 
Blood collection (at 30 minutes post-completion of the IP infusion on Day 1) 
◦ 
IgG levels 
- 
Blood collection (between 8 and 24 hours post-completion of the IP infusion 
on Day 1) 
◦ 
D-dimer 
◦ 
Hemolysis (whole blood hemoglobin, serum or plasma free hemoglobin, 
haptoglobin, LDH, DAT, ARC, RBC, hematocrit, TBL, indirect bilirubin, and 
blood smear). Note: Local laboratory is to be utilized for testing and reporting. 
If the local laboratory is unable to perform any of the assessments, the central 
laboratory may be utilized. 
• Thromboembolic events risk monitoring (Appendix 6) (post-completion of the IP 
infusion on Day 1)  
• Hemolysis detection assessment (Appendix 7) (post-completion of the IP infusion 
on Day 1) 
• Documentation of total infusion volume prepared (as received from pharmacist or 
designee), total time to infuse, total volume infused, and, if necessary, any infusion 
interruption with explanation 
• AE, concomitant medication 
 
STUDY VISIT AT DAY 7  
The following procedures and assessments will be conducted during the visit at Day 7 ± 1 
day: 
• AE, concomitant medication  
• Vital signs including T, RR, HR, SBP, and DBP 
• Laboratory assessments (see Section 3.7.3): 
- 
Urine collection 
◦ 
Hemolysis (urine sediment and measuring of hemoglobinuria). Note: Local 
laboratory is to be utilized for testing and reporting. If the local laboratory is 

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unable to perform any of the assessments, the central laboratory may be 
utilized. 
- 
Blood collection 
◦ 
D-dimer 
◦ 
Hemolysis (whole blood hemoglobin, serum or plasma free hemoglobin, 
haptoglobin, LDH, DAT, ARC, RBC, hematocrit, TBL, indirect bilirubin, and 
blood smear). Note: Local laboratory is to be utilized for testing and reporting. 
If the local laboratory is unable to perform any of the assessments, the central 
laboratory may be utilized. 
◦ 
IgG levels 
◦ 
Retain samples for future biomarker testing (These samples will be collected 
and retained for future biomarker testing only for subjects who provide 
consent for this portion of the study) 
• Thromboembolic events risk monitoring (Appendix 6) 
• Hemolysis detection assessment (Appendix 7) 
• QMG score 
• MG Composite 
• MG-ADL 
 
STUDY VISIT AT DAY 14 
The following procedures and assessments will be conducted during the visits at Day 14 ± 1 
day: 
• AE, concomitant medication  
• Vital signs including T, RR, HR, SBP, and DBP 
• Laboratory assessments (see Section 3.7.3): 
- 
Blood collection 
◦ 
AChR antibodies (or MuSK antibodies will be assessed, if subject tested 
negative for AChR antibodies and tested positive for MuSK antibodies at the 
Baseline Visit; See Section 3.7.3.4) 
◦ 
IgG levels 
◦ 
Retain samples for future biomarker testing (These samples will be collected 
and retained for future biomarker testing only for subjects who provide 
consent for this portion of the study) 
• QMG score 
• MG Composite 
• MG-ADL 
 
STUDY VISIT AT DAY 21 
The following procedures and assessments will be conducted during the visit at Day 21 ± 2 
days: 

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• AE, concomitant medication  
• Vital signs including T, RR, HR, SBP, and DBP 
• Laboratory assessments (see Section 3.7.3): 
- 
Blood collection 
◦ 
IgG levels 
◦ 
Retain samples for future biomarker testing (These samples will be collected 
and retained for future biomarker testing only for subjects who provide 
consent for this portion of the study) 
• QMG score 
• MG Composite 
• MG-ADL 
 
FINAL STUDY (DAY 28)/EARLY DISCONTINUATION VISIT 
Subjects will return to study site at Day 28 ± 2 days for a Final Study Visit. If a subject 
discontinues at any point during the study after receiving IP, the subject will be requested to 
return to the clinic to have the procedures and assessments outlined below conducted. 
The following procedures and assessments will be conducted at the Final Study/Early 
Discontinuation Visit: 
• AE, concomitant medication  
• Physical exam 
• Vital signs including T, RR, HR, SBP, and DBP 
• Laboratory assessments (see Section 3.7.3): 
- 
Urine collection 
◦ 
Urine Pregnancy Test (potential child-bearing females only) 
◦ 
Hemolysis (urine sediment and measuring of hemoglobinuria). Note: Local 
laboratory is to be utilized for testing and reporting. If the local laboratory is 
unable to perform any of the assessments, the central laboratory may be 
utilized. 
- 
Blood collection 
◦ 
Biochemistry  
◦ 
Haematology 
◦ 
D-dimer 
◦ 
Hemolysis (whole blood hemoglobin, serum or plasma free hemoglobin, 
haptoglobin, LDH, DAT, ARC, RBC, hematocrit, TBL, indirect bilirubin, and 
blood smearAChR antibodies (or MuSK antibodies will be assessed, if subject 
tested negative for AChR antibodies and tested positive for MuSK antibodies 
at the Baseline Visit; See Section 3.7.3.4) 
◦ 
IgG levels 
◦ 
Retain samples for future biomarker testing (These samples will be collected 
and retained for future biomarker testing only for subjects who provide 
consent for this portion of the study) 
◦ 
Retain samples for virus safety testing as detailed in Table 3-1 (These 
retention samples will be tested only if the subject exhibits clinical signs and 

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symptoms consistent with hepatitis A, hepatitis B, hepatitis C, HIV, or 
parvovirus B19 infection while participating in the study. These samples will 
be retained until all analyses in support of the study are complete.) 
• Thromboembolic events risk monitoring (Appendix 6) 
• Hemolysis detection assessment (Appendix 7) 
• QMG score 
• MG Composite 
• MG-ADL 

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3.7.3 
Description of Laboratory Tests and Procedures 
Table 3-1 Name, Description, and Location of Laboratory Tests and Procedures 
Test Panel 
Description 
Location a 
Haematology b   
Haemoglobin, haematocrit, platelets, RBC count, including RBC 
morphology, white blood cell count with differential 
Local 
Biochemistry b   
Creatinine, blood urea nitrogen (BUN), aspartate transaminase 
(AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), 
total bilirubin (TBL)  
Local 
Hemolysis c 
Blood: Whole blood hemoglobin, serum or plasma free hemoglobin, 
haptoglobin, LDH, DAT, ARC, RBC, hematocrit, TBL, indirect 
bilirubin, and blood smear 
Local 
Urine: Urine sediment and measuring of hemoglobinuria 
Thromboembolic 
events risk 
D-dimer 
Local 
AChR (or MuSK) 
Antibody b   
Acetylcholine Receptor Antibody (if negative, then test for MuSK 
antibody. Please see Section 3.7.3.4 for details) 
Central 
IgG levels 
Immunoglobulin G levels  
Central 
Urine pregnancy b   
Urine pregnancy test for females of child-bearing potential. Results 
must be negative to continue in the study. 
Local 
Viral Nucleic Acid 
Testing (NAT) 
Retains d  -  
Hepatitis A virus (HAV) RNA, Hepatitis B virus (HBV) DNA, 
Hepatitis C virus (HCV) RNA, Human immunodeficiency virus 
(HIV) RNA, Parvovirus B19 (B19V) DNA 
Central 
Viral Serology 
Retains d 
HAV antibody differential (Immunoglobulin M [IgM]/IgG), HBV 
core antibody differential (IgM/IgG), HCV antibody, HIV-1/-2 + 
Group O antibody, B19V antibody differential (IgM/IgG) 
Central 
Blood for 
biomarkers 
 Plasma and cellular pellet samples to be frozen and retained up to 5 
years after the end of the study for possible future analysis f 
Central 
a 
Central laboratory results may not be provided to sites. 
b 
Samples collected for laboratory analyses that are non-analyzable due to any factor (i.e., lost, quantity not 
sufficient, laboratory error) need to be recollected by contacting the subject and arranging for re-sampling. 
c 
Local laboratory is to be utilized for testing and reporting. If the local laboratory is unable to perform any 
of the assessments, the central laboratory may be utilized. 
d 
Blood samples for viral NAT and viral serology will be collected at the Baseline (Day 0) Visit, prior to 
infusion, and the Study Visit Day 28/Early Discontinuation Visit but will be tested only if the subject 
exhibits clinical signs and symptoms consistent with hepatitis A, hepatitis B, hepatitis C, HIV or parvovirus 
B19 infection while participating in the study. These samples will be retained until all analyses in support 
of the study are complete. Additional blood samples for viral NAT and viral serology may be collected and 
tested during the study only if the subject exhibits signs and symptoms consistent with hepatitis A, hepatitis 
B, hepatitis C, HIV or parvovirus B19 infection while participating in the study. 
e 
At specific study sites due to logistical limitations, See Section 3.7.3.6. 
f 
To be collected only for subjects who provide consent for this portion of the study. 
 

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3.7.3.1 
Thromboembolic Events Risk Testing 
Measurement of D-dimer blood levels will be performed at Day 0 (prior infusion), Day 1 
(after the infusion), Day 7 ± 1 and Day 28 ± 2 for TEs risk testing. 
3.7.3.2 
Hemolysis Testing 
Laboratory assessments (whole blood hemoglobin, serum or plasma free hemoglobin, 
haptoglobin, LDH, DAT, ARC, RBC, hematocrit, TBL, indirect bilirubin, and blood smear) 
will be conducted on Day 0 (prior infusion), Day 1 (after infusion), Day 7 ± 1 and Day 28 ± 2 
for hemolysis detection. Note: Local laboratory is to be utilized for testing and reporting. If 
the local laboratory is unable to perform any of the assessments, the central laboratory may 
be utilized. 
3.7.3.3 
Virus Safety Testing 
Viral NAT and viral serology retain samples will be collected at the Baseline (Day 0) Visit, 
prior to infusion, and at the Study Visit Day 28/Early Discontinuation Visit, but will be tested 
only if the subject exhibits clinical signs and symptoms consistent with hepatitis A, hepatitis 
B, hepatitis C, HIV or parvovirus B19 infection while participating in the study. These 
samples will be retained until all analyses in support of the study are complete. Additional 
blood samples for viral NAT and viral serology may be collected and tested only if the 
subject exhibits clinical signs and symptoms consistent with hepatitis A, hepatitis B, 
hepatitis C, HIV or parvovirus B19 infection while participating in the study. If samples 
collected for laboratory analyses are non-analyzable due to various factors (i.e., lost, quantity 
not sufficient, laboratory error), they will need to be recollected by contacting the subject and 
arranging for re-sampling.  
3.7.3.4 
AChR Antibody (or MuSK) Testing 
AChR (or MuSK) antibody levels will be measured in all subjects at specified visits based on 
the following:  
• If AChR antibody test is positive at the Baseline Visit, then AChR antibody testing will 
be conducted at Day 14 and Day 28  
• If AChR antibody test is negative at the Baseline Visit, then MuSK antibody testing will 
be conducted as described below. 
- 
If MuSK antibody test is positive at the Baseline Visit, then MuSK antibody testing 
will be conducted at Day 14 and Day 28 
- 
If MuSK antibody test is negative at the Baseline Visit, then no further antibody 
testing will be conducted during the study. 
 
All measurements will be conducted using validated assays. Specific details regarding all 
aspects of sample collection and processing can be found in the Laboratory Manual at each 
site. Information regarding contact details of central laboratories for sample collection and 
handling purposes can also be found in the Laboratory Manual at each site. 

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3.7.3.5 
IgG Concentration Measurements 
Serum total IgG concentrations will be measured in all subjects at specified visits. All 
measurements will be conducted using validated assays. Specific details regarding all aspects 
of sample collection and processing can be found in the Laboratory Manual at each site. 
Information regarding contact details of central laboratories for sample collection and 
handling purposes can also be found in the Laboratory Manual at each site. 
3.7.3.6 
Biomarker Testing 
Samples will be collected and retained (up to 5 years after study completion) for future 
biomarker testing at all study sites (only for subjects who provide consent for this portion of 
the study). Specific details regarding all aspects of sample collection and processing can be 
found in the Laboratory Manual at each site. Information regarding contact details of central 
laboratories for sample collection and handling purposes can also be found in the Laboratory 
Manual at each site. 
3.8 
Screen Failures 
Screening evaluations will be used to determine the eligibility of each subject for enrollment 
at the Baseline visit. Subjects who fail to meet eligibility criteria during screening evaluations 
will be considered screen failures and will not participate in the study. 
3.9 
Removal of Subjects 
Subjects may withdraw or be withdrawn from the study for the following reasons: 
1. At their own request or at the request of their legally acceptable representative. 
2. If, in the Investigator's opinion, continuation in the study would be detrimental to the 
subject's well-being. 
3. At the specific request of the Sponsor.  
 
Also, subjects must be withdrawn for the following reasons:  
• Subjects not meeting the inclusion and exclusion criteria prior to the Baseline (Day 0) 
Visit based on local laboratory results 
• Subjects with an occurrence of a concomitant disease or any medical condition 
which, either because of its severity or duration or necessary change in treatment, 
contravenes the condition of the study or puts the patient at unnecessary risk or harm  
• Subjects with an occurrence of an AE which in the opinion of the Investigator and/or 
subject requires termination of treatment  
• Subjects who are noncompliant with the protocol per the Investigator’s discretion 
• Pregnancy 
 
In all cases, the reason for withdrawal must be recorded in the eCRF and in the subject's 
records.  

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3.10 Follow-up of Subjects Withdrawn from Study 
Subjects who receive any amount of IP and discontinue early from the study will be 
requested to return for the Final Study/Early Discontinuation Visit procedures as close as 
practical to 28 days after their last administration of the IP. 
3.11 Premature Termination of Study/Closure of Center 
The Sponsor, Institutional Review Board/Ethics Committee (IRB/EC), and/or regulatory 
authorities have the right to close this study or a study center, and the Investigator/Sponsor 
has the right to close a center, at any time, although this should occur only after consultation 
between involved parties. The IRB/EC must be informed. Should the study/center be closed 
prematurely, all study materials (except documentation that has to remain stored at site) must 
be returned to the Sponsor. The Investigator will retain all other documents until notification 
given by the Sponsor for destruction. 
A study center can be closed for the following reasons: 
• Lack of enrollment  
• Non-compliance with the requirements of the study protocol 
• Non-compliance with International Conference on Harmonization Good Clinical 
Practice (ICH GCP) 
 
4 
ADVERSE EVENTS  
4.1 
Warnings/Precautions 
For complete IGIV-C safety information, refer to the current IGIV-C IB. It is possible that 
unknown, unforeseen adverse reactions may occur in subjects with MG exacerbations. 
4.1.1 
Interaction/Overdose 
In an overdosage situation, cardiovascular overload would be the primary concern and should 
be managed accordingly. Since up to 2 g/kg have been tolerated by many patients, and the 
maximum g/kg dose allowed at any single infusion in this study is 1 g/kg, no cardiovascular 
events are expected. 
4.1.2 
Preparation and Handling 
IGIV-C should be infused using a separate line by itself, without mixing with other IV fluids 
or medications the subject might be receiving. The IGIV-C infusion line can be flushed with 
5% dextrose in water (D5/W) or 0.9% sodium chloride for injection. Do not flush with 
heparin. 
4.1.3 
Live Viral Vaccines 
Passive transfer of antibodies may transiently interfere with the immune response to live 
virus vaccines such as measles, mumps, rubella and varicella. Inform patients that IGIV-C 

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can interfere with their immune response to live viral vaccines. Inform patients to notify their 
healthcare professional/immunizing physician of recent therapy with IGIV-C and this 
potential interaction prior to receiving vaccinations so that appropriate measures may be 
taken. 
4.2 
Specification of Safety Parameters 
Aspects of clinical safety will be evaluated in this clinical trial.  
Safety endpoints will include: 
• AEs, SAEs and suspected ADRs 
• Vital signs  
• Physical assessments 
• Blood biochemistry and haematology 
• Thromboembolic events risk 
• Hemolysis 
 
4.3 
Methods and Timing for Assessing, Recording and Analyzing 
Safety Parameters 
Safety will be assessed throughout the clinical trial for all individuals who have received at 
least one infusion of the IP. 
4.3.1 
Adverse Events 
AEs (includes suspected ADRs) occurring at any time between signature of the subject’s ICF 
and the last day of the subject’s participation in the clinical trial will be reported and recorded 
on the appropriate subject’s eCRF entry.  
It is the Investigator’s responsibility to ensure that all AEs are appropriately recorded.  
AEs will be elicited by spontaneous reporting by the study individual or by a non-leading 
inquiry or direct observation by the study staff. 
4.3.2 
Vital Signs  
During all IP infusions, vital signs (T, RR, HR, SBP and DBP) will be monitored by the 
Investigator or study staff. Monitoring will be routinely performed within 15 ± 5 minutes 
before the beginning of infusion as well as every 30 ± 10 minutes during the first hour of 
infusion. Thereafter, vital signs will be monitored and recorded at 30 ± 10 minutes post 
completion of infusion. 
Clinically relevant changes in vital signs during infusions of IP will be reported as AEs 
temporally associated to the infusion. Clinical relevance will be based on the Investigator’s 
criteria. 

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In addition, vital signs will be assessed at scheduled visits. Abnormal vital signs judged as 
clinically relevant by the Investigator will be considered AEs. 
4.3.3 
Physical Assessment 
Physical exams will be registered as normal or abnormal, according to the physician’s 
judgment or study staff’s criteria. Abnormal findings judged as clinically relevant by the 
Investigator will be considered AEs. 
4.3.4 
Blood Biochemistry and Haematological Parameters 
All clinical laboratory data for renal (creatinine, BUN), hepatic (ALT, AST, ALP and TBL) 
and haematological parameters (CBC including differential leukocyte count) will be listed 
for each clinical trial subject (See Table 3-1).  
The Investigator will be required to classify laboratory results out of the normal range 
reported by the laboratory as clinically relevant or not according to his/her criteria.  
Laboratory results out of the normal range judged by the Investigator as clinically relevant 
will be considered AEs. 
4.3.5 
Thromboembolic Events Risk 
Procedures for the monitoring of TEs risk are provided in Appendix 6.  
All TEs will be recorded as an AE.   
4.3.6 
Hemolysis 
Procedures for hemolysis detection are provided in Appendix 7. 
Hemolysis will be recorded as AEs.   
4.4 
Procedures for Eliciting Reports of and for Recording and 
Reporting Adverse Events and Intercurrent Illnesses 
4.4.1 
Adverse Event 
An AE is defined as any untoward medical occurrence in a patient or clinical investigation 
subject administered a medicinal product or study treatment and which does not necessarily 
have a causal relationship with this administration. An AE can therefore be any unfavorable 
and unintended sign (including any abnormal laboratory finding, for example), symptom or 
disease temporally associated with the use of a medicinal product, whether or not considered 
related to the medicinal product. 
Any AE that occurs at any time between signature of the ICF and last day of the subject’s 
participation in the clinical trial must be reported and recorded on the AE eCRF entry. 
However, MG exacerbations defined as inclusion criteria will not be considered an AE. 

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4.4.2 
Suspected Adverse Drug Reaction (ADR)/Adverse Reaction (AR) 
All noxious and unintended responses to a medicinal product related to any dose should be 
considered suspected ADRs. The phrase “response to a medicinal product” means that a 
causal relationship between a medicinal product and an AE is at least a reasonable 
possibility, that is, the relationship cannot be ruled out. In the framework of this study, a 
suspected ADR with a causal relationship of “definite” will be labeled as an adverse reaction 
(AR); thus, ARs are a subset of suspected ADR. 
The Sponsor is responsible for assessing the suspected ADR expectedness during the clinical 
trial. 
4.4.3 
Causality of Adverse Event 
The Investigator is required to provide a causality assessment for each AE reported to the 
Sponsor. The Sponsor will consider the Investigator’s causality assessment. Assessment of 
the causal relationship to the study drug will be made according to the following 
classifications based on Karch FE, et al (32): 
Definite: An event that follows a reasonable temporal sequence from administration of the 
treatment or in which the treatment level has been established in body fluids or tissues; that 
follows a known response pattern to the suspected treatment; and that is confirmed by 
improvement on stopping the treatment (dechallenge), and reappearance of the event on 
repeated exposure (rechallenge). 
Probable: An event that follows a reasonable temporal sequence from administration of the 
treatment; that follows a known response pattern to the suspected treatment; that is confirmed 
by dechallenge; and that could not be reasonably explained by the known characteristics of 
the patient’s clinical state. 
Possible: An event that follows a reasonable temporal sequence from administration of the 
treatment that follows a known response pattern to the suspected treatment but that could 
have been produced by the patient’s clinical state or other modes of therapy administered to 
the patient. 
Doubtful/Unlikely: An event that follows a reasonable temporal sequence from 
administration of the treatment; that does not follow a known response pattern to the 
suspected treatment; but that could not be reasonably explained by the known characteristics 
of the patient’s clinical state. 
Unrelated: Any event that does not meet the criteria above. 
The operational tool to decide the AE causal relationship is based on algorithms by Karch 
and Lasagna and Naranjo et al (33,34). 
When an AE is classified, assessing causal relationship by the Investigator, as definitive, 
probable, possible or doubtful/unlikely, the event will be defined as a suspected ADR. A 
suspected ADR with a causal relationship of “definite” will be defined as an AR. When the 

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causal relationship is labeled “Unrelated”, then it will be considered that the AE is not 
imputable to the study treatment and it is not a suspected ADR. 
In addition, when a causal relationship between the study treatment and the AE cannot be 
ruled out by the Investigator and/or Sponsor, it means that the AE cannot be labeled 
“unrelated”. 
For any subject, all AEs that occur at any time, between the beginning of the first infusion of 
IGIV-C and the final visit of the clinical trial, will be considered treatment emergent adverse 
events (TEAEs). 
AEs occurring during the two-day infusion period (i.e., from the initiation of the IP infusion 
on the first day to the completion of the total dose of IP on the last day) and within 72 hours 
following the completion of the infusion of the total dose of IP on the last day, regardless of 
other factors that may impact a possible causal association with product administration, will 
be defined as infusional AEs (i.e., an AE temporally associated with an infusion of the IP) 
and labeled TEAEs. 
For AEs that occur during infusions, the infusion rate in effect at the time of onset of the AE, 
the time of onset of the AE and the time of AE change materially in intensity and/or resolve 
will be captured. 
4.4.4 
Intensity of Adverse Event or Suspected Adverse Drug Reaction 
AEs and suspected ADRs will be classified depending on their intensity (severity) according 
to the following definitions: 
1. Mild: an AE which is well tolerated by the subject, causing minimum degree of malaise 
and without affecting normal activities. 
2. Moderate: an AE that interferes with the subject’s normal activities. 
3. Severe: an AE that prevents the subject from performing their normal activities. 
 
AE and suspected ADR intensity gradation must be distinguished from AE and suspected 
ADR seriousness gradation, which is defined according to event consequence. For example, 
headache can be mild, moderate or severe but unusually is serious in all these cases. 
The Investigator will be responsible for assessing the AE and suspected ADR intensity 
during the clinical trial, taking into account current criteria included in this section. 
4.4.5 
Expectedness of Adverse Event or Suspected Adverse Drug Reaction 
An AE or suspected ADR is considered “unexpected” if the nature, seriousness, severity or 
outcome of the reaction(s) is not consistent with the reference information. The expectedness 
of a suspected ADR shall be determined by the Sponsor according to the reference document 
(IB or SPC). 
Events not listed for the particular drug under investigation in the IB or SPC are considered 
“unexpected” and those listed are considered “expected.” When serious ADRs (serious 

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potentially related AEs) are received, it is the Sponsor’s responsibility to determine whether 
the events are  “unexpected” for expedited safety reporting purposes. 
4.4.6 
Seriousness of Adverse Event or Suspected Adverse Drug Reaction; 
Serious Adverse Event 
An AE or suspected ADR is considered “serious” if, in the view of either the Investigator or 
Sponsor, it results in any of the following outcomes:  
1. Death 
2. Life-threatening AE (life-threatening in the definition of “serious” refers to an event in 
which the subject was at risk of death at the time of the event; it does not refer to an event 
which hypothetically might have caused death if it were more severe) 
3. In-patient hospitalization or prolongation of existing hospitalization 
4. A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
5. A congenital anomaly/birth defect 
6. An important medical event (important medical event in the definition of “serious”) 
refers to those events which may not be immediately life-threatening, or result in death, 
or hospitalization, but from medical and scientific judgment may jeopardize the subject 
or/and may require medical or surgical intervention to prevent one of the other outcomes 
listed above 
 
This definition permits either the Sponsor or the Investigator to decide whether an event is 
“serious”. If either the Sponsor or the Investigators believes that the event is serious, the 
event must be considered “serious” and evaluated by the Sponsor for expedited reporting.  
A distinction should be drawn between serious and severe AEs. The term “severe” is used to 
describe the intensity (severity) of a specific event; the event itself, however, may be of 
relative minor medical significance (such as severe headache). This is not the same as 
“serious”, which is defined on subject/event outcome or action criteria usually associated 
with events that pose a threat to a subject’s life or functioning. Seriousness (not severity) is a 
medical term while severity is a subjective term.  
According to the medical criteria, an AE or a suspected ADR can be classified as serious, 
although it does not fulfill the conditions fixed in this section, if it is considered important 
from a medical point of view. 
4.4.6.1 
Serious Adverse Event Management 
An MG exacerbation would not be considered an SAE in any of the following scenarios: 
• The patient arrives at the hospital with an MG exacerbation class IVb or V present 
(Inclusion Criterion 3). 
• The patient arrives at the hospital with an MG exacerbation class IVb and the 
exacerbation worsens to class V prior to receiving treatment with IGIV-C (Inclusion 
Criterion 3). 

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If the patient arrives at the hospital with an MG exacerbation class IVb and the exacerbation 
worsens to class V after receiving treatment with IGIV-C, the MG exacerbation should be 
considered an SAE if the event results in any of the outcomes presented in Section 4.4.6. 
4.4.6.2 
Hospitalization or Prolongation of Hospitalization 
An AE or suspected ADR is considered “serious” if, in the view of either the Investigator or 
Sponsor, it results in hospitalization or prolongation of hospitalization UNLESS this 
hospitalization or prolongation of hospitalization is part of the clinical practice (according to 
the Investigator’s criteria) for the treatment of the MG exacerbation defined as inclusion 
criteria. 
On the other hand, if the AE or suspected ADR results in a prolongation of the 
hospitalization beyond what is considered part of the clinical practice (according to the 
Investigator’s criteria) for the treatment of the MG exacerbation defined as inclusion criteria, 
then the AE or suspected ADR will be considered “serious”. 
4.4.7 Adverse Events of Special Interest 
4.4.7.1 
Thromboembolic events 
Subjects will be monitored for signs and symptoms of arterial and venous thromboses. In 
addition, the Grifols Medical Monitor will routinely review reported AEs for possible 
thromboses. Arterial and venous thromboses will be identified according to definitions in the 
International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). 
Such thrombotic events include, but are not limited to, DVT, PE, myocardial infarction, 
cerebrovascular accident, acute coronary syndrome, limb thrombosis, sagittal sinus 
thrombosis, and portal vein or mesenteric artery thrombosis. All thrombosis will be recorded 
as AEs and reported accordingly.   
4.4.7.2 
Hemolysis 
Subjects will be monitored for signs and symptoms of hemolysis. In addition, the Grifols 
Medical Monitor will routinely review reported AEs for possible hemolysis. Hemolysis will 
be recorded as an AE and reported accordingly.   
4.4.8 Procedures for Eliciting Reports of and for Recording and Reporting Adverse 
Events and Suspected Adverse Drug Reactions 
The occurrence and follow-up details of all AEs experienced by any of the subjects during 
the clinical trial, from signature of the Clinical Trial Written Informed Consent Form to the 
last follow-up visit, will be recorded on the AE eCRF entry and in the subject’s hospital 
record. If no AE has occurred during the study period, this should also be indicated in the 
eCRF. 
At each visit, AEs will be elicited by asking the individual a non-leading question such as 
“Do you feel different in any way since the last visit?” Moreover, AEs will also be collected 
through directly observed events or spontaneously volunteered by the subject. Clearly related 

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signs, symptoms and abnormal diagnostic procedures should preferably be grouped together 
and recorded as a single diagnosis or syndrome wherever possible. It is responsibility of the 
Investigator to ensure that AEs are appropriately recorded. 
The following variables must be recorded on the AE eCRF entry: 
1. the verbatim term (a diagnosis is preferred) 
2. date/time of onset 
3. date/time of resolution 
4. intensity (mild, moderate, severe) 
5. causality (unrelated, doubtful/unlikely, possible, probable, definite)* 
6. seriousness (yes, no) 
7. action taken (with regard to IP) 
8. other action (to treat the event) 
9. outcome and sequel (follow-up on AE) 
AEs occurring before subject's exposure to IP will be always labeled as "unrelated". 
 
For AEs that occur during infusions, the infusion rate in effect at the time of onset of the AE, 
the time of onset of the AE and the time of AE change materially in intensity and/or resolve 
will be captured the eCRF entry. 
In addition to the Investigator’s own description of the AEs, each AE will be encoded by the 
Sponsor or clinical research organization (CRO) according to the Medical Dictionary for 
Regulatory Activities (MedDRA®). 
A pregnancy not verified before the Baseline visit but occurring during the course of the 
study will be not considered an AE, unless a relation to the study drug is suspected. In any 
case, a Pregnancy Report Form must be completed and sent as soon as possible to the 
Sponsor, and the study treatment must be discontinued. A copy of the form should be filed at 
the study site for follow-up until the end of the pregnancy. 
4.4.9 
Timelines and Reporting of Serious Adverse Events 
Any SAE (see Section 4.4.6) that occurs after signing the ICF through the last day of 
subject´s participation in the clinical trial must be expeditiously reported whether or not 
considered attributable to the study drug. Each SAE must be fully recorded in the subject’s 
eCRF or SAE Report form. 
SAEs will be reported using the designated SAE Report form. When the Investigator 
becomes aware of an SAE, she/he must submit electronically through EDC system or when 
EDC system is not available submit a completed, signed and dated SAE Report Form (in 
English) within 24 hours to the Sponsor by email/fax.  
Each SAE must be followed up until resolution or stabilization. After the initial report, all 
relevant information for SAE follow up, and for the outcome, must also be supplied to the 
Sponsor in a timely manner (within 3 days from its identification or within 24 hours for 
relevant new information) by means of the SAE Report Form. In addition, the Sponsor or 
CRO may request additional information and/or reports. 

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All SAE Report Forms must be reported to Grifols electronically through EDC system or 
when EDC system is not available, reported to: 
Grifols Global Pharmacovigilance 
 
Email: 
 
FAX (back-up only): 
 
and 
 
 
When required, and according to local law and regulations, SAEs must be reported to the 
IRB/EC and regulatory authorities. 
4.4.10 
Type and Duration of the Follow-Up of Subjects after Adverse Event or 
Suspected ADR 
In so far as is possible, all individuals will be followed up until the AE or suspected ADR has 
been resolved. If an AE/suspected ADR/SAE is present when the subject has completed the 
study, the course of the event must be followed until the final outcome is known or the event 
has been stabilized and no further change is expected and the Investigator decides that no 
further follow-up is necessary. 
Any pregnancy must be followed by the Investigator until delivery or to the end of 
pregnancy. 
5 
STATISTICAL METHODS AND DETERMINATION OF SAMPLE 
SIZE 
5.1 
Statistical and Analytical Plans 
Unless otherwise specified, descriptive statistics will include the number of non-missing 
observations, mean, standard deviation (SD), median, minimum and maximum values for the 
continuous/quantitative data or absolute and relative frequency counts and percentages for 
categorical/qualitative data. 
Data handling and evaluation procedures will be described in the Statistical Analysis Plan. 
5.1.1 
Subject Population(s) for Analysis 
Safety Population 
The Safety population consists of all subjects who received any amount of IP.   
Evaluable Population 
The evaluable population consists of all subjects who received the entire dose of IP (2 g/kg 
over 2 consecutive days) and had valid Baseline and Day 14 QMG Score measurements. 

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Any deviations from the protocol will be recorded in the protocol deviation list. The validity 
of a subject for inclusion in each of these two populations (safety and evaluable) will be 
assessed at a review meeting that will take place before finalizing the database. The review 
meeting will review the protocol deviation list, as well as data listings. If additional protocol 
deviations are identified which justify removing a subject from any population, then these 
decisions will be documented. 
5.1.2 
Demographic and Baseline Characteristics 
Demographic and baseline characteristics will be summarized using descriptive statistics. 
5.1.3 
Efficacy Analyses 
Efficacy data will be summarized by visit on evaluable population and safety population (if 
different). 
5.1.3.1 
Primary Efficacy Analyses 
The primary efficacy variable is the change from Baseline in QMG score at Day 14. The 
primary efficacy variable will be summarized. A paired t-test (comparison between the pre 
and post) will be used to test for the treatment effect. The hypothesis test is to test the null 
hypothesis: H0: µd = 0 versus alternative hypothesis Ha: µd ≠ 0 where µd is the mean change 
from Baseline to Day 14.  
If the assumptions for parametric test are not met, the non-parametric test (Wilcoxon signed 
rank test) will be used.  
5.1.3.2 
Secondary Efficacy Analyses 
The following secondary efficacy variables will be summarized for evaluable population:  
• Percentage of subjects who experience a clinical improvement assessed by QMG from 
Baseline (Day 0) to Day 14 where clinical improvement is defined as at least 3 point 
decrease in QMG 
• Percentage of subjects who experience a clinical improvement assessed by MG-ADL 
from Baseline (Day 0) to Day 14 where clinical improvement is defined as at least 2 point 
decrease in MG-ADL 
• Percentage of subjects who experience a clinical improvement assessed by the MG 
Composite from Baseline (Day 0) to Day 14 where clinical improvement is defined as at 
least 3 point decrease in the MG Composite 
 
5.1.3.3 
Exploratory Efficacy Analyses 
Summary statistics will be provided and paired t-test or Wilcoxon signed rank test will be 
used for testing the treatment effect at different visits for:  
• Change in QMG score from Baseline (Day 0) to Day 7, Day 21 and Day 28 
• Change in MG-ADL from Baseline (Day 0) to Day 7, Day 14, Day 21 and Day 28 

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• Change in MG Composite from Baseline (Day 0) to Day 7, Day 14, Day 21 and Day 28 
• Change in AChR antibodies (or MuSK antibodies) from Baseline (Day 0) to Day 14 and 
Day 28 
• Change in IgG levels from Baseline (Day 0) to Day 1 (after completion of infusion), Day 
7, Day 14, Day 21 and Day 28 
 
The number and percentage of subjects who experience a clinical improvement based on the 
following measures and at the following timepoints will be summarized.  
• Clinical improvement in QMG score from Baseline (Day 0) to Day 7, Day 21 and Day 28 
where clinical improvement is defined as at least 3 point decrease in QMG score 
• Clinical improvement in MG-ADL from Baseline (Day 0) to Day 7, Day 14, Day 21 and 
Day 28 where clinical improvement is defined as at least 2 point decrease in MG-ADL 
• Clinical improvement in MG Composite from baseline (Day 0) to Day 7, Day 14, Day 21 
and Day 28 where clinical improvement is defined as at least 3 point decrease in MG 
Composite 
 
The number of subjects who need ICU admission, the length of ICU stay, need for 
intubation, and length of intubation will be collected and summarized.  
5.1.4 
Safety Analyses 
The safety analysis will be based on safety population. 
The safety analyses will be addressed by listing and tabulation of AEs (includes suspected 
ADRs), vital signs, physical assessments and clinical laboratory tests. Data will be described 
using descriptive analyses. 
• Adverse events: 
 
Safety analysis will be primarily focused on a descriptive analysis of suspected ADRs. Safety 
assessment will be based on the prevalence of suspected ADRs that occurred during the 
clinical trial. 
Adverse events will be coded and classified using MedDRA® terms (system organ class and 
preferred terms).  
Adverse events will be classified as TEAEs or non-TEAEs depending on the comparison of 
AE onset date/time with the start date/time of study treatment with the IP. A TEAE will be 
defined as an AE which occurs between the beginning of the first infusion of IGIV-C and the 
final visit of the clinical trial. A non-TEAE will be defined as an AE which occurs prior to 
the 1st dose of IP. Non-TEAEs and TEAEs will be summarized separately.  
All AEs will be summarized by presenting subject incidences and percentages, and they will 
also be listed by body systems with subject identification codes.   

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In addition, TEAEs, including suspected ADRs, will be summarized, system organ class, 
preferred term, causal-relationship, intensity (severity) and seriousness (serious vs. non-
serious) using descriptive statistics. At each level of summarization, a subject will only be 
counted once per system organ class or preferred term using the most severe or causal 
relationship AE.  
AEs temporally associated to the infusion of the IP (i.e., infusional AEs, including infusional 
suspected ADRs), will be summarized by presenting infusion/subject incidences and 
percentage and listed. In addition, the infusion rate in effect at the time of onset of the AE, 
the time the AE is first reported and the time the AE changes materially in intensity and/or 
resolves will be also reported and listed. 
Subjects with deaths, SAEs, suspected ADRs and AEs leading to premature discontinuation 
from the study will be listed and presented in a narrative form.   
AEs for which the Investigator causality assessment is missing or undetermined will be 
individually listed. 
• Vital signs: 
Vital signs (T, RR, HR, SBP and DBP) will be listed for each clinical trial subject. 
Abnormal vital signs judged as clinically relevant by the Investigator will be considered 
AEs. In case a subject presents a clinically relevant abnormality of vital signs during an 
infusion, the event will be flagged and reported as an AE temporally associated to the 
infusion. For each subject and for each infusion, every vital sign will be considered. 
Clinical relevance will be based on the Investigator’s criteria.   
 
• Physical Assessment: 
Physical Exam findings (normal and abnormal) will be listed for each clinical trial 
subject. Abnormal findings judged as clinically relevant by the Investigator will be 
considered AEs.  
 
• Blood biochemistry and hematology: 
All clinical laboratory data for renal (creatinine, BUN), hepatic (ALT, AST, ALP, and 
TBL) and haematological parameters (CBC including differential leukocyte count) will 
be listed for each clinical trial subject. Laboratory results out of the normal range judged 
by the Investigator as clinically relevant will be considered AEs. 
 
• Lab tests for TEs and hemolysis: 
The D-dimer for TE assessment and the laboratory tests for detecting hemolysis 
(including whole blood hemoglobin, serum or plasma free hemoglobin, haptoglobin, 
LDH, DAT, ARC, RBC, hematocrit, TBL and indirect bilirubin, and blood smear) will be 
listed and out of normal range results will be flagged.  
 
5.2 
Determination of Sample Size 
The data analysis from the single center study by Zinman et al (24) indicated that the SD for 
change from Baseline to Day 14 in QMG score is in the range of 2.74 – 3.48. To be 

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conservative considering multi-national study, the SD of 6.0 for QMG score change from 
Baseline to Day 14 is assumed, with 2-sided test, 33 subjects are needed to have 90% power 
to detect a clinically significant improvement of 3.5 in mean change in QMG (24). Fifty 
subjects are planned to be enrolled for the study. 
6 
ADMINISTRATIVE 
6.1 
Investigators, Other Study Personnel and External Committees 
Information regarding additional key personnel involved in the conduct of the study, 
including names and contact details of participating Investigators, monitors, clinical 
laboratories, technical departments and/or institutions, as well as information on members of 
additional study committees, will be found in the study files of the Sponsor and at the 
Investigator sites within the Study Reference Manual/file. 
Investigators and staff will receive training via an Investigators meeting, site initiation visit 
or other appropriate individual site training session(s). 
6.2 
Data Quality 
Monitoring and auditing procedures defined/agreed by the Sponsor will be followed, in order 
to comply with ICH GCP guidelines. Each center will be visited at regular intervals by a 
monitor to ensure compliance with the study protocol, ICH GCP and legal aspects. The on-
site verification of the eCRF for completeness and clarity will include cross checking with 
source documents and clarification of administrative matters. Query verification of data will 
be described in the Data Management Plan. 
6.3 
Documentation 
The study data will be recorded and kept current in the eCRF by the site study personnel 
directly responsible for the information. Entries made in the eCRF must be verifiable against 
source documents or have been directly entered into the eCRF, in which case the entry in the 
eCRF will be considered the source data. 
The data in the eCRF will be monitored at the site by Grifols Therapeutics Inc. 
representatives at regular intervals and reviewed for completeness and compared with the 
source documents. Examples of source documents include individual subject medical 
records, which are separate from the eCRFs. 
All AEs and SAEs must be recorded. All SAEs must be recorded on the SAE form. The SAE 
form must be kept in site records with a copy provided to the designated person as detailed in 
Section 4.4.9. 
6.3.1 
Record Retention 
At study completion, all study data will be transferred to Grifols Therapeutics Inc. according 
to ICH GCP guidelines, local laws, regulations and Grifols Therapeutics Inc. requirements. 

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The study file and all source data should be retained until notification is given by the Sponsor 
for destruction. 
An Investigator is required by ICH GCP guidelines to retain the study files. If an Investigator 
moves, withdraws from an investigation or retires, the responsibility for maintaining the 
records may be transferred to another person (e.g., other Investigator). Grifols Therapeutics 
Inc. must be notified in writing of the person responsible for record retention and the 
notification will be retained in the Sponsor study file and the Investigator site file. 
6.3.2 
Access to Information for Monitoring 
The data will be recorded and kept current in eCRFs by the study site personnel directly 
responsible for the information and reviewed for completeness by the monitor. Grifols 
Therapeutics Inc. personnel or designee can review the records. 
In accordance with ICH GCP guidelines, the monitor must have direct access to the 
Investigator’s source documentation in order to verify the data recorded in the eCRFs for 
consistency and to verify adherence to the protocol and the completeness, consistency and 
accuracy of data entered. “Source documentation” includes individual subject files, separate 
from the eCRFs, which should be maintained and include visit dates, laboratory results, 
concomitant treatment, vital signs, medical history, examinations, AEs, IP dispensing logs 
and other notes as appropriate. The Investigator agrees to cooperate with the monitor to 
ensure that any problems noted during the course of these monitoring visits are resolved. 
6.3.3 
Access to Information for Audits or Inspections 
Representatives of regulatory authorities or of Grifols Therapeutics Inc. may conduct audits 
or inspections of the Investigator study site. If the Investigator is notified of an audit or 
inspection by a regulatory authority, the Investigator agrees to notify the Grifols Therapeutics 
Inc. Medical Monitor immediately. The Investigator agrees to provide to representatives of a 
Regulatory Agency or Grifols Therapeutics Inc. access to records, facilities and personnel for 
the effective conduct of an audit or inspection. 
7 
ETHICAL AND LEGAL ASPECTS 
7.1 
Institutional Review Board/Ethics Committee   
Documented approval from appropriate IRBs/ECs will be obtained for all participating 
centers/countries prior to study start, according to ICH GCP guidelines, local laws, 
regulations and organizations. When necessary, an extension, amendment or renewal of the 
IRBs/ECs approval must be obtained and also forwarded to the Sponsor. The IRBs/ECs must 
supply to the Sponsor, upon request, a list of the IRBs/ECs members involved in the vote and 
a statement to confirm that the IRB/EC is organized and operates according to ICH GCP 
guidelines and applicable laws and regulations. 

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7.2 
Ethical Conduct of the Study 
The procedures set out in this protocol, pertaining to the conduct, evaluation and 
documentation of this study, are designed to ensure that the Sponsor and Investigator abide 
by ICH GCP guidelines. The study will also be carried out in keeping with applicable local 
law(s) and regulation(s). This may include an audit by the Sponsor representatives and/or an 
inspection by Regulatory Authority representatives at any time. The Investigator must agree 
to the audit or inspection of study-related records by the Sponsor representatives and/or 
Regulatory Authority representatives and must allow direct access to source documents to the 
Sponsor and/or Regulatory Authority representatives. 
Modifications to the study protocol will not be implemented by either the Sponsor or the 
Investigator without agreement by both parties. However, the Investigator may implement a 
deviation from, or a change to, the protocol to eliminate an immediate hazard(s) to the study 
subjects without prior IRB/EC/Sponsor approval/favorable opinion. As soon as possible, the 
implemented deviation or change, the reasons for it and if appropriate the proposed protocol 
amendment should be submitted to the IRB/EC/Sponsor. Any deviations from the protocol 
must be fully explained and documented by the Investigator. 
7.3 
Regulatory Authority Approvals/Authorizations 
Regulatory Authority approvals/authorizations/notifications, where required, must be in place 
and fully documented prior to study start. Study information including contact information 
for Investigator sites responsible for conducting the study will be posted on a publicly 
accessible clinical registry(ies) as required by local law. 
7.4 
Subject Information and Informed Consent Form 
Subject information and ICF will be provided to Investigator sites. Prior to the beginning of 
the study, the Investigator must have the IRB/EC written approval/favorable opinion of the 
written ICF and any other written information to be provided to subjects. The written 
approval of the IRB/EC together with the approved subject information/ICF must be filed in 
the study files and a copy of the documents must also be provided to Sponsor by the 
Investigator site.  
Written ICF must be obtained before any study specific procedure takes place. Considering 
the nature of this emergency indication, potential subjects may receive information regarding 
the study in advance of experiencing an MG exacerbation. However, when experiencing an 
MG exacerbation, the subject or legally authorized representative will be informed again and 
will sign the written ICF prior to any study specific procedure being conducted.  
 
If applicable, a legally authorized representative may provide informed consent on behalf of 
the subject. Participation in the study and date of ICF given by the subject should be 
documented appropriately in the subject’s files. A signed copy of the subject ICF will be 
provided to the subject or subject’s authorized representative. 

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7.5 
Insurance 
All subjects participating in the study will have insurance coverage by the Sponsor, which is 
in line with applicable laws and/or regulations. 
7.6 
Confidentiality 
All records identifying the subject will be kept confidential and, to the extent permitted by 
the applicable laws and/or regulations, will not be made publicly available. 
Subject names will not be supplied to the Sponsor. Only the subject number will be recorded 
in the eCRF, and if the subject’s name appears on any other document (eg, pathologist 
report), it must be obliterated before a copy of the document is supplied to the Sponsor. 
Study findings stored on a computer will be stored in accordance with local data protection 
laws. Subjects will be informed in writing that representatives of the sponsor, IRB/EC or 
Regulatory Authorities may inspect their medical records to verify the information collected 
and that all personal information made available for an audit or inspection will be handled in 
strictest confidence and in accordance with local data protection laws. 
If the results of the study are published, the subject’s identity will remain confidential.  
The Investigator will maintain a list to enable subjects’ records to be identified. 
8 
USE OF DATA AND PUBLICATION 
Institution and the Investigator agree that the first publication shall be made in conjunction 
with the presentation of a joint, multi-center publication of the study results from all 
appropriates sites. If such a multi-center publication is not submitted within twelve (12) 
months after conclusion of the study at all sites or after Grifols confirms there will be no 
joint, multi-center publication, then institution and/or Investigator shall have the right, at 
their discretion, to publish, either in writing or orally, the results of the study performed 
under the protocol, subject to the conditions outlined below: 
• The results of the study will be reported in the publicly accessible registry(ies). 
• Institution and/or Investigator shall furnish Grifols with a copy of any proposed 
publication at least thirty (30) days in advance of the date of submission for publication.   
• Within said thirty (30) day period, Grifols shall:   
- 
Review such proposed publication for Confidential Information (other than Study 
results) and for subject information subject to the Health Insurance Portability and 
Accountability Act of 1996 (“HIPAA”) and other applicable privacy laws; 
- 
Review such proposed publication for the unauthorized use of the name, symbols 
and/or trademarks of Grifols; 
- 
By written notice to the Investigator, identify with specificity the text or graphics in 
such proposed publication that Grifols contends contains Confidential Information, 
protected subject information or the unauthorized use of Grifols’ name, symbols 
and/or trademarks so that the proposed publication may be edited appropriately to 
remove such text or graphics before publication; and  

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- 
By written request, Grifols may delay proposed publications up to sixty (60) days to 
allow Grifols to protect its interests in Grifols Inventions described in such 
publications.   
• Institution and/or Investigator shall give Grifols the option of receiving an 
acknowledgment for its sponsorship of the study in all such publications or presentation.  

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9 
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15. Godoy DA, Vaz de Mello LJ, Mascotti L, et al. The myasthenic patient in crisis: an 
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23. Gajdos P, Chevret S, Toyka KV. Intravenous immunoglobulin for myasthenia gravis. 
Cochrane Database of Systematic Reviews 2012, Issue 12. 
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25. Barth D, Nabavi M, Nouri, Ng E, et al. Comparison of IVIg and PLEX in patients with 
myasthenia gravis. Neurology 2011; 76: 2017–2023. 
26. Gajdos P, Tranchant C, Clair B, et al. Treatment of myasthenia gravis exacerbation with 
intravenous immunoglobulin: a randomized double-blind clinical trial. Archives of 
Neurology 2005; 62(11): 1689–1693. 
27. Hughes RAC, Swan AV, van Doorn PA. Intravenous immunoglobulin for Guillain-Barré 
syndrome. Cochrane Database of Systematic Reviews 2012;7. Art. No.: CD002063. DOI: 
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28. Benatar M, Sanders DB, Burns T, et al. Recommendations for myasthenia gravis clinical 
trials. Muscle Nerve 2012;45: 909-917. 
29. Burns TM, Conaway M, Sanders DB, et al. The MG composite: A valid and reliable 
outcome measure for myasthenia gravis. Neurology 2010; 74: 1434-1440. 
30. Burns TM. The MG composite: an outcome measure for myasthenia gravis for use in 
clinical trials and everyday practice. Ann. N.Y. Acad. Sci. 2012; 1274: 99-106. 
31. Muppidi S. The myasthenia gravis-specific activities of daily living profile. Ann. N.Y. 
Acad. Sci. 2012; 1274: 114-119. 
32. Karch FE, Lasagna L. Adverse drug Reactions. A critical review. JAMA 1975; 234: 
1236-1241. 
33. Karch FE, Lasagna L. Towards the operational identification of adverse drug reactions. 
Clin Pharmacol Ther 1977; 21: 247-254. 
34. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of 
adverse drug reactions. Clin Pharmacol Ther 1981; 30: 239-245. 
35. http://www.who.int/classifications/icd/en/ 
36. Wells PS. Integrated strategies for the diagnosis of venous thromboembolism. J Thromb 
Haemost 2007; 5 Suppl 1: 41-50. 
37. Adam SS, Key NS, Greenberg CS. D-dimer antigen: current concepts and future 
prospects. Blood 2009; 113(13): 2878-2887. 
38. Health Canada. Canadian Adverse Reaction Newsletter. Intravenous immune globulin 
(IVIG): hemolytic reactions. 2009; 19(4).  
39. Thavendiranathan P, Bagai A, Ebidia A, et al. Do Blood Tests Cause Anemia in 
Hospitalized Patients? The Effect of Diagnostic Phlebotomy on Hemoglobin and 
Hematocrit Levels. J Gen Intern Med 2005; 20: 520–524. 
40. Tuncer Elmaci N, Ratip S, Ince-Günal D, et al. Myasthenia gravis with thymoma and 
autoimmune haemolytic anaemia. A case report. Neurol Sci. 2003; 24(1): 34-36. 
41. Chant C, Wilson G, Friedrich J. Anemia, transfusion, and phlebotomy practices in 
critically ill patients with prolonged ICU length of stay: a cohort study. Critical Care 
2006, 10:R140 (doi:10.1186/cc5054). 
42. Kameoka J, Endo K, Sugawara T, et al. Autoimmune hemolytic anemia and myasthenia 
gravis. Jpn J Med. 1991; 30(4): 330-332. 
43. http://www.who.int/classifications/icd/en/ 

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44. Wells PS. Integrated strategies for the diagnosis of venous thromboembolism. J Thromb 
Haemost 2007; 5 Suppl 1: 41-50. 
45. Adam SS, Key NS, Greenberg CS. D-dimer antigen: current concepts and future 
prospects. Blood 2009; 113(13): 2878-2887. 
46. Health Canada. Canadian Adverse Reaction Newsletter. Intravenous immune globulin 
(IVIG): hemolytic reactions. 2009; 19(4).  
47. Thavendiranathan P, Bagai A, Ebidia A, et al. Do Blood Tests Cause Anemia in 
Hospitalized Patients? The Effect of Diagnostic Phlebotomy on Hemoglobin and 
Hematocrit Levels. J Gen Intern Med 2005; 20: 520–524. 
48. Tuncer Elmaci N, Ratip S, Ince-Günal D, et al. Myasthenia gravis with thymoma and 
autoimmune haemolytic anaemia. A case report. Neurol Sci. 2003; 24(1): 34-36. 
49. Chant C, Wilson G, Friedrich J. Anemia, transfusion, and phlebotomy practices in 
critically ill patients with prolonged ICU length of stay: a cohort study. Critical Care 
2006, 10:R140 (doi:10.1186/cc5054). 
50. Kameoka J, Endo K, Sugawara T, et al. Autoimmune hemolytic anemia and myasthenia 
gravis. Jpn J Med. 1991; 30(4): 330-332. 
 

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10 APPENDICES 
 
 

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Appendix 1 
Schedule of Study Procedures 
Visit Type 
Baseline Visit 
Study Visit 
Study Visit 
Study Visit 
Final Study /Early 
Discontinuation Visit 
Study Day  
Day 0 
Day 1 
Day 7 a 
Day 14 a 
Day 21 a 
Day 28 a 
Informed Consent 
X 
 
 
 
 
 
Subject Number Assigned 
X 
 
 
 
 
 
Inclusion/Exclusion Criteria  
X 
  
 
 
 
 
Medical History b  
X 
 
 
 
 
 
Physical Exam c 
X 
 
 
 
 
X 
Height 
X 
 
 
 
 
 
Weight d 
X 
 
 
 
 
 
Vital Signs e 
X 
X 
X 
X 
X 
X 
Viral NAT/Serology 
X k, n 
 
 
 
 
X n 
Urine Pregnancy Test f 
X 
 
 
 
 
X 
Biochemistry and Hematology 
X k 
 
 
 
 
X 
Thromboembolic events risk monitoring 
X k 
X m 
X 
 
 
X 
Hemolysis assessment g 
X k 
X m 
X 
 
 
X 
Biomarker Retains (only for subjects who provide consent for this 
portion of the study) 
X k 
 
X 
X 
X 
X 
AChR (or MuSK) Antibody testing (See Section 3.7.3.4 for details) 
X k 
 
 
X 
 
X 
QMG scale 
X k 
 
X 
X 
X 
X 
MG-Composite Scale 
X k 
 
X 
X 
X 
X 
MG-ADL 
X 
 
X 
X 
X 
X 
IgG levels 
X k 
X l 
X 
X 
X 
X 
Preparation/Dispensing of IP h 
X 
X 
 
 
 
 
IP Infusion i 
X j 
X 
 
 
 
 
AE Assessment 
X 
X 
X 
X 
X 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
X 

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Note: Each MG assessment should be performed by the same clinical staff member whenever possible. 
a 
A ± 1 day window is allowed for Study Visits at Days 7 and 14. A ± 2 day window is allowed for study visits at Days 21 and 28 
b 
Includes demographics and concomitant diseases 
c 
Excludes breast and genitourinary exam 
d 
The recorded weight will be used to calculate the IP infusion dose at the Baseline (Day 0, Day 1) Visit 
e 
Vitals signs will be monitored per standard site/caregiver procedures; any clinically significant vital sign will be recorded as an AE in the eCRF 
f 
Potential child-bearing females only; results must be negative for subject to continue in the study 
g 
Local laboratory is to be utilized for testing and reporting. If the local laboratory is unable to perform any of the assessments, the central laboratory may be 
utilized. 
h 
To be performed by a pharmacist, or designee, per the Pharmacy Manual 
i 
Documentation of total infusion volume prepared (as received from pharmacist or designee), total time to infuse, total volume infused, and, if necessary, any 
infusion interruption with explanation. Please refer to Section 3.7.2.1 to review monitoring vital signs during the two consecutive infusions on Day 0 and 
Day 1 
j 
Inclusion/exclusion criteria must be satisfied before the subject receives the first IP infusion 
k 
Samples (or assessments) to be collected (or conducted) within 8 hours prior to IP infusion on Day 0 
l 
Sample to be collected 30 ± 10 minutes post-completion of the IP infusion on Day 1. 
m 
Samples (or assessments) to be collected (or conducted) between 8 and 24 hours post-completion of  IP infusion on Day 1 
n 
Collect samples but test only if the subject exhibits clinical signs and symptoms consistent with hepatitis A, hepatitis B, hepatitis C, HIV, or parvovirus B19 
infection while participating in the study; These samples will be retained until all analyses in support of the study are complete; see Table 3-1. 
 

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Appendix 2 
MGFA Clinical Classification 
Classification 
Description 
Class I 
Any ocular muscle weakness; may have weakness of eye closure. All other 
muscle strength 
Class II 
Mild weakness affecting muscles other than ocular muscles; may also have 
ocular muscle weakness of any severity 
IIa 
Predominantly affecting limb, axial muscles, or both. May also have lesser 
involvement of oropharyngeal muscles 
IIb 
Predominantly affecting oropharyngeal, respiratory muscles, or both. May 
also have lesser or equal involvement of limb, axial muscles, or both 
Class III 
Moderate weakness affecting muscles other than ocular muscles; may also 
have ocular muscle weakness of any severity 
IIIa 
Predominantly affecting limb, axial muscles, or both. May also have lesser 
involvement of oropharyngeal muscles 
IIIb 
Predominantly affecting oropharyngeal, respiratory muscles, or both. May 
also have lesser or equal involvement of limb, axial muscles, or both 
Class IV 
Severe weakness affecting muscles other than ocular muscles; may also 
have ocular muscle 
IVa 
Predominantly affecting limb, axial muscles, or both. May also have lesser 
involvement of oropharyngeal muscles 
IVb 
Predominantly affecting oropharyngeal, respiratory muscles, or both. May 
also have lesser or equal involvement of limb, axial muscles, or both 
Class V 
Defined as intubation, with or without mechanical ventilation, except when 
employed during routine postoperative management. The use of a feeding 
tube without intubation places the patient in class IVb 

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Appendix 3 
QMG Test Items 
 

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Appendix 4 
MG Composite Scale 
 

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Appendix 5 
MG Activities of Daily Living (MG-ADL) Profile 
 
 
   

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Appendix 6 
Monitoring of Thromboembolic Events Risk  
Subjects will be monitored for signs and symptoms of arterial and venous thromboembolic 
(TE) events. Arterial and venous TE events will be identified according to definitions in the 
International Classification of Diseases (ICD) [35]. Such events include, but are not limited 
to, deep vein thrombosis (DVT), pulmonary embolism (PE), acute myocardial infarction, 
cerebral infarction, acute ischemic heart disease, embolism or thrombosis of arteries of lower 
extremities, sagittal sinus thrombosis, portal vein thrombosis and injury of mesenteric artery.   
All TE events will be recorded as adverse events (AEs) and reported accordingly. Any TE 
event fulfilling any of the criteria for “serious” will be reported as a serious adverse event 
(SAE). 
The Sponsor’s Medical Monitor (or designee) will routinely review reported AEs for possible 
TE events. 
Thromboembolic events risk will be determined by the Investigator or appropriate study staff 
as indicated by the following schedule (Table 1): 
Table 1. Schedule of Monitoring of Thromboembolic Events Risk 
 
Study visit 
Wells score 
D-dimer 
Signs & symptoms of 
DVT and PE* 
Day 0 (prior IP infusion) 
X 
X 
(within 8 hours prior IP infusion) 
X 
Day 1 (post-completion 
IP infusion) 
X 
 
X 
(between 8 and 24 hours post-
completion of  IP infusion) 
X 
Day 7 (±1 day) 
X 
X 
X 
Day 28 (±2 days) 
X 
X 
X 
* Evaluation of clinical signs and symptoms of arterial and venous TE as part of AEs 
assessment. 
Monitoring of thromboembolic events risk may be performed later, once laboratory results 
are available, blood collection for the D-dimer testing as well as the Wells score and 
evaluation signs and symptoms of DVT and PE must be performed as stated in the schedule 
of procedures. 
Thromboembolic events risk will be determined using the following assessments:  
1. The Wells Score [36] will be utilized to assess the clinical characteristics indicative of 
possible DVT or PE (Table 2);  
2. Measurement of D-dimer blood levels [37];  
3. Evaluation of clinical signs and symptoms of arterial and venous TE as part of AEs 
assessment.  

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Table 2. Schedule of Monitoring of Thromboembolic Events Risk 
 
DEEP VEIN THROMBOSIS 
 
Clinical Characteristic 
Score 
Active cancer (treatment ongoing, within previous 6 months or palliative) 
  1 
Paralysis, paresis, or recent plaster immobilization of the lower extremities 
  1 
Recently bedridden >3 days or major surgery within previous 12 weeks 
requiring general or regional anesthesia 
  1 
Previously documented DVT 
  1 
Localized tenderness along distribution of deep venous system 
  1 
Entire leg swollen 
  1 
Calf Swelling 3 cm larger than asymptomatic side (measured 10 cm below 
tibial tuberosity) 
  1 
Pitting edema confined to the symptomatic leg 
  1 
Collateral superficial veins (non-varicose) 
  1 
Alternative diagnosis at least as likely as DVT 
 -2 
Total Score:  
PULMONARY EMBOLISM 
 
Clinical Characteristic 
Score 
Previous DVT or PE  
  1.5 
Surgery or bedridden for 3 days during past 4 weeks 
  1.5 
Active cancer (treatment within 6 months or palliative) 
  1 
Hemoptysis 
  1 
Heart rate > 100 beats/min 
  1.5 
Clinical signs of DVT 
  3 
Alternative diagnosis less likely than PE 
  3 
Total Score: 
 
 

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Thromboembolic events risk will be assessed according to the following algorithm adapted 
from Wells [36] (Figure 1 and Figure 2):  
Figure 1. Algorithm to Assess Thromboembolic Events Risk for DVT 
•
The Wells Score
•
D-dimer
•
Signs & symptoms of TE
No TE risk
The Wells Score 
(>1 in DVT)
TE risk
The Wells Score 
(≤1 in DVT)
D-dimer (-)
D-dimer (-)
D-dimer (+)
D-dimer (+)
Signs & 
symptoms of 
TE (present)
Signs & 
symptoms of TE 
(not present)
No TE risk
TE risk
TE risk 
 
Any subject with a total Wells prediction score >1 for DVT assessment should have further 
diagnostic testing per study site standard of care to confirm the occurrence of a TE  
(Figure 1).  
Any subject with a total Wells prediction score ≤1 for DVT assessment and a positive D-
dimer value (i.e., above Baseline and out of normal range of the reporting laboratory) in 
combination with clinical signs or symptoms of a TE (as per AEs assessment and such as 
pain, dyspnea, discoloration -paleness or redness- in lower extremities) should have further 
diagnostic testing per study site standard of care to confirm the occurrence of a TE  
(Figure 1).  
 
 
 

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Figure 2. Algorithm to Assess Thromboembolic Events Risk for PE 
 
•
The Wells Score
•
D-dimer
•
Signs & symptoms of TE
No TE risk
The Wells Score 
(>4 in PE)
TE risk
The Wells Score 
(≤4 in PE)
D-dimer (negative)
D-dimer (positive)
TE risk
D-dimer (negative)
D-dimer (positive)
TE risk
 
Any subject with a total Wells prediction score >4 for PE assessment should have further 
diagnostic testing per study site standard of care to confirm the occurrence of a TE  
(Figure 2).  
Any subject with a total Wells prediction score ≤4 for PE assessment and a positive D-dimer 
value (i.e., above Baseline and out of normal range of the reporting laboratory) should have 
further diagnostic testing per study site standard of care to confirm the occurrence of a TE 
(Figure 2).  
 
 
 
 

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Appendix 7 
Hemolysis Detection 
Schedule of the Procedures: 
Study visit 
Blood collection 
Urine collection 
Clinical 
parameters 
Hemolysis 
detection 
assessment 
Day 0 (prior IP 
infusion) 
X 
(within 8 hours 
prior IP infusion) 
X 
(within 8 hours 
prior IP infusion) 
X 
X 
Day 1 (post-
completion of IP 
infusion) 
X 
(between 8 and 24 
hours post-
completion of IP 
infusion) 
X 
(between 8 and 24 
hours post-
completion of IP 
infusion) 
X 
X 
Day 7 (± 1 day) 
X 
X 
X 
X 
Day 28 (± 2 days) 
X 
X 
X 
X 
Assessment of hemolysis detection may be performed later, once laboratory results are 
available, blood and urine collection as well as the evaluation of clinical parameters must be 
performed as stated in the schedule of procedures. 
 
Description of the procedures: 
For the detection of hemolysis, the following procedure will be carried out to all the study 
population: 
1. Blood testing: whole blood hemoglobin, serum or plasma free hemoglobin, haptoglobin, 
LDH, DAT, ARC, RBC, hematocrit, TBL and indirect bilirubin, and blood smear. 
2. Urine testing: urinary sediment and hemoglobinuria. 
3. Clinical parameters including red/dark urine, jaundice, as well as other signs and 
symptoms of anemia (such as pallor or tachycardia). 
 
 
Definition of hemolysis associated with the use of IGIV:  
In this clinical trial, an IVIG-associated hemolytic reaction is one in which there is evidence 
of a new hemolytic process within 7 days of the first IGIV administration [38]. The following 
laboratory signs must be present:  
1. Drop in whole blood hemoglobin of ≥ 10 g/L* 
AND 
2. Positive DAT 
AND 
3. At least 2 of: 

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- 
increased ARC* 
- 
hemoglobulemia 
- 
increased LDH level* 
- 
hemoglobinuria 
- 
significant spherocytosis 
- 
low haptoglobin level* 
- 
unconjugated hyperbilirubinemia 
 
*Changes from the previous blood testing i.e. from Day 0 to Day 1, from Day 1 to Day 7 (±1 day) 
and from Day 7 (±1 day) to Day 28 (±2 days).  
 
Subjects from this study may be severely ill and may have anemia for a number of reasons. 
Therefore, it is important to exclude the underlying conditions and concomitant medications 
as a cause of anemia. The exclusions are: 
- 
History or examination consistent with an alternative cause of anemia including blood 
loss (e.g. frequent phlebotomy is highly associated with changes in hemoglobin and 
hematocrit levels for patients admitted to an internal medicine service [39-40]), iron-
deficiency anemia, other drug-induced hemolytic anemia, or anemia associated with an 
underlying disease (e.g. autoimmune hemolytic anemia [41-42]). 
- 
Negative DAT. 
- 
Absence of other inclusion criteria, in particular absence of evidence for hemolysis. 
 

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Appendix 8 
Summary of Changes for Amendment 3 
(Note: Administrative changes including minor administrative corrections and the changes in the protocol synopsis are not included in 
Protocol Summary of Changes.) 
Sections 
Change From: 
(Strikethrough is added to highlight deleted text): 
Change To: 
(Underline is added to highlight new text) 
Rationale: 
3.2.2 – Exclusion 
Criteria 
15. Subjects with a history of chronic alcoholism or 
illicit drug abuse (addiction) in the 12 months 
preceding the Screening Visit. 
 
19. Subjects currently receiving, or having received 
within 3 months prior to the Screening Visit, any 
investigational medicinal product or device. 
 
24. Subjects with haemoglobin levels <9mg/dL. 
15. Subjects with a history of chronic alcoholism or 
illicit drug abuse (addiction) in the 12 months 
preceding the Baseline Visit. 
 
19. Subjects currently receiving, or having received 
within 3 months prior to the Baseline Visit, any 
investigational medicinal product or device. 
 
24. Subjects with haemoglobin levels <9g/dL. 
Clarification provided as 
there is no Screening Visit 
in this study. 
 
 
 
 
 
Haemoglobin units 
corrected.