Clinical trial NCT02473965
Conditions: Myasthenia Gravis
Sponsor: Grifols Therapeutics LLC
Start date: 2015-06-01; Completion date: 2019-02-01
Enrollment: 60 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of Immune Globulin (Human), 10% Caprylate/Chromatography Purified (IGIV-C) as a corticosteroid (CS)-sparing agent in subjects with CS-dependent Myasthenia Gravis (MG).

Detailed description:
This study consists of 2 phases: IGIV-C Run-in Phase and Corticosteroid Tapering/IGIV-C Maintenance Phase.

In the Run-in Phase, subjects will receive a total of 3 doses of IGIV-C (1 loading dose of 2 g/kg and 2 maintenance doses of 1 g/kg) while maintaining a stable dose of corticosteroids.

In the CS Tapering/IGIV-C Maintenance Phase, subjects will continue 1 g/kg IGIV-C and begin a prescribed CS tapering regimen where the CS dose is decreased every 3 weeks.

Approximately 60 subjects are planned to be enrolled in the study across multiple centers in North America and Europe. The total duration of study participation for each subject is up to 45 weeks.

Arms: arm 1: An IGIV-C loading dose of 2 g/kg and maintenance dose of 1 g/kg will be administered in CS dependent subjects with MG. arm 2: 0.9% sodium chloride injection, USP or equivalent
Interventions: intervention 1: IGIV-C intervention 2: Placebo
Intervention descriptions: intervention 1: Run-Phase: 1 loading dose of 2 g/kg IGIV-C and 2 maintenance doses of 1 g/kg IGIV-C

Corticosteroid Tapering/IGIV-C Maintenance Phase: 1 g/kg IGIV-C every 3 weeks for up to 36 weeks intervention 2: None

Protocol documents:
Prot_001.pdf: 


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Summary of Changes for Amendment 2
Protocol Version
Date of Approval
3.0
Amendment 2 + Integrated Protocol
23 Dec 2016
2.0
Amendment 1 + Integrated Protocol
15 Jul 2015
1.0
Original
20 Aug 2014
Amendment 2
The protocol for GTI1306 (Version 2.0, dated 15 Jul 2015) has been amended and reissued 
as Protocol Amendment 2, Version 3.0, dated 23 Dec 2016. See Appendix 11for a summary 
of changes for Amendment .


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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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PROTOCOL SYNOPSIS
Title of Study:
A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the 
Efficacy and Safety of Immune Globulin (Human), 10% Caprylate/Chromatography Purified 
(IGIV-C) as a Corticosteroid Sparing Agent in Corticosteroid Dependent Patients with 
Generalized Myasthenia Gravis 
Study Number
GTI1306
Phase:
2
Number of Subjects Planned:
Approximately 60 adult subjects will be randomized in this study.
Study Centers Planned:
Approximately 40 study centers
Study Objectives:
The primary objective of this study is to evaluate the efficacy of intravenous (IV) infusions 
of IGIV-C as compared to Placebo in reducing the maintenance dosage of corticosteroids in 
corticosteroid (CS)-dependent subjects with myasthenia gravis (MG) by assessing the percent 
of subjects achieving a 50% or greater reduction in CS dose (prednisone or equivalent) at 
Week 39 (Visit 14) from Baseline/Week 0 (Visit 1).
The safety objective of this study is to evaluate the safety and tolerability of IGIV-C loading 
dose of 2 g/kg followed by 12 maintenance dosages of 1 g/kg every 3 weeks through Week 
36 in CS-dependent subjects with MG.
Target Population:
Eligible participants for this study will include adult subjects with a confirmed diagnosis of 
generalized MG who have required systemic CS therapy for at least the preceding three 
months prior to Screening in order to control their signs and symptoms of MG. Subjects may 
be receiving immunosuppressive therapies within the confines stipulated in eligibility criteria 
and stable dosage of acetylcholinesterase inhibitors (e.g., pyridostigmine, neostigmine).
Overall Study Description: 
Eligible subjects will be randomly allocated in a 1:1 ratio into IGIV-C treatment group and 
Placebo treatment group to receive either IGIV-C or matched Placebo every three weeks in a 
double-blinded fashion. Randomization will be stratified by baseline CS dose: 
!
15 mg to 40 mg prednisone equivalent per day
!
41 mg to 60 mg prednisone equivalent per day
For those subjects randomized to receive IGIV-C, an initial loading dose of 2 g/kg will be 
administered at the Baseline/Week 0 Visit (Visit 1). The loading dose is divided over 2 days 
as standard infusion time (extensions up to 4 days are allowed for tolerability issues or higher 


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weight, i.e., limit for IGIV-C infusion is no more than 80 g/day [corresponding to 80 kg body 
weight]). The loading dosage is followed by maintenance doses of 1 g/kg administered every 
third week until Visit 13 (Week 36). The maintenance dosage is infused in 1 day as standard 
infusion (extensions are allowed for divided dosage over 2 days for tolerability issues or 
higher weight, i.e., limit for IGIV-C infusion is no more than 80 g/day [corresponding to 80 
kg body weight]). For those subjects randomized to receive Placebo, sterile 0.9% sodium 
chloride injection, United States Pharmacopeia (USP) or equivalent will be infused at the 
Baseline/Week 0 Visit (Visit 1) in a manner that the blind is maintained. The volumes of 
Placebo will be equal to the volumes required for an initial loading dose of IGIV-C at the 
Baseline Visit (Visit 1) and subsequent maintenance doses will be administered every third 
week until Visit 13 (Week 36). 
Tapering of the CS dose will not be initiated until the subject receives a total of 3 complete 
doses of the investigational product (IP), including the initial loading dose (Week 0 [Visit 1]) 
and the first two maintenance doses (Week 3 [Visit 2] and Week 6 [Visit 3]). The subject will 
begin a prescribed CS tapering regimen at Week 9 [Visit 4], coincident with receiving the 
fourth dose of IP. The tapering will be based on the CS dose (prednisone equivalent) as 
described under Study Phases below. 
During the CS Tapering/IP Maintenance Phase, study visits will occur every three weeks 
while the subject continues his/her CS tapering and maintenance doses of IP. Implementation 
of the CS dose reductions will last a maximum of 27 weeks. The investigator will attempt to 
hold the non-CS therapy (e.g., pyridostigmine) of the subjects’ MG medical regimen constant 
through the end of the study (Week 45 [Visit 16]) unless there are worsening symptoms or 
adverse effects due to other components of the subject’s non-CS therapy.
During the CS Tapering Phase, the last CS dose reduction can occur at Week 36 (Visit 13). 
Week 39 (Visit 14) will constitute the time point for the primary endpoint, an opportunity to 
assess the effect of the final CS dose reduction made at Week 36 (Visit 13), and the initiation 
of the Safety/Follow-up Phase. 
Subjects will receive 3 safety/follow-up visits following the last dose of IP (Weeks 39, 42, 45 
corresponding to Visits 14, 15, 16, respectively). It is suggested that the investigator consider 
an increase in CS dose after subjects complete the Week 39 (Visit 14) assessments if 
considered medically indicated.
Study Phases:
1. Screening Period 
During the three-week Screening period, assessments will be performed to determine 
subject’s eligibility.
2. Investigational Product Run-in Phase:
Subjects will receive a total of 3 complete doses of the IP in the IP Run-In Phase, which 
includes the initial loading dose at the Baseline/Week 0 (Visit 1), and the first two 
maintenance doses at Weeks 3 and 6 (Visits 2 and 3). The CS dose will remain stable in this 


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phase. CS tapering will begin at Week 9 (Visit 4), coincident with the third maintenance dose 
of IP.
3. Corticosteroid Tapering/IP Maintenance Phase  
After completion of the third maintenance dose at Week 9 (Visit 4), subjects will begin a 
prescribed tapering regimen of their CS dose as described below.
CS Tapering Regimen: CS dosage in subjects will be decreased at scheduled visits every 
three weeks during the CS Tapering Phase (Week 9 through Week 36 [Visit 4 through Visit 
13], inclusive) as described in the tables below, provided that clinical status has not 
worsened.
The final CS taper step from 5 mg prednisone equivalent daily to 0 mg prednisone equivalent 
daily is the Principal Investigator’s decision and is not mandatory per protocol. The Principal 
Investigator may choose to taper to 0 mg prednisone equivalent daily based on best medical 
judgment for each subject given individual variability with regards to sensitivity to complete 
CS withdrawal and perceived MG exacerbation risk while CS-free.
4.   Follow-up Visits
Subjects will receive 3 safety/follow-up visits at Weeks 39, 42, 45 (corresponding to Visits 
14, 15, 16, respectively). It is suggested that the investigator consider an increase in CS dose 
after subjects complete the Week 39 (Visit 14) assessments if considered clinically indicated.
Daily CS Dose Tapering (prednisone equivalent)
Daily CS Dose (mg/day)
Daily Dose Decrease (mg/day) every 3 weeks
> 40 
10
≤ 40
5
Every Other Day CS Dose Tapering (prednisone equivalent)
Every Other Day CS Dose (mg/every other 
day)
Every Other Day Dose Decrease (mg/every other 
day) every 3 weeks
> 80 mg every other day
decrease by 20 mg on CS dosing days (every other day)
≤ 80 mg every other day
decrease by 10 mg on CS dosing days (every other day)
Diagnosis and Main Eligibility Criteria: Eligible participants for this study will include 
adult subjects with a confirmed diagnosis of MG who have required systemic CS therapy for 
at least the preceding three months in order to control their signs and symptoms of MG. 
Subjects may be receiving immunosuppressive therapies within confines stipulated below 
and stable dosage of acetylcholinesterase inhibitors (e.g., pyridostigmine, neostigmine).
Inclusion Criteria:
A subject must meet all the following inclusion criteria to be eligible for participation in this 


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study:
1. Male or female ages 18 to 85 years
2. Anti-acetylcholine receptor (AChR) antibody positive
3. Confirmed diagnosis of generalized MG historically meeting the clinical criteria for 
diagnosis of MG defined by the Myasthenia Gravis Foundation of America (MGFA) 
classification of Class II, III, IV, or V historically (Appendix 2). 
4. At Screening, subjects may have symptoms controlled by CS (for example, only ocular 
[Class I] symptoms may be evident or there may be no symptoms) or be MGFA Class 
II-IVa inclusive (Class IVb and Class V excluded). Note: Subjects who only have a 
history of ocular MG may not enroll.
5. On systemic CS for a minimum period of at least three months and on a stable CS dose of 
≥15 mg/day and ≤60 mg/day (prednisone equivalent) for the month prior to Screening. 
Individuals on alternate day CS dosing will be judged to be on a daily dose equivalent to 
half their alternate day dose (i.e., 40 mg/every other day = 20 mg/day)
6. The investigator feels that tapering the CS dose is currently appropriate (to be 
commenced as prescribed during this protocol) 
7. At least one previous completed attempt to taper CS in order to minimize CS dose
(lowest feasible dose based on observed MG signs and symptoms)  
8. Subjects must be willing and able to provide written informed consent.
9. Subjects must be willing to comply with all aspects of the clinical trial protocol.
Exclusion Criteria:
A subject meeting any of the following exclusion criteria is NOT eligible for participation in 
the study:
1. Any dose change in concomitant immunosuppressant therapy, other than CS, in the prior 
six months
2. Any change in CS dose or acetylcholinesterase inhibitor (e.g., pyridostigmine) dose in the 
one month prior to Screening
3. A three-point change in Quantitative Myasthenia Gravis (QMG) score, increased or 
decreased, between the Screening/Week -3 (Visit 0) and Baseline (Week 0 [Visit 1])
4. Any episode of myasthenic crisis (MC) in the one month prior to Screening, or (at any 
time in the past) MC or hospitalization for MG exacerbation associated with a previous 
CS taper attempt
5. Evidence of malignancy within the past 5 years (non-melanoma skin cancer, carcinoma 
in situ of cervix is allowed) or thymoma potentially requiring surgical intervention during 
the course of the trial (intent to perform thymectomy)
6. Thymectomy within the preceding six months prior to Screening
7. Rituximab, belimumab, eculizumab or any monoclonal antibody used for 
immunomodulation within the past 12 months prior to Screening
8. History of non-response to intravenous immunoglobulin (IVIg) when used in 
maintenance therapy of the subject’s MG, as judged by the investigator
9. Have received immune globulin treatment given by IV, subcutaneous, or intramuscular 
route within the last 3 months prior to Screening
10. Received plasma exchange (PLEX) performed within the last 3 months prior to Screening


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11. Inadequate venous access
12. History of anaphylactic reactions or severe reactions to any blood-derived product
13. History of intolerance to any component of the IPs 
14. Documented diagnosis of thrombotic complications to polyclonal IVIg therapy in the past
15. History of recent (within the last year) myocardial infarction or stroke
16. Uncontrolled congestive heart failure; embolism; or historically documented (within the 
last year) electrocardiogram (ECG) changes indicative of myocardial ischemia or atrial 
fibrillation   
17. Current known hyperviscosity or hypercoagulable state
18. Currently receiving anti-coagulation therapy (vitamin K antagonists, nonvitamin K 
antagonist oral anticoagulants [e.g., dabigatran etexilate targeting Factor IIa, rivaroxaban, 
edoxaban, and apixaban targeting Factor Xa], parenteral anticoagulants [e.g., 
fondaparinux]). Note that oral anti-platelet agents are allowed (e.g., aspirin, clopidogrel, 
ticlodipine)
19. History of chronic alcoholism or illicit drug abuse (addiction) in the 12 months preceding 
the Screening/Week -3 (Visit 0)
20. Active psychiatric illness that interferes with compliance or communication with health 
care personnel
21. Females of child-bearing potential who are pregnant, have a positive serum pregnancy 
test (human chorionic gonadotropin [HCG]-based assay), breastfeeding, or are 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.)
22. Currently receiving, or having received, within 1 month prior to the Screening/Week -3 
(Visit 0), any investigational medicinal product or device. In the case of an 
investigational medicinal product trial, at least five half-lives (if known) must have 
elapsed prior to Screening.
23. Known Immunoglobulin A (IgA) deficiency and anti-IgA serum antibodies
24. 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)
25. 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.
26. Hemoglobin levels <9 g/dL
27. 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. Any factor that in 
the opinion of the Principal Investigator would compromise safety of the subject or the 
ability of the subject to complete the trial. No subject whose only MG treatment is CS 
alone may enroll, because in the blinded placebo arm this would mean that all MG 
treatment would be discontinued during CS taper, posing a substantial risk for the 
subject. 


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Investigational Product, Dose, and Mode of Administration:
Immune Globulin (Human), 10% Caprylate/Chromatography Purified (IGIV-C) 
Immune Globulin Injection (Human), 10%, Caprylate/Chromatography Purified (IGIV-C) is 
the active IP for this study, which is a marketed product. IGIV-C glass vials may be supplied 
in the vial sizes of 10 mL, 25 mL, 50 mL, 100 mL, and 200 mL. The unblinded pharmacist or 
designee will prepare the IP to maintain the blind for all parties during infusions and study 
assessments. 
The loading dose is 2 g/kg divided over 2 days starting after the randomization at Week 0 
(Visit 1), followed by maintenance doses of 1 g/kg over 1 day every three weeks until Week 
36 (Visit 13). IGIV-C will be infused intravenously. Infusion solution will be visually 
masked to maintain the blind.
Note that the loading dosage is divided over 2 days as standard infusion time; however, 
extensions up to 4 days are allowed for tolerability issues or higher weight, i.e., limit for 
IGIV-C infusion is no more than 80 g/day (corresponding to 80 kg body weight). Similarly, 
the maintenance dosage is infused in 1 day as standard; however, extension is allowed for 
divided dosage over 2 days for tolerability issues or higher weight, i.e., limit for IGIV-C 
infusion is no more than 80 g/day (corresponding to 80 kg body weight).
Placebo
Sterile 0.9% sodium chloride injection, USP (0.9% NaCl, USP) or equivalent will be used as 
Placebo. Placebo will be visually masked and at a volume approximate to that required for 
the appropriate weight-based dose of IGIV-C in order to maintain blinding of the subject, 
caregivers, investigator, and assessors. Placebo will be infused intravenously. 
Clinical Outcome Measures:
Primary Efficacy Variable:
The primary efficacy endpoint will be the percent of subjects in each arm achieving a 50% or 
greater reduction in CS dose (prednisone or equivalent) at Week 39 (Visit 14) from 
Baseline/Week 0 (Visit 1).
Secondary Efficacy Variables:
!
Percent reduction in daily CS (prednisone or equivalent) dose from Baseline/Week 0 to 
Week 39 (Visit 14)
!
Time to first episode of MG worsening, as defined in Section 3.3.3 “Definition and 
Management of MG Worsening,” from Week 0 through Week 39 (Visit 1 through Visit 
14)
Exploratory Variables:
!
Percent of subjects achieving a 75% or greater reduction in CS dose (prednisone or 


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equivalent) at Week 39 (Visit 14) from Baseline/Week 0 (Visit 1)
!
Percent of subjects CS-free at Week 39 (Visit 14)
!
Percent of subjects achieving a dose of CS of less than or equal to 7.5 mg per day of 
prednisone (or equivalent) at Week 39 (Visit 14)
!
Change from Baseline/Week 0 in fasting serum glucose at Week 39 (Visit 14)
!
Percent of subjects with fasting glucose less than or equal to 125 mg/dL at Week 39 
(Visit 14) compared to Baseline (Week 0)
!
Percent of subjects experiencing MC (as defined in Section 3.3.5) or episode of MG 
worsening requiring inpatient care from Baseline/Week 0 (Visit 1) through Week 39 
(Visit 14)
!
Percent of subjects experiencing MC or episode of MG worsening requiring inpatient 
care from Week 39 to Week 45 (at Visit 14 and Visit 16)
!
Number of episodes of MG worsening, as defined in Section 3.3.3 “Definition and 
Management of MG Worsening,” from Baseline/Week 0 to Week 39 (Visit 1 to 
Visit 14)
!
Change in 15-Item MG Quality-of-Life Instrument (MG-QOL) 15 from Baseline/Week 0 
to Week 39 (Visit 1 to Visit 14), and from Baseline to Week 42 and Week 45 (Visit 15 
and Visit 16)
!
Change in Myasthenia Gravis-Activities of Daily Living (MG-ADL) from 
Baseline/Week 0 to Week 39 (Visit 14), and from Baseline to Week 42 and Week 45 
(Visit 15 and Visit 16)
!
Change from baseline in serum Immunoglobulin (IgG) trough at Week 9 (Visit 4), 
Week 24 (Visit 9), and Week 39 (Visit 14)
!
Change from baseline in binding, blocking, and modulating AChR antibodies at Week 39 
(Visit 14) 
!
Change from baseline in glycated hemoglobin A1c (HbA1c) at Week 39 (Visit 14)
Safety Study Variables
!
Adverse events (AEs), suspected adverse drug reactions (suspected ADRs), adverse 
reactions (ARs), serious AEs (SAEs), and discontinuations due to AEs and SAEs
!
Vital Signs (temperature [T], respiratory rate [RR], heart rate [HR], systolic blood 
pressure [SBP] and diastolic blood pressure [DBP]); during infusions vital signs will be 
carefully monitored.
!
Physical Assessments: physical exams will be recorded as normal or abnormal, according 
to the physician’s judgment criteria, and findings will be recorded.
!
Blood chemistry and Hematology
!
Thromboembolic events (TEs)
!
Hemolysis
!
WHO-Five (WHO-5) Well-Being Index 
Study Procedures:
Eligible subjects based on Screening evaluations will complete the Baseline assessments, 
thereby initiating the Treatment. Subjects will continue with assessments for 45 weeks, with 
scheduled assessments at Week 0 (Visit 1) (Baseline, post-Baseline, and loading infusion 


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over 2 days), followed by assessments and maintenance dosages every 3 weeks through 
Week 36 (Visit 13). The protocol-specified CS tapering will commence at Week 9 (Visit 4) 
and continue through Week 36 (Visit 13), inclusive, in conjunction with continued 
maintenance dosages of IP. Safety/Follow-up assessment visits are scheduled for Weeks 39, 
42, and 45 (Visits 14, 15, and 16). Visits/procedures and assessments should be scheduled at 
the protocol specified study day ± 3 days.
Screening: Week -3 (Visit 0)
All subjects (or legally authorized representative) will start their participation in the study 
upon the signing of the informed consent form (ICF). Subjects will be assessed for study 
eligibility during the Screening Period. During Screening, subject numbers will also be 
assigned.
Subjects must hold their acetylcholinesterase inhibitor (e.g., pyridostigmine) dosage for 
12 hours prior to the Screening/Week -3 (Visit 0) to assure accurate assessment of the QMG 
score.
The procedures and assessments conducted during Screening (Week -3, Visit 0) are listed in 
the full protocol text and Schedule of Study Procedures (Appendix 1).
Baseline, Randomization, and Loading Infusion: Week 0 (Visit 1)
Baseline, Prior to Randomization
Eligible subjects based on Screening evaluations will complete the Baseline assessments, 
thereby initiating the Treatment.  
Subjects must hold their acetylcholinesterase inhibitor (e.g., pyridostigmine) dosage for 
12 hours prior to the Baseline/Week 0 (Visit 1) to assure accurate assessment of the QMG 
score. Additionally, subjects must fast for at least 8 hours (e.g., overnight) to allow accurate 
measurement of fasting serum glucose at Baseline. All screening laboratory results and 
assessments must be available and all inclusion and exclusion criteria must have been 
satisfied prior to initiating treatment. For eligible subjects, following completion of all 
Baseline assessments, IGIV-C (or Placebo) will be administered as a loading dose of 2 g/kg 
(20 mL/kg) given in divided doses over two days; extensions up to 4 days are allowed for 
tolerability issues or higher weight, i.e., limit for IGIV-C infusion is no more than 80 g/day 
(corresponding to 80 kg body weight).
The procedures and assessments conducted at Baseline/Week 0 (Visit 1) are listed in the full 
protocol text and Schedule of Study Procedures (Appendix 1). Baseline assessments will be 
immediately followed by randomization and initiation of IP loading infusions.
Randomization 
Randomization will occur via Interactive Web Response System (IWRS) once all Baseline 
assessments are performed and eligibility is confirmed.


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Post-Baseline/Post-Randomization Loading Dose Infusion 
An unblinded Pharmacist or designee will prepare and dispense the IP per the randomization 
assignment and pharmacy manual. For each infusion, 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. The procedures and 
assessments conducted Post-Baseline/Post-Randomization are listed in the full protocol text 
and Schedule of Study Procedures (Appendix 1).
Investigational Product Run-in Maintenance Phase: Weeks 3 and 6 (Visits 2 and 3)
The first two maintenance dosages comprise the IP Run-In phase. An unblinded Pharmacist 
or designee will prepare and dispense the IP per the randomization assignment and pharmacy 
manual. For each infusion, documentation of total infusion volume prepared (as received 
from the pharmacist or designee), total time to infuse, total volume infused, and, if necessary, 
any infusion interruption with explanation. Subjects must hold their acetylcholinesterase 
inhibitor (e.g., pyridostigmine) dosage for 12 hours prior to Weeks 3 and 6 (Visits 2 and 3) to 
assure accurate assessment of the QMG score. The procedures and assessments performed at 
Week 3 and Week 6 (Visits 2 and 3) are listed in the full protocol text and Schedule of Study 
Procedures (Appendix 1).
Corticosteroid Tapering/IP Maintenance Phase: Week 9 to Week 36 (Visit 4 to Visit 13) 
Inclusive
Corticosteroid tapering will begin at Week 9 (Visit 4) after completion of the third 
maintenance IP dose. CS dosage in stable or improving subjects will be decreased at 
scheduled visits every three weeks during the CS Tapering phase (Week 9 through Week 36 
[Visit 13]) predicated on current CS dose (prednisone equivalents): (a) if CS dosage 
> 40 mg/day, the dose decrease every 3 weeks is 10 mg/day; (b) if CS dosage is ≤ 40 mg/day, 
the dose decrease every 3 weeks is 5 mg/day. Commensurate dose changes are required for 
subjects receiving every other day CS dosing. Note that the rate of CS dose decrease is 
slower as subjects fall below the 40-mg per day threshold. During the CS Tapering phase, the 
last CS dose reduction can occur at Week 36 (Visit 13). The standardized CS tapering will 
continue unless there is worsening of MG (a priori per protocol definition). The final CS 
taper step from 5 mg prednisone equivalent daily to 0 mg prednisone equivalent daily is the 
Principal Investigator’s decision and is not mandatory per protocol. The Principal 
Investigator may choose to taper to 0 mg prednisone equivalent daily based on best medical 
judgment for each subject given individual variability with regards to sensitivity to complete 
CS withdrawal and perceived MG exacerbation risk while CS-free. 
Subjects must hold their acetylcholinesterase inhibitor (e.g., pyridostigmine) dosage for 
12 hours prior to the Weeks 9, 12, 15, 18, 21, 24, 27, 30, 33, and 36 visits to assure accurate 
assessment of the QMG score. Additionally, subjects must fast for at least 8 hours (e.g., 
overnight) to allow for accurate measurement of fasting serum glucose at Week 9 (Visit 4) 
and Week 24 (Visit 9). The procedures and assessments performed during the CS 
Tapering/IP Maintenance Phase are listed in the full protocol text and Schedule of Study 


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Procedures (Appendix 1).
After completion of IP infusion
!
Continue CS tapering as delineated in Section 3.3 (Week 36 [Visit 13] is last visit in 
which CS tapering occurs)
Safety/Follow-up Phase: Week 39 to Week 45 (Visit 14 to Visit 16) Inclusive
Following the last step of the CS tapering at Week 36 (Visit 13), three additional visits will 
be performed at Weeks 39, 42, and 45 (Visits 14, 15, and 16). The primary efficacy endpoint 
is evaluated at Week 39 (Visit 14), given the long half-life of IP. Subjects must hold their 
acetylcholinesterase inhibitor (e.g., pyridostigmine) dosage for 12 hours prior to the 
Weeks 39, 42, and 45 visits (Visits 14, 15, and 16) to assure accurate assessment of the QMG 
score. Additionally, subjects must fast for at least 8 hours (e.g., overnight) to allow accurate 
measurement of fasting serum glucose at Week 39 (Visit 14). It is suggested that the 
investigator consider an increase in CS dose after subjects complete the Week 39 (Visit 14) 
assessments if considered medically indicated. The procedures and assessments performed 
during the Safety/Follow-up Phase are listed in the full protocol text and Schedule of Study 
Procedures (Appendix 1).


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Definition and Management of MG Worsening:
During the study, MG worsening will be defined as:
!
QMG score increase by ≥4 points relative to Baseline/Week 0
During the CS Tapering phase, if a subject meets the definition of MG worsening as defined 
above, then the following increase in CS dose will occur as shown in the tables below:
Daily CS Dose Increase in Response to Worsening MG (CS Tapering Phase 
Only) (prednisone equivalent)
CS Dose (mg/day) at Which Worsening Occurs
Dose Increase (mg/day)
≥ 15
20
< 15
15
Every Other Day CS Dose Increase in Response to Worsening MG (CS 
Tapering Phase Only) (prednisone equivalent)
Every Other Day CS Dose (mg/every other day)          
at Which Worsening Occurs
Every Other Day Dose Increase      
(mg/every other day)
≥ 30
40
< 30
30
If an episode of MG worsening fails to improve with the above CS dose increase within 
6 weeks (by the second subsequent visit), or if another specific episode requires a second 
dose increase at any time, the subject will be withdrawn from the study. 
Special Note for subjects tapered to 0 mg CS per day: Some subjects with MG are 
uniquely sensitive to complete CS withdrawal (0 mg prednisone equivalent daily), and may 
become more vulnerable to MG triggers and sudden MG exacerbations. Therefore if a 
subject has tapered to 0 mg prednisone equivalent daily, any worsening MG signs or 
symptoms must be evaluated in clinic as soon as possible (recommended within 24 hours, 
allowed up to 48 hours) and treated aggressively with CS dose increase as delineated in the 
tables above. Once tapered to 0 mg CS per day, a 4-point QMG increase from Baseline/
Week 0 is not required for re-initiating CS because deterioration can be of greater severity 
and speed than expected and may be difficult to reverse.
Second Attempt to Taper CS:
Following a CS dose increase due to worsening MG as noted above, a second attempt at CS 
tapering may be made after the subject shows evidence of stabilization on the new CS dose 
for at least two visits (six weeks), and in the opinion of the investigator, there is no 
contraindication to resuming the tapering. This second attempt requires that there are still 
visits remaining in the CS Tapering phase.
Stabilization will be defined as a return to the subject’s Baseline/Week 0 status prior to the 
episode of worsening, with QMG score ≤3 points relative to Baseline/Week 0, and return to 


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the baseline clinical symptom(s) that initially triggered the definition of worsening of MG as 
judged by physician.
On this second attempt to taper, the CS dose will be reduced in the same fashion as outlined 
in the above tables; however, the dose will not decrease below the last dose at which the 
subject was stable prior to their episode of MG worsening. During the CS Tapering phase, 
the last CS dose reduction can occur at Week 36 (Visit 13). An illustrative hypothetical 
example of three attempts to taper CS is provided in Appendix 10.


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Statistical and Analytical Methods:
Determination of Sample Size
In order to provide 80% power to detect a 40% treatment difference (70% IGIV-C group 
versus 30% Placebo group) in the percent of subjects achieving a 50% or greater reduction in 
CS dosage at Week 39, alpha level = 0.05, a minimum of 24 subjects per treatment group is 
required. Assuming a discontinuation rate in the range of 20%, 60 subjects are planned to be 
randomized for the study. This is necessary to accommodate attrition anticipated.
Subject Populations for Analysis
!
Intent-to-Treat (ITT) Population
The ITT population consists of all subjects who are randomized. Efficacy analyses will be 
performed on the ITT population. 
!
Safety Population
The Safety population consists of all subjects who received any amount of IP.  
!
Per Protocol Population
Any deviations from the protocol will be recorded in the protocol deviation list.  The validity 
of a subject for inclusion in the per-protocol population 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 protocol deviations are identified which 
justify removing a subject from the per-protocol population, then these decisions will be 
documented. 
Demographic and Baseline Characteristics
Demographic and baseline characteristics will be summarized using descriptive statistics.
Primary Efficacy Analyses
The primary endpoint is the percent of subjects achieving a 50% or greater reduction in CS 
dose (prednisone or equivalent) at Week 39 (Visit 14) from Baseline/Week 0 (Visit 1). The 
treatment comparison will be analyzed using Cochran-Mantel-Haenszel (CMH) test adjusted 
for baseline CS dose (15-40 mg versus 41-60 mg). The null hypothesis (H0) and the 
alternative hypothesis (Ha) are:  
H0: P1 = P2 
Ha: P1 ≠ P2
Where P1 and P2 represent the percent of subjects achieving a 50% or greater reduction in 
CS dose in the IGIV-C and the Placebo group, respectively.
Subjects who discontinued the study early due to the MG worsening will be considered as 
not achieving a 50% or greater reduction.  
Primary efficacy analyses will be based on the ITT population. For sensitivity analysis, the 


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same analysis will be repeated using per-protocol population.
Secondary Efficacy Analyses
!
Percent reduction in daily CS (prednisone or equivalent) dose from Baseline (Visit 1) to 
Week 39 (Visit 14)
The percent daily CS dose reduction from baseline will be analyzed using analysis of 
covariance (ANCOVA). The ANCOVA model will include the percent daily CS dose 
reduction as dependent variable, treatment as fixed effect, and Baseline daily CS dose as 
a covariate.
!
Time to first episode of MG worsening, as defined in Section 3.3.3 “Definition and 
Management of MG Worsening,” from Baseline/Week 0 through Week 39 (Visit 1 
through Visit 14)
Kaplan-Meier estimates will be provided for time to first episode of MG worsening for 
each treatment group. The treatment comparison will be performed using log-rank test 
adjusted for baseline CS dose (15 to 40 mg versus 41 to 60 mg).
Exploratory Efficacy Analyses
Exploratory efficacy variables that will be evaluated in this study include the following:
!
Percent of subjects achieving a 75% or greater reduction in CS dose (prednisone or 
equivalent) at Week 39 (Visit 14) from Baseline/Week 0 (Visit 1)
!
Percent of subjects CS-free at Week 39 (Visit 14)
!
Percent of subjects achieving a dose of CS of less than or equal to 7.5 mg per day of 
prednisone (or equivalent) at Week 39 (Visit 14)
!
Percent of subjects with fasting glucose less than or equal to 125 mg/dL at Week 39 
(Visit 14)
!
Percent of subjects experiencing MC (as defined in Section 3.3.5) or episode of MG 
worsening requiring inpatient care from Baseline/Week 0 (Visit 1) through Week 39 
(Visit 14)
!
Percent of subjects experiencing MC or episode of MG worsening requiring inpatient 
care from Week 39 to Week 45 (at Visit 14 and Visit 16)
!
Percent of subjects with 0, 1, or 2 episodes of MG worsening from Baseline/Week 0 to 
Week 39 (Visit 1 to Visit 14) (in aggregate and by number of episodes/subject).
The following exploratory endpoints will be analyzed using the ANCOVA with treatment as 
main factor and baseline CS dose as covariate. In addition, the mixed model for repeated 
measurement (MMRM) will also be performed.
!
Change from Baseline/Week 0 in fasting serum glucose at Week 39 (Visit 14)
!
Change in 15-Item MG-QOL 15 from Baseline/Week 0 to Week 39 (Visit 1 to Visit 14), 
and from Baseline to Week 42 and Week 45 (Visit 15 and Visit 16)
!
Change in MG-ADL from Baseline/Week 0 to Week 39 (Visit 14), and from Baseline to 
Week 42 and Week 45 (Visit 15 and Visit 16)
!
Change from baseline in serum IgG trough at Week 9 (Visit 4), Week 24 (Visit 9), and 
Week 39 (Visit 14)


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!
Change from baseline in binding, blocking, and modulating AChR antibodies at Week 39 
(Visit 14) 
!
Change from baseline in HbA1c at Week 39 (Visit 14)
Safety Analysis
The safety analysis will be based on safety population.
The incidence of AEs, SAEs, suspected ADRs, and AEs by severity will be summarized by 
treatment, system organ class and preferred term using descriptive statistics. Subjects with 
deaths, SAEs, and AEs leading to premature discontinuation from the study will be listed.  
Clinical laboratory results and the change from baseline values will be summarized by 
treatment group using summary statistics. Shift tables will be provided to summarize values 
that fall outside the normal ranges.
Vital signs will be summarized by treatment using summary statistics at each time point and 
on the change from baseline.
Physical exam data will be provided in data listings.
This study will utilize an Independent Safety Review Committee (ISRC) whose members 
(from Grifols) will be impartial and independent of the clinical trial team. The clinical trial 
team will remain blinded to subject treatment assignment. The ISRC will review relevant 
safety information from the study as outlined in the ISRC Charter. At a minimum, after the 
first 20 subjects are enrolled and have completed half of the treatment period, the ISRC will 
conduct a safety review of the following data at a minimum:
!
AEs, SAEs, and discontinuations due to AEs and SAEs
!
Vital signs
!
Blood chemistry and hematology
!
Assessing for TEs
!
Assessing for hemolysis
During the study, the Medical Monitor will review all relevant safety information from the 
study in order to protect subject welfare and preserve study integrity. Data to be reviewed 
include but are not limited to the following: eCRFs, listings from the clinical and safety 
databases, AEs/SAE reports, concomitant medications, laboratory data, vital signs, and 
physical examinations data.


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TABLE OF CONTENTS
PROTOCOL SYNOPSIS ..........................................................................................................4
GLOSSARY AND ABBREVIATIONS..................................................................................23
1
INTRODUCTION ...........................................................................................................25
1.1
Myasthenia Gravis .................................................................................................25
1.2
Treatment of Myasthenia Gravis ...........................................................................26
1.3
Immune Globulin (Human), 10% Caprylate/Chromatography Purified (IGIV-
C)............................................................................................................................27
1.4
Study Rationale and Dose Selection......................................................................27
1.4.1
Study Rationale............................................................................................27
1.4.2
Dose Rationale.............................................................................................28
2
STUDY OBJECTIVES....................................................................................................28
2.1
Efficacy Objectives................................................................................................28
2.1.1
Primary Objective........................................................................................28
2.1.2
Secondary Objectives...................................................................................28
2.1.3
Exploratory Objectives ................................................................................29
2.2
Safety Objective.....................................................................................................29
3
INVESTIGATIONAL PLAN..........................................................................................29
3.1
Study Design and Plan...........................................................................................29
3.2
Selection of Study Population................................................................................33
3.2.1
Inclusion Criteria .........................................................................................33
3.2.2
Exclusion Criteria ........................................................................................33
3.3
Study Time Periods and Definitions......................................................................35
3.3.1
Investigational Product Run-in Phase..........................................................35
3.3.2
Corticosteroid Tapering/IP Maintenance Phase...........................................35
3.3.3
Definition and Management of MG Worsening..........................................36
3.3.4
Second Attempt to Taper CS .......................................................................37
3.3.5
Myasthenic Crisis.........................................................................................37
3.4
Treatments..............................................................................................................37
3.4.1
Treatments to Be Administered ...................................................................37
3.4.1.1
Immune Globulin (Human), 10% Caprylate/Chromatography 
Purified (IGIV-C)...............................................................................37
3.4.1.2
Placebo...............................................................................................37
3.4.1.3
Labeling of Investigational Products .................................................38
3.4.1.4
Storage of Investigational Products ...................................................38
3.4.1.5
Preparation of Investigational Products.............................................38
3.4.1.6
Accountability for Investigational Products ......................................38
3.4.2
Rationale for Selection of Doses/Timing of Investigational Product in 
the Study ......................................................................................................39


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3.4.2.1
Selection of IGIV-C Dose and Dosing Interval in the Study.............39
3.4.3
Method of Assigning Subjects to Treatment Groups...................................39
3.4.3.1
Subject Numbering ............................................................................39
3.4.3.2
Blinding..............................................................................................40
3.4.3.3
Administration and Timing of Investigational Products for Each 
Subject................................................................................................40
3.4.3.4
Preparation and Handling of Investigational Products ......................40
3.4.3.5
Treatment Compliance.......................................................................40
3.5
Prior and Concomitant Therapy.............................................................................41
3.5.1
Prohibited Medications Prior to Study Participation ...................................41
3.5.2
Prohibited Concomitant Medications during the Study...............................41
3.5.3
Restricted Concomitant Medications during the Study ...............................42
3.6
Efficacy Study Variables .......................................................................................42
3.6.1
Primary Variable..........................................................................................42
3.6.2
Secondary Variables ....................................................................................42
3.6.3
Exploratory Variables ..................................................................................42
3.6.4
Quantitative Myasthenia Gravis (QMG) Score ...........................................43
3.6.5
MG Composite Scale...................................................................................43
3.6.6
Myasthenia Gravis-Activities of Daily Living (MG-ADL).........................44
3.6.7
15-item Myasthenia Gravis Quality-of-Life Instrument (MG-QOL 15).....44
3.7
Safety Study Variables...........................................................................................44
3.7.1
Thromboembolic Events Risk......................................................................44
3.7.2
Hemolysis ....................................................................................................45
3.7.3
WHO-Five (WHO-5) Well-Being Index .....................................................45
3.8
Assessments...........................................................................................................45
3.8.1
Assessment Periods......................................................................................45
3.8.2
Observations and Measurements .................................................................46
3.8.2.1
Overview of Screening, Treatment, and Post Infusion Follow-up 
Phases.................................................................................................46
3.8.2.2
Screening: Week -3 (Visit 0) .............................................................46
3.8.2.3
Baseline, Randomization, and Loading Infusion: Week 0 (Visit 1)..47
3.8.2.4
Investigational Product Run-in Maintenance Phase: Weeks 3 and 
6 (Visits 2 and 3)................................................................................49
3.8.2.5
Corticosteroid Tapering/IP Maintenance Phase: Week 9 to Week 
36 (Visit 4 to  Visit 13) Inclusive.......................................................50
3.8.2.6
Safety / Follow-up Phase: Week 39 to Week 45 (Visit 14 to Visit 
16) Inclusive.......................................................................................57
3.8.3
Description of Laboratory Tests and Procedures.........................................60
3.8.3.1
Thromboembolic Events Risk Testing...............................................60
3.8.3.2
Hemolysis Testing .............................................................................61
3.8.3.3
Virus Safety Testing ..........................................................................61
3.8.3.4
AChR Antibody Testing ....................................................................61


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3.8.3.5
IgG Concentration Measurements .....................................................61
3.9
Screen Failures.......................................................................................................62
3.10
Removal of Subjects ..............................................................................................62
3.11
Follow-up of Subjects Withdrawn from Study......................................................62
3.12
Premature Termination of Study/Closure of Center..............................................63
4
ADVERSE EVENTS.......................................................................................................63
4.1
Warnings/Precautions ............................................................................................63
4.1.1
Interaction/Overdose....................................................................................63
4.1.2
Live Viral Vaccines .....................................................................................63
4.2
Specification of Safety Parameters ........................................................................63
4.3
Methods and Timing for Assessing, Recording and Analyzing Safety 
Parameters..............................................................................................................64
4.3.1
Adverse Events ............................................................................................64
4.3.2
Vital Signs....................................................................................................64
4.3.3
Physical Assessment ....................................................................................64
4.3.4
Blood Chemistry and Hematological Parameters........................................65
4.3.5
Thromboembolic Event Risk.......................................................................65
4.3.6
Hemolysis ....................................................................................................65
4.4
Procedures for Eliciting Reports of and for Recording and Reporting Adverse 
Events and Intercurrent Illnesses ...........................................................................65
4.4.1
Adverse Event..............................................................................................65
4.4.2
Suspected Adverse Drug Reaction/Adverse Reaction.................................66
4.4.3
Causality of Adverse Event .........................................................................66
4.4.4
Intensity of Adverse Event or Suspected Adverse Drug Reaction ..............67
4.4.5
Expectedness of Adverse Event or Suspected Adverse Drug Reaction ......68
4.4.6
Seriousness of Adverse Event or Suspected Adverse Drug Reaction,  
Serious Adverse Event.................................................................................68
4.4.6.1
Hospitalization or Prolongation of Hospitalization ...........................69
4.4.7
Adverse Events of Special Interest ..............................................................69
4.4.7.1
Thromboembolic Events....................................................................69
4.4.7.2
Hemolysis ..........................................................................................69
4.4.7.3
MG Events That Are Not Considered AEs........................................69
4.4.8
Procedures for Eliciting Reports of and for Recording and Reporting 
Adverse    Events and Suspected Adverse Drug Reactions.........................69
4.4.9
Timelines and Reporting of Serious Adverse Events ..................................70
4.4.10
Type and Duration of the Follow-Up of Subjects after Adverse Event or 
Suspected ADR............................................................................................71
5
STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE................71
5.1
Statistical and Analytical Plan ...............................................................................71
5.1.1
Subject Populations for Analysis.................................................................72


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5.1.2
Demographic and Baseline Characteristics .................................................72
5.1.3
Efficacy Analyses ........................................................................................72
5.1.3.1
Primary Efficacy Analyses ................................................................72
5.1.3.2
Secondary Efficacy Analyses ............................................................73
5.1.3.3
Exploratory Efficacy Analyses ..........................................................73
5.1.4
Safety Analyses............................................................................................74
5.2
Determination of Sample Size ...............................................................................76
6
ADMINISTRATIVE .......................................................................................................76
6.1
Investigators, Other Study Personnel and External Committees...........................76
6.1.1
Independent Safety Review Committee.......................................................76
6.2
Data Quality...........................................................................................................77
6.3
Documentation.......................................................................................................77
6.3.1
Record Retention .........................................................................................77
6.3.2
Access to Information for Monitoring.........................................................77
6.3.3
Access to Information for Audits or Inspections.........................................78
7
ETHICAL AND LEGAL ASPECTS...............................................................................78
7.1
Institutional Review Board/Ethics Committee ......................................................78
7.2
Ethical Conduct of the Study.................................................................................78
7.3
Regulatory Authority Approvals/Authorizations...................................................79
7.4
Subject Information and Informed Consent Form.................................................79
7.5
Insurance................................................................................................................79
7.6
Confidentiality .......................................................................................................79
8
USE OF DATA AND PUBLICATION ..........................................................................80
9
REFERENCES ................................................................................................................81
10
APPENDICES .................................................................................................................86
LIST OF APPENDICES
Appendix 1
Schedule of Study Procedures ...................................................................87
Appendix 2
MGFA Clinical Classification ...................................................................90
Appendix 3
QMG Score Test Items ..............................................................................91
Appendix 4
MG Composite Scale.................................................................................92
Appendix 5
MG Activities of Daily Living (MG-ADL) Profile...................................93
Appendix 6
MG-Quality of Life (MG-QOL) 15...........................................................94
Appendix 7
Monitoring of Thromboembolic Events Risk............................................95
Appendix 8
Hemolysis Detection..................................................................................99
Appendix 9
WHO-Five (WHO-5) Well-Being Index (1998 version).........................101
Appendix 10
Examples of CS Tapering with an Exacerbation/Second CS Tapering 
Attempt and Successful CS Tapering ........................................................................102
Appendix 11 Summary of Changes for Amendment .................................................104


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GLOSSARY AND ABBREVIATIONS
AAN
American Academy of Neurology
AChR
Acetylcholine receptor
ADR
Adverse drug reaction
AE
Adverse event
ALP
Alkaline phosphatase
ALT
Alanine aminotransferase
ANCOVA
Analysis of covariance
AR
Adverse reaction
ARC
Absolute reticulocyte count 
AST
Aspartate aminotransferase
B19V
Parvovirus B19
BUN
Blood urea nitrogen
CBC
Complete blood count
CIDP
Chronic inflammatory demyelinating polyneuropathy
CMH
Cochran-Mantel-Haenszel
CRO
Clinical research organization
CS
Corticosteroid
DAT
Direct antiglobulin test
DBP
Diastolic blood pressure
DVT
Deep venous thrombosis
ECG
Electrocardiogram
EDC
Electronic data capture 
eCRF
Electronic case report form 
GBS
Guillain-Barré syndrome
HAV
Hepatitis A virus
Hb
Hemoglobin 
HbA1c
Glycated hemoglobin A1c
HBV
Hepatitis B virus
HCG
Human chorionic gonadotropin
HCV
Hepatitis C virus
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-C
Immune Globulin (Human), 10% Caprylate/Chromatography Purified
IgM
Immunoglobulin M
IND
Investigational New Drug 
IP
Investigational product
IRB/EC
Institutional Review Board/Ethics Committee
ISRC
Independent Safety Review Committee
ITP
Idiopathic thrombocytopenic purpura
IV
Intravenous
IVIg
Intravenous immunoglobulin
IWRS
Interactive Web Response System 
LDH
Lactate dehydrogenase
MC
Myasthenic crisis 
MedDRA
Medical Dictionary for Regulatory Activities
MG
Myasthenia gravis
MG-ADL
Myasthenia Gravis-Activities of Daily Living
MGFA
Myasthenia Gravis Foundation of America
MG-QOL 15
15-Item MG Quality-of-Life Instrument
MMRM
Mixed model for repeated measurement
NaCl
Sodium chloride
NAT
Nucleic acid testing
NINDS
National Institute of Neurological Disorders and Stroke 
PE
Pulmonary embolism
PLEX
Plasma exchange
QMG
Quantitative myasthenia gravis  
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
ULN
Upper limit of normal
USP
United States Pharmacopeia
WHO-5
WHO-Five Well-Being Index


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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 
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 
(AChRs) 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). Manifest weakening during 
continued activity, quick restoration of power with rest, and dramatic improvement in 
strength following the administration of drugs inhibiting anticholinesterase such as 
neostigmine and pyridostigmine are other notable characteristics (3). The special 
vulnerability of the neuromuscular junctions in certain muscles gives myasthenia a highly 
characteristic clinical presentation. Usually the eyelids and the muscles of eye movement, 
and somewhat less often the face, jaws, throat, and neck are the first to be affected. 
Exacerbations of disease can lead to myasthenic crisis (MC) with severe respiratory 
weakness requiring intubation.
MG is a relatively rare disorder with an estimated prevalence of 1.7 to 10.4 per million 
depending on the location, and has been reported to be as high as 21 per million in 
Barcelona, Spain (4). While symptoms can be ameliorated with acetylcholinesterase 
inhibitors that prolong native acetylcholine activity, definitive therapy requires attenuation of 
the aberrant immune process. This can be achieved by treating patients with 
immunosuppressive medications, immunomodulation therapies, or plasma exchange (5). 
Immunosuppressive medications used in the treatment of MG include corticosteroids, 
azathioprine, cyclophosphamide, cyclosporine, and mycophenolate mofetil. B-cell targeted 
immunotherapies (e.g., rituximab, belimumab), and eculizumab have also been explored as 
investigational treatment modalities. Intravenous immunoglobulin (IVIg) is commonly used 
in the acute setting as an integral part of therapy (4, 6).
While there are a number of studies evaluating IVIg for the treatment of MG worsening or 
exacerbation (7, 8, 9, 10, 11), there are few prospective data from controlled trials in the 
public domain for IVIg treatment of chronic MG (12, 13). The latter 2 studies were in very 
small patient numbers 12 and 15 patients, respectively. The study by Wolfe and colleagues 
was terminated prematurely due to insufficient IVIg inventories, and that by Ronager and 
colleagues was a controlled crossover study wherein IVIg was given for 5 days with 16 
weeks observation followed by plasma exchange every other day (5 interventions) with 16 
weeks observation (or vice versa). Thus there is a need for definitive, prospective clinical 
studies of IVIg in the chronic/maintenance setting.
Corticosteroids have generally been considered a fairly reliable and appropriate modality for 
immunomodulation of MG, mainly based on clinical experience rather than rigorously 


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controlled studies (6). Prednisone (or prednisolone in Europe) is the initial 
immunosuppressive treatment used in many MG patients, although the optimal dosage and 
schedule of administration have not been precisely defined (14). The long-term use of 
steroids is complicated by severe and often intolerable adverse effects, the cumulative burden 
of steroid side effects is high (15), and therefore there has been much clinical interest in 
approaches to CS dose reduction. The minimum effective CS dose is the clinical target (16). 
1.2
Treatment of Myasthenia Gravis
Therapies for MG are based on two approaches, prolongation of the half-life of the 
neurotransmitter acetylcholine in the synaptic cleft and reduction in the burden of pathologic 
antibodies inhibiting neuromuscular transmission. 
Acetylcholinesterase inhibitors effectively prolong acetylcholine activity; neostigmine and 
pyridostigmine have been demonstrated to provide symptomatic improvement in muscle 
strength. Common adverse events (AEs) include diarrhea and abdominal cramps, whilst
overdose symptoms show features consistent with acute cholinergic poisoning (4).
Down regulation of the production of antibodies through immune modulation is a 
complementary approach, and corticosteroids, azathioprine, cyclosporine, tacrolimus, and 
cyclophosphamide have been employed. Clinical observation and limited trial data support a 
number of medications using this approach, however all require close monitoring for 
frequent and sometimes serious adverse effects (17, 18, 19, 20, 21). Additionally, onset of 
action is often reported to be slow with these agents, with the exception of corticosteroids 
(22). Although corticosteroids are the most common first-line immune suppressant employed 
in chronic MG, their adverse effect profile is considerable. Examples of adverse effects of 
systemic CS use include clinical adverse effects (e.g., adipose tissue redistribution, 
hypertension, cardiovascular risk, osteoporosis, peptic ulcer, adrenal insufficiency, 
infections, aseptic necrosis and pancreatitis as well as mood, ophthalmological, menstrual 
and skin disorders) and biological adverse effects (e.g., electrolyte homeostasis 
diabetogenesis, dyslipidemia and pregnancy-related AEs) (23, 24).
Additional therapies include complete thymectomy, an intervention that is the subject of an 
ongoing clinical trial supported by the National Institute of Neurological Disorders and 
Stroke (NINDS) (25) which presents an opportunity to reduce antibody production. Removal 
of an associated thymoma has shown benefit historically. In the setting of MC and 
exacerbations, plasmapheresis has been employed. However, a 2011 American Academy of 
Neurology (AAN) guideline update states that: “There is insufficient evidence to support or 
refute the use of plasmapheresis in myasthenia gravis” (26). Plasmapheresis requires highly 
specialized equipment, significant operator expertise, and often requires large gauge access 
to the central circulation.
IVIg derived from healthy donor plasma appears to mitigate immunologic events related to 
the pathologic antibodies in MG. While there are multiple theoretical mechanisms by which 
exogenous IVIg modulates the immune system, several generally accepted paths include 
competition with anti-idiotype antibodies, anti-complement effects, and Fc receptor 
saturation (27, 28, 29).


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The mechanism by which IVIg exerts its clinical effect in MG remains to be elucidated 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 (30, 31). Improvement in MG 
symptoms typically occurs in about 70% of patients, beginning during treatment or within a 
few days of initiating IVIg treatment and lasting for weeks to months (32).
The Therapeutics and Technology Assessment Subcommittee of AAN recently released 
updated evidence-based guidelines that consider IVIg as an effective therapy for 
moderate-to-severe cases of MG, but also acknowledges the need for additional clinical trials 
(33). 
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, 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 IVIg concentrates are a safe and effective treatment 
option as a short term treatment for acute exacerbation of MG. Moreover, IVIg has 
demonstrated a positive treatment effect in clinical studies of MG worsening or exacerbations 
(7, 9, 11), but further clinical data are needed to confirm the effectiveness of IVIg in the 
treatment of MG as a maintenance therapy (12, 13). Corticosteroids are commonly a first 
choice drug when immunosuppressive drugs are necessary in MG (16). However, there are 
many important side effects including weight gain, fluid retention, hypertension, diabetes, 
anxiety/depression/insomnia/psychosis, glaucoma, cataract, gastrointestinal hemorrhage and 
perforations, myopathy, increased susceptibility to infections and avascular joint necrosis 
(16). Thus tapering the CS dose to the minimum effective dosage is good practice.
This is a multicenter, prospective, double-blind, placebo-controlled study to assess the 
efficacy and safety of IGIV-C in CS-dependent subjects with generalized MG and a history 
of Myasthenia Gravis Foundation of America (MGFA) clinical class II-V (34). The aim of 
the study is to demonstrate that IGIV-C (versus Placebo) may enhance feasibility of CS 


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tapering. The primary measure of efficacy for this study is the proportion of subjects 
achieving a ≥50% reduction in CS dosage at Week 39.
1.4.2
Dose Rationale
The optimal dose of IVIg 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 (32, 35). More recent studies in 
MG have evaluated the administration of a total IVIg 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 (7, 9, 11). 
Likewise, in a study of subjects with Guillain-Barré syndrome (GBS), a total IVIg 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 (36).
Based on the above, subjects in this study will receive a loading IGIV-C dose of 2 g/kg of 
body weight followed by maintenance infusions at 3-week intervals at a dose of 1 g/kg of 
body weight. The loading and maintenance dosage is the same as that used for IGIV-C in 
CIDP which has been well tolerated, and is approved for CIDP at this dosage both in North 
America and Europe.
2
STUDY OBJECTIVES
2.1
Efficacy Objectives
2.1.1
Primary Objective
The primary objective of this study is to evaluate the efficacy of IV infusions of IGIV-C as 
compared to Placebo in reducing the maintenance dosage of corticosteroids in corticosteroid 
(CS)-dependent subjects with MG when given as an initial loading dose (2 g/kg) followed by 
12 maintenance doses (1 g/kg) every 3 weeks through Week 36 by assessing the percent of 
subjects achieving a 50% or greater reduction in CS dose (prednisone or equivalent) at Week 
39 (Visit 14) from Baseline/Week 0 (Visit 1).
2.1.2
Secondary Objectives
The secondary objectives of this study are to evaluate the efficacy of IGIV-C as compared to 
Placebo from baseline through Week 39 in the following:
!
Percent reduction in daily CS (prednisone or equivalent) dose from Baseline to Week 39 
(Visit 14)
!
Time to first episode of MG worsening, as defined in Section 3.3.3 “Definition and 
Management of MG Worsening,” from Baseline/Week 0 through Week 39 (Visit 1 
through Visit 14)


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2.1.3
Exploratory Objectives 
The exploratory objectives for this study are to evaluate the effect of IGIV-C on: 
!
Percent of subjects achieving a 75% or greater reduction in CS dose (prednisone or 
equivalent) at Week 39 (Visit 14) from Baseline/Week 0 (Visit 1)
!
Percent of subjects CS-free at Week 39 (Visit 14)
!
Percent of subjects achieving a dose of CS of less than or equal to 7.5 mg per day of 
prednisone (or equivalent) at Week 39 (Visit 14)
!
Change from Baseline/Week 0 in fasting serum glucose at Week 39 (Visit 14)
!
Percent of subjects with fasting glucose less than or equal to 125 mg/dL at Week 39 
(Visit 14) compared to Baseline (Week 0)
!
Percent of subjects experiencing MC (as defined in Section 3.3.5) or episode of MG 
worsening requiring inpatient care from Baseline/Week 0 (Visit 1) through Week 39 
(Visit 14)
!
Percent of subjects experiencing MC or episode of MG worsening requiring inpatient 
care from Week 39 to Week 45 (at Visit 14 and Visit 16)
!
Number of episodes of MG worsening, as defined in Section 3.3.3 “Definition and 
Management of MG Worsening,” from Baseline/Week 0 to Week 39 (Visit 1 to 
Visit 14)
!
Change in 15-Item MG Quality-of-Life Instrument (MG-QOL 15) from Baseline/Week 0 
to Week 39 (Visit 1 to Visit 14), and from Baseline to Week 42 and Week 45 (Visit 15 
and Visit 16)
!
Change in MG Activities of Daily Living (MG-ADL) from Baseline/Week 0 to Week 39 
(Visit 14), and from Baseline to Week 42 and Week 45 (Visit 15 and Visit 16)
!
Change from baseline in serum immunoglobulin G (IgG) trough at Week 9 (Visit 4), 
Week 24 (Visit 9), and Week 39 (Visit 14)
!
Change from baseline in binding, blocking, and modulating AChR antibodies at Week 39 
(Visit 14) 
!
Change from baseline in glycated hemoglobin A1c (HbA1c) at Week 39 (Visit 14)
2.2
Safety Objective
The safety objective of this study is to evaluate the safety and tolerability of one IGIV-C 
loading dose of 2 g/kg followed by 12 maintenance dosages of 1 g/kg every 3 weeks through 
Week 36 in CS-dependent subjects with MG.
3
INVESTIGATIONAL PLAN
3.1
Study Design and Plan
This is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the 
efficacy and safety of IGIV-C as a CS-sparing agent in CS-dependent MG. Approximately 
60 adult subjects will be randomized in this study.


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Subjects who have been dependent on systemic corticosteroids for at least the preceding 
three months and who have received a stable dose of CS for at least one month immediately 
prior to the Screening visit, will be randomly allocated in a 1:1 ratio into IGIV-C treatment 
group and Placebo treatment group to receive either IGIV-C or matched Placebo every three 
weeks in a double-blinded fashion. Randomization will be stratified by baseline CS dose: 
!
15 mg – 40 mg prednisone equivalent per day
!
41 mg – 60 mg prednisone equivalent per day
For those subjects randomized to receive IGIV-C at the Baseline/Week 0 (Visit 1), an initial 
loading dose of 2 g/kg will be administered at the Baseline Visit (Visit 1). Note that the 
loading dosage is divided over 2 days as standard infusion time (extensions up to 4 days are 
allowed for tolerability issues or higher weight, i.e., limit for IGIV-C infusion is no more 
than 80 g/day [corresponding to 80 kg body weight]). Loading dosage is followed by 
maintenance doses of 1 g/kg administered every third week until Visit 13 (Week 36). Note 
that the maintenance dosage is infused in 1 day as standard (extensions are allowed for 
divided dosage over 2 days for tolerability issues or higher weight, i.e., limit for IGIV-C 
infusion is no more than 80 g/day [corresponding to 80 kg body weight]). For those subjects 
randomized to receive Placebo at the Baseline Visit (Visit 1), sterile 0.9% sodium chloride 
injection, United States Pharmacopeia (USP) or equivalent will be infused in a manner that 
the blind is maintained. The volumes of Placebo will be equal to the volumes required for an 
initial loading dose at the Baseline Visit (Visit 1) and subsequent maintenance doses
administered every third week until Visit 13 (Week 36). 
Tapering of the CS dose will not be initiated until the subject receives a total of 3 complete 
doses of the investigational product (IP), which includes the initial loading dose (Visit 1 –
Week 0) and the first two maintenance doses (Week 3 [Visit 2] and Week 6 [Visit 3]). The 
subject will begin a prescribed CS tapering regimen at Week 9 [Visit 4], coincident with 
receiving the fourth dose of IP. This regimen is described in “CS Tapering Regimen,” 
Section 3.3.2. The tapering will be based on the CS dose (prednisone equivalent). If the CS 
dose is >40 mg/day the CS dose will be reduced in decrements of 10 mg at each visit (every 
3 weeks); if the CS dose is ≤40 mg, the CS will be reduced in 5 mg decrements at each visit 
(every 3 weeks) in accordance with Table 3-1 and Table 3-2. Tapering will occur under the 
observation of the investigator. The final CS taper step from 5 mg prednisone equivalent 
daily to 0 mg prednisone equivalent daily is the Principal Investigator’s decision and is not 
mandatory per protocol. The Principal Investigator may choose to taper to 0 mg prednisone 
equivalent daily based on best medical judgment for each subject given individual variability 
with regards to sensitivity to complete CS withdrawal and perceived MG exacerbation risk 
while CS-free. 
During the CS Tapering/IP Maintenance phase, study visits will occur every three weeks 
while the subject continues his/her CS tapering and maintenance doses of IP. Implementation 
of the CS dose reductions will last a maximum of 27 weeks. The investigator will attempt to 
hold the non-CS therapy (e.g., pyridostigmine) of the subjects’ MG medical regimen constant 
through the end of the study (Week 45 [Visit 16]) unless there are worsening symptoms 
(defined in Section 3.3.3) or adverse effects due to other components of the subject’s non-CS 
therapy.


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During the CS Tapering phase, the last CS dose reduction can occur at Week 36 (Visit 13). 
Week 39 (Visit 14) will constitute the time point for the primary endpoint, an opportunity to 
assess the effect of the final CS dose reduction made at Week 36 (Visit 13), and the initiation 
of the Safety/Follow-up phase. 
Subjects will receive 3 safety/follow-up visits (Weeks 39, 42, 45 corresponding to Visits 14, 
15, 16, respectively). It is suggested that the investigator consider an increase in CS dose 
after subjects complete the Week 39 (Visit 14) assessments if considered medically 
indicated.
A schematic of the overall study design and essential activities is shown in Figure 3-1, and a 
schedule of study procedures is provided in Appendix 1. Tools for assessing MG are 
provided in Appendix 2, Appendix 3, Appendix 4, Appendix 5, Appendix 6, and specific 
safety monitoring in Appendix 7, Appendix 8, and Appendix 9.
Worsening of MG symptoms
If at any point during the CS Tapering phase, the subject suffers a worsening of his/her MG 
symptoms, as defined in Section 3.3.3 “Definition and Management of MG Worsening,”
the CS dose will be increased by 20 mg if the CS dose (mg/day) at which worsening occurs 
is ≥15 mg/day or the dose will be increased by 15 mg/day if the CS dose (mg/day) at which 
worsening occurs is <15 mg/day in accordance with Table 3-3 and Table 3-4. The increased 
CS dose (prednisone equivalent) will be assessed over the next 2 consecutive visits 
(6 weeks). The subject’s symptoms of MG must have re-stabilized while receiving this 
higher dose of CS for the subject to continue in the study. Stabilization is defined as a 
Quantitative Myasthenia Gravis (QMG) score increase of ≤3 points relative to 
Baseline/Week 0 and a return to baseline of clinical symptom(s) that triggered the definition 
of worsening of MG as judged by the physician investigator. If the episode of MG worsening 
fails to improve with the above CS dose increase within 6 weeks (by the second subsequent 
visit), the subject will be withdrawn from the study. 
If the increased CS dose was successful in abating the QMG score worsening to within 
≤3 points relative to Baseline/Week 0 and a return to baseline of clinical symptom(s) that 
triggered the definition of MG worsening as judged by the physician investigator, then a 
second attempt at tapering of the subject’s new CS dose will be initiated according to 
Section 3.3.4. On this second attempt to taper, the CS dose will be reduced in the same 
fashion as outlined above; however, the dose will not decrease below the last dose at which 
the subject was stable prior to their episode of MG worsening. If the subject requires a 
second CS dose increase at any time, the subject will be withdrawn from the study. Also see 
Early Discontinuation Visit (Section 3.8.2.6) and Section 3.11.




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3.2
Selection of Study Population
Eligible participants for this study will include adult subjects with a confirmed diagnosis of 
MG who have required systemic CS therapy for at least the preceding three months in order 
to control their signs and symptoms of MG. Subjects may be receiving immunosuppressive 
therapies within confines stipulated below and stable dosage of acetylcholinesterase 
inhibitors (e.g., pyridostigmine, neostigmine).
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 ages 18 to 85 years
2. Anti-AChR antibody positive
3. Confirmed diagnosis of generalized MG historically meeting the clinical criteria for 
diagnosis of MG defined by the MGFA classification of Class II, III, IV, or V historically
(Appendix 2). 
4. At Screening, subjects may have symptoms controlled by CS (for example, only ocular 
[Class I] symptoms may be evident or there may be no symptoms) or be MGFA Class 
II-IVa inclusive (Class IVb and Class V excluded). Note: Subjects who only have a 
history of ocular MG may not enroll.
5. On systemic CS for a minimum period of at least three months and on a stable CS dose of 
≥15 mg/day and ≤60 mg/day (prednisone equivalent) for the month prior to Screening. 
Individuals on alternate day CS dosing will be judged to be on a daily dose equivalent to 
half their alternate day dose (i.e., 40 mg/every other day = 20 mg/day)
6. The investigator feels that tapering the CS dose is currently appropriate (to be 
commenced as prescribed during this protocol) 
7. At least one previous completed attempt to taper CS in order to minimize CS dose 
(lowest feasible dose based on observed MG signs and symptoms)
8. Subjects must be willing and able to provide written informed consent.
9. Subjects must be willing to comply with all aspects of the clinical trial protocol.
3.2.2
Exclusion Criteria
A subject meeting any of the following exclusion criteria is NOT eligible for participation in 
the study:
1. Any dose change in concomitant immunosuppressant therapy, other than CS, in the prior 
six months
2. Any change in CS dose or acetylcholinesterase inhibitor (e.g., pyridostigmine) dose in the 
one month prior to Screening
3. A three-point change in QMG score, increased or decreased, between the 
Screening/Week -3 (Visit 0) and Baseline (Week 0 [Visit 1])
4. Any episode of MC in the one month prior to Screening, or (at any time in the past) MC 
or hospitalization for MG exacerbation associated with a previous CS taper attempt


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5. Evidence of malignancy within the past 5 years (non-melanoma skin cancer, carcinoma 
in situ of cervix is allowed) or thymoma potentially requiring surgical intervention during 
the course of the trial (intent to perform thymectomy)
6. Thymectomy within the preceding six months prior to Screening
7. Rituximab, belimumab, eculizumab or any monoclonal antibody used for 
immunomodulation within the past 12 months prior to Screening
8. History of non-response to IVIg when used in maintenance therapy of the subject’s MG, 
as judged by the investigator
9. Have received immune globulin treatment given by IV, subcutaneous, or intramuscular 
route within the last 3 months prior to Screening 
10. Received plasma exchange (PLEX) performed within the last 3 months prior to Screening
11. Inadequate venous access
12. History of anaphylactic reactions or severe reactions to any blood-derived product
13. History of intolerance to any component of the IPs
14. Documented diagnosis of thrombotic complications to polyclonal IVIg therapy in the past
15. History of recent (within the last year) myocardial infarction or stroke
16. Uncontrolled congestive heart failure; embolism; or historically documented (within the 
last year) electrocardiogram (ECG) changes indicative of myocardial ischemia or atrial 
fibrillation   
17. Current known hyperviscosity or hypercoagulable state
18. Currently receiving anti-coagulation therapy (vitamin K antagonists, nonvitamin K 
antagonist oral anticoagulants [e.g., dabigatran etexilate targeting Factor IIa, rivaroxaban, 
edoxaban, and apixaban targeting Factor Xa], parenteral anticoagulants [e.g., 
fondaparinux]). Note that oral anti-platelet agents are allowed (e.g., aspirin, clopidogrel, 
ticlodipine)
19. History of chronic alcoholism or illicit drug abuse (addiction) in the 12 months preceding 
the Screening/Week -3 (Visit 0)
20. Active psychiatric illness that interferes with compliance or communication with health 
care personnel
21. Females of child-bearing potential who are pregnant, have a positive serum pregnancy 
test (human chorionic gonadotropin [HCG]-based assay), breastfeeding, or are 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.)
22. Currently receiving, or having received within 1 month prior to the Screening/Week -3 
(Visit 0), any investigational medicinal product or device. In the case of an 
investigational medicinal product trial, at least five half-lives (if known) must have 
elapsed prior to Screening.
23. Known Immunoglobulin A (IgA) deficiency and anti-IgA serum antibodies
24. 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)


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25. 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.
26. Hemoglobin (Hb) levels <9 g/dL
27. 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. Any factor that in 
the opinion of the Principal Investigator would compromise safety of the subject or the 
ability of the subject to complete the trial. No subject whose only MG treatment is CS 
alone may enroll, because in the blinded placebo arm this would mean that all MG 
treatment would be discontinued during CS taper, posing a substantial risk for the 
subject.
3.3
Study Time Periods and Definitions
3.3.1
Investigational Product Run-in Phase
Subjects will receive a total of 3 complete doses of the IP in the IP Run-In phase, which 
includes the initial loading dose at the Baseline/Week 0 (Visit 1), and the first two 
maintenance doses at Weeks 3 and 6 (Visits 2 and 3). The CS dose will remain stable in this 
phase. CS tapering will begin at Week 9 (Visit 4), coincident with the third maintenance dose 
of IP.
3.3.2
Corticosteroid Tapering/IP Maintenance Phase
After completion of the third maintenance dose at Week 9 (Visit 4), subjects will begin a 
prescribed tapering regimen of their CS dose as described below.
CS Tapering Regimen: CS dosage in subjects will be decreased at  scheduled visits every 
three weeks during the CS Tapering phase (Week 9 through Week 36 [Visit 4 through Visit 
13], inclusive) as described in Table 3-1 and Table 3-2, provided that clinical status has not 
worsened as defined in Section 3.3.3 "Definition and Management of MG Worsening.”
The final CS taper step from 5 mg prednisone equivalent daily to 0 mg prednisone equivalent 
daily is the Principal Investigator’s decision and is not mandatory per protocol. The Principal 
Investigator may choose to taper to 0 mg prednisone equivalent daily based on best medical 
judgment for each subject given individual variability with regards to sensitivity to complete 
CS withdrawal and perceived MG exacerbation risk while CS-free.
Table 3-1 Daily CS Dose Tapering (prednisone equivalent)
Daily CS Dose (mg/day)
Daily Dose Decrease (mg/day) every 3 weeks
> 40 
10
≤ 40
5


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3.3.3
Definition and Management of MG Worsening
During the study, MG worsening will be defined as:
!
QMG score increase by ≥4 points relative to Baseline/Week 0
During the CS Tapering phase, if a subject meets the definition of MG worsening as defined 
above, then the following increase in CS dose will occur as shown in Table 3-3 and 
Table 3-4:
Table 3-3 Daily CS Dose Increase in Response to Worsening MG (CS Tapering 
Phase Only) (prednisone equivalent)
CS Dose (mg/day) at Which Worsening Occurs
Dose Increase (mg/day)
≥ 15
20
< 15
15
Table 3-4 Every Other Day CS Dose Increase in Response to Worsening MG 
(CS Tapering Phase Only) (prednisone equivalent)
Every Other Day CS Dose (mg/every other day)           
at Which Worsening Occurs
Every Other Day Dose Increase      
(mg/every other day)
≥ 30
40
< 30
30
If an episode of MG worsening fails to improve with the above CS dose increase within 
6 weeks (by the second subsequent visit), or if another specific episode requires a second 
dose increase at any time, the subject will be withdrawn from the study. Also see Early 
Discontinuation Visit (Section 3.8.2.6 and Section 3.11).
Special Note for subjects tapered to 0 mg CS per day: Some subjects with MG are 
uniquely sensitive to complete CS withdrawal (0 mg prednisone equivalent daily), and may 
become more vulnerable to MG triggers and sudden MG exacerbations. Therefore if a 
subject has tapered to 0 mg prednisone equivalent daily, any worsening MG signs or 
symptoms must be evaluated in clinic as soon as possible (recommended within 24 hours, 
allowed up to 48 hours) and treated aggressively with CS dose increase as delineated in the 
tables above. Once tapered to 0 mg CS per day, a 4-point QMG increase from Baseline/
Table 3-2 Every Other Day CS Dose Tapering (prednisone equivalent)
Every Other Day CS Dose (mg/every other day)
Every Other Day Dose Decrease (mg/every other day) 
every 3 weeks
> 80 mg every other day
decrease by 20 mg on CS dosing days (every other day)
≤ 80 mg every other day
decrease by 10 mg on CS dosing days (every other day)


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Week 0 is not required for re-initiating CS because deterioration can be of greater severity 
and speed than expected and may be difficult to reverse.
3.3.4
Second Attempt to Taper CS
Following a CS dose increase due to worsening MG as noted in Section 3.3.3, a second 
attempt at CS tapering may be made after the subject shows evidence of stabilization on the 
new CS dose for at least two visits (six weeks), and in the opinion of the investigator, there is 
no contraindication to resuming the tapering. This second attempt requires that there are still 
visits remaining in the CS Tapering phase.
Stabilization will be defined as a return to the subject’s Baseline/Week 0 status prior to the 
episode of worsening, with QMG score ≤3 points relative to Baseline/Week 0, and return to 
the baseline clinical symptom(s) that initially triggered the definition of worsening of MG as 
judged by physician.
On this second attempt to taper, the CS dose will be reduced in the same fashion as outlined 
in Table 3-1 and Table 3-2; however, the dose will not decrease below the last dose at which 
the subject was stable prior to their episode of MG worsening. During the CS Tapering 
phase, the last CS dose reduction can occur at Week 36 (Visit 13). An illustrative 
hypothetical example of three attempts to taper CS is provided in Appendix 10.
3.3.5
Myasthenic Crisis
Myasthenic (or MG) crisis will be defined as an episode of worsening (as defined in 
Section 3.3.3) which requires hospitalization. Hospitalizations solely for socioeconomic 
reasons would not fulfill criteria for MG crisis. Also see Early Discontinuation Visit 
(Section 3.8.2.6 and Section 3.11).
3.4
Treatments
3.4.1
Treatments to Be Administered
3.4.1.1
Immune Globulin (Human), 10% Caprylate/Chromatography Purified (IGIV-C)
Immune Globulin Injection (Human), 10%, Caprylate/Chromatography Purified (IGIV-C) is 
the active IP for this study, which is a marketed product. IGIV-C glass vials may be supplied 
in the vial sizes of 10 mL, 25 mL, 50 mL, 100 mL, and 200 mL. Detailed information 
regarding IGIV-C can be found in the IGIV-C IB.
The unblinded pharmacist or designee will prepare IP to maintain the blind for all parties 
during infusions and study assessments. Reference the Pharmacy Manual for additional 
details.
3.4.1.2
Placebo
Sterile 0.9% sodium chloride injection, USP (0.9% NaCl, USP) or equivalent will be used as 
Placebo to maintain the blind. 


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3.4.1.3
Labeling of Investigational Products
Labeling will be according to the requirements of local law and legislation. Label text will be 
approved according to Grifols Therapeutics Inc. procedures, and a copy of the labels will be 
made available to the study site upon request.
3.4.1.4
Storage of Investigational Products
IPs must be stored in a secure area accessible to the unblinded pharmacist or designee 
responsible for the preparation and dispensing of IPs.
Active IP (IGIV-C) must be stored at temperatures of 2°C to 8°C (36°F to 46°F). Do not 
freeze. The unblinded pharmacist or designee is responsible for maintaining storage 
temperature records and for immediately reporting deviations in temperature to the unblinded 
study monitor. Reference the Pharmacy Manual for additional details.
3.4.1.5
Preparation of Investigational Products
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 
loading dose of 2 g/kg divided over 2 days starting after the randomization at Week 0 (Visit 
1), followed by maintenance doses of 1 g/kg over 1 day every three weeks until Week 36 
(Visit 13). Infusion solution will be visually masked to maintain the blind.
Note that the loading dosage is divided over 2 days as standard infusion time; however, 
extensions up to 4 days are allowed for tolerability issues or higher weight, i.e., limit for 
IGIV-C infusion is no more than 80 g/day (corresponding to 80 kg body weight). Similarly, 
the maintenance dosage is infused in 1 day as standard; however, extension is allowed for 
divided dosage over 2 days for tolerability issues or higher weight, i.e., limit for IGIV-C 
infusion is no more than 80 g/day (corresponding to 80 kg body weight).
Subjects randomized to Placebo will receive 0.9% sodium chloride injection, USP or 
equivalent, visually masked and at a volume approximate to that required for the appropriate 
weight-based dose of IGIV-C in order to maintain blinding of the subject, caregivers, 
investigator, and assessors. The IP will be prepared by the unblinded study site pharmacist or 
designee.
The unblinded pharmacist must inspect IGIV-C visually before preparing 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.
Reference the Pharmacy Manual for detailed IP preparation and administration instructions.
3.4.1.6
Accountability for Investigational Products
IPs are to be used only for the study in accordance with the directions given in this protocol. 
The study pharmacist or designee is responsible for the distribution of the IP in accordance 
with directions given in the protocol and Pharmacy Manual.


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The unblinded study pharmacist or designee 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 pharmacist. The 
inventory must be made available for inspection during the study by the unblinded 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 from Grifols 
or designee 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.
3.4.2
Rationale for Selection of Doses/Timing of Investigational Product in the 
Study
3.4.2.1
Selection of IGIV-C Dose and Dosing Interval in the Study
The optimal dose of IVIg for MG maintenance dosing is still unclear; however, recent studies 
have supported a loading dose of 2 g/kg administered in as little as 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 (7,9,11,32,35). Maintenance dosage of IGIV-C in CIDP has been well tolerated 
at 1 g/kg administered over 1 to 2 days every three weeks and has regulatory approval for 
this indication/dosage in both North America and Europe.
Based on the above, subjects will receive a loading IGIV-C dose of 2 g/kg of body weight 
followed by maintenance dosages at 3-week intervals at a dose of 1 g/kg of body weight. 
3.4.3
Method of Assigning Subjects to Treatment Groups
This is a randomized, double-blind, placebo-controlled study; subjects will be randomized in 
a 1:1 ratio via Interactive Web Response System (IWRS) into IGIV-C treatment group and 
Placebo treatment group to receive either IGIV-C or matching Placebo every three weeks in a 
double-blind fashion via IV administration. Each subject’s IGIV-C dose will be 
individualized based on the subject’s body weight and the protocol specified loading dose of 
2 g/kg over 2 consecutive days and maintenance dosage of 1 g/kg over 1 day every three 
weeks through Visit 13 (Week 36). Therefore, each subject’s infusion volume and duration 
of the infusion will vary from subject to subject, and must be carefully prepared by the 
unblinded pharmacist who will prepare IP consisting of either IGIV-C or an equivalent 
volume of 0.9% sodium chloride injection. Note that for the loading dosage, 2 days is 
standard (2-4 days is allowed as an extension for tolerability issues or higher weight, i.e., 
limit for IGIV-C infusion is no more than 80 g/day [corresponding to 80 kg body weight]). 
Similarly, the maintenance dosage is given over 1 day as the standard time interval (divided 
dosage over 2 days is allowed for tolerability issues or higher weight, i.e., limit for IGIV-C 
infusion is no more than 80 g/day [corresponding to 80 kg body weight]).
3.4.3.1
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, 


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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.
3.4.3.2
Blinding
This is a double-blind, placebo-controlled study. Placebo infusion will be visually 
indistinguishable from IGIV-C to maintain blinding. The unblinded pharmacist or designee 
will prepare all IP infusion bags with no visual differences between IGIV-C and Placebo and 
cover with a non-transparent blinding bag cover. 
Additionally, results of the central laboratory analysis of IgG levels will not be shared with 
the investigator, blinded study staff, clinical research organization (CRO) or blinded Sponsor 
personnel involved with study conduct.
3.4.3.3
Administration and Timing of Investigational Products for Each Subject
IGIV-C (or Placebo) will be administered as a loading dose of 2 g/kg divided over 
2 consecutive days starting after randomization at Week 0 (Visit 1), followed by maintenance 
doses of 1 g/kg over 1 day every three weeks through Week 36 (Visit 13). Note that for the 
loading dosage, 2 days are standard (2-4 days are allowed as an extension for tolerability 
issues or higher weight, i.e., limit for IGIV-C infusion is no more than 80 g/day 
[corresponding to 80 kg body weight]). Similarly, the maintenance dosage is given over 
1 day as the standard time interval (divided dosage over 2 days is allowed for tolerability 
issues or higher weight, i.e., limit for IGIV-C infusion is no more than 80 g/day 
[corresponding to 80 kg body weight]). Infusion administration, including infusion rate, is 
provided 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.
3.4.3.4
Preparation and Handling of Investigational Products
Blinded IP (IGIV-C or Placebo) should be infused using a separate line by itself, without 
mixing with other IV fluids or medications that the subject might be receiving. The IP 
infusion line can be flushed with 5% dextrose in water (D5/W) or 0.9% sodium chloride 
injection. Do not flush with heparin.
3.4.3.5
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.
All IV infusions will be administered at the study site under the supervision of the treating 
investigator or designee.


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3.5
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).
Diphenhydramine, acetaminophen/ibuprofen, and non-steroidal anti-inflammatory drugs are 
allowed during the trial as pre-medications for study drug infusions. These and any other 
concomitant medication taken during the study period must be documented in the subject’s 
medical records and the eCRF.
3.5.1
Prohibited Medications Prior to Study Participation
The following medications are prohibited for the specified timeframe prior to study 
participation.
!
Immunoglobulin treatment given by IV, subcutaneous or intramuscular route within the 
last 3 months
!
Rituximab, belimumab, eculizumab, or use of any monoclonal antibody for 
immunomodulation within the past 12 months
!
Subjects with PLEX within the last 3 months
!
Anti-coagulation therapy at the time of Screening or Baseline (vitamin K antagonists, 
nonvitamin K antagonist oral anticoagulants [e.g., dabigatran etexilate targeting Factor 
IIa, rivaroxaban, edoxaban, and apixaban targeting Factor Xa], parenteral anticoagulants 
[e.g., fondaparinux]). Note that oral anti-platelet agents are allowed (e.g., aspirin, 
clopidogrel, ticlodipine)
!
Any investigational drugs within 30 days of Screening (or five half-lives if known) 
3.5.2
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 investigational drugs which are not part of this study
!
Introduction of new immunosuppressant(s) that the subject was not already taking at 
Screening. Note: Methotrexate is allowed provided dose is stable for 6 months prior to 
Screening.
!
Rituximab, belimumab, eculizumab, use of any monoclonal antibody for 
immunomodulation or any other investigational agent for treatment of myasthenia gravis
!
Live viral vaccines (e.g., measles, mumps, rubella)
!
PLEX
Treatments needed for myasthenic crisis or MG exacerbation requiring hospitalization are 
not restricted per protocol as this constitutes a real medical necessity and required 
interventions to assure subject safety are always allowed.


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3.5.3
Restricted Concomitant Medications during the Study
This section describes medications that are restricted but not prohibited during the study 
participation:
!
Any dose change in concomitant immunosuppressant therapy (other than CS) in the six 
months prior to Screening is not allowed for study eligibility. During the study, changes 
in concomitant immunosuppressant therapy are not allowed unless there is a real medical 
necessity for safety reasons in the investigator’s opinion.
!
Any change in acetylcholinesterase inhibitor (e.g., Mestinon [pyridostigmine]) dose in 
the one month prior to Screening is not allowed for study eligibility. During the study, 
changes in dosage are not allowed unless there is a real medical necessity for safety 
reasons in the investigator’s opinion. 
Use of medications known to potentially worsen myasthenia gravis is discouraged (unless 
medically required) including telithromycin, fluoroquinolones (e.g., Ciprofloxacin and 
Levofloxacin), Zithromax (azithromycin), aminoglycoside antibiotics, botulinum toxin, 
quinine, quinidine, procainamide, D-penicillamine, and β-blockers.
3.6
Efficacy Study Variables 
3.6.1
Primary Variable
The primary efficacy endpoint will be the percent of subjects in each arm achieving a 50% or 
greater reduction in CS dose (prednisone or equivalent) at Week 39 (Visit 14) from 
Baseline/Week 0 (Visit 1).
3.6.2
Secondary Variables
Secondary efficacy variables assessed in this study are:
!
Percent reduction in daily CS (prednisone or equivalent) dose from Baseline/Week 0 to 
Week 39 (Visit 14)
!
Time to first episode of MG worsening, as defined in Section 3.3.3 “Definition and 
Management of MG Worsening,” from Week 0 through Week 39 (Visit 1 through 
Visit 14)
3.6.3
Exploratory Variables
The exploratory objectives for this study are to evaluate the effect of IGIV-C on: 
!
Percent of subjects achieving a 75% or greater reduction in CS dose (prednisone or 
equivalent) at Week 39 (Visit 14) from Baseline/Week 0 (Visit 1)
!
Percent of subjects CS-free at Week 39 (Visit 14)
!
Percent of subjects achieving a dose of CS of less than or equal to 7.5 mg per day of 
prednisone (or equivalent) at Week 39 (Visit 14)
!
Change from Baseline/Week 0 in fasting serum glucose at Week 39 (Visit 14)


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!
Percent of subjects with fasting glucose less than or equal to 125 mg/dL at Week 39 
(Visit 14) compared to Baseline (Week 0)
!
Percent of subjects experiencing MC (as defined in Section 3.3.5) or episode of MG 
worsening requiring inpatient care from Baseline/Week 0 (Visit 1) through Week 39 
(Visit 14)
!
Percent of subjects experiencing MC or episode of MG worsening requiring inpatient 
care from Week 39 to Week 45 (at Visit 14 and Visit 16)
!
Number of episodes of MG worsening, as defined in Section 3.3.3 “Definition and 
Management of MG Worsening,” from Baseline/Week 0 to Week 39 (Visit 1 to 
Visit 14)
!
Change in 15-Item MG-QOL 15 from Baseline/Week 0 to Week 39 (Visit 1 to Visit 14), 
and from Baseline to Week 42 and Week 45 (Visit 15 and Visit 16)
!
Change in MG-ADL from Baseline/Week 0 to Week 39 (Visit 14), and from Baseline to 
Week 42 and Week 45 (Visit 15 and Visit 16)
!
Change from baseline in serum IgG trough at Week 9 (Visit 4), Week 24 (Visit 9), and 
Week 39 (Visit 14)
!
Change from baseline in binding, blocking, and modulating AChR antibodies at Week 39 
(Visit 14) 
!
Change from baseline in HbA1c at Week 39 (Visit 14)
3.6.4
Quantitative Myasthenia Gravis (QMG) Score 
The MGFA, Inc. Task Force on Clinical Research Standards recognizes the utility of the 
QMG score in prospective clinical trials in MG (34) complemented by additional tools such 
as the MG composite. The QMG score is easy to administer by clinical evaluators and/or 
physicians in approximately 30 minutes with minimal equipment to measure spirometry and 
muscle strength testing. A 3-point improvement in QMG score indicates clinically 
meaningful improvement in terms of minimal clinically important difference and precedent 
set by endpoints in other MG studies (37,38). Subjects receiving cholinesterase inhibitors 
will be instructed not to take medication 12 hours prior to QMG score.
QMG score test items are attached in Appendix 3.
3.6.5
MG Composite Scale
The MG Composite scale takes less than five minutes to complete, and is made up of three 
ocular, three bulbar, one respiratory, one neck, and two limb items (39,40).
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 (41).
The MG Composite items are listed in Appendix 4.


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3.6.6
Myasthenia Gravis-Activities of Daily Living (MG-ADL)
The MG-ADL is an 8-item, patient reported (or investigator administered) questionnaire that 
is completed to assess the symptoms and activities in MG (42,43,44). A 2-point improvement 
in the MG-ADL indicates clinical improvement (42).
The questionnaire and scoring is provided in Appendix 5. 
3.6.7
15-item Myasthenia Gravis Quality-of-Life Instrument (MG-QOL 15)
MG symptoms significantly impact quality of life (QOL) particularly in aspects of physical 
functioning. The 15 items on the MG-QOL15 are derived from mobility, symptoms, general 
contentment, and emotional well-being categories assessed by the patient over the past few 
weeks. All individual items related to degree of disease-related impairment are rated on a 
Likert scale ranging from “not at all” (score 0 points) to “very much” (score 4 points) with 
higher scores indicating greater negative impact (worse disease) (45,46,47).
The MG-QOL15 and scoring are provided in Appendix 6.
3.7
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 (temperature [T], respiratory rate [RR], heart rate [HR], systolic blood 
pressure [SBP] and diastolic blood pressure [DBP]); during infusions vital signs will be 
carefully monitored.
!
Physical Assessments: physical exams will be recorded as normal or abnormal, according 
to the physician’s judgment criteria, and findings will be recorded.
!
Blood chemistry and Hematology
!
Thromboembolic events (TEs)
!
Hemolysis
!
WHO-Five (WHO-5) Well-Being Index
3.7.1
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 deep 
venous thrombosis (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 Baseline/Week 0 (Visit 1) prior to infusion, 
Visit 1 after the first loading infusion, at the time when the last loading infusion is complete, 
and at completion of each maintenance dosage at Week 3 (Visit 2), Week 6 (Visit 3), and 
Week 24 (Visit 9).
Procedures for the monitoring of TEs risk are provided in Appendix 7.


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3.7.2
Hemolysis
Blood assessments including whole blood Hb, serum free Hb, haptoglobin, lactate 
dehydrogenase (LDH), direct antiglobulin test (DAT), absolute reticulocyte count (ARC), red 
blood count (RBC), hematocrit, total (TBL) and indirect bilirubin, and blood smear, and 
urinalysis including urinary sediment and hemoglobinuria will be conducted at Baseline 
(prior to infusion), Day 1 (after the first loading infusion), at the time when the last loading 
infusion is complete, and at completion of each maintenance dosage at Week 3 (Visit 2), 
Week 6 (Visit 3), and Week 24 (Visit 9) 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 Baseline/Week 0 (Visit 1) and the time 
points specified above. Hemolysis laboratory assessments will also be performed 7 days post 
loading dose infusion at Baseline (Week 0) and 7 days post maintenance infusion at Weeks 3 
(Visit 2), 6 (Visit 3), and 24 (Visit 9).
Procedures for hemolysis detection are provided in Appendix 8.
3.7.3
WHO-Five (WHO-5) Well-Being Index
The WHO-5 Well-Being Index score will be used to measure CS side effects. This index is 
an easy to use 5-item questionnaire designed to measure current mental well-being (over the 
last 2 weeks) and may be a useful tool for reflecting mood (48,49,50,51). Cross cultural 
evaluation has been performed and the index has been utilized in clinical trials.
The WHO-5 Well-Being Index and scoring is provided in Appendix 9.
3.8
Assessments
3.8.1
Assessment Periods
The study consists of a three-week Screening period during which assessments are performed 
to determine eligibility. Eligible subjects will have Baseline assessments performed, and be 
randomized at Week 0 (Visit 1). At this time, an initial loading dose of blinded IP will be 
administered at a dose of 2 g/kg divided over 2 days starting after randomization. 
Maintenance infusions of blinded IP will be given at doses of 1 g/kg over 1 day every three 
weeks through Week 36 (Visit 13). Note that the loading dosage is divided over 2 days as 
standard infusion time; however, extensions to 4 days are allowed for tolerability issues or 
higher weight, i.e., limit for IGIV-C infusion is no more than 80 g/day (corresponding to 
80 kg body weight). Similarly the maintenance dosage is infused in 1 day as standard; 
however extensions for divided dosage over 2 days are allowed for tolerability issues or 
higher weight, i.e., limit for IGIV-C infusion is no more than 80 g/day (corresponding to 
80 kg body weight).
The IP Run-in consists of the loading infusion and maintenance infusions received prior to 
Week 9 (Visit 4). After completion of the third maintenance dosage at Visit 4 (Week 9), 
subjects will begin the protocol-prescribed CS tapering which will continue from Week 9 
(Visit 4) through Week 36 (Visit 13) provided that clinical status has not worsened as defined 
in Section 3.3.3, whilst continuing maintenance IP infusions at 3-week intervals. After 


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completion of the treatment period, there is a 9-week Safety/Follow-up period through 
Week 45 (Visit 16).
3.8.2
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 
possible. See the Overall Study Schema (Figure 3-1) and Schedule of Study Procedures in 
Appendix 1 for a summary of study visits and the procedures conducted at each visit. 
3.8.2.1
Overview of Screening, Treatment, and Post Infusion Follow-up Phases
All subjects will start their participation in the study upon the signing of the informed 
consent form (ICF). If applicable, a legally authorized representative may provide informed 
consent on behalf of the subject (see Section 7.4).
Eligible subjects based on Screening evaluations will complete the Baseline assessments, 
thereby initiating the Treatment. Subjects will continue with assessments for 45 weeks, with 
scheduled assessments at Week 0 (Visit 1) (Baseline, post-Baseline, and loading infusion 
over 2 days), followed by assessments and maintenance dosages every 3 weeks through 
Week 36 (Visit 13). The protocol-specified CS tapering will commence at Week 9 (Visit 4) 
and continue through Week 36 (Visit 13), inclusive, in conjunction with continued 
maintenance dosages of IP. Safety/Follow-up assessment visits are scheduled for Weeks 39, 
42, and 45 (Visits 14, 15, and 16). Visits/procedures and assessments should be scheduled at 
the protocol-specified study day ± 3 days.  
3.8.2.2
Screening: Week -3 (Visit 0)
Subjects must hold their acetylcholinesterase inhibitor (e.g., pyridostigmine) dosage for 12 
hours prior to the Screening/Week -3 (Visit 0) to assure accurate assessment of the QMG 
score. The following procedures and assessments will be conducted during the 
Screening/Week -3 (Visit 0) (Note: Screening is considered Visit 0; assessments are to be 
conducted within 3 weeks of Baseline/Week 0 [Visit 1]):
!
Informed consent prior to the initiation of screening procedures
!
Subject number assigned
!
Medical history including demographics and prior/concomitant diseases
!
Prior and concomitant medications 
!
Record CS dose prescribed this visit; instruct subjects to document CS doses taken during 
the entire study
!
Full physical exam (excluding breast and genitourinary areas) and waist circumference
!
Vital signs including T, RR, HR, SBP, and DBP
!
Inclusion/exclusion criteria review
!
Height
!
Weight (Screening will be used to calculate IP infusion dose for Visits 1-3)
!
Laboratory assessments (see Section 3.8.3) 
-
Blood 


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◦
Serum Pregnancy Test (β human chorionic gonadotropin [HCG]) (potential 
child-bearing females only; results must be negative for the subject to continue in 
the study)
◦
Chemistry 
◦
Hematology
◦
D-dimer  
◦
AChR antibodies (see Section 3.8.3.4)
!
TEs risk monitoring assessment 
!
QMG score
!
MGFA Clinical Classification
!
MG Composite Score
!
AEs with onset after informed consent is signed 
3.8.2.3
Baseline, Randomization, and Loading Infusion: Week 0 (Visit 1)
Subjects must hold their acetylcholinesterase inhibitor (e.g., pyridostigmine) dosage for 12 
hours prior to the Baseline/Week 0 (Visit 1) to assure accurate assessment of the QMG. 
Additionally, subjects must fast for at least 8 hours (e.g., overnight) to allow accurate 
measurement of fasting serum glucose at Baseline. All screening laboratory results and 
assessments must be available and all inclusion and exclusion criteria must have been 
satisfied prior to initiating treatment. For eligible subjects, following completion of all 
Baseline assessments, IGIV-C (or Placebo) will be administered as a loading dose of 2 g/kg 
(20 mL/kg) given in divided doses over two days.
The listed procedures and assessments will be conducted at Baseline/Week 0 (Visit 1). 
Baseline assessments will be immediately followed by randomization and initiation of IP 
loading infusions.
Baseline, Prior to Randomization
!
Laboratory assessments (see Section 3.8.3):
-
Urine 
◦
Urine sediment and measuring of hemoglobinuria/hematuria  
-
Blood 
◦
D-dimer  
◦
Chemistry 
◦
Hematology
◦
Whole blood Hb, RBC, hematocrit (from hematology specimen, see Section
3.8.3), ARC, blood smear for erythrocyte morphology, serum free Hb, 
haptoglobin, LDH, DAT, TBL (TBL from chemistry specimen, see Section 3.8.3) 
and indirect bilirubin (Hemolysis assessment Appendix 8)
◦
IgG levels
◦
HbA1c
◦
Fasting serum glucose (following which subject may eat)
◦
Quantitative/semi-quantitative binding, blocking, and modulating AChR 
antibodies 


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◦
Retain samples for virus safety testing as detailed in Table 3-5 (These retention 
samples will be tested only if the subject exhibits clinical signs and symptoms 
consistent with hepatitis A virus [HAV], hepatitis B virus [HBV], hepatitis C 
virus [HCV], human immunodeficiency virus [HIV], or parvovirus B19 [B19V] 
infection while participating in the study. These samples will be retained until all 
analyses in support of the study are complete.)
!
TEs risk monitoring assessment (Appendix 7) (prior to IP infusion)
!
AEs (includes clinical observation of signs and symptoms suggestive of any significant 
disease or condition [e.g., thrombosis, anemia, etc.]) 
!
Prior and concomitant medications 
!
Record CS dose prescribed this visit; review subject’s prior adherence; instruct subject to 
continue to document CS doses taken
!
Full physical exam (excluding breast and genitourinary areas) and waist circumference.
In addition, assess the following features as either absent (0) or present with grading 
indicated as mild (1), moderate (2), or severe (3) for each of the following: 
a.
Moon face 
b. Centripetal obesity
c.
Dorsalcervical fat pad
d. Thin skin/easy bruising
e.
Skin striae
f.
Hirsutism (women)
g. Acne (both genders)
Changes in these graded parameters are not considered AEs.
!
Vital signs including T, RR, HR, SBP, and DBP
!
Inclusion/exclusion criteria review (e.g., QMG score relative to Screening [to be eligible 
must be within 3 points of Screening value])
!
QMG score
!
MG Composite
!
MG-ADL
!
MG-QOL 15
!
MGFA Class
!
WHO-5 Well-Being Index
RANDOMIZATION 
!
Randomization will occur via IWRS once all Baseline assessments are performed and 
eligibility is confirmed 
POST-BASELINE/POST-RANDOMIZATION LOADING DOSE INFUSION 
!
Unblinded Pharmacist or designee, to prepare and dispense the IP per randomization 
assignment and Pharmacy Manual
!
Administer the loading infusion dosage (blinded active or placebo) of 2 g/kg divided over 
2 days (per Pharmacy Manual). Note that for the loading dosage 2 days is standard (2-4 


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days is allowed as an extension for tolerability issues or higher weight, i.e., limit for 
IGIV-C infusion is no more than 80 g/day [corresponding to 80 kg body weight]).
!
During the infusions, abbreviated vital signs (HR, SBP, and DBP) will be recorded just 
before the start of each infusion (within 15 ± 5 minutes before the beginning of each 
infusion), 30 ± 10 minutes after starting infusion, and immediately after infusion 
completes.
!
Hemolysis evaluation (laboratory parameters: Hb, hematocrit, RBC, blood smear, serum 
free Hb, haptoglobin, LDH, DAT, ARC, total and indirect bilirubin; urine for urinary 
sediment and hemoglobinuria/hematuria), and thromboembolism evaluation (Wells score 
and D-dimer) will be performed at the end of the first infusion of the loading dose, and at 
the time when last loading infusion is complete. Appendix 7 and Appendix 8 provide 
details.
!
For each infusion, 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
!
AEs (includes clinical observation of signs and symptoms suggestive of any significant 
disease or condition [e.g., thrombosis, anemia, etc.]) 
!
Concomitant medication
!
Additional hemolysis evaluation (laboratory parameters) will be performed 7 days post
loading dose infusion
3.8.2.4
Investigational Product Run-in Maintenance Phase: Weeks 3 and 6 (Visits 2 
and 3)
The first two maintenance dosages comprise the IP Run-In phase. Subjects must hold their 
acetylcholinesterase inhibitor (e.g., pyridostigmine) dosage for 12 hours prior to the Week 3 
and 6 (Visits 2 and 3) to assure accurate assessment of the QMG. At Week 3 and Week 6 
(Visits 2 and 3), the following will be performed:
!
Maintain stable CS dose
!
QMG score to be assessed pre-infusion
!
MG Composite to be assessed pre-infusion
!
Record complete vital signs including T and RR
!
Unblinded Pharmacist or designee, to prepare and dispense the IP per randomization 
assignment and the Pharmacy Manual
-
Note: Screening subject weight is used for IP dose calculations for Visits 1 to 3.
!
Administer the maintenance dosage (blinded active or placebo) of 1 g/kg over 1 day (per 
Pharmacy Manual). Note that the maintenance dosage is given over 1 day as the standard 
time interval (divided dosage over 2 days is allowed for tolerability issues or higher 
weight, i.e., limit for IGIV-C infusion is no more than 80 g/day [corresponding to 80 kg 
body weight]).
!
During the infusions, abbreviated vital signs (HR, SBP, and DBP) will be recorded just 
before the start of each infusion (within 15±5 minutes before the beginning of each 
infusion), 30±10 minutes after starting infusion, and immediately after infusion 
completes.


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!
Hemolysis evaluation (laboratory parameters: Hb, hematocrit, RBC, blood smear, serum 
free Hb, haptoglobin, LDH, DAT, ARC, total and indirect bilirubin; urine for urinary 
sediment and hemoglobinuria/hematuria), and Thromboembolism evaluation (Wells 
score and D-dimer) will be performed after each maintenance infusion dosage is entirely 
completed. Appendix 7 and Appendix 8 provide details.
!
For each infusion, 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
!
AEs (includes clinical observation of signs and symptoms suggestive of any significant 
disease or condition [e.g., thrombosis, anemia, etc.])
!
Concomitant medication
!
Record CS dose prescribed at each visit; review subject’s prior adherence; instruct 
subject to continue to document CS doses taken
!
Additional hemolysis evaluation (laboratory parameters) will be performed 7 days post 
maintenance infusion
3.8.2.5
Corticosteroid Tapering/IP Maintenance Phase: Week 9 to Week 36 (Visit 4 to
Visit 13) Inclusive
CS tapering will begin at Week 9 (Visit 4) after completion of the third maintenance IP 
dose. CS dosage in stable or improving subjects will be decreased at scheduled visits every 
three weeks during the CS Tapering phase (Week 9 through Week 36 [Visit 13]) predicated 
on current CS dose (prednisone equivalents): (a) if CS dosage is >40 mg/day, the dose 
decrease every 3 weeks is 10 mg/day; (b) if CS dosage is ≤40 mg/day, the dose decrease 
every 3 weeks is 5 mg/day. Commensurate dose changes are required for subjects receiving 
every other day CS dosing (Table 3-1 and Table 3-2). Note that the rate of CS dose decrease 
is slower as subjects fall below the 40-mg per day threshold. During the CS Tapering phase, 
the last CS dose reduction can occur at Week 36 (Visit 13). The final CS taper step from 
5 mg prednisone equivalent daily to 0 mg prednisone equivalent daily is the Principal
Investigator’s decision and is not mandatory per protocol. The Principal Investigator may 
choose to taper to 0 mg prednisone equivalent daily based on best medical judgment for each 
subject given individual variability with regards to sensitivity to complete CS withdrawal and 
perceived MG exacerbation risk while CS-free.  
The standardized CS tapering will continue unless there is worsening of MG which is defined 
as:
!
QMG score increase by ≥ 4 points relative to Baseline 
During the CS Tapering phase, if a subject meets the definition of worsening then the CS 
dosage (prednisone equivalents) will increase based on the CS dosage at which worsening 
occurs. The CS dose increase will be 20 mg/day if the CS dosage (mg/day) at the time of 
worsening is ≥ 15 mg/day, or the CS dose increase will be 15 mg/day if the CS dosage 
(mg/day) at time of worsening is < 15 mg/day. Commensurate dose changes are required for 
subjects receiving every other day CS dosing (Table 3-3 and Table 3-4).


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If an episode of MG worsening fails to improve with the above CS dose increase within 
6 weeks (by the second subsequent visit), or if the specific episode requires a second dose 
increase at any time, the subject will be withdrawn from the study. Details are provided in 
Section 3.3.
Following a CS dose increase due to worsening MG, a second attempt at CS tapering may be 
made after the subject shows evidence of stabilization on the new CS dose for at least two 
visits (six weeks), and in the opinion of the PI, there is no contraindication to resuming the 
tapering. This second attempt requires that there are still visits remaining in the CS Tapering 
phase. Stabilization will be defined as a return to the subject’s Baseline/Week 0 status prior 
to the episode of worsening, with QMG score ≤3 points relative to Baseline/Week 0, and 
return to the baseline clinical symptom(s) that initially triggered the definition of worsening 
of MG as judged by the physician.
On this second attempt to taper, the CS dose will be reduced in the same fashion as before; 
however, the dose will not decrease below the last dose at which the subject was stable prior 
to their episode of MG worsening. Appendix 10 provides an example of this scenario.
During the CS Tapering phase, assessments and maintenance IP infusions occur every 3 
weeks. The assessments performed at the Week 9 (Visit 4) and Week 24 (Visit 9) are 
comprehensive and are nearly the same for both visits (with the exception that Week 24 
[Visit 9] includes assessments for hemolysis and thrombosis risk); assessments at Week 12, 
15, 18, 21, 27, 30, and 33 (Visits 5, 6, 7, 8, 10, 11, and 12) are identical though requiring 
fewer evaluations. The Week 36 (Visit 13) is the last visit which includes IP infusion and is 
the last time point for CS tapering.
STUDY WEEK 9 (VISIT 4)
Subjects must hold their acetylcholinesterase inhibitor (e.g., pyridostigmine) dosage for 12 
hours prior to the Week 9 Visit to assure accurate assessment of the QMG score. 
Additionally, subjects must fast for at least 8 hours (e.g., overnight) to allow accurate 
measurement of fasting serum glucose at Week 9 (Visit 4).
Assessments to be performed pre-infusion (except as specified):
!
Full physical exam (excluding breast and genitourinary areas) and waist circumference.
In addition, assess the following features as either absent (0) or present with grading 
indicated as mild (1), moderate (2), or severe (3) for each of the following: 
a.
Moon face 
b. Centripetal obesity
c.
Dorsalcervical fat pad
d. Thin skin/easy bruising
e.
Skin striae
f.
Hirsutism (women)
g. Acne (both genders)
!
Weight (to be used to calculate IP infusion dosage for the scheduled visit and subsequent 
IP infusions until the next scheduled weight is measured). 


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-
Note: Subject weight collected at Visit 4 is used for IP dose calculations for Visits 4 
to 8.
!
Full vital signs including T, RR, HR, SBP, and DBP
!
Clinical laboratory assessments: Hematology, Chemistry (see Section 3.8.3)
!
HbA1c
!
Blood for IgG (trough)
!
Fasting serum glucose (following which subject may eat)
!
QMG score
!
MG Composite
!
MG-QOL 15
!
MG-ADL
!
WHO-5 Well-Being Index
IP infusion:
!
Unblinded Pharmacist or designee, to prepare and dispense the IP per randomization 
assignment and Pharmacy Manual
!
Administer the maintenance dosage (blinded active or placebo) of 1 g/kg over 1 day (per 
Pharmacy Manual). Note that the maintenance dosage is given over 1 day as the standard 
time interval (divided dosage over 2 days is allowed for tolerability issues or higher 
weight, i.e., limit for IGIV-C infusion is no more than 80 g/day [corresponding to 80 kg 
body weight]).
!
During the infusions, abbreviated vital signs (HR, SBP, and DBP) will be recorded just 
before the start of each infusion (within 15 ± 5 minutes before the beginning of each 
infusion), 30 ± 10 minutes after starting infusion, and immediately after infusion 
completes.
!
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
!
AEs (includes clinical observation of signs and symptoms suggestive of any significant 
disease or condition [e.g., thrombosis, anemia, etc.]) 
!
Concomitant medications
After completion of IP infusion
!
Initiate CS tapering as delineated in Section 3.3.
!
Record CS dose prescribed this visit; review subject’s prior adherence; instruct subject to 
continue to document CS doses taken
STUDY WEEK 12, WEEK 15, WEEK 18, WEEK 21 (VISITS 5 TO 8 INCLUSIVE)
Subjects must hold their acetylcholinesterase inhibitor (e.g., pyridostigmine) dosage for 12 
hours prior to the Week 12, Week 15, Week 18, and Week 21 (Visits 5 to 8 inclusive) to 
assure accurate assessment of the QMG score.
Assessments to be performed pre-infusion:


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!
Full vital signs including T, RR, HR, SBP, and DBP
!
QMG score
!
MG Composite
IP infusion:
!
Unblinded Pharmacist or designee, to prepare and dispense the IP per randomization 
assignment and Pharmacy Manual. 
-
Note: Subject weight collected at Visit 4 (Week 9) is used for IP dose calculations for 
Visits 4 to 8 (Weeks 9 – 21).
!
Administer the maintenance dosage (blinded active or placebo) of 1 g/kg over 1 day (per 
Pharmacy Manual). Note that the maintenance dosage is given over 1 day as the standard 
time interval (divided dosage over 2 days is allowed for tolerability issues or higher 
weight, i.e., limit for IGIV-C infusion is no more than 80 g/day [corresponding to 80 kg 
body weight]).
!
During the infusions, abbreviated vital signs (HR, SBP, and DBP) will be recorded just 
before the start of each infusion (within 15 ± 5 minutes before the beginning of each 
infusion), 30 ± 10 minutes after starting infusion, and immediately after infusion 
completes.
!
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
!
AEs (includes clinical observation of signs and symptoms suggestive of any significant 
disease or condition [e.g., thrombosis, anemia, etc.])
!
Concomitant medications
After completion of IP infusion
!
Continue CS tapering as delineated in Section 3.3.
!
Record corticosteroid dose prescribed at each visit; review subject’s prior adherence; 
instruct subject to continue to document CS doses taken
STUDY WEEK 24 (VISIT 9)
Subjects must hold their acetylcholinesterase inhibitor (e.g., pyridostigmine) dosage for 12 
hours prior to the Week 24 (Visit 9) to assure accurate assessment of the QMG score. 
Additionally, subjects must fast for at least 8 hours (e.g., overnight) to allow accurate
measurement of fasting serum glucose at Week 24 (Visit 9).
Assessments to be performed pre-infusion (except as specified):
!
Full physical exam (excluding breast and genitourinary areas) and waist circumference.
In addition, assess the following features as either absent (0) or present with grading 
indicated as mild (1), moderate (2), or severe (3) for each of the following: 
a.
Moon face 
b. Centripetal obesity


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c.
Dorsalcervical fat pad
d. Thin skin/easy bruising
e.
Skin striae
f.
Hirsutism (women)
g. Acne (both genders)
!
Weight (to be used to calculate IP infusion dosage for the scheduled visit and subsequent 
IP infusions until the next scheduled weight is measured). 
!
Full vital signs including T, RR, HR, SBP, and DBP
!
Clinical laboratory assessments: Hematology, Chemistry (see Section 3.8.3)
!
HbA1c
!
Blood for IgG (trough)
!
Fasting serum glucose (following which subject may eat)
!
Hemolysis evaluation (laboratory parameters: Hb, hematocrit, RBC (from hematology 
specimen), blood smear, ARC, serum free Hb, haptoglobin, LDH, DAT, total and indirect 
bilirubin (TBL from chemistry specimen); urine for urinary sediment and 
hemoglobinuria/hematuria), and Thromboembolism evaluation (Wells score and 
D-dimer) will be performed at the time when last maintenance infusion is complete. 
Appendix 7 and Appendix 8 provide details.
!
QMG score
!
MG Composite
!
MG-QOL 15
!
MG-ADL
!
WHO-5 Well-Being Index
IP infusion:
!
Unblinded Pharmacist or designee, to prepare and dispense the IP per randomization 
assignment and Pharmacy Manual. 
-
Note: Visit 9 (Week 24) subject weight is used for IP dose calculations for Visits 9 to 
13 (Weeks 24 – 36).
!
Administer the maintenance dosage (blinded active or placebo) of 1 g/kg over 1 day (per 
Pharmacy Manual). Note: The maintenance dosage is given over 1 day as the standard 
time interval (divided dosage over 2 days is allowed for tolerability issues or higher 
weight, i.e., limit for IGIV-C infusion is no more than 80 g/day [corresponding to 80 kg 
body weight]).
!
During the infusions, abbreviated vital signs (HR, SBP, and DBP) will be recorded just 
before the start of each infusion (within 15 ± 5 minutes before the beginning of each 
infusion), 30 ± 10 minutes after starting infusion, and immediately after infusion 
completes.
!
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
!
AEs (includes clinical observation of signs and symptoms suggestive of any significant 
disease or condition [e.g., thrombosis, anemia, etc.])


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!
Concomitant medications
After completion of IP infusion
!
Continue CS tapering as delineated in Section 3.3.
!
Record CS dose prescribed this visit; review subject’s prior adherence; instruct subject to 
continue to document CS doses taken
!
Additional hemolysis evaluation (laboratory parameters) will be performed 7 days post 
maintenance infusion
STUDY WEEK 27, WEEK 30, WEEK 33 (VISITS 10 TO 12 INCLUSIVE)
Subjects must hold their acetylcholinesterase inhibitor (e.g., pyridostigmine) dosage for 12 
hours prior to the Week 27, Week 30, and Week 33 (Visits 10 to 12 inclusive) to assure 
accurate assessment of the QMG score.
Assessments to be performed pre-infusion:
!
Full vital signs including T, RR, HR, SBP, and DBP
!
QMG score
!
MG Composite
IP infusion:
!
Unblinded Pharmacist or designee, to prepare and dispense the IP per randomization 
assignment and Pharmacy Manual. 
-
Note: Visit 9 subject weight is used for IP dose calculations for Visits 9 to 13.
!
Administer the maintenance dosage (blinded active or placebo) of 1 g/kg over 1 day (per 
Pharmacy Manual). The maintenance dosage is given over 1 day as the standard time 
interval (divided dosage over 2 days is allowed for tolerability issues or higher weight, 
i.e., limit for IGIV-C infusion is no more than 80 g/day [corresponding to 80 kg body 
weight]).
!
During the infusions, abbreviated vital signs (HR, SBP, and DBP) will be recorded just 
before the start of each infusion (within 15 ± 5 minutes before the beginning of each 
infusion), 30 ± 10 minutes after starting infusion, and immediately after infusion 
completes.
!
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
!
AEs (includes clinical observation of signs and symptoms suggestive of any significant 
disease or condition [e.g., thrombosis, anemia, etc.])
!
Concomitant medications
After completion of IP infusion
!
Continue CS tapering as delineated in Section 3.3


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!
Record CS dose prescribed at each visit; review subject’s prior adherence; instruct 
subject to continue to document CS doses taken
STUDY WEEK 36 (VISIT 13)
The final maintenance IP dosage is administered during the Week 36 (Visit 13); this is also 
the final visit for the CS tapering adjustment. Subjects must hold their acetylcholinesterase 
inhibitor (e.g., pyridostigmine) dosage for 12 hours prior to the Week 36 (Visit 13) to assure 
accurate assessment of the QMG score.
Assessments to be performed pre-infusion:
!
Full vital signs including T, RR, HR, SBP, and DBP
!
QMG score
!
MG Composite
IP infusion:
!
Unblinded Pharmacist or designee, to prepare and dispense the IP per randomization 
assignment and Pharmacy Manual. 
-
Note: Visit 9 subject weight is used for IP dose calculations for Visits 9 to 13.
!
Administer the maintenance dosage (blinded active or placebo) of 1 g/kg over 1 day (per 
Pharmacy Manual). Note: The maintenance dosage is given over 1 day as the standard 
time interval (divided dosage over 2 days is allowed for tolerability issues or higher 
weight, i.e., limit for IGIV-C infusion is no more than 80 g/day [corresponding to 80 kg 
body weight]). 
!
During the infusions, abbreviated vital signs (HR, SBP, and DBP) will be recorded just 
before the start of each infusion (within 15 ± 5 minutes before the beginning of each 
infusion), 30 ± 10 minutes after starting infusion, and immediately after infusion 
completes.
!
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
!
AEs (includes clinical observation of signs and symptoms suggestive of any significant 
disease or condition [e.g., thrombosis, anemia, etc.])
!
Concomitant medications
After completion of IP infusion
!
Continue CS tapering as delineated in Section 3.3 (this is last visit in which CS 
tapering occurs)
!
Record CS dose prescribed this visit; review subject’s prior adherence; instruct subject to 
continue to document CS doses taken


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3.8.2.6
Safety / Follow-up Phase: Week 39 to Week 45 (Visit 14 to Visit 16) Inclusive
Following the last step of the CS tapering at Week 36 (Visit 13), three additional visits will 
be performed at Weeks 39, 42, and 45 (Visits 14, 15, and 16). The primary efficacy endpoint 
is evaluated at Week 39 (Visit 14), given the long half-life of IP. 
STUDY WEEK 39 (VISIT 14)
Subjects must hold their acetylcholinesterase inhibitor (e.g., pyridostigmine) dosage for 12 
hours prior to Week 39 (Visit 14) to assure accurate assessment of the QMG score. 
Additionally, subjects must fast for at least 8 hours (e.g., overnight) to allow accurate 
measurement of fasting serum glucose at Week 39 (Visit 14).
Assessments to be performed are the following:
!
Full physical exam (excluding breast and genitourinary areas) and waist circumference.
In addition, assess the following features as either absent (0) or present with grading 
indicated as mild (1), moderate (2), or severe (3) for each of the following: 
a.
Moon face 
b. Centripetal obesity
c.
Dorsalcervical fat pad
d. Thin skin/easy bruising
e.
Skin striae
f.
Hirsutism (women)
g. Acne (both genders)
Changes in these graded parameters are not considered AEs.
!
Weight
!
Full vital signs including T, RR, HR, SBP, and DBP
!
Clinical laboratory assessments: Hematology, Chemistry (see Section 3.8.3)
!
HbA1c
!
Blood for IgG (trough)
!
Fasting serum glucose (following which subject may eat)
!
Quantitative/semi-quantitative binding, blocking, and modulating AChR antibodies 
!
QMG score
!
MG Composite
!
MG-QOL 15
!
MG-ADL
!
WHO-5 Well-Being Index
!
AEs (includes clinical observation of signs and symptoms suggestive of any significant 
disease or condition [e.g., thrombosis, anemia, etc.])
!
Concomitant medications
!
It is suggested that the investigator consider an increase in CS dose after subjects 
complete the Week 39 (Visit 14) assessments if considered medically indicated.


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!
Record CS dose prescribed this visit; review subject’s prior adherence; instruct subject to 
continue to document CS doses taken
STUDY WEEK 42 (VISIT 15)
Subjects must hold their acetylcholinesterase inhibitor (e.g., pyridostigmine) dosage for 12 
hours prior to Week 42 (Visit 15) to assure accurate assessment of the QMG score.
Assessments to be performed are the following:
!
Full vital signs including T, RR, HR, SBP, and DBP
!
QMG score
!
MG Composite
!
AEs (includes clinical observation of signs and symptoms suggestive of any significant 
disease or condition [e.g., thrombosis, anemia, etc.])
!
Concomitant medications
!
It is suggested that the investigator consider an increase in CS dose after subjects 
complete the Week 39 (Visit 14) assessments if considered medically indicated.
!
Record CS dose prescribed this visit; review subject’s prior adherence; instruct subject to 
continue to document CS doses taken
STUDY WEEK 45 (VISIT 16)
Subjects must hold their acetylcholinesterase inhibitor (e.g., pyridostigmine) dosage for 12 
hours prior to Week 45 (Visit 16) to assure accurate assessment of the QMG score.
This is the Final Study Visit. Assessments to be performed are the following:
!
Full physical exam (excluding breast and genitourinary areas) and waist circumference
!
Weight
!
Full vital signs including T, RR, HR, SBP, and DBP
!
Clinical laboratory assessments: Hematology, Chemistry (see Section 3.8.3)
!
QMG score
!
MG Composite
!
MG-QOL 15
!
MG-ADL
!
AEs (includes clinical observation of signs and symptoms suggestive of any significant 
disease or condition [e.g., thrombosis, anemia, etc.]) 
!
Concomitant medications
!
Record CS dose prescribed this visit; review subject’s prior adherence
It is suggested that the investigator consider an increase in CS dose after subjects complete 
the Week 39 (Visit 14) assessments if considered medically indicated.


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EARLY DISCONTINUATION VISIT
The Early Discontinuation Visit includes the same assessments as the Week 45 visit with the 
exception of not including MG-QOL 15.
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 as soon as practical following the decision to withdraw (at least within 14 days 
after the termination date) if the subject is willing. Subjects must hold their 
acetylcholinesterase inhibitor (e.g., pyridostigmine) dosage for 12 hours prior to the Early 
Discontinuation Visit to assure accurate assessment of the QMG score.
The following procedures and assessments will be conducted at the Early Discontinuation 
Visit:
!
AEs (includes clinical observation of signs and symptoms suggestive of any significant 
disease or condition [e.g., thrombosis, anemia, etc.])
!
Concomitant medications 
!
Record CS dose prescribed this visit; review subject’s prior adherence
!
Full physical exam (excluding breast and genitourinary areas) and waist circumference
!
Weight
!
Vital signs including T, RR, HR, SBP, and DBP
!
Laboratory assessments (see Section 3.8.3):
-
Chemistry 
-
Hematology
!
QMG score
!
MG Composite
!
MG-ADL
Subjects who withdraw IP due to the occurrence of a treatment-emergent adverse event 
(TEAE) (or other reason) during the treatment period should be followed for safety by 
completing the two additional visits in the Follow-up Phase. Specifically subjects 
discontinuing during the IP Run-in maintenance and CS Tapering/IP Maintenance phases 
should complete assessments at the specified visit intervals for the Week 42 and Week 45 
visits, which are 6 and 9 weeks post end-of-IP administration. 


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3.8.3
Description of Laboratory Tests and Procedures
Table 3-5 Name, Description, and Location of Laboratory Tests and Procedures
Test Panel
Description
Location
Hematology a
Hb, hematocrit, platelets, RBC count, including RBC morphology, white 
blood cell count with differential
Central
Chemistry a
Creatinine, blood urea nitrogen (BUN), potassium, aspartate transaminase 
(AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total 
bilirubin (TBL) 
Central
Fasting serum 
glucose & HbA1c
Fasting serum glucose & HbA1c. HbA1c is produced by glycation of 
hemoglobin A, and reflects the mean blood glucose level over a period of one 
or two months before the blood sample is taken. Fasting serum glucose may 
reflect more immediate changes. 
Central
Hemolysis 
Whole blood Hb, RBC, hematocrit, serum free Hb, haptoglobin, LDH, DAT, 
ARC, TBL, and indirect bilirubin, and blood smear 
Central
Urine sediment and measuring of hemoglobinuria 
Thromboembolic 
events risk
D-dimer
Central
AChR a
Acetylcholine Receptor Antibody at Screening (diagnostic - defining MG); 
Baseline/Week 39 quantitative/semi-quantitative measurement of blinding, 
blocking, modulating AchR antibody (Please see Section 3.8.3.4 for details)
Central
IgG levels
Immunoglobulin G levels 
Central
Serum pregnancy a
Qualitative serum β human chorionic gonadotropin (HCG) for females of 
child-bearing potential. Results must be negative to continue in the study.
Central
Viral Nucleic 
Acid Testing 
(NAT)
Retains b:
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 b:
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
a
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.
b
Blood samples for viral NAT and viral serology will be collected at Baseline/Week 0 prior to 
randomization but will be tested only if the subject exhibits clinical signs and symptoms consistent with 
HAV, HBV, HCV, HIV, or B19V 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 HAV, HBV, HCV, HIV, or B19V infection while participating in the study.
3.8.3.1
Thromboembolic Events Risk Testing
Measurement of D-dimer blood levels and TEs risk testing will be performed at Screening, 
Baseline (Week 0 prior to randomization), at the end of the first infusion of the loading dose, 
at the time when last loading infusion is complete, and at the completion of maintenance 


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infusion dosage at Week 3 (Visit 2), Week 6 (Visit 3), and Week 24 (Visit 9). Appendix 7
provides details.
3.8.3.2
Hemolysis Testing
Laboratory assessments (urine; whole blood Hb, serum free Hb, haptoglobin, LDH, DAT, 
ARC, RBC, hematocrit, TBL and indirect bilirubin, and blood smear) will be conducted at 
Baseline (Week 0 prior to randomization), at the end of the first infusion of the loading dose, 
at the time when last loading infusion is complete, and at the completion of maintenance 
infusion dosage at Week 3 (Visit 2), Week 6 (Visit 3), and Week 24 (Visit 9). Hemolysis 
laboratory assessments will also be performed 7 days post loading dose infusion at Baseline 
(Week 0) and 7 days post maintenance infusion at Weeks 3 (Visit 2), 6 (Visit 3), and 24
(Visit 9). Appendix 8 provides details.
3.8.3.3
Virus Safety Testing
Viral NAT and viral serology retain samples will be collected at Baseline/Week 0 (Visit 1) 
prior to randomization, but will be tested only if the subject exhibits clinical signs and 
symptoms consistent with HAV, HBV, HCV, HIV, or B19V 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 HAV, HBV, 
HCV, HIV, or B19V infection while participating in the study.
3.8.3.4
AChR Antibody Testing
AChR antibody levels will be measured in all subjects at Screening and must be present for 
the subject to be eligible to participate in the study. Additionally, quantitative/semi-
quantitative binding, blocking, and modulating AChR antibodies will be measured at 
Baseline and Week 39.
Baseline and Week 39 results will not be shared during study conduct with the investigator, 
blinded study staff, CRO, or blinded Sponsor personnel involved with study conduct. All 
measurements will be conducted using validated assays. Specific details regarding all aspects 
of sample collection and processing can be found in the central laboratory Study Reference 
Manual.
3.8.3.5
IgG Concentration Measurements
Serum total IgG concentrations will be measured in all subjects at specified visits. Results of 
the central laboratory analysis of IgG levels will not be shared with the investigator, blinded 
study staff, CRO or blinded Sponsor personnel involved with study conduct. All 
measurements will be conducted using validated assays. Specific details regarding all aspects 
of sample collection and processing can be found in the Study Reference Manual at each site.


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3.9
Screen Failures
Screening evaluations will be used to determine the eligibility of each subject for 
randomization at the Baseline visit. Subjects who fail to meet eligibility criteria during 
screening evaluations will be considered screen failures. Subjects may re-screen for the study 
if the reason for screen failure is no longer relevant (e.g., CS dosage subsequently stable and 
meeting protocol entry requirements); a new informed consent form must be signed for 
re-screening.
3.10
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 (Week 0) 
Visit based on 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
!
If an episode of MG worsening fails to stabilize with the CS dose increase as described in 
Sections 3.3.3 and 3.3.4 within 6 weeks (by the second subsequent visit), or if another 
specific episode of MG worsening requires a second dose increase at any time, the 
subject will be withdrawn from the study. MG crisis requiring hospitalization in 
accordance with Section 3.3.5 would also be grounds for study discontinuation. 
!
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. 
3.11
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 Early Discontinuation Visit procedures (see Section 3.8.2.6) as 
soon as practical following decision to withdraw (at least within 14 days after the 
termination date) if the subject is willing. If discontinuation is due to a TEAE (or other 
reason) during the treatment period (which includes IP Run-in maintenance and CS 
Tapering/IP Maintenance phases) assessments specified for the two additional visits in the 


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Safety/Follow-up phase should be performed, i.e., Week 42 (Visit 15) and Week 45 (Visit 
16) corresponding to time points 6 and 9 weeks after the last IP administration.
3.12
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 overdose 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 day in this study is 1 g/kg, no 
cardiovascular events are expected.
4.1.2
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 blinded 
IGIV-C/Placebo can interfere with their immune response to live viral vaccines. Inform 
patients to notify their healthcare professional/immunizing physician of recent participation 
in a clinical study including blinded study drug (IGIV-C or Placebo). The investigator must 
consider any 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. 


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Safety endpoints will include:
!
AEs, SAEs and suspected ADRs
!
Vital signs 
!
Physical assessments
!
Blood chemistry and hematology
!
TEs
!
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 the infusions, abbreviated vital signs (HR, SBP, and DBP) will be recorded just 
before the start of each infusion (within 15 ± 5 minutes before the beginning of each 
infusion), 30 ± 10 minutes after starting infusion, and immediately after infusion completes.
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. 
In addition, vital signs will be assessed at scheduled visits. Abnormal vital signs judged as 
clinically relevant by the investigator in the context of the patient’s medical history 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 and findings will be recorded. Abnormal physical findings 
judged as clinically relevant by the investigator in the context of the patient’s medical history 
will be considered AEs. In addition to the routine physical exam, particular features will be 
evaluated as part of the physical exam performed at Baseline (Week 0), Visit 4 (Week 9), 


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Visit 9 (Week 24), and Visit 14 (Week 39) as an inventory of manifestations of steroid 
excess. Specifically, the following features will be assessed as either absent (0) or present 
with grading indicated as mild (1), moderate (2), or severe (3) for each of the following: 
a.
Moon face 
b. Centripetal obesity
c.
Dorsalcervical fat pad
d. Thin skin/easy bruising
e.
Skin striae
f.
Hirsutism (women)
g. Acne (both genders)
Changes in these graded parameters are not considered AEs.
4.3.4
Blood Chemistry and Hematological Parameters
All clinical laboratory data for renal (creatinine, BUN), hepatic (ALT, AST, ALP and TBL) 
and hematological parameters (complete blood count [CBC] including differential leukocyte 
count) will be listed for each clinical trial subject (See Table 3-5). 
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 in the 
context of the patient’s medical history.
Laboratory results out of the normal range judged by the investigator as clinically relevant in 
the context of the patient’s medical history/underlying comorbid conditions will be 
considered AEs.
4.3.5
Thromboembolic Event Risk
Procedures for the monitoring of TE risk are provided in Appendix 7. Pulmonary embolism 
and deep venous thrombosis will be considered AEs and/or SAEs if criteria for seriousness 
are met.
4.3.6
Hemolysis
Procedures for hemolysis detection are provided in Appendix 8. In the event that true 
hemolytic anemia develops, it will be considered an AE and/or an SAE depending on 
whether seriousness criteria are met. Hemolytic ARs are defined as temporally associated 
with the study drug within 7 days post infusion.
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 


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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 the 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.
4.4.2
Suspected Adverse Drug Reaction/Adverse Reaction
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 AR; thus, ARs 
are a subset of suspected ADRs.
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 (52):
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.


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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 (53,54).
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 
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 TEAEs.
AEs occurring during the actual IP infusions (i.e., from the initiation of the IP infusion on the 
first day to the completion of the total dosage of IP on the last day) and within 72 hours 
following the completion of the infusion of the total dosage 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 infusional TEAEs (a subset of 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 resolves 
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 is unusual to be 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 criteria currently included in this section.


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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 summary of product characteristics [SPC] or product label).
Events not listed for the particular drug under investigation in the IB or SPC are considered
“unexpected” and those listed are considered “expected.” When new Serious ADRs (Serious 
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.


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4.4.6.1
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.
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, reported accordingly, and if serious, may require early discontinuation from study. 
See Appendix 7 for details. 
4.4.7.2
Hemolysis
Subjects will be monitored for signs and symptoms of hemolysis. In addition, Grifols 
Medical Monitor will routinely review reported AEs for possible hemolysis. Hemolysis will 
be recorded as an AE, and reported accordingly, and if resulting in serious hemolytic anemia, 
may require early discontinuation from study. See Appendix 8 for details.
4.4.7.3
MG Events That Are Not Considered AEs
Given that variations in symptoms are an inherent part of the natural history of MG, all 
recorded information regarding severity of MG manifestations will be considered efficacy 
data. 
For the purpose of this study, variation in MG symptoms will not be considered an AE unless 
an exacerbation of MG, or MC requires hospitalization. If a subject is hospitalized for MG, it 
will be reported as an SAE.
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 medical 
record. If no AE has occurred during the study period, this should also be indicated in the 
eCRF.


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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 
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. severity (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 resolves 
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 CRO according to the Medical Dictionary for Regulatory Activities (MedDRA®).
For example, a laboratory test abnormality considered clinically relevant, e.g., causing the 
subject to withdraw from the study, requiring treatment or causing apparent clinical 
manifestations, or judged relevant by the investigator, should be reported as an AE. Each 
event must be described in detail along with start and stop dates, severity, relationship to IP, 
action taken and outcome. Each event must be adequately supported by documentation as it 
appears in the subject’s medical or case file.
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.




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Data handling and evaluation procedures will be described in the Statistical Analysis Plan.
5.1.1
Subject Populations for Analysis
INTENT-TO-TREAT (ITT) POPULATION
The ITT population consists of all subjects who are randomized. Efficacy analyses will be 
performed on the ITT population. 
SAFETY POPULATION
The Safety population consists of all subjects who received any amount of IP.  
PER-PROTOCOL POPULATION
The per-protocol population consists of all subjects in the ITT population without any major 
protocol deviation that has an impact on the primary efficacy data. Any deviations from the 
protocol will be recorded in the protocol deviation list. The validity of a subject for inclusion 
in the per-protocol population 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 protocol deviations are identified which justify removing a subject from the 
per-protocol 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
5.1.3.1
Primary Efficacy Analyses
The primary endpoint is the percent of subjects achieving a 50% or greater reduction in CS 
dose (prednisone or equivalent) at Week 39 (Visit 14) from Baseline/Week 0 (Visit 1). The 
treatment comparison will be analyzed using Cochran-Mantel-Haenszel (CMH) test adjusted 
for baseline CS dose (15-40 mg versus 41-60 mg). The null hypothesis (H0) and the 
alternative hypothesis (Ha) are:  
H0: P1 = P2
Ha: P1 ≠ P2
Where P1 and P2 represent the percent of subjects achieving a 50% or greater reduction in 
CS dose in IGIV-C and Placebo group, respectively.
Subjects who discontinued the study early due to the MG worsening will be considered as 
not achieving a 50% or greater reduction. In subjects who discontinue the study early due to 
other reasons, the last observation carried forward (LOCF) method will be used to compute 
the missing CS dose and drive the primary efficacy endpoint. Also, as a sensitivity analysis,
the primary efficacy endpoint will be analyzed for all subjects who complete the CS dose up 
to Week 39 (Visit 14).


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Primary Efficacy analyses will be based on the ITT population. For sensitivity analysis, the 
same analysis will be repeated using the per-protocol population. 
5.1.3.2
Secondary Efficacy Analyses
The following secondary efficacy variables will be analyzed using the ITT population: 
!
Percent reduction in daily CS (prednisone or equivalent) dose from Baseline to Week 39 
(Visit 14)
The percent daily CS dose reduction from baseline will be analyzed using analysis of 
covariance (ANCOVA). The ANCOVA model will include the percent daily CS dose 
reduction as dependent variable, treatment as fixed effect, and Baseline daily CS dose as 
a covariate.
!
Time to first episode of MG worsening, as defined in Section 3.3.3 “Definition and 
Management of MG Worsening,” from Baseline/Week 0 through Week 39 (Visit 1 
through Visit 14)
Kaplan-Meier estimates will be provided for time to first episode of MG worsening for 
each treatment group. The treatment comparison will be performed using log-rank test 
adjusted for baseline CS dose (15 to 40 mg versus 41 to 60 mg).
5.1.3.3
Exploratory Efficacy Analyses
Exploratory efficacy analyses will be based on the ITT population. The following 
exploratory efficacy variables will be analyzed with the same approach as the primary 
efficacy endpoint using the ITT population: In the situation where the CMH method is not 
appropriate due to the sparse events, the Fisher exact test will be used for treatment 
comparison.
Exploratory efficacy variables that will be evaluated in this study include the following:
!
Percent of subjects achieving a 75% or greater reduction in CS dose (prednisone or 
equivalent) at Week 39 (Visit 14) from Baseline/Week 0 (Visit 1)
!
Percent of subjects CS-free at Week 39 (Visit 14)
!
Percent of subjects achieving a dose of CS of less than or equal to 7.5 mg per day of 
prednisone (or equivalent) at Week 39 (Visit 14)
!
Percent of subjects with fasting glucose less than or equal to 125 mg/dL at Week 39 
(Visit 14)
!
Percent of subjects experiencing MC (as defined in Section 3.3.5) or episode of MG 
worsening requiring inpatient care from Baseline/Week 0 (Visit 1) through Week 39 
(Visit 14)
!
Percent of subjects experiencing MC or episode of MG worsening requiring inpatient 
care from Week 39 to Week 45 (at Visit 14 and Visit 16)
!
Percent of subjects with 0, 1, or 2 episodes of MG worsening from Baseline/Week 0 to 
Week 39 (Visit 1 to Visit 14) (in aggregate and by number of episodes/subject).


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The following exploratory endpoints will be analyzed using the ANCOVA with treatment as 
main factor and baseline CS dose as covariate. In addition, the mixed model for repeated 
measurement (MMRM) will also be performed.
!
Change from Baseline/Week 0 in fasting serum glucose at Week 39 (Visit 14)
!
Change in 15-Item MG-QOL 15 from Baseline/Week 0 to Week 39 (Visit 1 to Visit 14), 
and from Baseline to Week 42 and Week 45 (Visit 15 and Visit 16)
!
Change in MG-ADL from Baseline/Week 0 to Week 39 (Visit 14), and from Baseline to 
Week 42 and Week 45 (Visit 15 and Visit 16)
!
Change from baseline in serum IgG trough at Week 9 (Visit 4), Week 24 (Visit 9), and 
Week 39 (Visit 14)
!
Change from baseline in binding, blocking, and modulating AChR antibodies at Week 39 
(Visit 14) 
!
Change from baseline in HbA1c at Week 39 (Visit 14)
In addition, exploratory analyses of the correlation between CS dose reduction and blood 
pressure (hypertension), measures of glycemic control, weight, body habitus/Cushingoid 
features, and mood/emotional well-being will be explored.
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.
AEs will be coded and classified using MedDRA terms (system organ class and preferred 
terms). 
AEs 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 first 
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.  
In addition, TEAEs, including suspected ADRs, will be summarized, system organ class, 
preferred term, causal-relationship, intensity (severity) and seriousness (serious vs. 


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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 with 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 and 
summarized by treatment group. 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. Abnormal vital 
signs judged as clinically relevant by the investigator in the context of the patient’s medical 
history will be considered AEs. 
Physical Assessment:
Physical Exam findings (normal and abnormal) will be listed for each clinical trial subject 
with the specific findings observed included in the listing. Abnormal findings judged as 
clinically relevant by the investigator in the context of the patient’s medical history will be 
considered AEs. In addition, additional features related to CS side effects (graded as absent 
[0], mild [1], moderate [2], or severe [3]) will be listed and summarized. 
Blood chemistry and hematology:
All clinical laboratory data for renal (creatinine, BUN, potassium), hepatic (ALT, AST, ALP, 
and TBL) and hematological parameters (CBC including differential leukocyte count) will be 
listed for each clinical trial subject. Laboratory results out of the normal range judged as 
clinically relevant by the investigator in the context of the patient’s medical history will be 
considered AEs. Clinical laboratory results and the change from baseline values will be 
summarized by treatment group using summary statistics. Shift tables will be provided to 
summarize values that fall outside the normal ranges.
Lab tests for TEs and hemolysis:
The D-dimer for TE assessment and the laboratory tests for detecting hemolysis (including 
whole blood Hb, serum free Hb, haptoglobin, LDH, DAT, ARC, RBC, hematocrit, TBL and 


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indirect bilirubin, and blood smear) will be listed and out of normal range results will be 
flagged. 
5.2
Determination of Sample Size
In order to provide 80% power to detect a 40% treatment difference (70% IGIV-C versus 
30% Placebo group) in the percent of subjects achieving a 50% or greater reduction in CS 
dosage at Week 39, alpha level = 0.05, a minimum of 24 subjects per treatment group is 
required. Assuming a discontinuation rate in the range of 20%, 60 subjects are planned to be 
randomized for the study. This is necessary to accommodate attrition anticipated.
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).
6.1.1
Independent Safety Review Committee
This study will utilize an Independent Safety Review Committee (ISRC) whose members 
(from Grifols) will be impartial and independent of the clinical trial team. The clinical trial 
team will remain blinded to subject treatment assignment. The ISRC will review relevant 
safety information from the study as outlined in the ISRC Charter. At a minimum, after the 
first 20 subjects are enrolled and have completed half of the treatment period, the ISRC will 
conduct a safety review of the following data at a minimum:
!
AEs, SAEs, and discontinuations due to AEs and SAEs
!
Vital signs
!
Blood chemistry and hematology
!
Assessing for TEs
!
Assessing for hemolysis
During the study, the Medical Monitor will review all relevant safety information from the 
study in order to protect subject welfare and preserve study integrity. Data to be reviewed 
include but are not limited to the following: eCRFs, listings from the clinical and safety 
databases, AEs/SAE reports, concomitant medications, laboratory data, vital signs, and 
physical examinations data.


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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.  
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 


Protocol GTI1306 – Amendment 2 
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CONFIDENTIAL
Page 78 of 106
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.
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.


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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 the Sponsor by the 
investigator site. 
Written ICF must be obtained before any study specific procedure takes place. 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.
7.5
Insurance
Sponsor shall maintain comprehensive general liability insurance or self-insurance in 
amounts adequate to cover any damage, demand, claim, loss or liability caused or incurred 
by Sponsor, or as otherwise required by 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 (e.g., 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.


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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 
-
By written request, Grifols may delay proposed publications up to 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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56. Wells PS. Integrated strategies for the diagnosis of venous thromboembolism. J Thromb 
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57. Adam SS, Key NS, Greenberg CS.  D-dimer antigen: current concepts and future 
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58. Health Canada. Canadian Adverse Reaction Newsletter. Intravenous immune globulin 
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60. Tuncer Elmaci N, Ratip S, Ince-Günal D, et al. Myasthenia gravis with thymoma and 
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61. Chant C, Wilson G, Friedrich J. Anemia, transfusion, and phlebotomy practices in 
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10 APPENDICES


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Appendix 1
Schedule of Study Procedures
Study Period
                    
Procedures/Assessments
Screening Baseline
Loading IP 
Dose over 2 
Days
IP Run-In Maintenance
Corticosteroid Tapering/IP Maintenance
Safety/Follow-
up
Visit 
0
1
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Study Week (or days post 
study drug infusion)
-3
0
0
+7 days 
post
3
+7 days 
post
6
+7 days 
post
9
12
15
18
21
24
+7 days 
post
27
30
33
36
39
42
45 o
Informed Consent
X
Inclusion/Exclusion Criteriaa
X
X
Randomizationb
X
Serum Pregnancy Testc
X
Demographics/Medical 
History
X
Full Physical Exam and waist 
circumferenced
X
Xd,e
Xe
Xe
Xd
X
Height
X
Weightf
X
Xe
Xe
X
X
Vital signsg
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Collection of Virus Safety 
Retain Samplesh
Xe
Clinical Laboratory 
Assessments (Hematology, 
Chemistry)
X
Xe
Xe
Xe
X
X
Fasting Serum Glucose & 
HbA1ci
Xe
Xe
Xe
X
QMG scorej
X
Xe
Xe
Xe
Xe
Xe
Xe
Xe
Xe
Xe
Xe
Xe
Xe
Xe
X
X
X
MG Composite
X
Xe
Xe
Xe
Xe
Xe
Xe
Xe
Xe
Xe
Xe
X
Xe
Xe
X
X
X
MG-QOL 15
Xe
Xe
Xe
X
X
MG-ADL
Xe
Xe
Xe
X
X
WHO-5 Well-Being Index
Xe
Xe
Xe
X
MGFA Class
X
X e
Blood for IgG (trough)
X e
Xe
Xe
X


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Study Period
                    
Procedures/Assessments
Screening Baseline
Loading IP 
Dose over 2 
Days
IP Run-In Maintenance
Corticosteroid Tapering/IP Maintenance
Safety/Follow-
up
Visit 
0
1
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Study Week (or days post 
study drug infusion)
-3
0
0
+7 days 
post
3
+7 days 
post
6
+7 days 
post
9
12
15
18
21
24
+7 days 
post
27
30
33
36
39
42
45 o
Blood for Anti- AchR 
Antibodies
X
Quantitative/Semi-
quantitative Binding, 
Blocking, and Modulating 
AChR Antibodies
Xe
X
Hemolysis Evaluationl
Xl
Xl
Xl
Xl
Xl
Xl
Xl
Xl
Xl
Thromboembolism 
Evaluation (Wells Score and 
D-Dimers)l
X
Xl
Xl
Xl
Xl
Xl
AE Assessment/Review of 
Clinical Signs/Symptomsk
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Prior & Concomitant 
Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Administration of IP
Xm
Xm
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Corticosteroid Tapering
X
X
X
X
X
X
X
X
X
X
Record corticosteroid dose 
prescribed 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Review subject’s adherence 
based on subject’s 
documentation of CS doses 
taken
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AChR = anti-acetylcholine receptor, CS = corticosteroid, HbA1c = hemoglobin A1c, IgG = immunoglobulin, IP = investigational product, MG = myasthenia 
gravis, MG-ADL = Myasthenia Gravis-Activities of Daily Living, MGFA = Myasthenia Gravis Foundation of America, MG-QOL = Myasthenia Gravis-Quality 
of Life, QMG = Quantitative Myasthenia Gravis 
a
Inclusion/exclusion criteria must be satisfied before the subject is randomized and receives the first IP infusion.
b
A randomization number will be assigned to each subject based on a 1:1 randomization schedule.
c
Potential child-bearing females only; results must be negative for subject to continue in the study.
d
Excludes breast and genitourinary exam. At Baseline Visit (Week 0, prior to randomization), Visit 4 (Week 9), Visit 9 (Week 24), and Visit 14 (Week 39), 
full physical exam includes additional assessment of the following features as either absent (0) or present with grading indicated as mild (1), moderate (2), or 


Protocol GTI1306 – Amendment 2 
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severe (3) for each of the following: (a) moon face, (b) centripetal obesity, (c) dorsalcervical fat pad, (d) thin skin/easy bruising, (e) skin striae, (f) hirsutism 
(women), (g) acne (both genders). Changes in these graded parameters are not considered AEs.
e
Assessments to be performed pre-infusion on study visits during which IP dosage occurs.
f
Each recorded weight will be used to calculate the IP infusion dose for the scheduled visit and subsequent IP infusions until the next scheduled weight is 
measured. Screening subject weight is used to calculate the IP infusion dose for IP Visits 1-3, Visit 4 (Week 9) subject weight for IP Visits 4-8, and Visit 9 
(Week 24) subject weight for IP Visits 9-13.
g
Full vital signs including T, RR, HR, SBP, and DBP will be recorded at each visit. During the infusions, abbreviated vital signs (HR, SBP, and DBP) will be 
recorded just before the start of each infusion (within 15 ± 5 minutes before the beginning of each infusion), 30 ± 10 minutes after starting infusion, and 
immediately after infusion completes.
h
Collect blood samples at Baseline/Week 0 (Visit 1) prior to randomization but test only if the subject exhibits clinical signs and symptoms consistent with 
HAV, HBV, HCV, HIV, or B19V infection while participating in the study. These samples will be retained until all analyses in support of the study are 
complete. See Section 3.8.3 and Table 3-5 for details.
i
Subjects must fast for at least 8 hours (e.g. overnight) to allow accurate measurement of fasting serum glucose. 
j
Subjects must hold their acetylcholinesterase inhibitor (e.g., pyridostigmine) dosage for 12 hours prior to the Visit to assure accurate assessment of the 
QMG score.
k
Includes clinical observation of signs and symptoms suggestive of any significant disease or condition (e.g., thrombosis, anemia etc)
l
Hemolysis evaluation (laboratory parameters) and thromboembolism evaluation will be performed at Baseline prior to start of first IP loading infusion, at the 
end of the first infusion of the loading dose, at the time when last loading infusion is complete, and at the completion of each designated maintenance dosage 
at Week 3 and Week 6 (Visit 2 and 3) and at Week 24 (Visit 9). Hemolysis evaluation includes Hb, hematocrit, RBC, blood smear, serum free Hb, 
haptoglobin, LDH, DAT, ARC, total and indirect bilirubin, urine for urinary sediment and hemoglobinuria, and hematuria. Hemolysis evaluation (laboratory 
parameters) will also be performed 7 days post loading dose infusion at Baseline (Week 0) and 7 days post study drug infusion at Weeks 3 (Visit 2), 6 (Visit 
3), and 24 (Visit 9).
m
Initiation of induction (loading) dose of IGIV-C 2.0 g/kg begins after all Baseline assessments are complete and subject is randomized. Loading dose is 
infused over 2 days. Note that for the loading dosage 2 days is standard (2 to 4 days is allowed as an extension for tolerability issues or higher weight, i.e., 
limit for IGIV-C infusion is no more than 80 g/day [corresponding to 80 kg body weight]). 
n
Maintenance doses of 1 g/kg are administered over 1 day every three weeks through Week 36. Note that the maintenance dosage is given over 1 day as the 
standard time interval (divided dosage over 2 days is allowed for tolerability issues or higher weight, i.e., limit for IGIV-C infusion is no more than 80 g/day 
[corresponding to 80 kg body weight]).
o
The Early Discontinuation Visit will consist of the same assessments as Week 45 (Visit 16) with the exception of the MG-QOL 15 which is not required.


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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 is normal
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 weakness of any severity
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 Score Test Items
Subjects receiving cholinesterase inhibitors will be instructed not to take medication 12 hours 
prior to assessments such as QMG Score. Scores for each individual item are added together 
for total score (range 0-39).


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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
MG-Quality of Life (MG-QOL) 15


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Appendix 7
Monitoring of Thromboembolic Events Risk
Subjects will be monitored for signs and symptoms of arterial and venous thromboembolic 
events (TE). Arterial and venous TE events will be identified according to definitions in the 
International Classification of Diseases (ICD) [55]. 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.
TEs 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*
Screening
X
X
X
Baseline (Week 0/prior to 
randomization)
X
X
X
End of first IP loading dose 
X
X
X
At the time when last loading 
infusion is complete
X
X
X
Weeks 3, 6, and 24 following 
completion of each 
maintenance infusion dosage
X
X
X
* Evaluation of clinical signs and symptoms of arterial and venous TE as part of AEs assessment.
And using the following assessments: 
The Wells Score [56] will be utilized to assess the clinical characteristics indicative of 
possible DVT or PE (Table 2); 
Measurement of D-dimer blood levels [57]; 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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TEs risk will be assessed according to the following algorithm adapted from Wells [56] 
(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, 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, 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 8
Hemolysis Detection
Schedule of the Procedures:
Study visit
Blood testing
Urine testing
Clinical 
parameters
Baseline (Week 0/prior to randomization)
X
X
X
End of first IP loading dose
X
X
X
At the time when last loading infusion is 
complete a
X
X
X
Weeks 3, 6, and 24 following completion of 
each maintenance infusion dosage a
X
X
X
a
Hemolysis evaluation (laboratory parameters) will also be performed 7 days post loading dose infusion at 
Baseline (Week 0) and 7 days post study drug infusion at Weeks 3 (Visit 2), 6 (Visit 3), and 24 (Visit 9).
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 Hb, serum free Hb, 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-C: 
In this clinical trial, an IVIg-associated hemolytic reaction is one in which there is evidence 
of a new hemolytic process [58]. Consideration of possible hemolysis as defined below 
should only be triggered if other explanatory factors/conditions can be excluded. 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 Hb and hematocrit 
levels for patients admitted to an internal medicine service [59,60]), iron-deficiency 
anemia, other drug-induced hemolytic anemia, or anemia associated with an underlying 
disease (e.g. autoimmune hemolytic anemia [61,62]).
-
Negative DAT.
Absence of other inclusion criteria, in particular absence of evidence for hemolysis.


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Potential events would require the following laboratory signs to be present (with the above 
caveats): 
1. Drop in whole blood Hb of ≥10 g/L*
AND
2. Positive DAT
AND
3. At least 2 of:
-
increased ARC*
-
hemoglobulemia
-
increased LDH level*
-
hemoglobinuria 
-
significant spherocytosis
-
low haptoglobin level*
-
unconjugated hyperbilirubinemia
* Abnormal values without other explanation (e.g., LDH elevation due to muscle damage or 
increased reticulocyte count in the setting of hemorrhage) which show a clinically relevant change 
from pre-treatment values.


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Appendix 9
WHO-Five (WHO-5) Well-Being Index (1998 version)








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Sections
Change From:
Change To:
Rationale:
Synopsis; 3.2.2 
Exclusion Criteria
Added text to 
exclusion criteria
4.
Any episode of myasthenic crisis (MC) in 
the one month prior to Screening, or (at any 
time in the past) MC or hospitalization for 
MG exacerbation associated with a 
previous CS taper attempt
27. 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. Any factor that in the 
opinion of the Principal Investigator would 
compromise safety of the subject or the 
ability of the subject to complete the trial. No 
subject whose only MG treatment is CS 
alone may enroll, because in the blinded 
placebo arm this would mean that all MG 
treatment would be discontinued during CS 
taper, posing a substantial risk for the 
subject.
Exclusion 4: As safety measure given 50% active: 50% placebo 
randomization, prior MC or hospitalization due to MG 
exacerbation associated with a previous CS taper attempt is 
exclusionary since CS tapering is a fundamental, integral part of 
GTI1306 study design.
Exclusion 27: Clarification of original intention of eligibility 
criteria to assure this specific potential risk is fully appreciated 
when evaluating patients for possible study participation. If a 
patient is treated for MG solely with CS alone as the only MG 
medication, inclusion in protocol GTI1306 would not be 
appropriate, because all patients will be tapered off CS during 
study (primary efficacy measure), in the setting of 50% active: 
50% placebo randomization. This text is introduced as a safety 
measure to prevent any misconception.


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Sections
Change From:
Change To:
Rationale:
Synopsis; Section 
3.3.3 Definition and 
Management of MG 
Worsening
Added text
Special Note for subjects tapered to 0 mg 
CS per day: 
Some subjects with MG are uniquely 
sensitive to complete CS withdrawal (0 mg 
prednisone equivalent daily), and may 
become more vulnerable to MG triggers 
and sudden MG exacerbations. Therefore if 
a subject has tapered to 0 mg prednisone 
equivalent daily, any worsening MG signs 
or symptoms must be evaluated in clinic as 
soon as possible (recommended within 24
hours, allowed up to 48 hours) and treated 
aggressively with CS dose increase as 
delineated in the tables above. Once 
tapered to 0 mg CS per day, a 4-point 
QMG increase from Baseline/Week 0 is not 
required for re-initiating CS because 
deterioration can be of greater severity and 
speed than expected and may be difficult to 
reverse.
As safety measure for subjects whose CS is tapered to 0 mg 
prednisone equivalent daily, new text added to assure rapid 
medical evaluation, CS re-initiation, and medical intervention 
because of vulnerability of some subjects to severe MG 
exacerbations which may be difficult to reverse. Some subjects 
on 0 mg prednisone equivalent daily (completely CS-free) 
require immediate increase in CS dose (and/or other 
interventions) because initially mild MG signs/symptoms may 
deteriorate with greater severity and speed than expected, even 
if QMG was previously improved or stable while on 0 mg CS 
relative to baseline QMG. 
Section 3.5.2
Prohibited 
Concomitant 
Medications during 
the Study
Added text
Treatments needed for myasthenic crisis or 
MG exacerbation requiring hospitalization 
are not restricted per protocol as this 
constitutes a real medical necessity and 
required interventions to assure subject
safety are always allowed.
To clarify that MG treatment measures for MG crisis or 
hospitalization for MG exacerbation are always allowed for 
emergent medical need.

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