A Phase III, Open-label Extension Trial of ECU-MG-301 to Evaluate the Safety and Efficacy of Eculizumab in Subjects With Refractory Generalized Myasthenia Gravis (gMG)
Phase: PHASE3
Conditions: Refractory Generalized Myasthenia Gravis
Sponsor: Alexion Pharmaceuticals, Inc.

A Phase III, Open-Label, Extension Trial of ECU-MG-301 
to Evaluate the Safety and Efficacy of Eculizumab in 
Subjects with Refractory Generalized Myasthenia Gravis 
(gMG) 
 
 
Unique Protocol ID: 
ECU-MG-302 
NCT Number: 
NCT02301624 
EudraCT Number:  
2013-002191-41 
Date of Protocol:  
19 December 2016 
 

ECU-MG-302, Amendment 2 
 
Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
1. 
 TITLE PAGE 
ECULIZUMAB 
ECU-MG-302 
A PHASE III, OPEN-LABEL, EXTENSION TRIAL OF 
ECU-MG-301 TO EVALUATE THE SAFETY AND 
EFFICACY OF ECULIZUMAB IN SUBJECTS WITH 
REFRACTORY GENERALIZED MYASTHENIA GRAVIS 
(gMG) 
IND 101,219 
EudraCT NUMBER: 2013-002191-41 
Sponsor: 
Alexion Pharmaceuticals, Inc. 
100 College Street 
New Haven, CT 06510, USA 
 
Sponsor Contact: 
 
 
Alexion Pharmaceuticals, Inc. 
100 College Street, New Haven, CT 06510, USA 
Telephone: 
 Facsimile: 
 
 
Medical Monitor: 
 
 
 
Alexion Pharmaceuticals, Inc. 
100 College Street, New Haven, CT 06510, USA 
Telephone: 
 Facsimile
 
Version: 
 
Amendment 2 
 
Date of Protocol: 
 
19 December 2016 
 
Amended: 
 
Original Protocol Version 1.0, 08 April 2015 
Amendment 1 (GLOBAL), 24 June 2015 
Amendment 1.1 (DENMARK), 24 June 2015 
Amendment 2 (GLOBAL), 19 December 2016  
 
Proprietary Notice: 
 
This confidential information about an investigational agent is provided for the exclusive 
use of investigators of this agent and is subject to recall at any time. The information in this 
document may not be disclosed unless such disclosure is required by federal or state law or 
regulations subject to the foregoing. This information may be disclosed only to those 
persons involved in the study who have a need to know with the obligation not to further 
disseminate this information. These restrictions on disclosure will apply equally to all 
future oral or written information supplied to you by Alexion, which is designated as 
“privileged” or “confidential.” 
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ECU-MG-302, Amendment 2 
 
Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
INVESTIGATOR’S AGREEMENT 
 
PROTOCOL TITLE: A Phase III, Open-Label, Extension Trial of ECU-MG-301 to 
Evaluate the Safety and Efficacy of Eculizumab in Subjects with Refractory Generalized 
Myasthenia Gravis (gMG) 
PROTOCOL NUMBER: ECU-MG-302 (Amendment 2) 
 
I have received and read the ECU-MG-302 study protocol and agree to conduct the study as 
outlined. I agree to maintain the confidentiality of all information received or developed in 
connection with this protocol. I agree to conduct the trial in accordance with ethical principles 
that have their origin in the Declaration of Helsinki and are consistent with International 
Conference on Harmonisation (ICH)/Good Clinical Practice (GCP) and applicable regulatory 
requirements. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Printed Name of Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Investigator 
 
 
 
 
 
 
 
 
Date 
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19 December 2016 
 
 
 
PROCEDURES IN CASE OF EMERGENCY 
Table 1: 
Emergency Contact Information 
Role in Trial 
Name 
Address and Telephone number 
Clinical Project Leader 
 
 
Alexion Pharmaceuticals, Inc. 
100 College Street  
New Haven, CT 06510, USA 
Tel: 
 
Mobile: 
 
Fax: 
 
Email: 
 
Responsible Physician (Medical 
Monitor) 
 
Alexion Pharmaceuticals, Inc. 
100 College Street  
New Haven, CT 06510, USA 
Tel: 
 
Mobile: 
 
Fax: 
 
Email: 
 
After-Hour Emergency Contact 
24 Hour Emergency Contact 
24 hour Telephone Number 
USA: 
Tel: 
  
Europe: 
Tel: 
 
Australia: 
Tel: 
 
Serious Adverse Event Reporting 
Alexion Pharmaceuticals, Inc. 
Alexion Pharmaceuticals, Inc. 
100 College Street 
New Haven, CT 06510, USA 
Email: 
 
Fax: 
 
Clinical Supplies 
Almac Clinical Services 
4204 Technology Drive 
Durham NC 27704 
USA 
Tel: 
 
Fax: 
 
9 Charlestown Road 
Seagoe Industrial Estate 
Craigavon BT63 5PW 
United Kingdom 
Tel: 
 
Bioanalytical Analysis (PK/PD and 
C5 Assays and Report Writing) 
MPI 
 
 
 
MPI Research 
54943 North Main Street 
Mattawan, MI 49071 
USA 
Tel: 
 
Interactive Voice/Web Response 
System 
Almac Clinical Technologies 
Almac Clinical Technologies 
25 Fretz Road  
Souderton, PA 18964 
USA 
Tel: 
 
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ECU-MG-302, Amendment 2 
 
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19 December 2016 
 
 
 
Table 1: 
Emergency Contact Information 
Role in Trial 
Name 
Address and Telephone number 
Clinical Laboratory 
Q2 Solutions (formerly QLab) 
North America: 
Q2 Solutions Central Laboratory 
27027 Tourney Road 
Valencia, CA 91355 
USA 
Tel: 
 
Fax: 
 
Europe: 
Quintiles Laboratories Europe  
The Alba Campus  
Rosebank  
Livingston  
West Lothian EH54 7EG  
United Kingdom  
Tel: 
  
Fax: 
 
Japan: 
Quintiles Laboratories Japan  
2-18-17 Nishi-ochiai  
Shinjuku-ku Tokyo,  
161-0031  
Japan 
Tel: 
  
Fax: 
 
Argentina: 
Coordination Center - Latin America 
(QLAT) 
Centro de Coordinación de Q2 
Solutions 
QSquared Solutions Argentina 
Av. Triunvirato 3030 
C1427AAQ  CABA – Buenos 
Aires 
Tel: 
 
Fax: 
 
Brazil: 
Latin America 
(QLAT) 
Diagnósticos da América 
Av. Juruá 434 
Alphaville – São Paulo 
06455‐010 
Tel: 
 
Tel: 
  
Fax: 
 
Singapore:  
Q Squared Solutions Pte. Ltd 
79 Science Park Drive, #06‐08, 
Cintech IV 
Singapore Science Park I, 118264 
Tel: 
 
Fax: 
 
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ECU-MG-302, Amendment 2 
 
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19 December 2016 
 
 
 
Table 1: 
Emergency Contact Information 
Role in Trial 
Name 
Address and Telephone number 
Site Management and Monitoring 
Quintiles IMS 
4820 Emperor Boulevard 
Durham, NC 27703 
USA 
Tel: 
 
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19 December 2016 
 
 
 
2. 
SYNOPSIS 
Name of Sponsor/Company: Alexion Pharmaceuticals, Inc. 
Name of Investigational Product: Eculizumab 
Name of Active Ingredient: h5G1.1-mAb 
Title of Study:  
A Phase III, open-label extension trial of ECU-MG-301 to evaluate the safety and efficacy of eculizumab in 
subjects with refractory generalized Myasthenia Gravis (gMG) 
Study Rationale:  
Trial ECU-MG-301, a Phase 3 clinical trial, has been initiated to evaluate the safety and efficacy of eculizumab in 
the treatment of refractory gMG. This extension trial is designed to provide the subjects who have participated in 
the ECU-MG-301 trial an opportunity to receive eculizumab and to collect clinical data that will provide 
long-term safety and efficacy information on eculizumab in patients with refractory gMG. 
Study Center(s): Approximately 100 centers in North America, South America, Europe, Asia-Pacific, and 
Middle East 
Principal Investigator: 
 
Investigators: A list containing all Investigators will be provided with the final study report.  
Study period (years): 4 years 
Estimated date first subject enrolled: 2014 
Estimated date last subject completed: 2018 
The end of trial is defined as last subject’s last visit.  
Phase of development: 3 
Objectives:  
Primary: 
• 
To evaluate the long-term safety of eculizumab in subjects with refractory gMG 
Secondary: 
• 
To evaluate the long-term efficacy of eculizumab in subjects with refractory gMG as measured by the 
improvement or maintenance of the MG-specific Activities of Daily Living profile (MG-ADL) 
• 
To evaluate the long-term efficacy of eculizumab by additional efficacy measures including: 
- 
Quantitative Myasthenia Gravis (QMG) score; 
- 
Myasthenia Gravis Composite (MGC) score, and 
- 
Improvement or maintenance in primary symptoms that are most clinically meaningful to the 
subjects 
• 
To characterize the effect of eculizumab on quality of life measures 
• 
To describe the pharmacokinetics (PK) and pharmacodynamics (PD) of eculizumab in subjects with 
gMG. 
Methodology: 
This is an open-label trial. All subjects who have completed the ECU-MG-301 trial may be eligible to participate 
in this extension trial. Prior to initiating any extension trial procedures, informed consent form must be signed 
and inclusion/exclusion criteria must be evaluated and met. 
Subjects will enter this extension trial within 2 weeks after completing Visit 17 (Week 26) in the ECU-MG-301 
trial. 
Blind Induction Phase (Visits 1-4, Day 1 and Weeks 1-3): 
To preserve the blinded nature of the ECU-MG-301 trial, all subjects must undergo a blind induction phase prior 
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ECU-MG-302, Amendment 2 
 
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19 December 2016 
 
 
 
to entering the open-label maintenance phase of this trial (ie, all subjects will receive blinded Investigational 
Product [IP] weekly for 4 doses). Patients who were randomized to the placebo arm in the ECU-MG-301 trial 
will receive 4 vials IP (3 vials/900 mg eculizumab plus 1 vial placebo) at Visits 1 to 4. Patients who were 
randomized to the eculizumab arm in the ECU-MG-301 trial will continue to receive 4 vials IP (1200 mg 
eculizumab) every two weeks at Visits 1 and 3 and placebo at Visits 2 and 4. All patients will receive 
4 vials/1200 mg eculizumab open-label at Visit 5 and onward throughout the trial.  
Open-Label Maintenance Phase (Visit 5 and onward): 
All subjects will receive open-label eculizumab (4 vials/1200 mg) every 2 weeks during the maintenance phase. 
All subjects must be present at the trial site for Visits 1 to 16, 23, 29, 42, 55, 68, 81, 94, and 107 for visit-specific 
procedures and assessments (including IP administration). For other visits, subjects may have the opportunity to 
receive IP administration remotely at a medical facility that is located near the subject’s home or at the subject’s 
home with the permission of the Principal Investigator (PI) in accordance with all national, state, and local laws 
or regulations of the pertinent regulatory authorities. These visits will be conducted by a qualified staff member 
from the medical facility near the subject’s home or by home care health professionals. The trial medication will 
be prepared at the Investigator’s pharmacy, at the designated homecare pharmacy, or at the subject’s home, and 
transported under controlled conditions to the subject’s home or to the medical facility for administration. During 
a remote dosing visit, information on adverse events (AEs), concomitant medications, and signs or symptoms of 
Clinical Deterioration in MG will be collected and sent by the qualified staff that performs the remote infusion to 
the Investigator’s site for evaluation on the day of the visit. Subjects must go to the trial site for evaluation if the 
subject reports any signs or symptoms that suggest a serious AE (SAE) or Clinical Deterioration.  
Supportive immunosuppressive therapy (IST) is allowed during the extension trial at the Investigator’s discretion. 
Change in IST or its dose/schedule will be allowed if due to intolerance or if medically indicated, at the discretion 
of the Investigator. However, use of rituximab is prohibited during the trial. Subjects may continue participation 
in this study and receive the IP until the product is registered and available to treat subjects diagnosed with 
refractory gMG (in accordance with country specific regulations) or for maximum of 4 years, whichever occurs 
first. In Denmark, patient participation may continue for a maximum of 48 months. 
Subjects must be informed of the potential signs and symptoms of MG crisis and instructed to contact the 
Investigator site as soon as possible after the onset of symptoms. Every effort should be made to evaluate the 
subject reporting Clinical Deterioration as soon as possible and within 48 hours of notification of the Investigator 
site of symptom onset. At the evaluation visit, the Investigator or his/her designee will perform the assessments as 
specified by this protocol. The Investigator will determine whether or not the subject meets the Clinical 
Deterioration as defined by this protocol and treat the subject accordingly (reference below “On-Trial Rescue 
Therapies”). 
On-Trial Rescue Therapies:  
On-Trial Rescue Therapy (for example, high dose corticosteroid, plasma exchange [PE] or intravenous 
immunoglobulin [IVIg]) will be allowed when a subject’s health is in jeopardy if rescue therapy is not 
administered (eg, emergency, and/or emergent but not life-threatening situations), or if a subject experiences 
Clinical Deterioration as defined in this protocol. The rescue therapy used for a particular subject will be at the 
discretion of the Investigator. Every effort should be made to notify the Sponsor within 24 hours should a subject 
require a rescue therapy.  
For this protocol, Clinical Deterioration warranting use of On-Trial Rescue Therapy is as follows: 
• 
Subjects who experience an MG Crisis, which is defined as weakness due to MG that is severe enough 
to necessitate intubation or to delay extubation following surgery. The respiratory failure is due to 
weakness of respiratory muscles. Severe bulbar (oropharyngeal) muscle weakness often accompanies the 
respiratory muscle weakness, or may be the predominant feature in some subjects); or, 
• 
Significant symptomatic worsening to a score of 3 or a 2-point worsening on any one of the individual 
MG-ADL items other than double vision or eyelid droop or,   
• 
Subjects for whom the Investigator believes that the subjects’ health is in jeopardy if rescue therapy is 
not given (eg, emergency, and/or emergent but not life-threatening situations). 
Follow-up Period: 
Safety Follow-up (8 weeks): If a subject withdraws from the extension trial or discontinues eculizumab treatment 
at any time and for any reason after receiving any amount of IP, the subject will be required to complete an Early 
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Termination (ET) Visit at the time of the withdrawal and a Follow-up Visit 8 weeks following the last dose of IP 
administration. If a subject is discontinued due to an AE, the event will be followed until it is resolved or, in the 
opinion of the PI, is determined medically stable. Subjects who withdraw from the extension trial and transition 
to treatment with the commercially available eculizumab will not be required to complete a Follow-up Visit. 
Post-Treatment Follow-up (up to 1 year): The Sponsor may seek to collect follow-up information concerning MG 
status in patients post-treatment for up to 1 year from the end of study (EOS)/early termination (ET) visit (refer to 
Section 7.1.3.2, Section 7.3.6, and Appendix 11). 
Number of Patients (Planned): Approximately 92. 
This is an extension trial to the ECU-MG-301 trial. Approximately 92 patients with gMG will be enrolled in the 
ECU-MG-301 trial. Patients who complete the 26-week treatment period (Visit 17) in the ECU-MG-301 trial may 
potentially enter this extension trial.  
Study Endpoints: 
Primary Endpoint: 
• 
Safety and tolerability of eculizumab 
Primary Efficacy Endpoint: 
• 
Change from baseline in the MG-ADL total score 
Secondary Efficacy Endpoints: 
• 
Change from baseline in QMG total score 
• 
Proportion of subjects with at least a 3-point reduction in the MG-ADL total score from baseline and 
with no rescue therapy 
• 
Proportion of subjects with at least a 5-point reduction in the QMG total score from baseline and with no 
rescue therapy 
• 
Change from baseline in the MGC scale total score 
• 
Change from baseline in MG-QOL-15 
Tertiary Efficacy Endpoints: 
• 
Time to response as measured by the reduction in the MG-ADL total score (3-point reduction from 
baseline) 
• 
Change from baseline in Neuro-QOL Fatigue 
• 
Change from baseline in EQ-5D 
• 
Change from baseline in the MG-ADL individual items and sub-categories for the bulbar (items 1, 2, 
and 3), respiratory (item 4), limb (items 5 and 6) and ocular (items 7 and 8) in subjects with abnormal 
baseline scores for the particular item or sub-categories 
Pharmacokinetics and Pharmacodynamics (PK/PD): 
PK and PD parameters during blinded induction phase and open-label maintenance phase of treatment 
Inclusion Criteria: 
1. Subject has completed the ECU-MG-301 trial. 
2. Subject has given written informed consent. 
3. Subject is willing and able to comply with the protocol requirements for the duration of the trial. 
4. Female subjects of child-bearing potential must have a negative pregnancy test (serum human chorionic 
gonadotropin [HCG]). All subjects must practice an effective, reliable, and medically approved 
contraceptive regimen during the trial and for up to 5 months following discontinuation of treatment.  
Exclusion Criteria: 
1. Subjects who withdrew from the ECU-MG-301 trial as a result of an AE related to trial drug. 
2. Female subjects who are pregnant, breastfeeding or intend to conceive during the course of the trial.  
3. Unresolved meningococcal infection 
4. Hypersensitivity to murine proteins or to one of the excipients of eculizumab 
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5. Any medical condition or circumstances that, in the opinion of the Investigator, might interfere with the 
subject’s participation in the trial, pose any added risk for the subject, or confound the assessment of the 
subjects. 
Investigational product, dosage, and mode of administration: Investigational Product (eculizumab and/or 
placebo [placebo used only during the blind-induction phase]), will be administered intravenously according to 
the following regimen:  
Blind Induction Phase:  
To maintain the blind of the ECU-MG-301 trial, all subjects will undergo a blind induction phase (Visits 1 to 4, 
Day1, and Weeks 1 to 3). Investigational product (eculizumab, placebo or eculizumab plus placebo) will be 
administered weekly during the induction phase according to the following schedule:  
 
 
Treatment Group 
 
Eculizumab Amount during Blind 
Induction Phase  
Equivalent 
Eculizumab 
Dose 
 
 
Visits 
Subjects from the ECU-MG-301 
Trial Eculizumab arm  
4 vials of eculizumab (300 mg/vial) 
1200 mg 
1 and 3 
4 vials of placebo 
0 mg 
2 and 4 
Subjects from the ECU-MG-301 
Trial Placebo arm 
3 vials of eculizumab (300 mg/vial)  
plus 1 vial of placebo 
900 mg 
1 through 4 
Open-Label Maintenance Phase: 
All subjects will receive 4 vials of eculizumab (1200 mg) every 2 weeks starting with Visit 5 and throughout the 
remainder of the trial.  
Supplemental Dose: 
If a subject undergoes plasmapheresis or PE for Clinical Deterioration during the Study Period, a supplemental 
dose of 2 vials of IP (600 mg of eculizumab) must be administered within 1 to 2 hours after each PE session 
unless the PE session is on the day of a scheduled IP infusion. If the PE is on the day of a scheduled IP infusion, 
the scheduled dose of IP (instead of the supplemental dose) should be administered within 1 to 2 hours after the 
completion of PE session. In addition, subjects are to continue eculizumab infusion according to the protocol 
specified dosing regimen. 
Duration of treatment: Approximately 4 years 
The duration for an individual subject may vary depending on when the subject enters the trial, the maximum 
time being 4 years.  
Reference therapy, dosage and mode of administration: Not Applicable 
Criteria for evaluation: 
Efficacy: 
Duration of treatment commences with the first IP (eculizumab) infusion during the Induction Phase.  
• 
The MG-ADL focuses on relevant symptoms and performance of ADL in subjects with MG. The 
MG-ADL consists of 8 items, derived from symptom-based components of the original 13-item QMG, 
to assess disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor 
or limb (2 items) impairment related to the effects of MG. In this functional status instrument, each 
response is graded 0 (normal) to 3 (most severe). The range of total MG-ADL score is 0 to 24. In this 
trial, the recall period for MG-ADL is the last 7 days. If the number of days since the last visit is less 
than 7, the recall period is since the last visit. MG-ADL will be performed by a trained evaluator at the 
protocol specified time points and preferably by the same evaluator each time throughout the study.  
• 
The QMG scoring system is considered to be an objective evaluation of MG therapy and is based on a 
quantitative testing of muscle strength and endurance/fatigability of sentinel muscle groups. The QMG 
consists of 13 items: ocular (2 items), facial (1 item), bulbar (2 items), gross motor (6 items), axial 
(1 item) and respiratory (1 item); each graded 0 to 3, with 3 being the most severe. The range of total 
QMG score is 0 – 39. The QMG will be administered at approximately the same time of day throughout 
the study by a trained evaluator at the protocol specified time points and preferably by the same 
evaluator each time. 
• 
The MGC assesses 10 important functional areas most frequently affected by MG: ocular (2 items), 
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facial (1 item), bulbar (3 items), respiratory (1 item), axial (1 item) and gross motor (2 items). The scales 
are weighted for clinical significance that incorporates subject-reported outcomes. Higher scores indicate 
more functional impairment. The range of total MGC score is 0 – 50. MGC will be administered at the 
approximately same time of day throughout the study by a well-trained evaluator at the protocol 
specified time points, and preferably by the same evaluator each time. 
Safety: 
The safety of eculizumab will be assessed based on: 
• 
The AEs, SAEs, and changes from baseline through trial completion in vital signs, electrocardiogram 
(ECG), routine clinical laboratory tests (chemistry, hematology), Columbia-Suicide Severity Rating 
Scale (C-SSRS), and pregnancy tests for female subjects of childbearing potential.  
• 
Immunogenicity: blood samples will be collected for evaluation for anti-drug antibody (ADA) at 
specified time points to describe the presence or absence of an immune response to eculizumab and to 
evaluate, if antibodies are detected, whether the antibodies neutralize the activity of eculizumab (ability 
of eculizumab to inhibit C5 cleavage by C5 convertase). 
Pharmacokinetics: 
Blood samples will be collected at specified time points to study the concentration of eculizumab versus time. PK 
parameters such as maximum concentration, trough and peak eculizumab concentration during the blinded 
induction and open-label maintenance phases will be reported. Clearance and terminal half-life will be estimated. 
Pharmacodynamics: 
Blood samples for PD analyses will be collected at specified time points to assess pre- and post-treatment serum 
hemolytic activity and therefore C5 complement activity inhibition. Free C5 concentration also may be 
monitored. 
Biomarkers: 
Blood samples for acetylcholine receptor antibody (AChR Ab) will be collected at protocol specified time points.  
Quality of Life: 
The MG-QOL15, Neuro-QOL Fatigue, and EQ-5D will be used. 
Statistical methods:  
Analyses will be produced using data from this trial alone (Extension Trial) as well as combined analyses that 
will include data from the ECU-MG-301 trial (Combined Trial Analyses). The analyses will include safety, 
efficacy and PK/PD analyses. The Statistical Analysis Plan (SAP) will cover both the standalone trial analyses 
and the combined ECU-MG-301 and ECU-MG-302 trial analyses. 
Treatment groups will be indicated by eculizumab/eculizumab for the subjects originally randomized to the 
eculizumab arm in the ECU-MG-301 trial and placebo/eculizumab for the subjects originally randomized to the 
placebo arm in the ECU-MG-301 trial. The Extension Trial analyses will be presented by treatment group. The 
Combined Trial Analyses, where the data are aligned based on the subject’s first dose date of eculizumab, will 
only be presented as 1 combined eculizumab treatment group since all subjects will have received eculizumab.  
Interim statistical analyses for safety and the primary and secondary efficacy endpoints may be performed at the 
discretion of the Sponsor. All analyses will be prospectively defined in the statistical analysis plan. The final 
statistical analyses will be performed after the study ends and the database has been locked. 
 
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3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES 
TABLE OF CONTENTS 
1. 
TITLE PAGE ................................................................................................................1 
2. 
SYNOPSIS ...................................................................................................................7 
3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............12 
4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS .............................19 
5. 
INTRODUCTION ......................................................................................................21 
6. 
TRIAL OBJECTIVES AND PURPOSE ....................................................................22 
6.1. 
Primary Objective .......................................................................................................22 
6.2. 
Secondary Objectives .................................................................................................22 
7. 
INVESTIGATIONAL PLAN .....................................................................................23 
7.1. 
Overall Trial Design ...................................................................................................23 
7.1.1. 
Blind Induction Phase .................................................................................................23 
7.1.2. 
Open-Label Maintenance Phase .................................................................................23 
7.1.3. 
Follow-up Period ........................................................................................................24 
7.1.3.1. 
Safety Follow-up (8 Weeks) .......................................................................................24 
7.1.3.2. 
Post-Treatment Follow-up (Up to 1 Year) ..................................................................24 
7.1.4. 
Clinical Deterioration Definition and Rescue Therapies ............................................24 
7.1.5. 
Clinical Evaluator .......................................................................................................25 
7.1.6. 
Responsibilities for MG Assessments ........................................................................25 
7.1.7. 
Neisseria meningitidis Re-vaccination .......................................................................25 
7.2. 
Study Design and Schedule of Assessments ..............................................................26 
7.3. 
Trial Visit Procedures .................................................................................................38 
7.3.1. 
Blind Induction Phase .................................................................................................38 
7.3.1.1. 
Baseline (Visit 1/Day 1) .............................................................................................38 
7.3.1.2. 
Visit 2 (Week 1) ..........................................................................................................40 
7.3.1.3. 
Visits 3 and 4 (Weeks 2 and 3) ...................................................................................40 
7.3.2. 
Open-Label Maintenance Phase Year 1 .....................................................................41 
7.3.2.1. 
Visit 5 (Week 4) ..........................................................................................................41 
7.3.2.2. 
Visits 6, 8, 10, 12, 14, and 15 (Weeks 6, 10, 14, 18, 22, and 24) ...............................42 
7.3.2.3. 
Visit 7 (Week 8) ..........................................................................................................42 
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7.3.2.4. 
Visit 9 (Week 12) ........................................................................................................43 
7.3.2.5. 
Visit 11 (Week 16) ......................................................................................................44 
7.3.2.6. 
Visit 13 (Week 20) ......................................................................................................44 
7.3.2.7. 
Visit 16 (Week 26) ......................................................................................................45 
7.3.2.8. 
Visits 17 to 22 and 24 to 28 (Weeks 28 to 38 and 42 to 50) ......................................46 
7.3.2.9. 
Visit 23 (Week 40) ......................................................................................................46 
7.3.2.10. 
Visit 29 (Week 52) ......................................................................................................47 
7.3.3. 
Open-Label Maintenance Phase Year 2 .....................................................................49 
7.3.3.1. 
Visits 30-34 and 36-41 (Weeks 54-62 and 66-76) ......................................................49 
7.3.3.2. 
Visit 35 (Week 64) ......................................................................................................49 
7.3.3.3. 
Visit 42 (Week 78) ......................................................................................................49 
7.3.3.4. 
Visits 43 to 48 and 50 to 54 (Weeks 80 to 90 and 94 to 102) ....................................51 
7.3.3.5. 
Visit 49 (Week 92) ......................................................................................................51 
7.3.3.6. 
Visit 55 (Week 104) ....................................................................................................51 
7.3.4. 
Open-Label Maintenance Phase Year 3 .....................................................................53 
7.3.4.1. 
Visits 56 to 60 and 62 to 67 (Weeks 106 to 114 and 118 to 128) ..............................53 
7.3.4.2. 
Visit 61 (Week 116) ....................................................................................................53 
7.3.4.3. 
Visit 68 (Week 130) ....................................................................................................53 
7.3.4.4. 
Visits 69 to 74 and 76 to 80 (Weeks 132 to 142 and 146 to 154) ..............................54 
7.3.4.5. 
Visit 75 (Week 144) ....................................................................................................55 
7.3.4.6. 
Visit 81 (Week 156) ....................................................................................................55 
7.3.5. 
Open-Label Maintenance Phase Year 4 .....................................................................56 
7.3.5.1. 
Visits 82 to 86 and 88 to 93 (Weeks 158 to 166 and 170 to 180) ..............................56 
7.3.5.2. 
Visit 87 (Week 168) ....................................................................................................57 
7.3.5.3. 
Visit 94 (Week 182) ....................................................................................................57 
7.3.5.4. 
Visits 95 to 100 and 102 to 106 (Weeks 184 to 194 and 198 to 206) ........................58 
7.3.5.5. 
Visit 101 (Week 196) ..................................................................................................59 
7.3.5.6. 
Visit 107 (Week 208) ..................................................................................................59 
7.3.6. 
End of Study / Early Termination ...............................................................................60 
7.3.7. 
Visits for Evaluation of Clinical Deterioration ...........................................................61 
7.3.8. 
Unscheduled Visit .......................................................................................................63 
7.3.9. 
Safety Follow-up Period (Post-Treatment +Week 8) .................................................63 
7.3.10. 
Post-Treatment Follow-up Period (Up to 1 Year) ......................................................64 
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7.4. 
Number of Subjects ....................................................................................................64 
7.5. 
Treatment Assignment ................................................................................................64 
8. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................65 
8.1. 
Subject Inclusion Criteria ...........................................................................................65 
8.2. 
Subject Exclusion Criteria ..........................................................................................65 
8.3. 
Subject Withdrawal Criteria .......................................................................................65 
8.3.1. 
Withdrawal of Subjects from the Trial .......................................................................65 
8.3.2. 
Handling of Withdrawals ............................................................................................66 
8.3.3. 
Sponsor’s Termination of Trial ..................................................................................66 
9. 
TREATMENT OF SUBJECTS ..................................................................................67 
9.1. 
Description of Investigational Product .......................................................................67 
9.2. 
Concomitant Medications ...........................................................................................67 
9.2.1. 
Allowed Medications ..................................................................................................67 
9.2.1.1. 
Palliative and Supportive Care ...................................................................................67 
9.2.2. 
Disallowed Medications .............................................................................................68 
9.3. 
Treatment Compliance ................................................................................................69 
9.4. 
Randomization ............................................................................................................69 
9.5. 
Blinding and Unblinding ............................................................................................69 
10. 
INVESTIGATIONAL PRODUCT MATERIALS AND MANAGEMENT .............71 
10.1. 
Investigational Product ...............................................................................................71 
10.2. 
Investigational Product Packaging and Labeling .......................................................71 
10.3. 
Investigational Product Storage ..................................................................................71 
10.4. 
Investigational Product Preparation ............................................................................72 
10.5. 
Administration ............................................................................................................72 
10.6. 
Investigational Product Accountability ......................................................................73 
10.7. 
Investigational Product Handling and Disposal .........................................................73 
11. 
ASSESSMENT OF EFFICACY ................................................................................74 
11.1. 
Efficacy Endpoints ......................................................................................................74 
11.2. 
MG Activities of Daily Living Profile (MG-ADL) ....................................................74 
11.3. 
QMG Scoring System .................................................................................................75 
11.4. 
MGC Score .................................................................................................................75 
11.5. 
Quality of Life Assessments .......................................................................................75 
11.5.1. 
MG-QOL 15 ...............................................................................................................75 
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11.5.2. 
Neuro-QOL Fatigue ....................................................................................................75 
11.5.3. 
EUROQOL .................................................................................................................75 
11.6. 
Other Efficacy Assessments .......................................................................................76 
11.6.1. 
Negative Inspiratory Force (NIF) and Forced Vital Capacity (FVC) .........................76 
11.6.2. 
MGFA Post-Intervention Status .................................................................................76 
12. 
ASSESSMENT OF SAFETY .....................................................................................77 
12.1. 
Safety Parameters .......................................................................................................77 
12.1.1. 
Vital Signs ..................................................................................................................77 
12.1.2. 
Weight .........................................................................................................................77 
12.1.3. 
Physical Examination .................................................................................................77 
12.1.4. 
Electrocardiogram .......................................................................................................77 
12.1.5. 
Laboratory Assessments .............................................................................................77 
12.1.6. 
Columbia-Suicidal Severity Rating Scale ..................................................................78 
12.2. 
Adverse Events ...........................................................................................................78 
12.2.1. 
Detection of Adverse Events ......................................................................................78 
12.2.2. 
Definition of an Adverse Event ..................................................................................78 
12.2.2.1. 
Procedure ....................................................................................................................78 
12.2.2.2. 
Abnormal Test Findings .............................................................................................79 
12.2.2.3. 
Lack of Efficacy .........................................................................................................79 
12.2.2.4. 
Events of Interest (EOI) ..............................................................................................79 
12.2.3. 
Recording Adverse Events .........................................................................................79 
12.2.4. 
Serious Adverse Event and SAE Criteria ...................................................................80 
12.2.4.1. 
Severity Assessment ...................................................................................................81 
12.2.4.2. 
Causality Assessment .................................................................................................82 
12.2.5. 
Expectedness Assessment of Serious Adverse Event .................................................82 
12.2.6. 
Outcome ......................................................................................................................82 
12.2.6.1. 
Exposure during Pregnancy and Lactation .................................................................83 
12.2.7. 
Reporting of Adverse Event(s) & Serious Adverse Event(s) to Sponsor ...................83 
12.2.8. 
Sponsor Reporting Requirements ...............................................................................84 
12.2.9. 
Investigator Reporting Requirements .........................................................................84 
13. 
ASSESSMENT OF BIOMARKER ............................................................................85 
13.1. 
MG Disease Biomarker ..............................................................................................85 
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14. 
ASSESSMENT OF PHARMACOKINETICS AND 
PHARMACODYNAMICS ........................................................................................86 
15. 
STATISTICS ..............................................................................................................87 
15.1. 
General Considerations ...............................................................................................87 
15.2. 
Determination of Sample Size ....................................................................................87 
15.3. 
Analyses Sets ..............................................................................................................87 
15.3.1. 
Full Analysis Set (FAS) ..............................................................................................87 
15.3.1.1. 
Extension FAS Population ..........................................................................................87 
15.3.1.2. 
Combined FAS Population .........................................................................................87 
15.3.2. 
Per Protocol Set ..........................................................................................................88 
15.3.2.1. 
Extension Per-Protocol (PP) Population .....................................................................88 
15.3.2.2. 
Combined PP Population ............................................................................................88 
15.3.3. 
Safety Set ....................................................................................................................88 
15.3.4. 
Other Set .....................................................................................................................88 
15.4. 
Subject Disposition and Treatment Compliance ........................................................88 
15.5. 
Prior and Concomitant Medications ...........................................................................89 
15.5.1. 
Extension Trial Analyses ............................................................................................89 
15.5.2. 
Combined Trial Analyses ...........................................................................................89 
15.6. 
Efficacy Analyses .......................................................................................................89 
15.6.1. 
Primary Efficacy Analyses .........................................................................................89 
15.6.1.1. 
Extension Trial Analyses ............................................................................................89 
15.6.1.2. 
Combined Trial Analyses ...........................................................................................89 
15.6.2. 
Secondary Efficacy Analyses .....................................................................................89 
15.6.2.1. 
Extension Trial Analyses ............................................................................................90 
15.6.2.2. 
Combined Trial Analyses ...........................................................................................90 
15.6.3. 
Tertiary Efficacy Analyses .........................................................................................91 
15.6.3.1. 
Extension Trial Analyses ............................................................................................91 
15.6.3.2. 
Combined Trial Analyses ...........................................................................................91 
15.7. 
Safety Analyses ..........................................................................................................92 
15.7.1. 
Physical Examinations and Vital Signs ......................................................................92 
15.7.2. 
Laboratory Assessments .............................................................................................92 
15.7.2.1. 
Extension Trial Analyses ............................................................................................92 
15.7.2.2. 
Combined Trial Analyses ...........................................................................................92 
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15.7.3. 
AEs .............................................................................................................................92 
15.7.3.1. 
Extension Trial Analyses ............................................................................................92 
15.7.3.2. 
Combined Trial Analyses ...........................................................................................92 
15.7.4. 
Columbia-Suicide Severity Rating Scale ....................................................................92 
15.7.5. 
Other Safety Endpoints ...............................................................................................92 
15.8. 
PK/PD Analyses .........................................................................................................93 
15.8.1. 
Biomarker Analysis ....................................................................................................93 
15.9. 
Other Statistical Issues ................................................................................................93 
15.9.1. 
Significance Levels .....................................................................................................93 
15.9.2. 
Missing or Invalid Data ..............................................................................................93 
15.9.3. 
Interim Analyses .........................................................................................................93 
16. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS .........................................94 
16.1. 
Trial Monitoring .........................................................................................................94 
16.2. 
Audits and Inspections ................................................................................................94 
16.3. 
Institutional Review Board / Independent Ethics Committee ....................................95 
17. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................96 
18. 
ETHICS ......................................................................................................................97 
18.1. 
Ethics Review .............................................................................................................97 
18.2. 
Ethical Conduct of the Study ......................................................................................97 
18.3. 
Written Informed Consent ..........................................................................................97 
19. 
DATA HANDLING AND RECORDKEEPING .......................................................98 
19.1. 
Inspection of Records .................................................................................................98 
19.2. 
Retention of Records ..................................................................................................98 
20. 
LIST OF REFERENCES ............................................................................................99 
APPENDIX 1. QUANTITATIVE MYASTHENIA GRAVIS (QMG) SCORE FOR 
DISEASE SEVERITY ..............................................................................................100 
APPENDIX 2. MG ACTIVITY OF DAILY LIVING (MG-ADL) PROFILE.........................101 
APPENDIX 3. MYASTHENIA GRAVIS QUALITY-OF-LIFE (MG-QOL 15) ....................102 
APPENDIX 4. NEURO-QOL FATIGUE .................................................................................103 
APPENDIX 5. SUMMARY OF LABORATORY PANELS AND TESTS ............................104 
APPENDIX 6. MYASTENIA GRAVIS FOUNDATION OF AMERICA (MGFA) MG 
THERAPY STATUS ................................................................................................105 
APPENDIX 7. MG COMPOSITE SCORE ..............................................................................106 
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APPENDIX 8. MGFA POST-INTERVENTIONAL STATUS (MGFA-PIS) .........................107 
APPENDIX 9. COLUMBIA-SUICIDE SEVERITY RATING SCALE (C-SSRS) – 
SINCE LAST VISIT QUESTIONNAIRE (VERSION 1/14/09)* ...........................108 
APPENDIX 10. EUROQOL (EQ-5D) ......................................................................................112 
APPENDIX 11. COLLECTION OF FOLLOW-UP INFORMATION FROM 
PATIENTS WHO WITHDRAW FROM THE STUDY ..........................................114 
 
LIST OF TABLES 
Table 1: 
Emergency Contact Information ...................................................................................4 
Table 2: 
Abbreviations and Specialist Terms ...........................................................................19 
Table 3: 
MG Assessments (Responsibilities) ...........................................................................25 
Table 4: 
Schedule of Assessments: Visits 1 to 16 ....................................................................28 
Table 5: 
Schedule of Assessments: Visits 17 to 29 ..................................................................30 
Table 6: 
Schedule of Assessments: Year 2 Visits 30 to 42, Year 3 Visits 56 to 68, and 
Year 4 Visits 82 to 94 .................................................................................................32 
Table 7: 
Schedule of Assessments: Year 2 Visits 43 to 55, Year 3 Visits 69 to 81, and 
Year 4 Visits 95 to 107 ...............................................................................................34 
Table 8: 
Schedule of Assessments: Evaluation Visit for Clinical Deterioration ......................36 
Table 9: 
Schedule of Assessments: Safety Follow-up Visit .....................................................37 
Table 10: Treatment Assignment during the Blind Induction Phase ..........................................67 
Table 11: Investigational Product ...............................................................................................71 
Table 12: Investigational Product Reconstitution .......................................................................72 
 
LIST OF FIGURES 
Figure 1: 
Study Design for Trial ECU-MG-302 ........................................................................27 
 
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4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
Table 2: 
Abbreviations and Specialist Terms  
Abbreviation or Specialist Term 
Explanation 
Ab 
Antibody 
AChR 
Acetylcholine Receptor  
ADA 
Anti-drug antibody 
ADL 
Activities of Daily Living 
AE 
Adverse Event 
AZA 
Azathioprine 
BP 
Blood Pressure 
C5 
Complement Protein 5 
CBC 
Complete Blood Count 
eCRF 
Electronic Case Report Form 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
ECG 
Electrocardiogram  
EIU 
Exposure in-utero 
EOI 
Event of Interest 
EOS 
End of Study  
EQ-5D 
EuroQOL 
EQ VAS 
EuroQOL Visual Analog Scale  
ET 
Early Termination 
FAS 
Full Analysis Set 
FVC 
Forced Vital Capacity 
GCP 
Good Clinical Practice 
gMG 
Generalized Myasthenia Gravis 
HCG 
Human Chorionic Gonadotropin 
HR 
Heart Rate 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
ICU 
Intensive Care Unit  
IEC 
Independent Ethics Committee 
IP 
Investigational Product 
IRB 
Institutional Review Board 
IST 
Immunosuppressant Therapy 
IV 
Intravenous  
IVIg 
Intravenous Immunoglobulin 
IXRS 
Interactive Voice or Web Response System 
MG 
Myasthenia Gravis 
MG-ADL 
Myasthenia Gravis Activity of Daily Living profile 
MGFA-PIS 
Myasthenia Gravis Foundation of America Post Interventional Status 
MGC 
Myasthenia Gravis Composite 
MGFA 
Myasthenia Gravis Foundation of America 
MM 
Minimal Manifestation  
MMF 
Mycophenolate Mofetil 
MTX 
Methotrexate 
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Table 2: 
Abbreviations and Specialist Terms (Continued) 
Abbreviation or Specialist Term 
Explanation 
NIF 
Negative Inspiratory Force 
NMJ 
Neuromuscular Junction 
PD 
Pharmacodynamics 
PE 
Plasmapheresis or Plasma Exchange 
PI 
Principal Investigator 
PK 
Pharmacokinetics  
PP 
Per-Protocol Population 
PR 
Pharmacological Remission 
QOL 
Quality of Life  
QMG 
Quantitative Myasthenia Gravis 
RR 
Respiration Rate 
RSI 
Reference Safety Information 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SOC 
System Organ Class 
US 
United States 
WHO Drug 
World Health Organization Drug Dictionary 
 
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5. 
INTRODUCTION 
Myasthenia Gravis (MG) is a rare, debilitating, acquired autoimmune disease of the 
neuromuscular junction (NMJ), caused by the failure of neuromuscular transmission, which 
results from the binding of auto-antibodies (Abs) to proteins involved in signaling at the NMJ 
(Conti-Fine 2006). Myasthenia Gravis is clinically characterized by weakness and fatigability of 
skeletal muscles; however, in the MG patient population there is a wide range of disease 
severity. Although many patients with MG can be managed with anticholinesterase inhibitor 
therapy and immunosuppressant therapy (IST), there is a cohort of patients who continue to have 
marked generalized weakness and bulbar signs and symptoms of the disease despite adequate 
dosing of IST (Conti-Fine 2006). For these patients, there is a medical need for alternative 
treatment strategies targeting different pathophysiological aspects of the disease. Since 
complement activation plays a pivotal role in the pathophysiology of MG (Conti-Fine 2006, 
Vincent 2002), eculizumab, a terminal complement inhibitor, may benefit patients who continue 
to have generalized weakness and bulbar signs and symptoms despite current standard of care. 
Following the completion of a Phase 2 pilot trial in subjects with refractory generalized 
Myasthenia Gravis (gMG), Alexion has initiated a Phase 3 trial, Study ECU-MG-301, to 
evaluate the safety and efficacy of eculizumab in the same subject population. This extension 
trial is designed to provide the subjects that completed the ECU-MG-301 trial with the 
opportunity to receive eculizumab, and to collect clinical data that will provide long term safety 
and efficacy information on eculizumab in subjects with refractory gMG. Since this is an 
extension trial of the ECU-MG-301 trial, the same maintenance dose of eculizumab will be used. 
Refer to the current Investigator’s Brochure (IB) for detailed information on the safety and 
efficacy data of eculizumab. 
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6. 
TRIAL OBJECTIVES AND PURPOSE 
6.1. 
Primary Objective 
The primary objective of this trial is to evaluate the long-term safety of eculizumab in subjects 
with refractory gMG. 
6.2. 
Secondary Objectives 
The secondary objectives of this trial are: 
• To evaluate the long-term efficacy of eculizumab in subjects with refractory gMG as 
measured by the improvement or maintenance of the MG-specific Activities of Daily 
Living profile (MG-ADL) 
• To evaluate the long-term efficacy of eculizumab by additional efficacy measures 
including: 
− Quantitative Myasthenia Gravis (QMG) score; 
− Myasthenia Gravis Composite (MGC) score, and 
− Improvement or maintenance in primary symptoms that are most clinically 
meaningful to the subject. 
• To characterize the effect of eculizumab on quality of life measures 
• To describe the pharmacokinetics (PK) and pharmacodynamics (PD) of eculizumab 
in subjects with refractory gMG 
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7. 
INVESTIGATIONAL PLAN 
7.1. 
Overall Trial Design 
This is an open-label, multi-center trial to evaluate the safety and efficacy of eculizumab for the 
treatment of subjects with refractory gMG. All subjects who have completed the ECU-MG-301 
trial may be eligible to participate in this extension trial. Prior to initiating any extension trial 
procedures, informed consent form (ICF) must be signed and inclusion/exclusion criteria must be 
evaluated and met.  
Subjects will enter this extension trial within 2 weeks after they have completed Visit 17 
(Week 26) in the ECU-MG-301 trial. There will be 2 phases in this trial: Blind Induction Phase 
and Open-Label Maintenance Phase. The schedule of assessments for Visits 1 to 16 (beginning 
of Year 1) are provided in Table 4. The schedule of assessments for Visits 17 to 29 (end of 
Year 1) are provided in Table 5. The schedules of assessments for Years 2 through 4 are 
provided in Table 6 and Table 7. The schedule of assessments for the safety follow-up visit is 
provided in Table 9.  
Subjects may continue participation in this trial and receive the investigational product (IP) until 
the product is registered and available to treat subjects diagnosed with refractory gMG (in 
accordance with country specific regulations) or for a maximum of 4 years, whichever occurs 
first. In Denmark, patient participation may continue for a maximum of 48 months. The end of 
trial is defined as last subject’s last visit. 
7.1.1. 
Blind Induction Phase 
To preserve the blinded nature of the ECU-MG-301 trial, all subjects must undergo a Blind 
Induction Phase prior to entering the Open-Label Maintenance Phase of this trial, ie, all subjects 
will receive blinded IP weekly for 4 weeks. Table 10 provides details on treatment assignment 
during the Blind Induction Phase. 
7.1.2. 
Open-Label Maintenance Phase 
All subjects will receive open-label eculizumab (4 vials/1200 mg) every 2 weeks during the 
Open-Label Maintenance Phase starting at Visit 5 and onward. The duration of the trial for an 
individual subject will vary depending on when the subject enters the trial, the maximum time 
being up to 4 years.  
All subjects must be present at the trial site for Visits 1 to 16, 23, 29, 42, 55, 68, 81, 94, and 107, 
as applicable, for visit-specific procedures/assessments including IP administration. For other 
visits, subjects may have an opportunity to receive IP administration remotely at a medical 
facility that is located near the subject’s home or at the subject’s home with the permission of the 
Principal Investigator (PI) in accordance with all national, state, and local laws or regulations of 
the pertinent regulatory authorities. These visits will be conducted by a qualified staff member 
from the medical facility near the subject’s home or by home care health professionals. The trial 
medication will be prepared at the Investigator’s pharmacy, at a designated homecare pharmacy, 
or at the subject’s home, and transported under controlled conditions to the subject’s home or to 
the medical facility for administration. During a remote dosing visit, information on adverse 
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events (AEs), concomitant medications, and signs or symptoms of Clinical Deterioration in MG 
will be collected by the qualified staff that performs the remote visit, and sent to the 
Investigator’s site for evaluation on the day of the visit. Subjects must go to the trial site for 
evaluation if the subject reports any signs or symptoms that suggest a serious AE (SAE) or 
Clinical Deterioration.  
Supportive IST is permitted during the extension trial at the Investigator’s discretion. Change in 
IST or its dose/schedule will be allowed if due to intolerance or medically indicated at the 
discretion of the Investigator. However, use of rituximab is prohibited during the trial.  
Subjects must be informed of the potential signs and symptoms of MG crisis and instructed to 
contact the Investigator as soon as possible after onset of symptoms. Every effort should be made 
for the subject reporting Clinical Deterioration to be evaluated as soon as possible and within 48 
hours of notification of the Investigator of symptom onset. At the evaluation visit, the 
Investigator or his/her designee will perform the assessments as specified by this protocol 
(refer to Table 8). The Investigator will determine whether or not the subject meets the Clinical 
Deterioration as defined by this protocol and treat the subject accordingly (refer to 
Section 7.1.4). 
Subjects may continue participation in this trial and receive IP for a maximum of 4 years or until 
the product is registered and commercially available to treat patients diagnosed with gMG (in 
accordance with country specific regulations), whichever occurs first. 
7.1.3. 
Follow-up Period  
7.1.3.1. 
Safety Follow-up (8 Weeks) 
If a subject withdraws from the extension trial or discontinues eculizumab treatment at any time 
and for any reason after receiving any amount of IP, the subject will be required to complete an 
Early Termination (ET) Visit at the time of the withdrawal (refer to Table 7 end of study 
[EOS]/ET) and a Follow-up Visit (refer to Table 9) 8 weeks following the last dose of IP 
administration. If a subject is discontinued due to an AE, the event will be followed until it is 
resolved or, in the opinion of the Investigator, is determined medically stable. Subjects who 
withdraw from the extension trial and transition to treatment with the commercially available 
eculizumab will not be required to complete a Follow-up Visit. 
7.1.3.2. 
Post-Treatment Follow-up (Up to 1 Year) 
The Sponsor may seek to collect follow-up information concerning MG status in patients post-
treatment for up to 1 year from the EOS/ET visit (refer to Appendix 11). 
7.1.4. 
Clinical Deterioration Definition and Rescue Therapies 
On-Trial Rescue Therapy, eg, high dose corticosteroid, plasma exchange (PE), or intravenous 
immunoglobulin (IVIg), will be allowed when a subject’s health is in jeopardy if rescue therapy 
is not administered (eg, emergency, and/or emergent but not life-threatening situations), or if a 
subject experiences Clinical Deterioration as defined in this protocol. The rescue therapy used 
for a particular subject will be at the discretion of the Investigator. Every effort should be made 
to notify the Sponsor within 24 hours should a subject require a rescue therapy.  
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For this protocol, Clinical Deterioration warranting the use of On-Trial Rescue Therapy is as 
follows: 
• Subjects who experience an MG Crisis, which is defined as weakness due to MG that 
is severe enough to necessitate intubation or to delay extubation following surgery. 
The respiratory failure is due to weakness of respiratory muscles. Severe bulbar 
(oropharyngeal) muscle weakness often accompanies the respiratory muscle 
weakness, or may be the predominant feature in some subjects; or, 
• Significant symptomatic worsening to a score of 3 or a 2-point worsening from 
Baseline (ie, Study ECU-MG-302 Day 1) on any one of the individual MG-ADL 
items other than double vision or eyelid droop; or, 
• Subjects for whom the Investigator believes that the subjects’ health is in jeopardy if 
rescue therapy is not given (eg, emergency, and/or emergent but not life-threatening 
situations). 
7.1.5. 
Clinical Evaluator 
The Clinical Evaluators are study staff that have been trained and certified in administering the 
MG-ADL, QMG, and MGC. The Clinical Evaluator may be a neurologist, physical therapist, or 
other study team member delegated by the Investigator. Clinical Evaluator training and 
certification for this protocol will take place either at the Investigator's meeting or via the 
sponsor's designated on-line training portal. 
7.1.6. 
Responsibilities for MG Assessments 
Responsibilities for MG assessments are listed in Table 3. Throughout the trial, MG assessments 
should be performed at approximately the same time of day by a properly trained evaluator, 
preferably the same evaluator.  
Table 3: 
MG Assessments (Responsibilities) 
Assessment 
Evaluator 
MG-ADL 
Clinical Evaluator 
QMG including FVC 
Clinical Evaluator  
NIF 
Clinical Evaluator 
MGC (non-MMT Components) 
Clinical Evaluator  
MGC (MMT Components: neck flexion or extension, 
shoulder abduction, and hip flexion) 
PI or Neurologist  
MGFA-PIS  
PI or Neurologist  
MGFA Classification 
PI or Neurologist 
Abbreviations: FVC = forced vital capacity; MG-ADL = Myasthenia Gravis Activity of Daily Living Profile; 
MGC = Myasthenia Gravis Composite; MGFA = Myasthenia Gravis Foundation of America; 
MGFA-PIS = Myasthenia Gravis Foundation of America Post Intervention Status; MMT = manual muscle test; 
NIF = negative inspiratory force; PI = Principal Investigator; QMG = Quantitative MG. 
7.1.7. 
Neisseria meningitidis Re-vaccination 
Due to the length of this extension trial, patients must be revaccinated for N. meningitidis to 
provide active coverage as specified by the vaccine manufacturer or according to current 
medical/country guidelines. During the first visit (Visit 1 on Day 1), Investigators are to assess 
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the need for re-vaccination and are to record the anticipated date of re-vaccination in the source 
documents and electronic case report form (eCRF). 
7.2. 
Study Design and Schedule of Assessments 
Figure 1 presents the overall study design and Table 4 through Table 9 present the Schedule of 
Assessments for the study. 
 
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Figure 1: 
Study Design for Trial ECU-MG-302 
 
 
 
Day 1
Week 1
Week 2
Week 3
Week 4
Week 208
Blind 
Induction 
Phase
Open-Label Phase
Year 1
Year 2
Year 3
Year 4
IP 
infusion
Eculizumab infusion every other week
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Table 4: 
Schedule of Assessments: Visits 1 to 16 
Phase 
Blind Induction 
Open-Label Maintenance 
Visit Location1 
In Clinic 
In Clinic 
Trial Visit  
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
UNS2 
Trial Day or Week 
Day 1 
W1 
W2 
W3 
W4 
W6 
W8 
W10 
W12 
W14 
W16 
W18 
W20 
W22 
W24 
W26 
 
Review Inclusion / 
Exclusion Criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Physical Examination 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
12-Lead ECG  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
MG Therapy Status 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Adverse Event 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
MG-QOL15  
X 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
X 
 
Neuro-QOL Fatigue 
X 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
X 
 
EQ-5D 
X 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
X 
 
MG-ADL3 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
 
X 
 
QMG3 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
 
X 
 
NIF3 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
 
X 
 
MGC3 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
 
X 
 
MGFA-PIS4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
C-SSRS 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
AChR Abs Test 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
Clinical Laboratory Tests5 
X 
 
 
 
X 
 
X 
 
X 
 
 
 
 
 
 
X 
 
Pregnancy Test (Serum)6 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
PK/PD/Free C5 (Serum)7 
B 
T/P 
 
 
T/P 
 
T/P 
 
T/P 
 
 
 
T/P 
 
 
T/P 
 
ADA7 
B 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
 
X 
 
Medically Indicated Tests 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 28 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 
 
Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
Table 4: 
Schedule of Assessments: Visits 1 to 16 (Continued) 
Phase 
Blind Induction 
Open-Label Maintenance 
Visit Location 
In Clinic 
In Clinic 
Trial Visit  
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
UNS2 
Trial Day or Week 
Day 1 
W1 
W2 
W3 
W4 
W6 
W8 
W10 
W12 
W14 
W16 
W18 
W20 
W22 
W24 
W26 
 
Check for N. meningitidis 
Revaccination 8 
X 
 
 
 
 
 
X 
 
X 
 
 
 
 
 
 
X 
 
Patient Safety Information 
Card8  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
IP Infusion9,10 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Abbreviations: AChR Abs = acetylcholine receptor antibodies; B = baseline; C-SSRS = Columbia-Suicide Severity Rating Scale; ECG = electrocardiogram; eCRF = electronic 
Case Report Form; EQ-5D = EUROQOL; ADA = anti-drug antibody; IP=Investigational Product; MG = Myasthenia Gravis; MG-ADL = Myasthenia Gravis Activities of Daily 
Living profile; MGFA-PIS = Myasthenia Gravis Foundation of America Post Interventional Status; MG-QOL15 = 15 item Myasthenia Gravis quality of life; MGC = 
Myasthenia Gravis Composite; Neuro-QOL = neurological quality of life; NIF = negative inspiratory force; P = peak sample; PK = pharmacokinetics; PD = pharmacodynamics; 
QMG = Quantitative MG (QMG) Score for Disease Severity; T = trough sample; UNS = unscheduled visit. 
 If a subject undergoes plasma exchange (PE) for a Clinical Deterioration, 3 blood samples for PK, PD and free C5 will be collected [1] 5 – 90 minutes prior to PE; [2] after PE 
and before IP infusion; and [3] at 1 to 2 hours after the completion of IP infusion. 
1 In Clinic – visits must be conducted at the Investigational sites; Remote – visits may be conducted remotely at a medical facility that is located near the subject’s home or at the 
subject’s home with the permission of the Investigator in accordance with all national, state and local laws or regulations of the pertinent regulatory authorities.  
2 Unscheduled visit and procedures will be performed at the investigator's discretion and results will be recorded in the eCRF.  
3 Throughout the study, it is preferred that the same properly trained evaluator perform the clinical assessments of MG-ADL, QMG, NIF and MGC. Additionally, the clinical 
assessments of QMG, NIF and MGC shall be performed at approximately the same time of day. If a subject is taking a cholinesterase inhibitor, the dose must be withheld for at 
least 10 hours prior to the tests. 
4 MGFA-PIS must be performed by the PI or the same neurologist throughout the trial. 
5 Clinical Lab Tests will be performed at the central laboratory. Refer to Appendix 5 for a summary of clinical lab test panels and tests. 
6 Pregnancy tests must be performed on all women of child bearing potential at the specified time points. Additional pregnancy test (urine or serum) may also be performed at any 
visit at the PI’s discretion. 
7 Baseline and trough blood samples for PK, PD and free C5 and all samples for ADA are to be taken 5 – 90 minutes before the IP  infusion. Peak blood samples for PK, PD and 
free C5 testing are to be taken 60 minutes after the completion of the IP infusion. 
If a subject undergoes PE for a Clinical Deterioration, 3 blood samples for PK, PD and free C5 will be collected [1] 5 – 90 minutes prior to PE; [2] after PE and before IP infusion; 
and [3] at 60 minutes after the completion of IP infusion. 
8 Subjects must be revaccinated for N. meningitidis to provide active coverage as specified by the vaccine manufacturer or according to current medical/country guidelines. 
Subjects will be given a Patient Safety Information Card prior to the first dose of trial medication. At each visit throughout the trial, site staff will ensure that the subject has the 
Patient Safety Information Card, and document in the source documents.  
9 IP will be administered after completion of all other tests and procedures, excluding the peak blood sampling for PK/PD and free C5 assay (Refer to Section 10.5). 
10 If a subject undergoes PE for a Clinical Deterioration (as defined by this protocol) a supplemental dose (2 vials IP) must be administered within 1 to 2 hours after the end of each 
PE session unless the PE session is on the day of a scheduled IP infusion. Per-protocol, scheduled IP administration will be continued according to the specified dose-
administration schedule for the subject. If the subject is scheduled to receive the protocol-scheduled dose on the day of a PE session, then the scheduled dose (instead of the 
supplemental dose) should be administered within 1 to 2 hours after the end of the PE. 
 
Page 29 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 
 
Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
Table 5: 
Schedule of Assessments: Visits 17 to 29  
Phase 
Open-Label Maintenance 
Visit Location1 
In Clinic/Remote 
In Clinic 
In Clinic/Remote 
In Clinic 
Trial Visit Year 1 
V17 
V18 
V19 
V20 
V21 
V22 
V23 
V24 
V25 
V26 
V27 
V28 
EOS /ET/ 
V29 
Trial Week Year 1 
W28 
W30 
W32 
W34 
W36 
W38 
W40 
W42 
W44 
W46 
W48 
W50 
W52 
Weight  
 
 
 
 
 
 
 
 
 
 
 
 
X 
Vital Signs  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical Examination  
 
 
 
 
 
 
 
 
 
 
 
 
X 
12-Lead ECG  
 
 
 
 
 
 
 
 
 
 
 
 
X 
Concomitant Medication  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
MG Therapy Status 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Adverse Events  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
MG-QOL15 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
Neuro-QOL Fatigue   
 
 
 
 
 
 
X 
 
 
 
 
 
X 
EQ-5D 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
MG-ADL2 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
QMG2 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
MGC2 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
MGFA-PIS3 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
C-SSRS 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
AChR Abs Test 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Clinical Laboratory Tests4 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
Pregnancy serum test (serum)5 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
PK/PD/Free C56 
 
 
 
 
 
 
T/P 
 
 
 
 
 
T/P 
ADA6 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
Page 30 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 
 
Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
Table 5: 
Schedule of Assessments: Visits 17 to 29 (Continued) 
Phase 
Open-Label Maintenance 
Visit Location 
In Clinic/Remote 
In Clinic 
In Clinic/Remote 
In Clinic 
Trial Visit Year 1 
V17 
V18 
V19 
V20 
V21 
V22 
V23 
V24 
V25 
V26 
V27 
V28 
EOS / ET / 
V29 
Trial Week Year 1 
W28 
W30 
W32 
W34 
W36 
W38 
W40 
W42 
W44 
W46 
W48 
W50 
W52 
Medically indicated tests  
 
 
 
 
 
 
 
 
 
 
 
 
 
Check for N. meningitidis revaccination
7 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
Patient Safety Information Card7 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IP Infusion 8,9 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: AChR Abs = acetylcholine receptor antibodies; C-SSRS = Columbia-Suicide Severity Rating Scale; ECG = electrocardiogram; EQ-5D = EUROQOL; EOS = end 
of study; ADA = anti-drug antibody; IP=Investigational Product; MG = Myasthenia Gravis; MG-ADL = Myasthenia Gravis Activities of Daily Living profile; MGFA-PIS = 
Myasthenia Gravis Foundation of America Post Interventional Status; MG-QOL15 = 15 item Myasthenia Gravis quality of life; MGC = Myasthenia Gravis composite; 
Neuro-QOL = neurological quality of life; NIF = negative inspiratory force; P = peak sample; PK = pharmacokinetics; PD = pharmacodynamics; QMG = Quantitative MG 
(QMG) Score for Disease Severity; T = trough sample. 
1 In Clinic – visits must be conducted at the Investigational sites; Remote – visits may be conducted remotely at a medical facility that is located near the subject’s home or at the 
subject’s home with the permission of the Investigator in accordance with all national, state and local laws or regulations of the pertinent regulatory authorities.  
2 Throughout the study, it is preferred that the same properly trained evaluator perform the clinical assessments of MG-ADL, QMG, and MGC. Additionally, the clinical 
assessments of QMG, NIF and MGC shall be performed at approximately the same time of day. If a subject is taking a cholinesterase inhibitor, the dose must be withheld for at 
least 10 hours prior to the tests. 
3 MGFA-PIS must be performed by the PI or the same neurologist throughout the trial. 
4 Clinical Lab Tests will be performed at the central laboratory. Refer to Appendix 5 for a summary of clinical lab test panels and tests. 
5 Pregnancy tests must be performed on all women of child bearing potential at the specified time points. Additional pregnancy test (urine or serum) may also be performed at any 
visit at the PI’s discretion. 
6 Baseline and trough blood samples for PK, PD and free C5 and all samples for ADA are to be taken 5 – 90 minutes before the IP infusion. Peak blood samples for PK, PD and 
free C5 testing are to be taken 60 minutes after the completion of the IP infusion. 
If a subject undergoes plasma exchange (PE) for a Clinical Deterioration, 3 blood samples for PK, PD and free C5 will be collected [1] 5 – 90 minutes prior to PE; [2] after PE 
and before IP infusion; and [3] at 60 minutes after the completion of IP infusion. 
7 Subjects may be revaccinated for N. meningitidis to provide active coverage as specified by the vaccine manufacturer or according to current medical/country guidelines. 
Subjects will be given a Patient Safety Information Card prior to the first dose of trial medication. At each visit throughout the trial, site staff will ensure that the subject has the 
Patient Safety Information Card, and document in the source documents.  
8 IP will be administered after completion of all other tests and procedures, excluding the peak blood sampling for PK/PD and free C5 assay (Refer to Section 10.5). 
9 If a subject undergoes PE for a Clinical Deterioration (as defined by this protocol) a supplemental dose (2 vials IP) must be administered within 1 to 2 hours after the end of each 
PE session unless the PE session is on the day of a scheduled IP infusion. Per-protocol, scheduled IP administration will be continued according to the specified dose-
administration schedule for the subject. If the subject is scheduled to receive the protocol-scheduled dose on the day of a PE session, then the scheduled dose (instead of the 
supplemental dose) should be administered within 1 to 2 hours after the end of the PE. 
 
 
Page 31 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 
 
Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
Table 6: 
Schedule of Assessments: Year 2 Visits 30 to 42, Year 3 Visits 56 to 68, and Year 4 Visits 82 to 94 
Phase  
Open-Label Maintenance 
Visit Location1 
In Clinic/Remote 
In Clinic 
 
Year 2 Trial Visit / Week 
 
V 30 
W 54 
V 31 
W 56 
V 32 
W 58 
V 33 
W 60 
V 34 
W 62 
V 35 
W 64 
V 36 
W 66 
V 37 
W 68 
V 38 
W 70 
V 39 
W 72 
V 40 
W 74 
V 41 
W 76 
V 42 
W 78 
 
Year 3 Trial Visit / Week 
 
V 56 
W 106 
V 57 
W 108 
V 58 
W 110 
V 59 
W 112 
V 60 
W 114 
V 61 
W 116 
V 62 
W 118 
V 63 
W 120 
V 64 
W 122 
V 65 
W 124 
V 66 
W 126 
V 67 
W 128 
V 68 
W 130 
 
Year 4 Trial Visit / Week 
 
V 82 
W 158 
V 83 
W 160 
V 84 
W 162 
V 85 
W 164 
V 86 
W 166 
V 87 
W 168 
V 88 
W 170 
V 89 
W 172 
V 90 
W 174 
V 91 
W 176 
V 92 
W 178 
V 93 
W 180 
V 94 
W 182 
Weight  
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital Signs  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical Examination 
 
 
 
 
 
 
 
 
 
 
 
 
 
12-Lead ECG  
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant Medication  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
MG-QOL15 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Neuro-QOL Fatigue   
 
 
 
 
 
 
 
 
 
 
 
 
X 
EQ-5D 
 
 
 
 
 
 
 
 
 
 
 
 
X 
MG-ADL2 
 
 
 
 
 
 
 
 
 
 
 
 
X 
QMG2 
 
 
 
 
 
 
 
 
 
 
 
 
X 
MGC2  
 
 
 
 
 
 
 
 
 
 
 
 
X 
MGFA-PIS3 
 
 
 
 
 
 
 
 
 
 
 
 
X 
C-SSRS 
 
 
 
 
 
 
 
 
 
 
 
 
X 
AChR Abs Test 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Clinical Laboratory Tests4 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Pregnancy serum test (serum)5 
 
 
 
 
 
 
 
 
 
 
 
 
X 
PK/PD/Free C56 
 
 
 
 
 
 
 
 
 
 
 
 
T/P 
ADA6 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Medically indicated tests  
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 32 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 
 
Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
Table 6: 
Schedule of Assessments: Year 2 Visits 30 to 42, Year 3 Visits 56 to 68, and Year 4 Visits 82 to 94 (Continued) 
Phase  
Open-Label Maintenance 
Visit Location 
In Clinic/Remote 
In Clinic 
 
Year 2 Trial Visit / Week 
 
V 30 
W 54 
V 31 
W 56 
V 32 
W 58 
V 33 
W 60 
V 34 
W 62 
V 35 
W 64 
V 36 
W 66 
V 37 
W 68 
V 38 
W 70 
V 39 
W 72 
V 40 
W 74 
V 41 
W 76 
V 42 
W 78 
 
Year 3 Trial Visit / Week 
 
V 56 
W 106 
V 57 
W 108 
V 58 
W 110 
V 59 
W 112 
V 60 
W 114 
V 61 
W 116 
V 62 
W 118 
V 63 
W 120 
V 64 
W 122 
V 65 
W 124 
V 66 
W 126 
V 67 
W 128 
V 68 
W 130 
 
Year 4 Trial Visit / Week 
 
V 82 
W 158 
V 83 
W 160 
V 84 
W 162 
V 85 
W 164 
V 86 
W 166 
V 87 
W 168 
V 88 
W 170 
V 89 
W 172 
V 90 
W 174 
V 91 
W 176 
V 92 
W 178 
V 93 
W 180 
V 94 
W 182 
Check for N.meningitidis revaccination7 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
Patient Safety Information Card7 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IP Infusion 8, 9 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: AChR Abs = acetylcholine receptor antibodies; C-SSRS = Columbia-Suicide Severity Rating Scale; ECG = electrocardiogram; EQ-5D = EUROQOL; ADA = anti-
drug antibody; IP=Investigational Product; MG = Myasthenia Gravis; MG-ADL = Myasthenia Gravis Activities of Daily Living profile; MGFA-PIS =  Myasthenia Gravis 
Foundation of America Post Interventional Status; MG-QOL15 = 15 item Myasthenia Gravis quality of life; MGC = Myasthenia Gravis composite; Neuro-QOL = neurological 
quality of life; NIF = negative inspiratory force; P = peak sample; PK = pharmacokinetics; PD = pharmacodynamics; QMG = Quantitative MG (QMG) Score for Disease 
Severity; T = trough sample.  
1 In Clinic – visits must be conducted at the Investigational sites; Remote – visits may be conducted remotely at a medical facility that is located near the subject’s home or at the 
subject’s home with the permission of the Investigator in accordance with all national, state and local laws or regulations of the pertinent regulatory authorities. 
2 Throughout the study, it is preferred that the same properly trained evaluator perform the clinical assessments of MG-ADL, QMG, and MGC. Additionally, the clinical 
assessments of QMG, NIF and MGC shall be performed at approximately the same time of day. If a subject is taking a cholinesterase inhibitor, the dose must be withheld for at 
least 10 hours prior to the tests. 
3 MGFA-PIS must be performed by the PI or the same neurologist throughout the trial. 
4 Clinical Lab Tests will be performed at the central laboratory. Refer to Appendix 5 for a summary of clinical lab test panels and tests. 
5 Pregnancy tests must be performed on all women of child bearing potential at the specified time points. Additional pregnancy test (urine or serum) may also be performed at any 
visit at the PI’s discretion. 
6 Baseline and trough blood samples for PK, PD and free C5 and all samples for ADA are to be taken 5 – 90 minutes before the IP infusion. Peak blood samples for PK, PD and 
free C5 testing are to be taken 60 minutes after the completion of the IP infusion. 
If a subject undergoes plasma exchange (PE) for a Clinical Deterioration, 3 blood samples for PK, PD and free C5 will be collected [1] 5 – 90 minutes prior to PE; [2] after PE 
and before IP infusion; and [3] at 60 minutes after the completion of IP infusion. 
7 Subjects may be revaccinated for N. meningitidis to provide active coverage as specified by the vaccine manufacturer or according to current medical/country guidelines. 
Subjects will be given a Patient Safety Information Card prior to the first dose of trial medication. At each visit throughout the trial, site staff will ensure that the subject has the 
Patient Safety Information Card, and document in the source documents.  
8 IP will be administered after completion of all other tests and procedures, excluding the peak blood sampling for PK/PD and free C5 assay (Refer to Section 10.5). 
9 If a subject undergoes PE for a Clinical Deterioration (as defined by this protocol) a supplemental dose (2 vials IP) must be administered within 1 to 2 hours after the end of each 
PE session unless the PE session is on the day of a scheduled IP infusion. Per protocol, scheduled IP administration will be continued according to the specified dose-
administration schedule for the subject. If the subject is scheduled to receive the protocol-scheduled dose on the day of a PE session, then the scheduled dose (instead of the 
supplemental dose)  should be administered within 1 to 2 hours after the end of the PE. 
Page 33 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 
 
Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
Table 7: Schedule of Assessments: Year 2 Visits 43 to 55, Year 3 Visits 69 to 81, and Year 4 Visits 95 to 107 
Phase 
Open-Label Maintenance 
Visit Location 1 
In Clinic/Remote 
In Clinic 
 
Year 2 Trial Visit / Week 
 
V 43 
W 80 
V 44 
W 82 
V 45 
W 84 
V 46 
W 86 
V 47 
W 88 
V 48 
W 90 
V 49 
W 92 
V 50 
W 94 
V 51 
W 96 
V 52 
W 98 
V 53 
W 100 
V 54 
W 102 
EOS / ET2 
V 55 / W 104 
 
Year 3 Trial Visit / Week 
 
V 69 
W 132 
V 70 
W 134 
V 71 
W 136 
V 72 
W 138 
V 73 
W 140 
V 74 
W 142 
V 75 
W 144 
V 76 
W 146 
V 77 
W 148 
V 78 
W 150 
V 79 
W 152 
V 80 
W 154 
EOS / ET / 
V 81 
W 156 
 
Year 4 Trial Visit / Week 
 
V 95 
W 184 
V 96 
W 186 
V 97 
W 188 
V 98 
W 190 
V 99 
W 192 
V 100 
W 194 
V 101 
W 196 
V 102 
W 198 
V 103 
W 200 
V 104 
W 202 
V 105 
W 204 
V 106 
W 206 
EOS / ET / 
V 107 
W 208 
Weight  
 
 
 
 
 
 
 
 
 
 
 
 
X 
Vital Signs  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical Examination 
 
 
 
 
 
 
 
 
 
 
 
 
X 
12-Lead ECG  
 
 
 
 
 
 
 
 
 
 
 
 
X 
Concomitant Medication  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
MG-QOL15 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Neuro-QOL Fatigue  
 
 
 
 
 
 
 
 
 
 
 
 
X 
EQ-5D 
 
 
 
 
 
 
 
 
 
 
 
 
X 
MG-ADL3 
 
 
 
 
 
 
 
 
 
 
 
 
X 
QMG3 
 
 
 
 
 
 
 
 
 
 
 
 
X 
MGC3  
 
 
 
 
 
 
 
 
 
 
 
 
X 
MGFA-PIS4 
 
 
 
 
 
 
 
 
 
 
 
 
X 
C-SSRS 
 
 
 
 
 
 
 
 
 
 
 
 
X 
AChR Abs Test 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Clinical Laboratory Tests5 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Pregnancy serum test (serum)6 
 
 
 
 
 
 
 
 
 
 
 
 
X 
PK/PD/Free C57 
 
 
 
 
 
 
 
 
 
 
 
 
T/P 
ADA7 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Medically indicated tests  
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 34 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 
 
Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
Table 7: 
Schedule of Assessments: Year 2 Visits 43 to 55, Year 3 Visits 69 to 81, and Year 4 Visits 95 to 107 (Continued) 
Phase 
Open-Label Maintenance 
Visit Location 
In Clinic/Remote 
In Clinic 
 
Year 2 Trial Visit / Week 
 
V 43 
W 80 
V 44 
W 82 
V 45 
W 84 
V 46 
W 86 
V 47 
W 88 
V 48 
W 90 
V 49 
W 92 
V 50 
W 94 
V 51 
W 96 
V 52 
W 98 
V 53 
W 100 
V 54 
W 102 
EOS / ET 
V 55 / W 104 
 
Year 3 Trial Visit / Week 
 
V 69 
W 132 
V 70 
W 134 
V 71 
W 136 
V 72 
W 138 
V 73 
W 140 
V 74 
W 142 
V 75 
W 144 
V 76 
W 146 
V 77 
W 148 
V 78 
W 150 
V 79 
W 152 
V 80 
W 154 
EOS / ET / 
V 81 
W 156 
 
Year 4 Trial Visit / Week 
 
V 95 
W 184 
V 96 
W 186 
V 97 
W 188 
V 98 
W 190 
V 99 
W 192 
V 100 
W 194 
V 101 
W 196 
V 102 
W 198 
V 103 
W 200 
V 104 
W 202 
V 105 
W 204 
V 106 
W 206 
EOS / ET / 
V 107 
W 208 
Check for N. meningitidis revaccination8 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
Patient Safety Information Card8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IP Infusion 9,10 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: AChR Abs = acetylcholine receptor antibodies; C-SSRS = Columbia-Suicide Severity Rating Scale; ECG = electrocardiogram; EOS/ET = end of study/early 
termination; EQ-5D = EUROQOL; ADA = anti-drug antibody; IP=Investigational Product; MG = Myasthenia Gravis; MG-ADL = Myasthenia Gravis Activities of Daily Living 
profile; MGFA-PIS = Myasthenia Gravis Foundation of America Post Interventional Status; MG-QOL15 = 15 item Myasthenia Gravis quality of life; MGC = Myasthenia 
Gravis composite; Neuro-QOL = neurological quality of life; NIF = negative inspiratory force; P = peak sample; PK = pharmacokinetics; PD = pharmacodynamics; QMG = 
Quantitative MG (QMG) Score for Disease Severity; T = trough sample. 
1 In Clinic – visits must be conducted at the Investigational sites; Remote – visits may be conducted remotely at a medical facility that is located near the subject’s home or at the 
subject’s home with the permission of the Investigator in accordance with all national, state and local laws or regulations of the pertinent regulatory authorities. 
2 If a subject withdraws early from the trial an Early Termination (ET) Visit will be performed. The assessments listed for Visit 55 will be performed at ET Visit. 
3 Throughout the study, it is preferred that the same properly trained evaluator perform the clinical assessments of MG-ADL, QMG, and MGC. Additionally, the clinical 
assessments of QMG, NIF and MGC shall be performed at approximately the same time of day. If a subject is taking a cholinesterase inhibitor, the dose must be withheld for at 
least 10 hours prior to the tests. 
4 MGFA-PIS must be performed by the PI or the same neurologist throughout the trial. 
5 Clinical Lab Tests will be performed at the central laboratory. Refer to Appendix 5 for a summary of clinical lab test panels and tests.  
6 Pregnancy tests must be performed on all women of child bearing potential at the specified time points. Additional pregnancy test (urine or serum) may also be performed at any 
visit at the PI’s discretion. 
7 Baseline and trough blood samples for PK, PD and free C5 and all samples for ADA are to be taken 5 – 90 minutes before the IP infusion. Peak blood samples for PK, PD and 
free C5 testing are to be taken 60 minutes after the completion of the IP infusion. 
If a subject undergoes plasma exchange (PE) for a Clinical Deterioration, 3 blood samples for PK, PD and free C5 will be collected [1] 5 – 90 minutes prior to PE; [2] after PE 
and before IP infusion; and [3] at 60 minutes after the completion of IP infusion. 
8 Subjects may be revaccinated for N. meningitidis to provide active coverage as specified by the vaccine manufacturer or according to current medical/country guidelines. 
Subjects will be given a Patient Safety Information Card prior to the first dose of trial medication. At each visit throughout the trial, site staff will ensure that the subject has the 
Patient Safety Information Card, and document in the source documents.  
9 IP will be administered after completion of all other tests and procedures, excluding the peak blood sampling for PK/PD and free C5 assay (Refer to Section 10.5). 
10 If a subject undergoes PE for a Clinical Deterioration (as defined by this protocol) a supplemental dose (2 vials IP) must be administered within 1 to 2 hours after the end of each 
PE session unless the PE session is on the day of a scheduled IP infusion. Per-protocol, scheduled IP administration will be continued according to the specified dose-
administration schedule for the subject. If the subject is scheduled to receive the protocol-scheduled dose on the day of a PE session, then the scheduled dose 
(instead of the supplemental dose) should be administered within 1 to 2 hours after the end of the PE. 
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19 December 2016 
 
 
 
Table 8: 
Schedule of Assessments: Evaluation Visit for Clinical Deterioration 
Visit Location 1 
In Clinic 
Trial Visit  
Clinical Deterioration Evaluation Visit2 
Vital Signs 
X 
Concomitant Medications 
X 
Adverse Event 
X 
MG-ADL3 
X 
QMG3 
X 
NIF3 
X 
MGC3 
X 
AChR Abs Test 
X 
Clinical Laboratory Tests 4 
X 
PK/PD/Free C55 
X 
Medically Indicated Tests  
X 
Patient Safety Information Card6 
X 
IP Infusion7,8 
X 
 
Abbreviations: AChR Abs = acetylcholine receptor antibodies; MG = Myasthenia Gravis; MG-ADL = Myasthenia Gravis Activities of Daily Living profile; MGC = Myasthenia 
Gravis composite; NIF = negative inspiratory force; PK = pharmacokinetics; PD = pharmacodynamics; QMG = Quantitative MG (QMG) Score for Disease Severity.  
1 In Clinic – visits must be conducted at the Investigational sites; Remote – visits may be conducted remotely at a medical facility that is located near the subject’s home or at the 
subject’s home with the permission of the Investigator in accordance with all national, state and local laws or regulations of the pertinent regulatory authorities. 
2 Evaluation visit for MG Clinical Deterioration must be performed as soon as possible and no later than 48 hours of notification of Investigator of the symptom onset. Additional 
unscheduled visits can be scheduled at the discretion of the investigator. 
3 Throughout the study, it is preferred that the same properly trained evaluator perform the clinical assessments of MG-ADL, QMG, NIF and MGC. Additionally, the clinical 
assessments of QMG, NIF and MGC shall be performed at approximately the same time of day. If a subject is taking a cholinesterase inhibitor, the dose must be withheld for at 
least 10 hours prior to the tests. 
4 Clinical Lab Tests will be performed at the central laboratory. Refer to Appendix 5 for a summary of clinical lab test panels and tests. 
5 Baseline and trough blood samples for PK, PD and free C5 and all samples for ADA are to be taken 5 – 90 minutes before the IP infusion. Peak blood samples for PK, PD and 
free C5 testing are to be taken 60 minutes after the completion of the IP infusion.  
If a subject undergoes plasma exchange (PE) for a Clinical Deterioration, 3 blood samples for PK, PD and free C5 will be collected [1] 5 – 90 minutes prior to PE; [2] after PE 
and before IP infusion; and [3] at 60 minutes after the completion of IP infusion. 
6 Subjects may be revaccinated for N. meningitidis to provide active coverage as specified by the vaccine manufacturer or according to current medical/country guidelines. 
Subjects will be given a Patient Safety Information Card prior to the first dose of trial medication. At each visit throughout the trial, site staff will ensure that the subject has the 
Patient Safety Information Card, and document in the source documents.  
7 IP will be administered after completion of all other tests and procedures, excluding the peak blood sampling for PK/PD and free C5 assay (Refer to Section 10.5). 
8 If a subject undergoes PE for a Clinical Deterioration (as defined by this protocol) a supplemental dose (2 vials IP) must be administered within 1 to 2 hours after the end of each 
PE session unless the PE session is on the day of a scheduled IP infusion. Per-protocol, scheduled IP administration will be continued according to the specified dose-
administration schedule for the subject. If the subject is scheduled to receive the protocol-scheduled dose on the day of a PE session, then the scheduled dose (instead of the 
supplemental dose) should be administered within 1 to 2 hours after the end of the PE. 
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19 December 2016 
 
 
 
Table 9: 
Schedule of Assessments: Safety Follow-up Visit 
Safety Follow-up 
Trial Visit 
Follow-up 
Trial Week 
+ Week 8 
Vital Signs 
X 
Concomitant Medications 
X 
Adverse Events 
X 
MG-QOL 15 
X 
MG-ADL 1 
X 
QMG 1 
X 
MGC 1 
X 
MGFA-PIS2 
X 
Check for N. meningitidis revaccination3 
X 
Patient Safety Information Card4 
X 
 
Abbreviations: C-SSRS = Columbia-Suicide Severity Rating Scale; MG-ADL = Myasthenia Gravis Activities of Daily Living profile; MG-QOL15 = 15 item Myasthenia Gravis 
quality of life; MGC = Myasthenia Gravis composite; MGFA-PIS = Myasthenia Gravis Post Interventional Status QMG = Quantitative MG (QMG) Score for Disease Severity.  
1 Throughout the study, it is preferred that the same properly trained evaluator perform the clinical assessments of MG-ADL, QMG, and MGC. Additionally, the clinical 
assessments of QMG, NIF and MGC shall be performed at approximately the same time of day. If a subject is taking a cholinesterase inhibitor, the dose must be withheld for at 
least 10 hours prior to the tests. 
2 MGFA-PIS must be performed by the PI or the same neurologist throughout the trial. 
4 Subjects may be revaccinated for N. meningitidis to provide active coverage as specified by the vaccine manufacturer or according to current medical/country guidelines. 
Subjects will be given a Patient Safety Information Card prior to the first dose of trial medication. At each visit throughout the trial, site staff will ensure that the subject has the 
Patient Safety Information Card, and document in the source documents. 
4 At each visit throughout the trial, site staff will ensure that the subject has the Patient Safety Information Card, and document in the source documents.  
 
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 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
7.3. 
Trial Visit Procedures 
Visit 1/Day 1 should occur within 2 weeks (14 days +2) of Visit 17 in Trial ECU-MG-301 in 
order to prevent a lapse in dosing. Visit intervals during Blind Induction Phase (Visits 1 to 4) are 
weekly (every 7 ±2 days after the last visit, based on PK profile). Visit intervals during the 
Open-Label Maintenance Phase (Visits 5 to 107) are every 2 weeks (every 14 ±2 days since the 
last visit). IP will be administered after completion of all other tests and procedures (excluding 
the peak blood sampling for PK/PD and free C5 assay) as described in Section 10.5. 
Subjects who fail to return for a scheduled visit must be contacted by the site study staff to 
determine the reason for missing the appointment. Subjects should be strongly encouraged to 
return to the investigational site for evaluation if Clinical Deterioration or an AE is suspected to 
have occurred. In the exceptional circumstance, if a subject cannot or does not come to the study 
site for examination, then the subject will be instructed to see his or her local neurologist or 
physician. In this event, the investigational site will obtain relevant medical records as 
documentation from the local physician’s examination, and enter relevant data in the eCRF as 
appropriate.  
As it is vital to obtain information on any subject’s missing visit to assure the missing 
appointment was not due to a Clinical Deterioration or an AE, every effort must be made to 
undertake protocol-specified follow-up procedures (Table 9). Follow-up due diligence 
documentation will consist of 3 phone calls followed by 1 registered letter to the subject’s last 
known address, and documented in both the source documents and the eCRF. 
Patients should be registered in the Interactive Voice or Web Response System (IXRS) as soon 
as the ECU-MG-302 ICF is signed. The initial shipment of study drug for ECU-MG-302 will be 
triggered by the IXRS when the first patient in the ECU-MG-301 trial is registered as completing 
the study (Visit 17), and moves to the ECU-MG-302 trial. 
7.3.1. 
Blind Induction Phase  
7.3.1.1. 
Baseline (Visit 1/Day 1)  
Once all the eligibility criteria have been confirmed by the Investigator and the subject has 
signed the ICF, the subject will be assigned to a Blind Induction Phase treatment group based on 
their treatment assignment in the ECU-MG-301 trial. The following tests and evaluations will be 
performed at the Baseline Visit (Visit 1/Day 1): 
• Review inclusion and exclusion criteria 
• Measure body weight 
• Perform a 12-lead electrocardiogram (ECG) 
• Measure vital signs, including assessments of systolic and diastolic blood pressure 
(BP), temperature, respiration rate (RR), and heart rate (HR) 
• Evaluate and record any new AEs or changes in AEs: 
− Since this an extension to the ECU-MG-301 trial, AEs with an onset date before 
the Day 1 of this extension trial will be recorded on the ECU-MG-301 eCRF 
regardless of when the subject signed the ECU-MG-302 ICF. 
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19 December 2016 
 
 
 
− Any ongoing AEs at the time of Day 1 of this extension trial will be recorded on 
both the ECU-MG-301 and ECU-MG-302 CRFs. Since this will be done 
automatically by the system, sites will not be required to record these data twice. 
− AEs with an end date before Day 1 of ECU-MG-302 will be recorded only on the 
ECU-MG-301 eCRF. 
• Record any new concomitant medications or changes to concomitant medications 
(including non-drug therapies): 
− Since this is an extension to the ECU-MG-301 trial, concomitant medication with 
an onset date before Day 1 of this extension trial will be recorded on the ECU-
MG-301 eCRF regardless of when the subject signed the ECU-MG-302 ICF. 
Since this will be done automatically by the system, sites will not be required to 
record these data twice. 
− Any ongoing concomitant medication (including non-drug therapies) at the time 
of Day 1 of this extension trial will have to be recorded on both ECU-MG-301 
and ECU-MG-302 eCRFs.  
− Concomitant medication (including non-drug therapies) with an end date before 
Day 1 of ECU-MG-302 trial will be recorded only on the ECU-MG-301 eCRF. 
• Record MG Therapy Status (refer to Appendix 6) 
• Administer MG-ADL by a properly trained evaluator and preferably by the same 
evaluator throughout the trial. The recall period is the preceding 7 days.  
• Administer clinical assessments QMG, negative inspiratory force (NIF), and MGC; 
these shall be performed at approximately the same time of day, preferably by a 
properly trained evaluator, preferably the same evaluator, throughout the trial. If the 
subject is taking a cholinesterase inhibitor, the dose must be withheld for at least 
10 hours prior to the QMG and MGC assessments.  
• Administer questionnaires to evaluate quality of life (MG-QOL15, Neuro-QOL 
Fatigue, and EuroQOL [EQ-5D]) 
• Perform Columbia-Suicide Severity Rating Scale (C-SSRS; Appendix 9) 
• Obtain blood samples for clinical laboratory tests (chemistry and hematology; refer to 
Appendix 5) 
• Obtain pregnancy test (serum) for all women of childbearing potential. Note: if the 
subject is taking/using contraceptive medication/device, please be sure to record the 
medication or device on the appropriate eCRF pages (concomitant medication or 
procedure). Pregnancy testing (urine or serum) may also be performed at any time 
during the trial at the Investigator’s discretion.  
• Determine if the subject needs Neisseria meningitidis (N. meningitidis) re-
vaccination. Re-vaccinate as needed to provide active coverage as specified by the 
vaccine manufacturer or according to current medical/country guidelines.  
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• Provide the Patient Safety Information Card describing the IP and emergency contact 
information to the subject prior to the first dose of IP.  
• Collect baseline blood samples for PK, PD, free Complement protein 5 (C5), and 
anti-drug antibody (ADA) assays before the infusion of IP.  
• Contact the IXRS to obtain the study drug kit assignment. 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion.  
7.3.1.2. 
Visit 2 (Week 1) 
The following tests and procedures will be completed at Visit 2 (Week1):  
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR 
• Record any new medications or changes to concomitant medications since the 
previous visit (including non-drug therapies) 
• Evaluate and record AEs since the previous visit 
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information 
• Administer MG-ADL by a properly trained evaluator and preferably by the same 
evaluator throughout the trial. The recall period is the preceding 7 days. If the number 
of days since the last visit was less than 7, the recall period is since the last visit.  
• Administer clinical assessments QMG, NIF, and MGC; these shall be performed at 
approximately the same time of day, by a properly trained evaluator, preferably the 
same evaluator, throughout the trial. If the subject is taking a cholinesterase inhibitor, 
the dose must be withheld for at least 10 hours prior to the QMG and MGC tests.  
• Collect trough blood samples for PK, PD, and free C5 assays 5 to 90 minutes before 
the IP infusion. Peak blood samples for PK, PD, and free C5 are to be taken at least 
60 minutes after the completion of the IP infusion.  
• Contact the IXRS to obtain the study drug kit assignment 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion. 
7.3.1.3. 
Visits 3 and 4 (Weeks 2 and 3) 
The following tests and procedures will be completed at these visits:  
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR. 
• Record any new medications or changes to concomitant medications since the 
previous visit (including non-drug therapies) 
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19 December 2016 
 
 
 
• Evaluate and record AEs since the previous visit 
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information 
• Administer MG-ADL by a properly trained evaluator and preferably by the same 
evaluator throughout the trial. The recall period is the preceding 7 days.  
• Administer clinical assessments QMG, NIF, and MGC; these shall be performed at 
approximately the same time of day, by a properly trained evaluator, preferably the 
same evaluator, throughout the trial. If the subject is taking a cholinesterase inhibitor, 
the dose must be withheld for at least 10 hours prior to the QMG and MGC tests.  
• Contact the IXRS to obtain the study drug kit assignment. 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion. 
7.3.2. 
Open-Label Maintenance Phase Year 1 
7.3.2.1. 
Visit 5 (Week 4) 
The following tests and procedures will be completed at this visit:  
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR. 
• Record any new medications or changes to concomitant medications since the 
previous visit (including non-drug therapies). 
• Evaluate and record AEs since the previous visit.  
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information.  
• Administer MG-ADL by a properly trained evaluator and preferably by the same 
evaluator throughout the trial. The recall period is the preceding 7 days.  
• Administer clinical assessments QMG, NIF, and MGC; these shall be performed at 
approximately the same time of day, by a properly trained evaluator, preferably the 
same evaluator, throughout the trial. If the subject is taking a cholinesterase inhibitor, 
the dose must be withheld for at least 10 hours prior to the QMG and MGC tests.  
• Administer questionnaires to evaluate quality of life (MG-QOL15, Neuro-QOL 
Fatigue, and EQ-5D). 
• Obtain blood samples for clinical laboratory tests (chemistry and hematology; refer to 
Appendix 5).  
• Collect trough blood samples for PK, PD, and free C5 assays 5 to 90 minutes before 
the IP infusion. Peak blood samples for PK, PD, and free C5 are to be taken at least 
60 minutes after the completion of the IP infusion.  
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19 December 2016 
 
 
 
• Collect a blood sample for ADA assay 5 to 90 minutes before the IP infusion.  
• Contact the IXRS to obtain the study drug kit assignment. 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion. 
7.3.2.2. 
Visits 6, 8, 10, 12, 14, and 15 (Weeks 6, 10, 14, 18, 22, and 24) 
The following tests and procedures will be completed at these visits:  
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR. 
• Record any new medications or changes to concomitant medications (including 
non-drug therapies). 
• Evaluate and record AEs since the previous visit.  
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information. 
• Contact the IXRS to obtain the study drug kit assignment. 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion. 
7.3.2.3. 
Visit 7 (Week 8) 
The following tests and procedures will be completed at these visits:  
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR. 
• Record any new medications or changes to concomitant medications (including 
non-drug therapies). 
• Evaluate and record AEs since the previous visit.  
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information. 
• Administer MG-ADL by a properly trained evaluator and preferably by the same 
evaluator throughout the trial. The recall period is the preceding 7 days.  
• Administer clinical assessments QMG, NIF, and MGC; these shall be performed at 
approximately the same time of day, by a properly trained evaluator, preferably the 
same evaluator, throughout the trial. If the subject is taking a cholinesterase inhibitor, 
the dose must be withheld for at least 10 hours prior to the QMG and MGC tests.  
• Administer questionnaires to evaluate quality of life (MG-QOL15, Neuro-QOL 
Fatigue, and EQ-5D). 
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19 December 2016 
 
 
 
• Obtain blood samples for clinical laboratory tests (chemistry and hematology; refer to 
Appendix 5).  
• Collect trough blood samples for PK, PD, and free C5 assays 5 to 90 minutes before 
the IP infusion. Peak blood samples for PK, PD, and free C5 are to be taken at least 
60 minutes after the completion of the IP infusion.  
• Contact the IXRS to obtain the study drug kit assignment. 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion. 
7.3.2.4. 
Visit 9 (Week 12) 
The following tests and procedures will be completed at these visits:  
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR. 
• Record any new medications or changes to concomitant medications (including 
non-drug therapies). 
• Evaluate and record AEs since the previous visit.  
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information. 
• Determine if the subject needs N. meningitidis re-vaccination. Re-vaccinate as needed 
to provide active coverage as specified by the vaccine manufacturer or according to 
current medical/country guidelines.  
• Administer MG-ADL by a properly trained evaluator and preferably by the same 
evaluator throughout the trial. The recall period is the preceding 7 days.  
• Administer clinical assessments QMG, NIF, and MGC; these shall be performed at 
approximately the same time of day, by a properly trained evaluator, preferably the 
same evaluator, throughout the trial. If the subject is taking a cholinesterase inhibitor, 
the dose must be withheld for at least 10 hours prior to the QMG and MGC tests.  
• Administer questionnaires to evaluate quality of life (MG-QOL15, Neuro-QOL 
Fatigue, and EQ-5D). 
• Perform C-SSRS (Appendix 9).  
• Obtain a blood sample for the acetylcholine receptor antibodies (AChR Abs) test.  
• Obtain blood samples for clinical laboratory tests (chemistry and hematology; refer to 
Appendix 5).  
• Collect trough blood samples for PK, PD, and free C5 assays 5 to 90 minutes before 
the IP infusion. Peak blood samples for PK, PD, and free C5 are to be taken at least 
60 minutes after the completion of the IP infusion.  
• Collect a blood sample for ADA assay 5 to 90 minutes before the IP infusion.  
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19 December 2016 
 
 
 
• Contact the IXRS to obtain the study drug kit assignment. 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion. 
7.3.2.5. 
Visit 11 (Week 16) 
The following tests and procedures will be completed at Visit 11:  
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR. 
• Record any new medications or changes to concomitant medications (including 
non-drug therapies). 
• Evaluate and record AEs since the previous visit.  
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information. 
• Administer MG-ADL by a properly trained evaluator and preferably by the same 
evaluator throughout the trial. The recall period is the preceding 7 days.  
• Administer clinical assessments QMG, NIF, and MGC; these shall be performed at 
approximately the same time of day, by a properly trained evaluator, preferably the 
same evaluator, throughout the trial. If the subject is taking a cholinesterase inhibitor, 
the dose must be withheld for at least 10 hours prior to the QMG and MGC tests.  
• Administer questionnaires to evaluate quality of life (MG-QOL15, Neuro-QOL 
Fatigue, and EQ-5D). 
• Contact the IXRS to obtain the study drug kit assignment. 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion. 
7.3.2.6. 
Visit 13 (Week 20) 
The following tests and procedures will be completed at Visit 13:  
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR. 
• Record any new medications or changes to concomitant medications (including 
non-drug therapies). 
• Evaluate and record AEs since the previous visit.  
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information. 
• Administer MG-ADL by a properly trained evaluator and preferably by the same 
evaluator throughout the trial. The recall period is the preceding 7 days.  
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19 December 2016 
 
 
 
• Administer clinical assessments QMG, NIF, and MGC; these shall be performed at 
approximately the same time of day, by a properly trained evaluator, preferably the 
same evaluator, throughout the trial. If the subject is taking a cholinesterase inhibitor, 
the dose must be withheld for at least 10 hours prior to the QMG and MGC tests.  
• Administer questionnaires to evaluate quality of life (MG-QOL15, Neuro-QOL 
Fatigue, and EQ-5D). 
• Collect trough blood samples for PK, PD, and free C5 assays 5 to 90 minutes before 
the IP infusion. Peak blood samples for PK, PD, and free C5 are to be taken at least 
60 minutes after the completion of the IP infusion.  
• Contact the IXRS to obtain the study drug kit assignment 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion. 
7.3.2.7. 
Visit 16 (Week 26) 
The following tests and procedures will be completed at these visits:  
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR. 
• Measure body weight.  
• Complete physical examination including assessments of the following organ/body 
systems: skin, head, ears, eyes, nose, throat, neck, lymph nodes, chest, heart, 
abdomen, extremities, and general neurologic examination. 
• Perform a 12-lead ECG.  
• Record any new medications or changes to concomitant medications (including 
non-drug therapies). 
• Evaluate and record AEs since the previous visit. 
• Record MG Therapy Status (refer to Appendix 6). 
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information. 
• Determine if the subject needs N. meningitidis re-vaccination. Re-vaccinate as needed 
to provide active coverage as specified by the vaccine manufacturer or according to 
current medical/country guidelines.  
• Administer MG-ADL by a properly trained evaluator and preferably by the same 
evaluator throughout the trial. The recall period is the preceding 7 days.  
• Administer clinical assessments QMG, NIF, and MGC; these shall be performed at 
approximately the same time of day, by a properly trained evaluator, preferably the 
same evaluator, throughout the trial. If the subject is taking a cholinesterase inhibitor, 
the dose must be withheld for at least 10 hours prior to the QMG and MGC tests.  
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19 December 2016 
 
 
 
• Administer questionnaires to evaluate quality of life (MG-QOL15, Neuro-QOL 
Fatigue, and EQ-5D). 
• Assess change from baseline in the MGFA-PIS (Appendix 8). The MGFA-PIS must 
be performed by the PI or the same neurologist throughout the trial. 
• Perform C-SSRS (Appendix 9). 
• Obtain a blood sample for the AChR Abs test. 
• Obtain blood samples for clinical laboratory tests (chemistry and hematology; refer to 
Appendix 5).  
• Obtain pregnancy test (serum) for all women of childbearing potential. Note: if the 
subject is taking/using contraceptive medication/device, please be sure to record the 
medication or device on the appropriate eCRF pages (concomitant medication or 
procedure).  
• Collect trough blood samples for PK, PD, and free C5 assays 5 to 90 minutes before 
the IP infusion. Peak blood samples for PK, PD, and free C5 are to be taken at least 
60 minutes after the completion of the IP infusion 
• Collect a blood sample for ADA assay 5 to 90 minutes before the IP infusion.  
• Contact the IXRS to obtain the study drug kit assignment. 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion. 
7.3.2.8. 
Visits 17 to 22 and 24 to 28 (Weeks 28 to 38 and 42 to 50) 
The following tests and procedures will be completed at these visits:  
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR. 
• Record any new medications or changes to concomitant medications (including 
non-drug therapies). 
• Evaluate and record AEs since the previous visit. 
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information. 
• Contact the IXRS to obtain the study drug kit assignment. 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion. 
7.3.2.9. 
Visit 23 (Week 40) 
The following tests and procedures will be completed at this visit:  
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19 December 2016 
 
 
 
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR. 
• Record any new medications or changes to concomitant medications (including 
non-drug therapies). 
• Evaluate and record AEs since the previous visit. 
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information. 
• Determine if the subject needs N. meningitidis re-vaccination. Re-vaccinate as needed 
to provide active coverage as specified by the vaccine manufacturer or according to 
current medical/country guidelines.  
• Administer MG-ADL by a properly trained evaluator and preferably by the same 
evaluator throughout the trial. The recall period is the preceding 7 days.  
• Administer clinical assessments QMG and MGC; these shall be performed at 
approximately the same time of day, by a properly trained evaluator, preferably the 
same evaluator, throughout the trial. If the subject is taking a cholinesterase inhibitor, 
the dose must be withheld for at least 10 hours prior to the QMG and MGC tests.  
• Administer questionnaires to evaluate quality of life (MG-QOL15, Neuro-QOL 
Fatigue, and EQ-5D). 
• Assess change from baseline in the MGFA-PIS (Appendix 8). The MGFA-PIS must 
be performed by the PI or the same neurologist throughout the trial. 
• Perform C-SSRS (Appendix 9). 
• Obtain blood samples for clinical laboratory tests (chemistry and hematology; refer to 
Appendix 5).  
• Obtain pregnancy test (serum) for all women of childbearing potential. Note: if the 
subject is taking/using contraceptive medication/device, please be sure to record the 
medication or device on the appropriate eCRF pages (concomitant medication or 
procedure).  
• Collect trough blood samples for PK, PD, and free C5 assays 5 to 90 minutes before 
the IP infusion. Peak blood samples for PK, PD, and free C5 are to be taken at least 
60 minutes after the completion of the IP infusion. 
• Collect a blood sample for ADA assay 5 to 90 minutes before the IP infusion. 
• Contact the IXRS to obtain the study drug kit assignment. 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion. 
7.3.2.10. Visit 29 (Week 52) 
The following tests and procedures will be completed at this visit:  
Page 47 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR. 
• Measure body weight. 
• Perform a 12-lead ECG. 
• Record any new medications or changes to concomitant medications (including 
non-drug therapies). 
• Record MG Therapy Status (refer to Appendix 6). 
• Evaluate and record AEs since the previous visit. 
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information. 
• Determine if the subject needs N. meningitidis re-vaccination. Re-vaccinate as needed 
to provide active coverage as specified by the vaccine manufacturer or according to 
current medical/country guidelines.  
• Administer MG-ADL by a properly trained evaluator and preferably by the same 
evaluator throughout the trial. The recall period is the preceding 7 days.  
• Administer clinical assessments QMG and MGC; these shall be performed at 
approximately the same time of day, by a properly trained evaluator, preferably the 
same evaluator, throughout the trial. If the subject is taking a cholinesterase inhibitor, 
the dose must be withheld for at least 10 hours prior to the QMG and MGC tests.  
• Administer questionnaires to evaluate quality of life (MG-QOL15, Neuro-QOL 
Fatigue, and EQ-5D). 
• Assess change from baseline in the MGFA-PIS (Appendix 8). The MGFA-PIS must 
be performed by the PI or the same neurologist throughout the trial. 
• Perform C-SSRS (Appendix 9). 
• Obtain a blood sample for the AChR Abs test. 
• Obtain blood samples for clinical laboratory tests (chemistry and hematology; refer to 
Appendix 5).  
• Obtain pregnancy test (serum) for all women of childbearing potential. Note: if the 
subject is taking/using contraceptive medication/device, please be sure to record the 
medication or device on the appropriate eCRF pages (concomitant medication or 
procedure).  
• Collect trough blood samples for PK, PD, and free C5 assays 5 to 90 minutes before 
the IP infusion. Peak blood samples for PK, PD, and free C5 are to be taken at least 
60 minutes after the completion of the IP infusion.  
• Collect a blood sample for ADA assay 5 to 90 minutes before the IP infusion. 
• Contact the IXRS to obtain the study drug kit assignment. 
Page 48 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion. 
7.3.3. 
Open-Label Maintenance Phase Year 2 
7.3.3.1. 
Visits 30-34 and 36-41 (Weeks 54-62 and 66-76) 
The following tests and procedures will be completed at these visits:  
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR. 
• Record any new medications or changes to concomitant medications (including 
non-drug therapies). 
• Evaluate and record AEs since the previous visit. 
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information. 
• Contact the IXRS to obtain the study drug kit assignment. 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion. 
7.3.3.2. 
Visit 35 (Week 64) 
The following tests and procedures will be completed at Visit 35:  
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR. 
• Record any new medications or changes to concomitant medications (including 
non-drug therapies). 
• Evaluate and record AEs since the previous visit. 
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information. 
• Determine if the subject needs N. meningitidis re-vaccination. Re-vaccinate as needed 
to provide active coverage as specified by the vaccine manufacturer or according to 
current medical/country guidelines.  
• Contact the IXRS to obtain the study drug kit assignment. 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion. 
7.3.3.3. 
Visit 42 (Week 78)  
The following tests and procedures will be completed at this visit:  
Page 49 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR. 
• Record any new medications or changes to concomitant medications (including 
non-drug therapies). 
• Evaluate and record AEs since the previous visit. 
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information. 
• Determine if the subject needs N. meningitidis re-vaccination. Re-vaccinate as needed 
to provide active coverage as specified by the vaccine manufacturer or according to 
current medical/country guidelines. 
• Administer MG-ADL by a properly trained evaluator and preferably by the same 
evaluator throughout the trial. The recall period is the preceding 7 days.  
• Administer clinical assessments QMG and MGC; these shall be performed at 
approximately the same time of day, by a properly trained evaluator, preferably the 
same evaluator, throughout the trial. If the subject is taking a cholinesterase inhibitor, 
the dose must be withheld for at least 10 hours prior to the QMG and MGC tests.  
• Administer questionnaires to evaluate quality of life (MG-QOL15, Neuro-QOL 
Fatigue, and EQ-5D). 
• Assess change from baseline in the MGFA-PIS (Appendix 8). The MGFA-PIS must 
be performed by the PI or the same neurologist throughout the trial. 
• Perform C-SSRS (Appendix 9). 
• Obtain a blood sample for the AChR Abs test. 
• Obtain blood samples for clinical laboratory tests (chemistry and hematology; refer to 
Appendix 5).  
• Obtain pregnancy test (serum) for all women of childbearing potential. Note: if the 
subject is taking/using contraceptive medication/device, please be sure to record the 
medication or device on the appropriate eCRF pages (concomitant medication or 
procedure).  
• Collect trough blood samples for PK, PD, and free C5 assays 5 to 90 minutes before 
the IP infusion. Peak blood samples for PK, PD, and free C5 are to be taken at least 
60 minutes after the completion of the IP infusion. 
• Collect a blood sample for ADA assay 5 to 90 minutes before the IP infusion. 
• Contact the IXRS to obtain the study drug kit assignment. 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion. 
Page 50 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
7.3.3.4. 
Visits 43 to 48 and 50 to 54 (Weeks 80 to 90 and 94 to 102) 
The following tests and procedures will be completed at these visits:  
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR. 
• Record any new medications or changes to concomitant medications (including 
non-drug therapies). 
• Evaluate and record AEs since the previous visit. 
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information. 
• Contact the IXRS to obtain the study drug kit assignment. 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion. 
7.3.3.5. 
Visit 49 (Week 92) 
The following tests and procedures will be completed at Visit 49:  
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR. 
• Record any new medications or changes to concomitant medications (including 
non-drug therapies). 
• Evaluate and record AEs since the previous visit. 
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information. 
• Determine if the subject needs N. meningitidis re-vaccination. Re-vaccinate as needed 
to provide active coverage as specified by the vaccine manufacturer or according to 
current medical/country guidelines.  
• Contact the IXRS to obtain the study drug kit assignment. 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion. 
7.3.3.6. 
Visit 55 (Week 104)  
The following tests and procedures will be completed at this visit:  
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR. 
• Measure body weight. 
• Perform a 12-lead ECG. 
Page 51 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
• Record any new medications or changes to concomitant medications (including 
non-drug therapies). 
• Evaluate and record AEs since the previous visit. 
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information. 
• Determine if the subject needs N. meningitidis re-vaccination. Re-vaccinate as needed 
to provide active coverage as specified by the vaccine manufacturer or according to 
current medical/country guidelines. 
• Administer MG-ADL by a properly trained evaluator and preferably by the same 
evaluator throughout the trial. The recall period is the preceding 7 days.  
• Administer clinical assessments QMG and MGC; these shall be performed at 
approximately the same time of day, by a properly trained evaluator, preferably the 
same evaluator, throughout the trial. If the subject is taking a cholinesterase inhibitor, 
the dose must be withheld for at least 10 hours prior to the QMG and MGC tests.  
• Administer questionnaires to evaluate quality of life (MG-QOL15, Neuro-QOL 
Fatigue, and EQ-5D). 
• Assess change from baseline in the MGFA-PIS (Appendix 8). The MGFA-PIS must 
be performed by the PI or the same neurologist throughout the trial. 
• Perform C-SSRS (Appendix 9). 
• Obtain a blood sample for the AChR Abs test. 
• Obtain blood samples for clinical laboratory tests (chemistry and hematology; refer to 
Appendix 5).  
• Obtain pregnancy test (serum) for all women of childbearing potential. Note: if the 
subject is taking/using contraceptive medication/device, please be sure to record the 
medication or device on the appropriate CRF pages (concomitant medication or 
procedure).  
• Collect trough blood samples for PK, PD, and free C5 assays 5 to 90 minutes before 
the IP infusion. Peak blood samples for PK, PD, and free C5 are to be taken at least 
60 minutes after the completion of the IP infusion. 
• Collect a blood sample for ADA assay 5 to 90 minutes before the IP infusion. 
• Contact the IXRS to obtain the study drug kit assignment. 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion. 
Page 52 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
7.3.4. 
Open-Label Maintenance Phase Year 3 
7.3.4.1. 
Visits 56 to 60 and 62 to 67 (Weeks 106 to 114 and 118 to 128) 
The following tests and procedures will be completed at these visits:  
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR. 
• Record any new medications or changes to concomitant medications (including 
non-drug therapies). 
• Evaluate and record AEs since the previous visit. 
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information. 
• Contact the IXRS to obtain the study drug kit assignment. 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion. 
7.3.4.2. 
Visit 61 (Week 116) 
The following tests and procedures will be completed at Visit 61:  
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR. 
• Record any new medications or changes to concomitant medications (including 
non-drug therapies). 
• Evaluate and record AEs since the previous visit. 
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information. 
• Determine if the subject needs N. meningitidis re-vaccination. Re-vaccinate as needed 
to provide active coverage as specified by the vaccine manufacturer or according to 
current medical/country guidelines. 
• Contact the IXRS to obtain the study drug kit assignment. 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion. 
7.3.4.3. 
Visit 68 (Week 130) 
The following tests and procedures will be completed at this visit:  
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR. 
Page 53 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
• Record any new medications or changes to concomitant medications (including 
non-drug therapies). 
• Evaluate and record AEs since the previous visit. 
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information. 
• Determine if the subject needs N. meningitidis re-vaccination. Re-vaccinate as needed 
to provide active coverage as specified by the vaccine manufacturer or according to 
current medical/country guidelines. 
• Administer MG-ADL by a properly trained evaluator and preferably by the same 
evaluator throughout the trial. The recall period is the preceding 7 days.  
• Administer clinical assessments QMG and MGC; these shall be performed at 
approximately the same time of day, by a properly trained evaluator, preferably the 
same evaluator, throughout the trial. If the subject is taking a cholinesterase inhibitor, 
the dose must be withheld for at least 10 hours prior to the QMG and MGC tests.  
• Administer questionnaires to evaluate quality of life (MG-QOL15, Neuro-QOL 
Fatigue, and EQ-5D). 
• Assess change from baseline in the MGFA-PIS, Appendix 8). The MGFA-PIS must 
be performed by the PI or the same neurologist throughout the trial. 
• Perform C-SSRS (Appendix 9). 
• Obtain a blood sample for the AChR Abs test. 
• Obtain blood samples for clinical laboratory tests (chemistry and hematology; refer to 
Appendix 5).  
• Obtain pregnancy test (serum) for all women of childbearing potential. Note: if the 
subject is taking/using contraceptive medication/device, please be sure to record the 
medication or device on the appropriate CRF pages (concomitant medication or 
procedure).  
• Collect trough blood samples for PK, PD, and free C5 assays 5 to 90 minutes before 
the IP infusion. Peak blood samples for PK, PD, and free C5 are to be taken at least 
60 minutes after the completion of the IP infusion. 
• Collect a blood sample for ADA assay 5 to 90 minutes before the IP infusion. 
• Contact the IXRS to obtain the study drug kit assignment. 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion. 
7.3.4.4. 
Visits 69 to 74 and 76 to 80 (Weeks 132 to 142 and 146 to 154) 
The following tests and procedures will be completed at these visits:  
Page 54 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR. 
• Record any new medications or changes to concomitant medications (including 
non-drug therapies). 
• Evaluate and record AEs since the previous visit. 
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information. 
• Contact the IXRS to obtain the study drug kit assignment. 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion. 
7.3.4.5. 
Visit 75 (Week 144) 
The following tests and procedures will be completed at Visit 75:  
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR. 
• Record any new medications or changes to concomitant medications (including 
non-drug therapies). 
• Evaluate and record AEs since the previous visit. 
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information. 
• Determine if the subject needs N. meningitidis re-vaccination. Re-vaccinate as needed 
to provide active coverage as specified by the vaccine manufacturer or according to 
current medical/country guidelines.  
• Contact the IXRS to obtain the study drug kit assignment. 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion. 
7.3.4.6. 
Visit 81 (Week 156)  
The following tests and procedures will be completed at this visit:  
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR. 
• Measure body weight.  
• Perform a 12-lead ECG. 
• Record any new medications or changes to concomitant medications (including 
non-drug therapies). 
Page 55 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
• Evaluate and record AEs since the previous visit. 
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information. 
• Determine if the subject needs N. meningitidis re-vaccination. Re-vaccinate as needed 
to provide active coverage as specified by the vaccine manufacturer or according to 
current medical/country guidelines. 
• Administer MG-ADL by a properly trained evaluator and preferably by the same 
evaluator throughout the trial. The recall period is the preceding 7 days.  
• Administer clinical assessments QMG and MGC; these shall be performed at 
approximately the same time of day, by a properly trained evaluator, preferably the 
same evaluator, throughout the trial. If the subject is taking a cholinesterase inhibitor, 
the dose must be withheld for at least 10 hours prior to the QMG and MGC tests.  
• Administer questionnaires to evaluate quality of life (MG-QOL15, Neuro-QOL 
Fatigue, and EQ-5D). 
• Assess change from baseline in the MGFA-PIS (Appendix 8). The MGFA-PIS must 
be performed by the PI or the same neurologist throughout the trial. 
• Perform C-SSRS (Appendix 9). 
• Obtain a blood sample for the AChR Abs test. 
• Obtain blood samples for clinical laboratory tests (chemistry and hematology; refer to 
Appendix 5).  
• Obtain pregnancy test (serum) for all women of childbearing potential. Note: if the 
subject is taking/using contraceptive medication/device, please be sure to record the 
medication or device on the appropriate eCRF pages (concomitant medication or 
procedure).  
• Collect trough blood samples for PK, PD, and free C5 assays 5 to 90 minutes before 
the IP infusion. Peak blood samples for PK, PD, and free C5 are to be taken at least 
60 minutes after the completion of the IP infusion.Collect a blood sample for ADA 
assay 5 to 90 minutes before the IP infusion. 
• Contact the IXRS to obtain the study drug kit assignment. 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion. 
7.3.5. 
Open-Label Maintenance Phase Year 4 
7.3.5.1. 
Visits 82 to 86 and 88 to 93 (Weeks 158 to 166 and 170 to 180) 
The following tests and procedures will be completed at these visits:  
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR. 
Page 56 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
• Record any new medications or changes to concomitant medications (including 
non-drug therapies). 
• Evaluate and record AEs since the previous visit. 
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information. 
• Contact the IXRS to obtain the study drug kit assignment. 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion. 
7.3.5.2. 
Visit 87 (Week 168) 
The following tests and procedures will be completed at Visit 87:  
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR. 
• Record any new medications or changes to concomitant medications (including 
non-drug therapies). 
• Evaluate and record AEs since the previous visit. 
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information. 
• Determine if the subject needs N. meningitidis re-vaccination. Re-vaccinate as needed 
to provide active coverage as specified by the vaccine manufacturer or according to 
current medical/country guidelines.  
• Contact the IXRS to obtain the study drug kit assignment. 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion. 
7.3.5.3. 
Visit 94 (Week 182)  
The following tests and procedures will be completed at this visit:  
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR. 
• Record any new medications or changes to concomitant medications (including 
non-drug therapies). 
• Evaluate and record AEs since the previous visit. 
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information. 
Page 57 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
• Determine if the subject needs N. meningitidis re-vaccination. Re-vaccinate as needed 
to provide active coverage as specified by the vaccine manufacturer or according to 
current medical/country guidelines.  
• Administer MG-ADL by a properly trained evaluator and preferably by the same 
evaluator throughout the trial. The recall period is the preceding 7 days.  
• Administer clinical assessments QMG and MGC; these shall be performed at 
approximately the same time of day, by a properly trained evaluator, preferably the 
same evaluator, throughout the trial. If the subject is taking a cholinesterase inhibitor, 
the dose must be withheld for at least 10 hours prior to the QMG and MGC tests.  
• Administer questionnaires to evaluate quality of life (MG-QOL15, Neuro-QOL 
Fatigue, and EQ-5D). 
• Assess change from baseline in the MGFA-PIS (Appendix 8). The MGFA-PIS must 
be performed by the PI or the same neurologist throughout the trial. 
• Perform C-SSRS (Appendix 9). 
• Obtain a blood sample for the AChR Abs test. 
• Obtain blood samples for clinical laboratory tests (chemistry and hematology; refer to 
Appendix 5).  
• Obtain pregnancy test (serum) for all women of childbearing potential. Note: if the 
subject is taking/using contraceptive medication/device, please be sure to record the 
medication or device on the appropriate eCRF pages (concomitant medication or 
procedure).  
• Collect trough blood samples for PK, PD, and free C5 assays 5 to 90 minutes before 
the IP infusion. Peak blood samples for PK, PD, and free C5 are to be taken at least 
60 minutes after the completion of the IP infusion. 
• Collect a blood sample for ADA assay 5 to 90 minutes before the IP infusion. 
• Contact the IXRS to obtain the study drug kit assignment. 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion. 
7.3.5.4. 
Visits 95 to 100 and 102 to 106 (Weeks 184 to 194 and 198 to 206) 
The following tests and procedures will be completed at these visits:  
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR. 
• Record any new medications or changes to concomitant medications (including 
non-drug therapies). 
• Evaluate and record AEs since the previous visit. 
Page 58 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information. 
• Contact the IXRS to obtain the study drug kit assignment. 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion. 
7.3.5.5. 
Visit 101 (Week 196) 
The following tests and procedures will be completed at Visit 101:  
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR. 
• Record any new medications or changes to concomitant medications (including 
non-drug therapies). 
• Evaluate and record AEs since the previous visit. 
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information. 
• Determine if the subject needs N. meningitidis re-vaccination. Re-vaccinate as needed 
to provide active coverage as specified by the vaccine manufacturer or according to 
current medical/country guidelines.  
• Contact the IXRS to obtain the study drug kit assignment. 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion. 
7.3.5.6. 
Visit 107 (Week 208)  
The following tests and procedures will be completed at this visit:  
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR. 
• Measure body weight.  
• Perform a 12-lead ECG. 
• Record any new medications or changes to concomitant medications (including 
non-drug therapies). 
• Evaluate and record AEs since the previous visit. 
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information. 
• Determine if the subject needs N. meningitidis re-vaccination. Re-vaccinate as needed 
to provide active coverage as specified by the vaccine manufacturer or according to 
current medical/country guidelines.  
Page 59 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
• Administer MG-ADL by a properly trained evaluator and preferably by the same 
evaluator throughout the trial. The recall period is the preceding 7 days.  
•  Administer clinical assessments QMG and MGC; these shall be performed at 
approximately the same time of day, by a properly trained evaluator, preferably the 
same evaluator, throughout the trial. If the subject is taking a cholinesterase inhibitor, 
the dose must be withheld for at least 10 hours prior to the QMG and MGC tests.  
• Administer questionnaires to evaluate quality of life (MG-QOL15, Neuro-QOL 
Fatigue, and EQ-5D). 
• Assess change from baseline in the MGFA-PIS (Appendix 8). The MGFA-PIS must 
be performed by the PI or the same neurologist throughout the trial. 
• Perform C-SSRS (Appendix 9). 
• Obtain a blood sample for the AChR Abs test. 
• Obtain blood samples for clinical laboratory tests (chemistry and hematology; refer to 
Appendix 5).  
• Obtain pregnancy test (serum) for all women of childbearing potential. Note: if the 
subject is taking/using contraceptive medication/device, please be sure to record the 
medication or device on the appropriate eCRF pages (concomitant medication or 
procedure).  
• Collect trough blood samples for PK, PD, and free C5 assays 5 to 90 minutes before 
the IP infusion. Peak blood samples for PK, PD, and free C5 are to be taken at least 
60 minutes after the completion of the IP infusion. 
• Collect a blood sample for ADA assay 5 to 90 minutes before the IP infusion. 
• Contact the IXRS to obtain the study drug kit assignment. 
• Administer the IP infusion over approximately 35 minutes according to the regimen 
described in Section 10.5 and observe subjects for at least 1 hour after the end of the 
IP infusion. 
7.3.6. 
End of Study / Early Termination  
An EOS visit will be performed before a subject leaves the study for any reason, including study 
termination. An ET visit will be performed if a subject withdraws early during the study. The 
tests and procedures for the EOS or ET visit are as follows:  
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR. 
• Complete physical examination including assessments of the following organ/body 
systems: skin, head, ears, eyes, nose, throat, neck, lymph nodes, chest, heart, 
abdomen, extremities,  and general neurologic examination. 
• Measure body weight. 
• Perform a 12-lead ECG. 
Page 60 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
• Record any new medications or changes to concomitant medications (including 
non-drug therapies). 
• Record MG Therapy Status (refer to Appendix 6). 
• Evaluate and record AEs since the previous visit. 
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information. 
• Determine if the subject needs N. meningitidis re-vaccination. Re-vaccinate as needed 
to provide active coverage as specified by the vaccine manufacturer or according to 
current medical/country guidelines.  
• Administer MG-ADL by a properly trained evaluator and preferably by the same 
evaluator throughout the trial. The recall period is the preceding 7 days or since the 
last visit whichever occurs earlier.  
• Administer clinical assessments QMG and MGC; these shall be performed at 
approximately the same time of day, by a properly trained evaluator, preferably the 
same evaluator, throughout the trial. If the subject is taking a cholinesterase inhibitor, 
the dose must be withheld for at least 10 hours prior to the QMG and MGC tests.  
• Administer questionnaires to evaluate quality of life (MG-QOL15, Neuro-QOL 
Fatigue, and EQ-5D). 
• Assess change from baseline in the MGFA-PIS (Appendix 8). The MGFA-PIS must 
be performed by the PI or the same neurologist throughout the trial. 
• Perform C-SSRS (Appendix 9). 
• Obtain a blood sample for the AChR Abs test. 
• Obtain blood samples for clinical laboratory tests (chemistry and hematology; refer to 
Appendix 5).  
• Obtain pregnancy test (serum) for all women of childbearing potential. Note: if the 
subject is taking/using contraceptive medication/device, please be sure to record the 
medication or device on the appropriate eCRF pages (concomitant medication or 
procedure).  
• Collect trough blood samples for PK, PD, and free C5 assays.  
• Seek consent from patients to allow the Sponsor to collect information concerning 
their post-treatment MG status for up to 1 year from the EOS/ET visit (refer to 
Section 7.1.3.2, Section 7.3.6, and Appendix 11). 
7.3.7. 
Visits for Evaluation of Clinical Deterioration 
The evaluation visit for Clinical Deterioration must be performed as soon as possible, ideally 
within 48 hours of the Investigator receiving notification of the symptom onset. Additional 
evaluation visits can be scheduled at the discretion of the Investigator. The following tests and 
procedures will be completed at this visit:  
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• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR.  
• Record any new medications or changes to concomitant medications (including 
non-drug therapies), including all treatments for MG.  
• Evaluate and record any new AEs or changes in AEs since the previous visit.  
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information. 
• Administer MG-ADL by a properly trained evaluator and preferably by the same 
evaluator throughout the trial. The recall period is the preceding 7 days or since the 
last visit whichever occurs earlier.  
− Administer clinical assessments QMG and MGC; these shall be performed at 
approximately the same time of day, by a properly trained evaluator, preferably the 
same evaluator, throughout the trial. If the subject is taking a cholinesterase inhibitor, 
the dose must be withheld for at least 10 hours prior to the QMG and MGC tests.  
• Collect blood sample for the AChR Abs test.  
• Collect blood samples for clinical laboratory tests (chemistry and hematology).  
• If medically indicated for evaluation of clinical deterioration, additional tests may be 
performed at the discretion of the Investigator.  
• PK/PD sampling at or during crisis or deterioration Visit:  
− Collect 1 blood sample for PK, PD, and free C5 assays if no IP is administered.  
− If IP is administered at the visit for Clinical Deterioration, baseline and trough 
blood samples for PK, PD, free C5, and all samples for ADA will be taken 5 – 90 
minutes before the IP infusion. Peak blood samples for PK, PD and free C5 
testing will be taken at least 60 minutes after the completion of the IP infusion. 
− If the subject receives PE at the time of Clinical Deterioration, a supplemental 
dose of IP will be administered. Collect 3 blood samples for PK, PD, and free C5 
at [1] 5 to 90 minutes before PE, [2] after PE and before IP infusion, and [3] at 
least 1 to 2 hours after completion of the IP infusion.  
• IP administration:  
− Subject will continue IP administration in accordance with protocol specified IP 
administration schedule.  
− If the crisis or Clinical Deterioration Visit coincides with a regular visit per 
protocol, subject will receive the regular IP administration per protocol schedule.  
− If subjects undergo PE, a supplemental dose (2 vials IP) must be administered 
within 1 to 2 hours after each PE session unless the PE session is on the day of a 
scheduled IP infusion. If the subject is scheduled to receive the protocol-
scheduled dose on the day of a PE session, then the scheduled dose instead of the 
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supplemental dose should be administered within 1 to 2 hours after the end of the 
PE. 
− Contact the IXRS to obtain the study drug kit assignment. 
7.3.8. 
Unscheduled Visit 
Additional (unscheduled) visits outside the specified visits are permitted at the discretion of the 
Investigator. Procedures, tests, and assessments will be performed at the discretion of the 
Investigator. If an Unscheduled Visit is performed, any tests, procedures, or assessments 
performed at the Unscheduled Visits must be recorded on the eCRF. 
7.3.9. 
Safety Follow-up Period (Post-Treatment +Week 8) 
If a subject withdraws from the trial at any time and for any reason after receiving any amount of 
IP, a follow-up visit for safety assessment is required at 8 weeks after the last dose of IP. 
Subjects who transition to treatment with the commercially available eculizumab directly from 
the extension trial will not be required to complete a Follow-up Visit. The following tests and 
procedures will be completed at the follow-up visit:  
• Measure vital signs, including assessments of systolic and diastolic BP, temperature, 
RR, and HR.  
• Record any new medications or changes to concomitant medications (including 
non-drug therapies).  
• Evaluate and record any new AEs or changes in AEs since the previous visit.  
• Ensure that the subject has the Patient Safety Information Card that describes the IP 
and emergency contact information. 
• Determine if the subject needs N. meningitidis re-vaccination. Re-vaccinate as needed 
to provide active coverage as specified by the vaccine manufacturer or according to 
current medical/country guidelines.  
• Administer MG-ADL by a properly trained evaluator and preferably by the same 
evaluator throughout the trial. The recall period is the preceding 7 days. 
• Administer MG-QOL15 questionnaire to evaluate quality of life.  
• Assess change from baseline in the MGFA-PIS (Appendix 8). The MGFA-PIS must 
be performed by the PI or the same neurologist throughout the trial. 
• Administer clinical assessments QMG and MGC; these shall be performed at 
approximately the same time of day, by a properly trained evaluator, preferably the 
same evaluator, throughout the trial. If the subject is taking a cholinesterase inhibitor, 
the dose must be withheld for at least 10 hours prior to the QMG and MGC tests.  
• Seek consent from patients to allow the Sponsor to collect information concerning 
their post-treatment MG status for up to 1 year from the EOS/ET visit (refer to 
Section 7.1.3.2, Section 7.3.6, and Appendix 11). An updated ICF (and/or ICF 
Addendum) will be provided to all patients. The updated ICF (and/or ICF Addendum) 
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will also be provided to discontinued patients, subject to IRB/IEC approval 
(Appendix 11). 
If a subject is discontinued due to an AE, the AE will be followed until it is resolved or, in the 
opinion of the PI, is determined medically stable. 
7.3.10. 
Post-Treatment Follow-up Period (Up to 1 Year) 
The Sponsor may seek to collect follow-up information concerning MG status in patients post-
treatment for up to 1 year from the EOS/ET visit (refer to Section 7.1.3.2, Section 7.3.6, and 
Appendix 11).  
7.4. 
Number of Subjects 
This trial is an extension to the ECU-MG-301 trial. Approximately 92 subjects with refractory 
gMG will be enrolled in the ECU-MG-301 trial at approximately 100 centers. Subjects who 
complete the ECU-MG-301 trial may potentially enter this extension trial.  
7.5. 
Treatment Assignment 
In order to maintain the blind of the ECU-MG-301 trial, all subjects will undergo a 4-week 
blinded induction treatment period. During this Blind Induction Phase, subjects will receive 
weekly blinded treatment (eculizumab or placebo or eculizumab plus placebo) for 4 weeks based 
upon the treatment received in the ECU-MG-301 trial (refer to Table 10 in Section 9.1). 
During the Open-Label Maintenance Phase, all subjects will receive 4 vials (1200 mg) 
eculizumab every 2 weeks from Visit 5 and onward throughout the trial.  
Study drug kit assignments will be provided by the IXRS during the Blind Induction and 
Open-Label Maintenance Phases. 
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8. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
8.1. 
Subject Inclusion Criteria 
1. Subject completed the ECU-MG-301 trial. 
2. Subject has given written informed consent. 
3. Subject is willing and able to comply with the protocol requirements for the duration of 
the trial. 
4. Female subjects of child-bearing potential must have a negative pregnancy test (serum 
human chorionic gonadotropin [HCG]). All subjects (female and male) must practice an 
effective, reliable and medically approved contraceptive regimen during the trial and for 
up to 5 months following discontinuation of treatment. 
8.2. 
Subject Exclusion Criteria 
1. Subjects who withdrew from the ECU-MG-301 trial as a result of an AE related to trial 
drug. 
2. Female subjects who are pregnant, breastfeeding, or intend to conceive during the course 
of the trial. 
3. Unresolved meningococcal infection. 
4. Hypersensitivity to murine proteins or to one of the excipients of eculizumab. 
5. Any medical condition or circumstances that, in the opinion of the Investigator, might 
interfere with the subject’s participation in the trial, pose any added risk for the subject, 
or confound the assessment of the subjects. 
8.3. 
Subject Withdrawal Criteria 
8.3.1. 
Withdrawal of Subjects from the Trial 
Subjects may withdraw consent for study participation or assessment of post-treatment MG 
status at any time. Every effort should be made to ensure subjects are willing to comply with trial 
participation prior to conducting the screening procedures. The subjects should be fully informed 
of the restrictions related to the change of concomitant medications during the trial. Investigators 
may choose to discontinue a subject’s treatment because of AEs, as well as conditions or 
illnesses that preclude compliance with the protocol from the standpoint of the subject’s safety or 
well-being. The study staff should notify the Sponsor and their site monitor of all trial 
withdrawals as soon as possible. 
Reproduction and development studies with eculizumab have not been performed; therefore, 
eculizumab should not be administered to pregnant women. At the time of the last follow-up 
visit, all subjects of childbearing potential must continue to use adequate contraception for up to 
5 months following discontinuation of eculizumab treatment. If a subject becomes pregnant, the 
IP must be immediately discontinued and the Sponsor must be notified. Each pregnancy will be 
followed to term and the Sponsor notified regarding the outcome. 
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8.3.2. 
Handling of Withdrawals 
When a subject withdraws or is withdrawn from the trial, the Investigator shall record the 
withdrawal reason(s) in the source documents and in the eCRF. Whenever possible, all subjects 
who prematurely withdraw from the trial will undergo all assessments at the ET visit per the 
Schedule of Assessments (Table 7).  
A follow-up visit for safety assessment is required at 8 weeks (±2 days) after the last dose of IP 
administration (Table 9).  
If a subject is discontinued due to an AE, the event will be followed until it is resolved or, in the 
opinion of the Investigator, the subject is determined to be medically stable. Every effort will be 
made to undertake protocol-specified safety follow-up procedures.  
Subjects who fail to return for final assessments will be contacted by the site study staff and 
reminded of the requirement for follow-up. As it is vital to obtain follow-up data on any subject 
withdrawn because of an AE or SAE, follow-up due diligence documentation will consist of 
3 phone calls followed by 1 registered letter to the subject’s last known address. In any case, 
every effort must be made to undertake protocol-specified safety follow-up procedures. 
8.3.3. 
Sponsor’s Termination of Trial 
The Sponsor or a regulatory authority may discontinue the trial at any time for any reason 
including, for example, clinical or administrative reasons.  
 
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9. 
TREATMENT OF SUBJECTS 
9.1. 
Description of Investigational Product 
Eculizumab (900 mg or 1200 mg) or matching placebo (only during the Blind Induction Phase) 
will be administered intravenously over approximately 35 minutes (range of 25 to 45 minutes).  
Blind Induction Phase 
To maintain the blind of ECU-MG-301, all subjects will undergo a Blind Induction Phase. 
During the Blind Induction Phase, IP will be administered weekly (7 days +2) according to the 
regimen in Table 10:  
Table 10: 
Treatment Assignment during the Blind Induction Phase 
Blind Induction Phase 
Eculizumab Amount during 
Blind Induction Phase  
Equivalent 
Eculizumab Dose 
Visits 
Subjects from ECU-MG-301 
Trial Eculizumab arm  
4 vials of eculizumab 
(300 mg/vial) 
1200 mg 
1 and 3 
4 vials of placebo 
0 mg 
2 and 4 
Subjects from ECU-MG-301 
Trial Placebo arm 
3 vials of eculizumab 
(300 mg/vial) plus 1 vial placebo 
900 mg 
1 through 4 
 
Open-Label Maintenance Phase 
During the Open-Label Maintenance Phase, all subjects will receive 4 vials eculizumab 
(1200 mg) every 2 weeks (14 days +2) starting with Visit 5 and continuing throughout the trial.  
Supplemental Doses 
If a subject undergoes PE for Clinical Deterioration during the Study Period, a supplemental 
dose of 2 vials of IP (600 mg of eculizumab) must be administered within 1 to 2 hours after each 
PE session, unless the PE session is on the day of a scheduled IP infusion. If the PE is on the day 
of a scheduled IP infusion, the scheduled dose of IP (instead of the supplemental dose) should be 
administered. In addition, subjects are to continue eculizumab infusion according to the protocol 
specified dosing regimen. 
9.2. 
Concomitant Medications 
9.2.1. 
Allowed Medications 
9.2.1.1. 
Palliative and Supportive Care 
Palliative and supportive care is permitted during the course of the trial for underlying 
conditions.  
The following medications are allowed under certain circumstances and restrictions.  
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9.2.1.1.1. Cholinesterase Inhibitors 
Cholinesterase inhibitor treatment must be withheld for at least 10 hours prior to any efficacy 
measurements (ie, QMG and MGC). Cholinesterase inhibitor therapy dose/schedule changes will 
be permitted due to intolerance or if medically indicated, at the discretion of the Investigator. 
Any changes in cholinesterase inhibitor will be recorded on the concomitant medication eCRF. 
9.2.1.1.2. Immunosuppressive Agents 
• Immunosuppressive agents, eg, corticosteroid, azathioprine (AZA), mycophenolate 
mofetil (MMF), methotrexate (MTX), tacrolimus, cyclosporine, or cyclophosphamide 
at the appropriate dose level to be used for an individual subject will be permitted at 
the discretion of the Investigator.  
Immunosuppressant therapy dose/schedule changes will be permitted due to 
intolerance or if medically indicated, at the discretion of the Investigator. Reductions 
in IST dosing should be performed slowly, and preferably only after the subject has 
been in the extension study for at least 12 weeks. Any changes in IST will be 
recorded on the concomitant medication eCRF. 
• High dose steroid as an On-Trial Rescue Therapy should be reserved for subjects that 
experience Clinical Deterioration as defined by this protocol. The rescue therapy used 
for a particular subject will be at the discretion of the Investigator. Every effort 
should be made to notify the Sponsor within 24 hours should a subject require a 
rescue therapy. 
9.2.1.1.3. Plasma Exchange / Plasmapheresis / IVIg 
• Plasma Exchange or IVIg will be allowed as On-Trial Rescue Therapy for subjects 
that experience a Clinical Deterioration as defined by this protocol. The rescue 
therapy used for a particular subject will be at the discretion of the Investigator.  
• Every effort should be made to notify the Sponsor within 24 hours should a subject 
require a rescue therapy. Routine use of Plasma Exchange or IVIg as maintenance 
therapy to control MG symptoms outside of rescue is not permitted. 
• If PE is administered, supplemental IP (2 vials) will be administered within 1 to 2 
hours after the end of each PE session unless the PE session is on the day of a 
scheduled IP infusion. Routine (per protocol schedule) IP administration will be 
continued per the specified dose-administration schedule for the subject (refer to 
appropriate Schedule of Assessments in Section 7.1). If the subject is scheduled to 
receive the protocol-scheduled dose on the day of a PE session, then the scheduled 
dose (instead of the supplemental dose) should be administered within 1 to 2 hours 
after the end of the PE session. 
9.2.2. 
Disallowed Medications 
The use of rituximab is prohibited during the trial.  
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9.3. 
Treatment Compliance 
The infusion of IP into subjects will be under the supervision of the Investigator or their designee 
to ensure that the subject received the appropriate dose at the appropriate time-points during the 
trial.  
Subjects who fail to return for a scheduled visit within the acceptable intervals must be contacted 
by the site study staff to determine the reason for missing the appointment. Instructions for 
handling of missing visits are provided in Section 7.3.  
9.4. 
Randomization  
To preserve the blinded nature of the ECU-MG-301 trial, all subjects must undergo a 4-week 
Blind Induction Phase prior to entering the open-label phase of this trial. Subjects who had been 
randomized to the placebo arm in the ECU-MG-301 trial will receive 4 vials of IP 
(3 vials/900 mg eculizumab plus 1 vial placebo) every week at Visits 1 through 4. Subjects who 
were randomized to the eculizumab arm in the ECU-MG-301 trial will receive 4 vials IP 
(1200 mg eculizumab) every 2 weeks at Visits 1 and 3 and placebo at Visits 2 and 4.  
During the Open-Label Maintenance Phase, all subjects will receive open-label eculizumab 
(4 vials/1200 mg) every other week starting with Visit 5 and continuing throughout the trial. 
The patient identification number and study drug kits assignation will be provided by the IXRS. 
9.5. 
Blinding and Unblinding 
All patients will receive eculizumab in this study, including during the 4-week Blind Induction 
Phase (Visits 1 to 4), and during the Open-Label Maintenance Phase (Visits 5 to 107).  
During the Blind Induction Phase, all patients, investigational site personnel, Sponsor staff, 
Sponsor designees, and all staff directly associated with the conduct of the trial will be blinded to 
the subject treatment assignments. The double-blind will be maintained by using identical IP kits 
and labels for eculizumab and placebo. The placebo will have an identical appearance to that of 
eculizumab.  
There is no antidote to reverse the effects of eculizumab; therefore unblinding would not be 
helpful in the planning of patient treatment for a given event. Unblinding should only be 
considered for the safety of the subject. If unblinding is deemed necessary by the Investigator, 
the Investigator can unblind the patient’s treatment allocation using IXRS. The Investigator must 
note the date, time and reason for unblinding. 
The Investigator should inform the Sponsor that the patient was unblinded, however they are not 
required to reveal to the Sponsor the patients’ treatment allocation. 
When an AE is an unexpected related SAE, the blind will be broken by the Sponsor only for that 
specific subject. The blind will be maintained for persons responsible for the ongoing conduct of 
the study (such as the management, monitors, investigators, etc.) and those responsible for data 
analysis and interpretation of results at the conclusion of the study, such as biometrics personnel. 
Unblinded information will only be accessible to those who need to be involved in the safety 
reporting to Health Authorities, Ethics Committees, and/or IRBs. 
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Investigators will receive only blinded information unless unblinded information is judged 
necessary for safety reasons. 
After the Blind Induction Phase, the remainder of the study is open-label; therefore, unblinding is 
not applicable.  
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10. 
INVESTIGATIONAL PRODUCT MATERIALS AND 
MANAGEMENT 
10.1. 
Investigational Product 
Each vial of IP contains eculizumab 300 mg or matching placebo (used only during Blind 
Induction Phase) for IV administration.  
10.2. 
Investigational Product Packaging and Labeling 
The active IP, eculizumab, is manufactured and supplied by Alexion in single 30 mL vials as a 
solution concentration of 10 mg/mL. The placebo is manufactured by Alexion Pharmaceuticals, 
Inc. as a matching sterile, clear, colorless solution in an identical 30-mL vial and without active 
ingredient but with the same buffer components as eculizumab. 
All IP will be prepared in vials, packaged in kits, and labeled at Almac Clinical Services in an 
identical manner. Almac Clinical Services or its affiliate will ship the IP and release to each 
participating trial center upon receipt of all required essential documents based upon federal, 
state, and local regulations. 
Table 11 provides detailed information for both eculizumab and the placebo. For additional 
information on eculizumab, refer to the current IB.  
Table 11: 
Investigational Product 
 
Investigational Product 
Product Name 
Eculizumab 
Placebo 
Dosage Form 
Concentrated solution for infusion 
Solution for infusion 
Unit Dose 
300 mg 
0 mg 
Route of Administration 
Intravenous infusion 
Intravenous infusion 
Physical Description 
30 mL vial 
30 mL vial 
Manufacturer 
Alexion Pharmaceuticals, Inc. 
Alexion Pharmaceuticals, Inc. 
10.3. 
Investigational Product Storage 
IP will be released to the site upon receipt of all required essential documents based upon 
federal, state, and local regulations. Each kit will have a 1-panel label describing the contents and 
a place for the pharmacist to record the subject number and initials.  
Upon arrival at the center, the IP should be promptly removed from the shipping cooler and 
stored in refrigerated conditions at 2 to 8°C in the original package in order to protect from light. 
The pharmacist should immediately record the reception of the IP in IXRS and notify the 
distributor and Sponsor if vials are damaged and/or if temperature excursions have occurred 
during transportation (please refer to the Pharmacy Manual for detailed instructions). IP must be 
stored in a secure, limited-access storage area with controlled temperature. Temperature must be 
recorded on a daily basis. 
Diluted solutions of IP are stable for 24 hours at 2 to 8°C (36 to 46°F) and at room temperature. 
The 24 hours start from the time of IP preparation until the end of infusion. 
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10.4. 
Investigational Product Preparation 
Infusions of IP should be prepared using aseptic technique. Each vial of IP contains 300 mg of 
active ingredient in 30 mL of product solution or matching placebo.  
Withdraw the required volume of IP from the vials. Transfer the recommended dose to an 
infusion bag. Dilute the IP by addition to the infusion bag of the appropriate amount (equal 
volume) of 1 of the following: 0.9% Sodium Chloride Injection, USP; 0.45% Sodium Chloride 
Injection, USP; 5% Dextrose in Water Injection, USP; or Ringer’s Injection, USP. The final 
volume of diluted IP solution is 240 mL for 900 mg doses (3 vials eculizumab plus 1 vial 
placebo) and 1200 mg doses (4 vials eculizumab), and 120 mL for 600 mg doses (2 vials 
eculizumab) (Table 12).  
Table 12: 
Investigational Product Reconstitution  
Trial Phase 
IP 
Volume of IP 
Volume of 
Diluent1 
Total Volume of 
Administration 
Blind Induction Phase 
900 mg (3 vials) eculizumab plus 
1 vial placebo 
90 mL 
30 mL 
90 mL 
30 mL 
240 mL 
 
1200 mg (4 vials) eculizumab 
120 mL 
120 mL 
240 mL 
Maintenance Phase 
1200 mg (4 vials) eculizumab 
120 mL 
120 mL 
240 mL 
Supplemental Dose2 
600 mg (2 vials) eculizumab 
60 mL 
60 mL 
120 mL 
1 Use one of the following diluents: (a) 0.9% sodium chloride; (b) 0.45% sodium chloride; (c) 5% dextrose in water; (d) Ringer’s 
injection. 
2 Supplemental dose that is not administered on a scheduled visit. 
 
Gently agitate the infusion bag containing the diluted IP solution to ensure thorough mixing of 
the product and diluents. Discard any unused portion left in a vial, as the product contains no 
preservatives. The diluted solution should be allowed to warm to room temperature by exposure 
to ambient air prior to administration.  
Refer to the Pharmacy Manual for additional information.  
10.5. 
Administration 
DO NOT ADMINISTER AS AN IV PUSH OR BOLUS INJECTION  
IP should only be administered via IV infusion; the infusion will be administered after 
completion of all other tests and procedures (excluding the peak blood sampling for PK/PD and 
free C5 assay). Prior to administration, the diluted solution should be allowed to warm to room 
temperature by exposure to ambient air. The diluted solution must not be heated in a microwave 
or with any heat source other than ambient air temperature. Parenteral drug products should be 
inspected visually for particulate matter and discoloration prior to administration.  
The diluted IP should be intravenously administered over approximately 35 minutes (range of 
25 to 45 minutes). It is not necessary to protect the infusion bags from light while IP is being 
administered to the subject. At the site’s discretion, the diluted IP may be administered via 
gravity feed, a syringe-type pump, or an infusion pump. The subjects will be monitored for at 
least 1 hour following infusion.  
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If an AE occurs during the administration of the IP, the infusion may be slowed or stopped at the 
discretion of the Investigator, depending upon the nature and severity of the event; however, the 
overall duration should not exceed 2 hours from the start of the infusion. The AE must be 
captured in the subject’s source document and eCRF. 
10.6. 
Investigational Product Accountability 
When an IP shipment is received at the site, the pharmacist should verify the contents, sign the 
packing invoice provided with the shipment, and maintain the original copy for review by the 
trial monitor. A signed copy should be faxed to the contact provided on the packing list and the 
duplicate copy kept in the pharmacy binder. Additionally, reception of IP (as well as reception 
conditions) must be reported to the IXRS system to allow drug randomization, resupply, 
estimations, and drug expiration control.  
Accountability logs and Inventory logs will be provided to assist the pharmacist in maintaining 
current and accurate inventory records covering receipt, dispensing, and disposition of the IP. 
During the trial, the following information must be noted in the accountability log: the subject 
number(s), initials of subject(s) to whom drug is dispensed, kit number, the date(s) and time that 
the IP is prepared and dispensed, and the initials of the pharmacist or designee who prepared the 
IP. Sites should keep a running total of their drug supply. Empty vials and vials with residual 
materials should be kept for inspection and accountability by the trial monitor prior to their 
destruction and handled per local site pharmacy standard operating procedures for clinical IPs. 
Destruction of used and unused vials, either locally or centrally, must be properly documented.  
Each kit will have a label and a place for the pharmacist to record the subject number and 
initials.  
The trial monitor will examine the inventory during the study. Additionally, the inventory 
records must be readily available and may be subject to regulatory authorities, the local 
regulatory agency, or an independent auditor’s inspection at any time. 
Refer to the Pharmacy Manual for additional information.  
10.7. 
Investigational Product Handling and Disposal 
At the completion of the trial, in order to satisfy regulatory requirements regarding IP 
accountability, all remaining IP inventory will be reconciled and retained, returned, or destroyed 
according to applicable provincial and federal regulations. 
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11. 
ASSESSMENT OF EFFICACY 
This extension trial is designed to provide the subjects who have participated in the 
ECU-MG-301 trial with an opportunity to receive eculizumab and to collect clinical data that 
will provide long term safety and tolerability information on eculizumab. Efficacy is a secondary 
objective of this trial. The long-term efficacy of eculizumab in subjects with refractory gMG will 
be measured by the improvement in the MG-ADL total score. Duration of treatment commences 
with the first infusion of IP (eculizumab). The Schedule of Assessments (refer to Section 7.2) 
defines the 4-year trial time period and assessments for the study efficacy endpoints. Efficacy 
will be assessed comparing eculizumab outcomes to placebo outcomes in the protocol ECU-MG-
301. Statistical analyses of the efficacy endpoints are summarized in Section 15 and described in 
more detail in the Statistical Analysis Plan (SAP). For all scales noted below except the 
EuroQOL Visual Analog Scale (EQ-VAS) and MGFA PIS, the higher the score the greater the 
impairment. 
11.1. 
Efficacy Endpoints 
The primary efficacy endpoint is the change from baseline in the MG-ADL total score. The 
secondary efficacy endpoints include: 
1. Change from baseline in QMG total score 
2. Proportion of subjects with at least a 3-point reduction in the MG-ADL total score from 
baseline and with no rescue therapy 
3. Proportion of subjects with at least a 5-point reduction in the QMG total score from 
baseline and with no rescue therapy 
4. Change from baseline in the Myasthenia Gravis Composite (MGC) scale total score 
5. Change from baseline in MG-QOL-15 
The tertiary efficacy endpoints for this trial include: 
1. Time to response as measured by the reduction in the MG-ADL total score (3-point 
reduction from baseline) 
2. Change from baseline in Neuro- QOL Fatigue 
3. Change from baseline in EQ-5D 
4. Change from baseline in the MG-ADL individual items and sub-categories for the bulbar 
(items 1, 2, and 3), respiratory (item 4), limb (items 5 and 6) and ocular (items 7 and 8) in 
subjects with abnormal baseline scores for the particular item or sub-categories 
11.2. 
MG Activities of Daily Living Profile (MG-ADL)  
The MG-ADL is an 8-point questionnaire that focuses on relevant symptoms and functional 
performance of ADL in MG subjects (refer to Appendix 2). The 8 items of the MG-ADL were 
derived from symptom-based components of the original 13-item QMG to assess disability 
secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb 
(2 items) impairment related to effects from MG. In this functional status instrument, each 
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response is graded 0 (normal) to 3 (most severe). The range of total MG-ADL score is 0 to 24. 
The recall period for MG-ADL is the preceding 7 days. MG-ADL will be performed by a 
properly trained evaluator at the protocol specified time points and preferably by the same 
evaluator each time throughout the study.  
11.3. 
QMG Scoring System  
The current QMG scoring system consists of 13 items: ocular (2 items), facial (1 item), bulbar 
(2 items), gross motor (6 items), axial (1 item), and respiratory (1 item); each graded 0 to 3, with 
3 being the most severe (refer to Appendix 1). The range of total QMG score is 0 to 39. The 
QMG scoring system is considered to be an objective evaluation of therapy for MG and is based 
on quantitative testing of sentinel muscle groups. The MGFA task force has recommended that 
the QMG score be used in prospective studies of therapy for MG (Benatar 2012). The QMG 
shall be administered at approximately the same time of day throughout the study by a properly 
trained evaluator at the protocol specified time points and preferably by the same evaluator each 
time throughout the study. 
11.4. 
MGC Score  
The MGC is a validated assessment tool for measuring clinical status of subjects with MG 
(Burns 2011). The MGC assesses 10 important functional areas most frequently affected by MG: 
ocular (2 items), facial (1 item), bulbar (3 items), respiratory (1 item), axial (1 item), and gross 
motor (2 items) (refer to Appendix 7). The scales are weighted for clinical significance that 
incorporates subject-reported outcomes. Higher scores indicate more functional impairment. The 
range of total MGC score is 0 to 50. The MGC shall be administered at approximately the same 
time of day throughout the study by a properly trained evaluator at the protocol specified time 
points and preferably by the same evaluator each time throughout the study. 
11.5. 
Quality of Life Assessments  
11.5.1. 
MG-QOL 15  
The 15-item Myasthenia Gravis Qualify of Life scale (MG-QOL 15; refer to Appendix 3) is a 
health-related quality of life evaluative instrument specific to subjects with MG. MG-QOL 15 
was designed to provide information about subjects’ perception of impairment and disability and 
the degree to which disease manifestations are tolerated and to be easy to administer and 
interpret (Burns 2011). The MG-QOL 15 will be completed by the subject. Higher scores 
indicate greater extent of and dissatisfaction with MG-related dysfunction.  
11.5.2. 
Neuro-QOL Fatigue  
The Neuro-QOL Fatigue is a reliable and validated brief 19-item survey of fatigue, completed by 
the subject (Cella 2010). Higher scores indicate greater fatigue and greater impact of MG on 
activities (refer to Appendix 4).  
11.5.3. 
EUROQOL  
The EQ-5D is a reliable and validated survey of health status in 5 areas: mobility, self-care, usual 
activities, pain/discomfort, and anxiety/depression, completed by the subject (Szende 2004) . 
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Each area has 3 levels: Level 1 (no problems), Level 2 (some problems), and Level 3 (extreme 
problems; refer to Appendix 10). The EQ VAS records the subject’s self-rated health on a 
vertical, 20 cm visual analogue scale where the endpoints are labeled “best imaginable health 
state,” marked as 100 and “worst imaginable health state,” marked as 0.  
11.6. 
Other Efficacy Assessments 
11.6.1. 
Negative Inspiratory Force (NIF) and Forced Vital Capacity (FVC)  
Subjects with increasingly severe MG can suffer from potentially fatal respiratory complications 
including profound respiratory muscle weakness. Respiratory function is monitored closely for 
evidence of respiratory failure in MG subjects and ventilator support is recommended in the 
event of consistent declines in serial measurements of FVC or NIF, loss of upper airway integrity 
(difficulty handling oral secretions, swallowing, or speaking) or in the setting of emerging 
respiratory failure. FVC as one of the test items in QMG will be performed when QMG is 
performed. NIF is to be performed using the NIF Meter.  
11.6.2. 
MGFA Post-Intervention Status  
The MG clinical state will be assessed using the MGFA Post-Intervention Status. Change in 
status categories of Improved, Unchanged, Worse, as well as Minimal Manifestation (MM) and 
Pharmacological Remission (PR) will be assessed and recorded by the PI or the same neurologist 
skilled in the evaluation of MG subjects throughout the trial. The sub-scores of MM (ie, MM-0, 
MM-1, and MM-3) will not be used in this protocol. For the purposes of assessing MGFA-PIS 
status in this study, Baseline is defined as the pre-treatment baseline of ECU-MG-301. 
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12. 
ASSESSMENT OF SAFETY 
12.1. 
Safety Parameters 
12.1.1. 
Vital Signs 
Vital signs will be measured at every visit and will include assessments of systolic and diastolic 
BP, temperature, RR, and HR. Vital signs will be obtained after the subject has been supine or 
seated for at least 5 minutes. Ideally, each subject’s BP should be measured using the same arm. 
Systolic and diastolic BPs will be documented in mmHg. Temperature will be obtained in 
degrees Celsius or Fahrenheit. HR will be documented in beats per minute. 
12.1.2. 
Weight  
Body weight will be measured in pounds or kilograms. Body weight will be measured at Visits 1, 
16, 29, 55, 81, and 107 or ET Visit.  
12.1.3. 
Physical Examination 
A complete physical examination will be performed at Visit 16. The complete physical 
examination will include assessments of the following organ/body systems: skin, head, ears, 
eyes, nose, throat, neck, lymph nodes, chest, heart, abdomen, extremities, and general neurologic 
examination. For consistency, all efforts should be made to have the physical examination 
performed by the same qualified study staff. 
12.1.4. 
Electrocardiogram 
A 12-lead ECG will be conducted at Visits 1, 16, 29, 55, 81, and 107 or ET Visit. The 
Investigator or designee will be responsible for reviewing the ECG to assess whether the ECG is 
within normal limits and to determine the clinical significance of the results. These assessments 
will be indicated on the CRF. For any clinically significant abnormal ECG results, the 
Investigator must contact the Sponsor to discuss the subject’s continued eligibility to participate 
in this protocol. 
12.1.5. 
Laboratory Assessments 
Subjects will have biologic samples collected for analysis of various parameters according to the 
Schedule of Assessments (refer to Section 7.2). The central laboratory will supply established or 
generally acknowledged methods, normal reference ranges, and shipping instructions.  
Chemistry panel, complete blood count and hemolytic markers, renal function measures, and 
serum pregnancy test (refer to Appendix 5 for details) will be prepared and shipped according to 
the instructions in the laboratory manual to the central laboratory. Samples will be analyzed at 
the central laboratory. Routine hematology laboratory assessment, including complete blood 
count (CBC), will be performed at various time points as specified by the protocol and should be 
reviewed as soon as the laboratory result is available.  
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Blood samples for PK, PD, free C5, and blood samples for ADA analysis will be prepared and 
shipped according to the instructions in the laboratory manual to the central laboratory. Sample 
analysis will be conducted by the Sponsor or Sponsor’s designee.  
Samples for AChR Abs test will be prepared and shipped according to the instructions in the 
laboratory manual. Sample analysis will be conducted at the central laboratory.  
Any clinically significant, abnormal laboratory result is to be reported as an AE. 
12.1.6. 
Columbia-Suicidal Severity Rating Scale 
The C-SSRS (Posner 2011)since Last Visit (refer to Appendix 9) will be performed by the 
Investigator or a trained designee according to the Schedule of Assessments (refer to 
Section 7.2). The “since last visit” period refers to the last visit the C-SSRS was administered. 
This is to ensure that subjects who are experiencing suicidal ideation or behavior are properly 
recognized and adequately managed or referred for further evaluation. 
12.2. 
Adverse Events 
12.2.1. 
Detection of Adverse Events 
The Investigator is responsible for detecting, assessing, documenting, and reporting of all AEs. 
Adverse Events reported by the subject and/or parent or legal guardian and/or identified in 
response to an open-ended question from study personnel or revealed by observation, physical 
examination, or other study procedures must be collected and recorded as described in 
Section 12.2.3. 
12.2.2. 
Definition of an Adverse Event 
Adverse event means any untoward medical occurrence in a subject or clinical trial subject 
administered a medicinal product and which does not necessarily have a causal relationship with 
this treatment. 
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding, for example), symptom, or disease temporally associated with the use of a medicinal 
product, whether or not considered related to the medicinal product. 
Exacerbation of a chronic or intermittent pre-existing condition including either an increase in 
frequency and/or intensity of the condition, and abnormal laboratory findings that are considered 
to be of clinical significance are all to be considered AEs. 
The definition of AE also covers medication errors and uses outside what is foreseen in the 
protocol, including misuse and abuse of the product. 
Situations where an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital), and anticipated day-to-day fluctuations of pre-existing disease(s) or 
condition(s) present or detected at the start of the study that do not worsen are not AEs. 
12.2.2.1. Procedure 
Elective procedures that were pre-planned prior to the time that written ICF was obtained are not 
AEs. Any complication or worsening of a pre-existing condition leading to the procedure must 
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be considered an AE. In addition, any AE that could occur as an outcome of the planned 
procedure should be considered as an AE. 
Diagnostic and therapeutic procedures (invasive and non-invasive) such as surgery or 
angiography should not be reported as an AE or Serious Adverse Event (SAE). However, the 
medical condition or the diagnosis that was responsible for the procedure should be recorded. 
The procedure should be recorded in the narrative as treatment for the AE or SAE 
(eg, laparoscopic cholecystectomy is the procedure or treatment for an SAE of necrotic gall 
bladder). 
12.2.2.2. Abnormal Test Findings 
Abnormal test findings may be considered AEs or SAEs; however, Investigators are strongly 
encouraged to report the diagnosis, sign, or symptom instead of just the abnormal result. The 
criteria for an abnormal test finding being classified as an AE or SAE are as follows: 
• Test result is associated with a sign or symptom 
• Test result requires additional diagnostic testing 
• Test result requires a medical or surgical intervention 
• Test result leads to a change in study dosing outside of the protocol defined dosing or 
discontinuation from the trial 
• Test result requires significant additional treatment (ie, addition of new medication, 
significant increase in dose of current medication) 
12.2.2.3. Lack of Efficacy 
Since eculizumab treatment in subjects with refractory gMG is not an approved indication, lack 
of efficacy need not be reported as an AE.  
12.2.2.4. Events of Interest (EOI) 
Events of Interest (EOI) will be identified by the Sponsor during the evaluation of safety data for 
the Clinical Study Report. Significant AEs of particular clinical importance, other than SAEs and 
those AEs leading to discontinuation of the subject from the trial, will be classified as EOIs. For 
each EOI, a narrative may be written and included in the Clinical Study Report. 
12.2.3. 
Recording Adverse Events 
All observed or volunteered AEs regardless of causal relationship must be recorded and reported 
as described in the Section 12.2.7.  
As this is an extension to the ECU-MG-301 trial, subjects may sign the ICF for the extension 
trial while still enrolled in the ECU-MG-301 trial. AEs with an onset date before Study Day 1 of 
ECU-MG-302 will be recorded in the eCRF of the ECU-MG-301 trial regardless of when the 
subject signed the ICF for the ECU-MG-302 trial. Any ongoing AEs at the time of Study Day 1 
of the ECU-MG-302 trial will be recorded in the ECU-MG-302 eCRF (since this will be done 
automatically by the system, sites will not be required to record these data twice). AEs with an 
end date before Study Day 1 of ECU-MG-302 will be recorded only on the ECU-MG-301 CRF. 
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For all AEs the investigator must obtain adequate information for the following: 1) determine the 
outcome of the AE; 2) determine if the event meets criteria for a SAE; 3) assess the severity of 
the AE; and 4) determine the causality of the AE. For all AEs regardless of casual relationships 
the instigator must follow-up on the outcome of the event until the event or sequelae either 
resolve or stabilize. 
AEs spontaneously reported by the subject, and/or parent or legal guardian and/or identified in 
response to an open-ended question from study personnel, or revealed by observation will be 
recorded during the study period by the Investigator. AE information will be collected from the 
signing of informed consent until 8 weeks after the last dose of IP (safety follow-up visit). No 
time limit exists on reporting SAEs that are thought to be causally related to the IP. 
AEs must be documented in clear, unambiguous medical terms. Study personnel are advised not 
to use abbreviations or acronyms.  
For each AE record only the diagnosis on the AE page of eCRF, do not report the characteristic 
signs and symptoms of the diagnosis as additional AEs.  
If a diagnosis is not available record each sign and symptom as an AE, when a diagnosis 
becomes available, study personnel are to update the AE page of the eCRF with relevant 
diagnosis only. 
All AEs that later increase in the frequency and or severity (medical and scientific judgment 
should be exercised by the Investigator) will be considered new AEs and will be recorded on a 
new line on the AE page or the eCRF. 
Initial AE should be closed-out with an end date consistent with the date that the AE increased in 
frequency and/or severity and the new AE recorded on a new line of the AE page with onset date 
consistent with the date of increase in frequency and or severity. 
If an AE is a chronic or long-term medical condition diagnosed during the study (eg, 
hypertension, diabetes), once the patient is medically stable and/or a treatment plan is in place 
for the condition, the AE should be closed out with the end date consistent with the patient’s 
stability and/or the implementation of the treatment plan.  
12.2.4. 
Serious Adverse Event and SAE Criteria 
Any AE that fulfills any 1 of the criteria listed below must be recorded as an SAE. An SAE 
(experience) or reaction is described as any untoward medical occurrence that at any dose: 
1. Results in death 
2. Is life-threatening 
NOTE: The term "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. Hospitalization (Requires inpatient hospitalization or prolongation of existing 
hospitalization, [AEs that are associated with hospitalization or prolongation of 
hospitalization are considered SAEs]. All admissions to a health care facility meet this 
criteria, even if less than 24 hours. Criteria for seriousness are also met if transfer within 
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the hospital is done to receive more intense medical / surgical care [eg, medical floor to 
the intensive care unit (ICU)]) 
• Hospitalization does not include the following: 
− Rehabilitation facility 
− Hospice facility 
− Nursing facility 
− Emergency Room 
− Same day surgery 
• Hospitalization or prolongation of hospitalization not associated with an AE and is 
not an SAE, examples include: 
− Admission for a pre-existing condition not associated with either a new AE or 
with worsening of a pre-existing AE 
− Protocol-specified admission, pre-planned admission 
4. Results in persistent or significant disability/incapacity 
5. Is a congenital anomaly/birth defect 
6. Is an important medical event 
NOTE: Medical and scientific judgment should be exercised in deciding whether expedited 
reporting is appropriate in other situations, such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization, but may jeopardize the subject 
or may require intervention to prevent one of the other outcomes listed in the definition above. 
These should also usually be considered SAEs. Examples of such events are intensive treatment 
in an emergency room or at home for allergic bronchospasm; blood dyscrasias or convulsions 
that do not result in hospitalization; or development of drug dependency or drug abuse. 
12.2.4.1. Severity Assessment 
Adverse Event severity will be rated by the Investigator as mild, moderate, or severe using the 
following criteria: 
• Mild: events require minimal or no treatment and do not interfere with the subject’s 
daily activities. 
• Moderate: events result in a low level of inconvenience or concerns with the 
therapeutic measures. Moderate events may cause some interference with 
functioning. 
• Severe: events interrupt a subject’s usual daily activity and may require systemic drug 
therapy or other treatment. Severe events are usually incapacitating. 
Change in severity of an AE should be documented based on specific instructions in the eCRF 
Completion Guidelines. 
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Severity and seriousness must be differentiated. Severity describes the intensity of an AE, while 
the term seriousness refers to an AE that has met the criteria for an SAE. 
12.2.4.2. Causality Assessment 
An Investigator causality assessment (Unrelated, Unlikely, Possible, Probable, or Definite) must 
be provided for all AEs, both serious and non-serious. This assessment must be recorded in the 
CRF and any additional SAE forms as appropriate. The definitions for the causality assessments 
appear below. 
• Not related (unrelated): This relationship suggests that there is no association between 
the IP and the reported event. 
• Unlikely related: This relationship suggests that the clinical picture is highly 
consistent with a cause other than the IP but attribution cannot be made with absolute 
certainty and a relationship between the IP and AE cannot be excluded with complete 
confidence. 
• Possibly related: This relationship suggests that treatment with the IP may have 
caused or contributed to the AE, ie, the event follows a reasonable temporal sequence 
from the time of drug administration and/or follows a known response pattern to the 
IP, but could also have been produced by other factors. 
• Probably related: This relationship suggests that a reasonable temporal sequence of 
the event with the IP administration exists and the likely association of the event with 
the IP. This will be based upon the known pharmacological action of the IP, known or 
previously reported adverse reactions to the IP or class of drugs, or judgment based 
on the Investigator’s clinical experience. 
• Definitely related: Temporal relationship to the IP, other conditions (concurrent 
illness, concurrent medication reaction, or progression/expression of disease state) do 
not appear to explain the event, corresponds with the known pharmaceutical profile, 
improvement on discontinuation or re-appearance on re-challenge. 
12.2.5. 
Expectedness Assessment of Serious Adverse Event 
The expectedness of a SAE is determined by the sponsor in the reference safety information 
(RSI). The RSI for interventional studies is the Investigator’s Brochure. 
12.2.6. 
Outcome 
If a subject experiences a SAE with an outcome of death:  
• The SAE resulting in death should have an outcome documented as death/fatal with 
an end date being the date of death. 
• If the subject had additional AE/SAEs that were ongoing at the time of death, these 
events would be documented as ongoing with no end date. 
• Only one event should have an outcome of death/fatal unless an autopsy report or 
investigator states otherwise. 
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12.2.6.1. Exposure during Pregnancy and Lactation 
Pregnancy data will be collected during this trial for all subjects. 
For all Alexion products, both in development or post approval, exposure during pregnancy must 
be recorded and followed. Exposure during pregnancy also called exposure in-utero (EIU) can be 
the result of either maternal exposure or transmission of drug product via semen following 
paternal exposure. 
If a subject within this trial or a subject’s partner becomes or is found pregnant while treated or 
exposed to IP, the investigator must submit a pregnancy form to Alexion via the same method as 
SAE reporting. Pharmacovigilance will supply the Investigator with a copy of a “Pregnancy 
Reporting and Outcome Form / Breast Feeding.”  Pharmacovigilance must be notified via the 
same method as SAE reporting. 
Exposure of an infant to an Alexion product during breastfeeding would need to be reported in 
the “Pregnancy Reporting and Outcome Form / Breast Feeding,” and any AEs an infant may 
experience following breastfeeding needs to be reported to the Sponsor. 
The subject or female partner should be followed until the outcome of the pregnancy is known 
(spontaneous miscarriage, elective termination, normal birth, or congenital abnormality), even if 
the subject discontinued IP or discontinues from the trial. When the outcome of the pregnancy 
becomes known the form should be completed and returned to the Sponsor. If additional follow-
up is required, the Investigator will be requested to provide the information. 
Pregnancy in itself is not regarded as an AE unless there is a suspicion that IP may have 
interfered with the effectiveness of a contraceptive medication. However, complications of 
pregnancy and abnormal outcomes of pregnancy are AEs and many may meet criteria for a SAE. 
Complications of pregnancy and abnormal outcomes of pregnancy such as ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly would 
meet criteria of an SAE and thus, should be reported as an SAE. Elective abortions without 
complications should not be handled as AEs. 
12.2.7. 
Reporting of Adverse Event(s) & Serious Adverse Event(s) to Sponsor 
All non-serious AEs must be recorded in the eCRF upon awareness.  
All SAEs must be reported to the Sponsor immediately or within 24 hours of the investigator or 
the site staff becoming aware of the event, regardless of the presumed relationship to the IP. The 
Investigator must complete, sign, and date the SAE pages, verify the accuracy of the information 
recorded on the SAE pages with the corresponding source documents, and send a copy via Email 
or fax to contact information provided below: 
Email:  
  
Fax:   
 
When further information becomes available, the SAE Form should be updated with the new 
information and reported immediately via the same contact information.  
Additional follow-up information, if required or available, should be faxed to the Sponsor within 
24 hours of the investigator site or their staff becoming aware of this additional information via 
same contact information as above. Follow-up information should be recorded on a follow-up 
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SAE eCRF and placed with the original SAE information and kept with the appropriate section 
of the eCRF and/or trial file.  
These reporting timelines need to be followed for all initial SAE cases and follow-up versions of 
the initial cases.  
All SAEs (related and unrelated) will be recorded from the signing of ICF until 8 weeks 
following the end of treatment exposure (follow-up time required depending on half-life of IP 
following the last dose of IP). 
If the event meets fatal or life threatening SAE criteria, the investigator should notify the Sponsor 
immediately. 
For all SAEs the investigator must provide the following: 
• Appropriate and requested follow-up information in the time frame detailed above 
• Causality of the serious event(s) 
• Outcome of the serious event(s) 
• Medical records and laboratory / diagnostic information 
12.2.8. 
Sponsor Reporting Requirements  
The sponsor or legal representative is responsible for notifying the relevant regulatory authorities 
of SAE’s meeting the reporting criteria as per regional and local regulations. 
12.2.9. 
Investigator Reporting Requirements  
The Investigator must fulfill all local regulatory obligations required for study investigators. It is 
the PI’s responsibility to notify the Institutional Review Board (IRB) or Independent Ethics 
Committee (IEC) of all SAEs that occur at his or her site. Investigators will also be notified of all 
unexpected, serious, drug-related events (7/15 Day Safety Reports) that occur during the clinical 
trial. Each site is responsible for notifying its IRB or IEC of these additional SAEs. 
 
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13. 
ASSESSMENT OF BIOMARKER 
13.1. 
MG Disease Biomarker 
Blood samples for assay of the AChR Ab will be collected at specified time points. 
 
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14. 
ASSESSMENT OF PHARMACOKINETICS AND 
PHARMACODYNAMICS 
The population PK analysis of eculizumab in subjects with gMG will be performed to assess the 
concentration of eculizumab versus time. PK parameters such as maximum concentration as well 
as trough and peak eculizumab concentration during the induction and maintenance treatment 
phases will be reported. Clearance and terminal half-life will be estimated. PD analysis will be 
performed to assess pre- and post-treatment serum hemolytic activity and therefore C5 
complement activity inhibition. Free C5 concentration may also be measured. 
 
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15. 
STATISTICS 
15.1. 
General Considerations 
Analyses will be produced using the data from this trial alone (Extension Trial) as well as 
combined analyses that will include data from the ECU-MG-301 trial (Combined Trial 
Analyses). The analyses will include safety, efficacy, and PK/PD analyses. The SAP will cover 
both the standalone trial analyses and the combined ECU-MG-301 and ECU-MG-302 trial 
analyses. 
Treatment groups will be indicated by eculizumab/eculizumab for the subjects originally 
randomized to the eculizumab arm in the ECU-MG-301 trial and placebo/eculizumab for the 
subjects originally randomized to the placebo arm in the ECU-MG-301 trial. The Extension Trial 
analyses will be presented by treatment group. The Combined Trial Analyses, where the data is 
aligned based on the subject’s first dose date of eculizumab, will only be presented as 
1 combined eculizumab treatment group since all subjects will have received eculizumab. 
Baseline for the Extension Trial analyses is defined as the last available assessment prior to 
starting treatment with eculizumab in ECU-MG-302. Baseline for the Combined Trial Analyses 
is defined as the last available assessment prior to starting treatment with eculizumab (that is, 
either in the ECU-MG-301 for subjects who received eculizumab in the ECU-MG-301 trial or in 
the ECU-MG-302 trial for subjects who received placebo in the ECU-MG-301 trial). For the 
Combined Trial Analyses, the analysis visits will be determined counting the subject’s first dose 
date (Day 1) with eculizumab regardless of the trial in which that first dose of eculizumab 
occurred and defining the visits based on this Day 1 going forward according to the schedule of 
assessments in both studies. 
15.2. 
Determination of Sample Size 
This is an extension trial to the ECU-MG-301 trial. Approximately 92 subjects will be enrolled 
in the ECU-MG-301 trial and may participate in this trial.  
15.3. 
Analyses Sets 
15.3.1. 
Full Analysis Set (FAS) 
15.3.1.1. Extension FAS Population  
The population on which primary, secondary, and tertiary efficacy analyses will be performed 
consists of all subjects who have received at least 1 dose of eculizumab in this extension trial and 
have a post-trial drug infusion efficacy assessment. 
15.3.1.2. Combined FAS Population 
The population on which primary, secondary, and tertiary efficacy analyses will be performed 
consists of all subjects who have received at least 1 dose of eculizumab in either ECU-MG-301 
or ECU-MG-302 and have a post-trial drug infusion efficacy assessment. 
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15.3.2. 
Per Protocol Set 
15.3.2.1. Extension Per-Protocol (PP) Population 
The PP population is a subset of the Extension Trial FAS population, excluding subjects with 
major extension trial protocol deviations. The Extension Trial PP population will include all 
subjects who: 
• Have no major protocol deviations or inclusion/exclusion criteria deviations that 
might potentially affect efficacy, and  
• Subjects who took at least 80% of the required eculizumab doses during participation 
in the extension trial. 
15.3.2.2. Combined PP Population  
The Combined PP population is a subset of the Combined FAS population, excluding subjects 
with major protocol deviations from either the ECU-MG-301 or ECU-MG-302 trial. The 
Combined PP population will include all subjects who: 
• Have no major protocol deviations or inclusion/exclusion criteria deviations that 
might potentially affect efficacy, and  
• Subjects who took at least 80% of the required eculizumab doses during participation 
in ECU-MG-301 and ECU-MG-302 trials. 
The Extension PP population as well as the Combined PP population will be determined prior to 
database lock. 
15.3.3. 
Safety Set 
Safety analyses will be performed on the Extension Safety Population from the ECU-MG-302 
trial and the Combined Safety Population from both the ECU-MG-301 and ECU-MG-302 trials. 
The Extension Safety Population includes all subjects who receive at least 1 dose of eculizumab 
in the ECU-MG-302 trial. The Combined Safety Population includes all subjects who receive at 
least 1 dose of eculizumab in either the ECU-MG-301 or ECU-MG-302 trial.  
15.3.4. 
Other Set 
PK/PD analyses will be performed on the PK/PD Analysis Set. The PK/PD Analyses Set will 
include subjects who have PK/PD data assessments during this trial.  
15.4. 
Subject Disposition and Treatment Compliance 
The number of subjects treated, completing the trial, and included in the safety and efficacy 
analysis sets will be tabulated by counts and percentage of subjects combined. Reasons for any 
subject withdrawals will be provided.  
Treatment compliance with IP will be summarized using descriptive statistics. The extra usage of 
IP for subjects who are treated with PE during the trial will be summarized and listings will be 
produced. 
Page 88 of 114 
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ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
15.5. 
Prior and Concomitant Medications 
Medications will be coded using the World Health Organization Drug Dictionary (WHO drug), 
the most current version available at the time of the analyses. 
15.5.1. 
Extension Trial Analyses 
Concomitant medications taken during the extension trial will be summarized by treatment group 
and overall. Changes in IST usage (ie, increases, decreases, switching ISTs, etc.) will be 
summarized by treatment group and overall. Prior and concomitant medications will be listed in 
subject listings. 
15.5.2. 
Combined Trial Analyses 
Concomitant medications taken during eculizumab treatment will be summarized.  
15.6. 
Efficacy Analyses 
Efficacy analyses will be performed on the Extension Trial FAS (Extension FAS) population as 
well as the Extension Trial Per-Protocol (Extension PP) population. In addition, efficacy 
analyses will be performed on the Combined FAS population as well as the Combined Per 
Protocol (Combined PP) population from the combined ECU-MG-301 trial and this Extension 
trial. 
15.6.1. 
Primary Efficacy Analyses 
15.6.1.1. Extension Trial Analyses 
The primary efficacy endpoint is the change from baseline in the MG-ADL total score. The 
primary analysis for the change from baseline in MG-ADL total score at a particular visit will be 
based on the repeated measures models with effects for baseline MG-ADL and visit. Since the 
subjects randomized to eculizumab in the ECU-MG-301 study would have already received 26 
weeks of eculizumab treatment, a separate repeated measures model will be fit for the two 
treatment arms: placebo/eculizumab and eculizumab/eculizumab. Confidence intervals and p-
values will be presented by treatment group and visit. Graphical displays over time by treatment 
group will be produced. Missing primary endpoint assessments will not be imputed. 
15.6.1.2. Combined Trial Analyses 
The primary efficacy endpoint is change from baseline in the MG-ADL total score. The primary 
analysis for the change from baseline in MG-ADL total score at a particular visit will be based 
on the repeated measures model with effects for baseline MG-ADL and visit. Confidence 
intervals and p-values will be presented by visit. Graphical displays over time will be produced. 
Missing primary endpoint assessments will not be imputed. 
15.6.2. 
Secondary Efficacy Analyses 
The secondary efficacy endpoints are:  
1. Change from baseline in QMG total score.  
Page 89 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
2. Proportion of subjects with at least a 3-point reduction in the MG-ADL total score from 
baseline and with no rescue therapy. 
3. Proportion of subjects with at least a 5-point reduction in the QMG total score from 
baseline and with no rescue therapy. 
4. Change from baseline in the Myasthenia Gravis Composite (MGC) score. 
5. Change from baseline in MG-QOL15.  
15.6.2.1. Extension Trial Analyses 
The secondary endpoints that involve changes from baseline will be analyzed at a particular visit 
based on the repeated measures models with effects for the particular baseline covariate and 
visit. Since the subjects randomized to eculizumab in the ECU-MG-301 study would have 
already received 26 weeks of eculizumab treatment, a separate repeated measures model will be 
fit for the two treatment arms: placebo/eculizumab and eculizumab/eculizumab. Confidence 
intervals and p-values will be presented by treatment group and visit. Graphical displays over 
time will be produced by treatment group and visit. Missing secondary endpoint assessments will 
not be imputed. 
The proportion of subjects with at least a 3-point reduction in the MG-ADL total score from 
baseline with no rescue therapy will be summarized at each visit for the placebo/eculizumab 
treatment group. Confidence intervals and p-values will be presented. Summaries of the number 
and percentage of subjects that improve, remain the same, or worsen in regard to MG-ADL 
assessments over time will be produced by treatment group as specified in the SAP. Graphical 
displays over time maybe produced by treatment group. 
The proportion of subjects with at least a 5-point reduction in the QMG total score from baseline 
with no rescue therapy will be summarized at each visit for the placebo/eculizumab treatment 
group. Confidence intervals and p-values will be presented. Summaries of the number and 
percentage of subjects that improve, remain the same, or worsen in regard to QMG assessments 
over time will be produced by treatment group as specified in the SAP. Graphical displays over 
time may be produced by treatment group. 
15.6.2.2. Combined Trial Analyses 
The secondary endpoints that involve changes from baseline will be analyzed at a particular visit 
based on the repeated measures model with effects for the particular baseline covariate and visit. 
Confidence intervals and p-values will be presented by visit. Graphical displays over time will be 
produced. Missing secondary endpoint assessments will not be imputed. 
The proportion of subjects with at least a 3-point reduction in the MG-ADL total score from 
baseline with no rescue therapy will be summarized at each visit. Confidence intervals and p-
values will be presented. Summaries of the number and percentage of subjects that improve, 
remain the same, or worsen in regard to MG-ADL assessments over time will be produced as 
specified in the SAP. Graphical displays over time may be produced. 
The proportion of subjects with at least a 5-point reduction in the QMG total score from baseline 
with no rescue therapy will be summarized at each visit. Confidence intervals and p-values will 
be presented. Summaries of the number and percentage of subjects that improve, remain the 
Page 90 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
same, or worsen in regard to QMG assessments over time will be produced as specified in the 
SAP. Graphical displays over time maybe produced. 
15.6.3. 
Tertiary Efficacy Analyses 
The tertiary efficacy endpoints are: 
1. Time to response as measured by the reduction in the MG-ADL total score (3-point 
reduction from baseline ). 
2. Change from baseline in Neuro-QOL Fatigue.  
3. Change from baseline in EQ-5D.  
4. Change from baseline in the MG-ADL individual items and change from baseline in the 
MG-ADL sub-categories for the bulbar (items 1, 2 and 3), respiratory (item 4), limb 
(items 5 and 6) and ocular (items 7 and 8) in subjects with abnormal baseline score for 
the particular item or sub-category. 
15.6.3.1. Extension Trial Analyses 
The time to response on the MG-ADL total score (3-point reduction in MG-ADL from baseline) 
will be summarized for the placebo/eculizumab treatment group. A Kaplan Meier curve will be 
produced. 
The tertiary endpoints that involve changes from baseline will be analyzed at a particular visit 
based on the repeated measures models with effects for the particular baseline covariate and 
visit. Since the subjects randomized to eculizumab in the ECU-MG-301 study would have 
already received 26 weeks of eculizumab treatment, a separate repeated measures model will be 
fit for the two treatment arms: placebo/eculizumab and eculizumab/eculizumab. Confidence 
intervals and p-values will be presented by treatment group and visit. Missing tertiary endpoint 
assessments will not be imputed. 
A summary of subjects shifting from abnormal to normal or from normal to abnormal for NIF 
and FVC will be presented by treatment group and visit. A summary of subjects shifting from 
abnormal to normal or from normal to abnormal for particular MG-ADL individual items and 
sub-categories will be produced by treatment group and visit. 
15.6.3.2. Combined Trial Analyses 
The time to response on the MG-ADL total score (3-point reduction in MG-ADL from baseline) 
will be summarized. A Kaplan Meier curve will be produced. 
The tertiary endpoints that involve changes from baseline will be analyzed at a particular visit 
based on the repeated measures model with effects for the particular baseline covariate and visit. 
Confidence intervals and p-values will be presented by visit. Missing tertiary endpoint 
assessments will not be imputed. 
A summary of subjects shifting from abnormal to normal or from normal to abnormal for NIF 
and FVC will be presented. A summary of subjects shifting from abnormal to normal or from 
normal to abnormal for particular MG-ADL individual items and sub-categories will be 
produced. 
Page 91 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
15.7. 
Safety Analyses 
Safety analyses will be performed on the Extension Safety Population and the Combined Safety 
Population from both studies. The Extension Safety Population includes all subjects who receive 
at least 1 dose of eculizumab in ECU-MG-302 trial. The Combined Safety Population includes 
all subjects who receive at least 1 dose of eculizumab in the ECU-MG-301 trial or ECU-MG-302 
trial. 
15.7.1. 
Physical Examinations and Vital Signs 
Physical examinations will be summarized by visit. Vital signs (systolic and diastolic BP, 
temperature, and sitting or lying HR), weight and changes from baseline in vital signs (including 
weight) will be summarized by visit. Listings of physical examinations and vital signs will be 
produced. 
15.7.2. 
Laboratory Assessments 
15.7.2.1. Extension Trial Analyses 
Changes from Baseline in laboratory assessments (chemistry and hematology) will be 
summarized by treatment group and overall. Shift tables (L [low], N [normal], H [high]) will be 
produced for clinical laboratory tests by treatment group and overall. 
15.7.2.2. Combined Trial Analyses 
Changes from Baseline in laboratory assessments (chemistry and hematology) will be 
summarized. Likewise, shift tables (L [low], N [normal], H [high]) will be produced for clinical 
laboratory tests. 
15.7.3. 
AEs 
15.7.3.1. Extension Trial Analyses 
Onset of AEs on or after the first dose date for eculizumab will be summarized by incidence, 
preferred term, system organ class (SOC), seriousness, severity, and relationship to treatment by 
treatment group and overall. 
15.7.3.2. Combined Trial Analyses 
AEs that occurred on or after the first dose of eculizumab whether in the ECU-MG-301 or this 
extension trial (ECU-MG-302) will be summarized by incidence, preferred term, SOC, 
seriousness, severity, and relationship to treatment. 
15.7.4. 
Columbia-Suicide Severity Rating Scale 
Shift tables for the C-SSRS will be produced for the Extension Trial by treatment group and 
overall. 
15.7.5. 
Other Safety Endpoints 
Pregnancy tests will be summarized in subject listings. Electrocardiogram (ECG) data will be 
summarized for the Extension Trial by treatment group and overall. 
Page 92 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
15.8. 
PK/PD Analyses 
Eculizumab concentrations, free C5 concentrations, and % hemolysis and immunogenicity as 
measured by ADA will be summarized in tabular form as well as a subject listing for both the 
Extension Trial and Combined Trial Analyses by treatment group and overall. A population PK 
and PK/PD analysis may be conducted based on the adequacy of the PK and PD data.  
15.8.1. 
Biomarker Analysis 
Changes from baseline in AChR Ab will be summarized and subject listings for the MG disease 
biomarker data will be created. 
15.9. 
Other Statistical Issues 
15.9.1. 
Significance Levels 
All hypothesis testing will be two-sided and performed at the 0.05 level of significance, unless 
otherwise specified. Estimates of treatment effect on efficacy parameters will be accompanied by 
two-sided 95% confidence intervals for the effect size. 
15.9.2. 
Missing or Invalid Data 
For efficacy and safety analyses, missing post-baseline efficacy and safety data will not be 
imputed unless indicated in the described analyses in the SAP.  
15.9.3. 
Interim Analyses 
Interim statistical analyses for safety and the primary and secondary efficacy endpoints may be 
performed at the discretion of the Sponsor. All analyses will be prospectively defined in the 
statistical analysis plan. The final statistical analyses will be performed after the study ends and 
the database has been locked.  
Page 93 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
16. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
16.1. 
Trial Monitoring 
Before an investigational site can enter a subject into the trial, a representative of Alexion 
Pharmaceuticals, Inc. or its designee will visit the investigational trial site to: 
• Determine the adequacy of the facilities 
• Discuss with the investigator(s) and other personnel their responsibilities with regard 
to protocol adherence, and the responsibilities of the Sponsor or its designee or its 
representatives. This will be documented in a Clinical Trial Agreement between the 
Sponsor or its designee and the Investigator. 
During the trial, the Sponsor, its designee or representative will have regular contacts with the 
investigational site, for the following: 
• Provide information and support to the investigator(s). 
• Confirm that facilities remain acceptable. 
• Confirm that the investigational team is adhering to the protocol, that data are being 
accurately recorded in the CRFs, and that IP accountability checks are being 
performed. 
• Perform source data verification. This includes a comparison of the data in the CRFs 
with the subject’s medical records at the hospital or practice, and other records 
relevant to the trial. This will require direct access to all original records for each 
subject (for example, clinic charts). 
• Record and report any protocol deviations not previously sent to the Sponsor or its 
designee. 
• Confirm AEs and SAEs have been properly documented on CRFs and confirm any 
SAEs have been forwarded to the Sponsor or its designee and those SAEs that met 
criteria for reporting have been forwarded to the IRB/IEC. 
The monitor will be available between visits if the investigator(s) or other staff needs 
information or advice. 
16.2. 
Audits and Inspections 
Authorized representatives of the Sponsor or designee, a regulatory authority, an IEC or an IRB 
may visit the site to perform audits or inspections, including source data verification. The 
purpose of an audit or inspection is to systematically and independently examine all trial-related 
activities and documents to determine whether these activities were conducted, and data were 
recorded, analyzed, and accurately reported according to the protocol, GCP guidelines of the 
ICH, and any applicable regulatory requirements. The investigator should contact the sponsor or 
designee immediately if contacted by a regulatory agency about an inspection. 
Page 94 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
16.3. 
Institutional Review Board / Independent Ethics Committee 
The PI must obtain IRB/IEC approval for the investigation. Initial IRB/IEC approval, and all 
materials approved by the IRB/IEC for this trial including the subject ICF and recruitment 
materials must be maintained by the Investigator and made available for inspection. 
 
Page 95 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
17. 
QUALITY CONTROL AND QUALITY ASSURANCE 
To ensure compliance with Good Clinical Practices and all applicable regulatory requirements, 
the Sponsor or its representative may conduct a quality assurance audit. Please refer to 
Section 16.2 for more details regarding the audit process. 
 
Page 96 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
18. 
ETHICS 
18.1. 
Ethics Review 
The final trial protocol, including the final version of the ICF, must be approved or given a 
favorable opinion in writing by an IRB or IEC as appropriate. The investigator must submit a 
copy of the written approval to the Sponsor or designee before he or she can enroll any subject 
into the trial. 
The PI is responsible for informing the IRB or IEC of any amendment to the protocol in 
accordance with local requirements. In addition, the IRB or IEC must approve written 
information to be provided to subjects for the trial. The protocol must be re-approved by the IRB 
or IEC upon receipt of amendments and reviewed annually, as local regulations require. 
The PI is also responsible for providing the IRB or IEC with reports of any reportable serious 
adverse drug reactions from any other trial conducted with the IP. The Sponsor or designee will 
provide this information to the PI. 
Progress reports and notifications of serious adverse drug reactions will be provided to the IRB 
or IEC according to local regulations and guidelines. 
18.2. 
Ethical Conduct of the Study 
The trial will be performed in accordance with ethical principles that have their origin in the 
Declaration of Helsinki and are consistent with ICH/GCP, applicable regulatory requirements. 
18.3. 
Written Informed Consent 
The PI(s) at each center will ensure that the subject is given full and adequate oral and written 
information about the nature, purpose, possible risk and benefit of the trial. Subjects must also be 
notified that they are free to discontinue from the study at any time. The subject should be given 
the opportunity to ask questions and allowed time to consider the information provided. 
The subject’s signed and dated ICF must be obtained before conducting any trial procedures. 
The PI(s) must maintain the original, signed ICF. A copy of the signed ICF must be given to the 
subject. 
 
Page 97 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
19. 
DATA HANDLING AND RECORDKEEPING 
19.1. 
Inspection of Records 
The Sponsor or designee will be allowed to conduct site visits to the investigation facilities for 
the purpose of monitoring any aspect of the trial. The Investigator agrees to allow the monitor to 
inspect the drug storage area, IP stocks, drug accountability records, subject charts and trial 
source documents, and other records relative to trial conduct. 
19.2. 
Retention of Records 
The PI must maintain confidentiality of all study documentation, and take measures to prevent 
accidental or premature destruction of these documents. 
The PI must maintain all documentation relating to the trial according to local regulations or a 
minimum period of 2 years after the last marketing application approval worldwide, or if not 
approved 2 years following the discontinuance of the test article for investigation. If it becomes 
necessary for the Sponsor or designee or the Regulatory Authority to review any documentation 
relating to the trial, the Investigator must permit access to such records. 
 
Page 98 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
20. 
LIST OF REFERENCES 
Benatar M, Sanders DB, Burns TM, Cutter GR, Guptill JT, Baggi F, et al. Recommendations for 
myasthenia gravis clinical trials. Muscle Nerve. 2012 Jun;45(6):909-917. 
Burns TM, Conaway M, Sanders DB. The MG Composite: A valid and reliable outcome 
measure for myasthenia gravis. Neurology. 2010 May 4;74(18):1434-1440. 
Burns TM, Grouse CK, Wolfe GI, Conaway MR, Sanders DB. The MG-QOL15 for following 
the health-related quality of life of patients with myasthenia gravis. Muscle Nerve. 2011 
Jan;43(1):14-18. 
Cella D. Measuring Quality of Life in Neurological Disorders; Final Report of the Neuro-QOL 
Study September 2010. 2010.  
Conti-Fine BM, Milani M, Kaminski HJ. Myasthenia gravis: past, present, and future. J Clin 
Invest. 2006 Nov;116(11):2843-2854. 
Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, et al. The Columbia-
Suicide Severity Rating Scale: initial validity and internal consistency findings from three 
multisite studies with adolescents and adults. Am J Psychiatry. 2011 Dec;168(12):1266-1277. 
Szende A, Williams A. Measuring Self-Reported Population Health: An International 
Perspective based on EQ-5D. 2004. Ref Type: Online Source 
Vincent A, Drachman DB. Myasthenia gravis. Adv Neurol. 2002;88:159-188. 
 
Page 99 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
APPENDIX 1. QUANTITATIVE MYASTHENIA GRAVIS (QMG) SCORE 
FOR DISEASE SEVERITY 
 
 
Page 100 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
APPENDIX 2. MG ACTIVITY OF DAILY LIVING (MG-ADL) PROFILE 
Items 
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Score (0,1,2,3) 
1. Talking  
Normal 
Intermittent 
slurring or nasal 
speech 
Constant slurring or 
nasal, but can be 
understood 
 
Difficult to 
understand speech 
 
2. Chewing 
Normal 
Fatigue with solid 
food 
Fatigue with soft 
food 
 
Gastric Tube 
 
3. Swallowing  
Normal 
Rare episode of 
choking  
Frequent choking 
necessitating changes 
in diet 
 
Gastric Tube 
 
4. Breathing 
Normal 
Shortness of breath 
with exertion 
 
Shortness of breath at 
rest 
Ventilator 
dependence 
 
5. Impairment 
of ability to 
brush teeth or 
comb hair 
None 
Extra effort, but no 
rest periods needed 
 
Rest periods needed  
Cannot do one of 
these functions 
 
6. Impairment 
of ability to 
arise from a 
chair 
None 
Mild, sometimes 
uses arms  
Moderate, always 
uses arms  
Severe, requires 
assistance 
 
7. Double 
vision 
None 
Occurs, but not 
daily 
 
Daily, but not 
constant 
Constant 
 
8. Eyelid droop 
None 
Occurs, but not 
daily 
Daily, but not 
constant 
Constant 
 
 
Page 101 of 114 
Alexion CONFIDENTIAL 

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E C U -M G -3 0 2, A me n d me nt 2  
 
 Ale xi o n P har mace uticals, I nc.  
1 9  Dece m ber  2 0 1 6   
 
 
 
A P P E N DI X 4.  N E U R O -Q O L F A TI G U E  
F ati g ue: Please res p o n d t o eac h q uesti o n or state me nt b y mar ki n g o ne b o x per r o w.  
 
I n t he p ast 7 d a ys … 
Ne ver  
R arel y  
S o meti mes  
Ofte n  
Al w a ys  
N Q F T G 1 3  
I felt e x ha uste d. 
 
1  
 
2  
 
3  
 
4  
 
5  
N Q F T G 1 1  
I felt t hat I ha d n o e ner g y. 
 
1  
 
2  
 
3  
 
4  
 
5  
N Q F T G 1 5  
I felt fati g ue d.    
 
1  
 
2  
 
3  
 
4  
 
5  
N Q F T G 0 6  
I was t o o tire d t o d o m y h o use h ol d 
c h ores.  
 
1  
 
2  
 
3  
 
4  
 
5  
N Q F T G 0 7  
I was t o o tire d t o lea ve t he h o use.  
 
1  
 
2  
 
3  
 
4  
 
5  
N Q F T G 1 0  
I was fr ustrate d b y bei n g t o o tire d t o 
d o t he t hi n gs I wa nte d t o d o.  
 
1  
 
2  
 
3  
 
4  
 
5  
N Q F T G 1 4  
I felt tire d. 
 
1  
 
2  
 
3  
 
4  
 
5  
N Q F T G 0 2  
I ha d t o li mit m y s ocial acti vit y 
beca use I was tire d. 
 
1  
 
2  
 
3  
 
4  
 
5  
N Q F T G 0 1  
I nee de d hel p d oi n g m y us ual 
acti vities beca use of m y fati g ue.  
 
1  
 
2  
 
3  
 
4  
 
5  
N Q F T G 0 3  
I nee de d t o slee p d uri n g t he da y. 
 
1  
 
2  
 
3  
 
4  
 
5  
N Q F T G 0 4  
I ha d tr o u ble starti n g t hi n gs beca use I 
was t o o tire d.  
 
1  
 
2  
 
3  
 
4  
 
5  
N Q F T G 0 5  
I ha d tr o u ble fi nis hi n g t hi n gs beca use 
I was t o o tire d.  
 
1  
 
2  
 
3  
 
4  
 
5  
N Q F T G 0 8  
I was t o o tire d t o ta ke a s h ort wal k. 
 
1  
 
2  
 
3  
 
4  
 
5  
N Q F T G 0 9  
I was t o o tire d t o eat. 
 
1  
 
2  
 
3  
 
4  
 
5  
N Q F T G 1 2  
I was s o tire d t hat I nee de d t o rest 
d uri n g t he da y.  
 
1  
 
2  
 
3  
 
4  
 
5  
N Q F T G 1 6  
I felt wea k all o ver.  
 
1  
 
2  
 
3  
 
4  
 
5  
N Q F T G 1 7  
I nee de d hel p d oi n g m y us ual 
acti vities beca use of wea k ness.  
 
1  
 
2  
 
3  
 
4  
 
5  
N Q F T G 1 8  
I ha d t o li mit m y s ocial acti vit y 
beca use I was p h ysicall y wea k.  
 
1  
 
2  
 
3  
 
4  
 
5  
N Q F T G 2 0  
I ha d t o f orce m yself t o get u p a n d d o 
t hi n gs beca use I was p h ysicall y t o o 
wea k.  
 
1 
 
2 
 
3 
 
4 
 
5 
 
 
 
 
Pa ge 1 0 3  of 1 1 4  
Ale xi o n C O N FI D E N TI A L  

ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
APPENDIX 5. SUMMARY OF LABORATORY PANELS AND TESTS 
 
Chemistry Panel  
Sodium 
Potassium 
Chloride 
Bicarbonate 
Blood urea nitrogen 
Creatinine 
Glucose 
Alkaline phosphatase 
Alanine amino transferase (ALT) 
Aspartate amino transferase (AST) 
Total bilirubin 
Albumin 
Total protein 
Uric acid 
Complete Blood Count (CBC) & Differential 
White blood cell count (WBC) 
White blood cell differential 
Red blood cell count (RBC) 
RBC mean corpuscular volume 
RBC distribution width 
Hemoglobin 
Hematocrit 
Platelet count 
Other 
Anti-drug antibody (ADA) 
Human Chorionic Gonadotropin (β-HCG) 
Anti-AChR Antibody 
Pharmacokinetics (PK)  
Pharmacodynamics (PD) 
Free C5 
 
Page 104 of 114 
Alexion CONFIDENTIAL 

ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
APPENDIX 6. MYASTENIA GRAVIS FOUNDATION OF AMERICA 
(MGFA) MG THERAPY STATUS 
 
 
Permission granted for use from MGFA 
 
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 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
APPENDIX 7. MG COMPOSITE SCORE 
 
 
Permission granted for use from 
 University of Virginia 
 
 
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PPD

ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
APPENDIX 8. MGFA POST-INTERVENTIONAL STATUS (MGFA-PIS) 
 
 
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19 December 2016 
 
 
 
APPENDIX 9. COLUMBIA-SUICIDE SEVERITY RATING SCALE (C-SSRS) – SINCE LAST VISIT 
QUESTIONNAIRE (VERSION 1/14/09)* 
 
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19 December 2016 
 
 
 
 
 
 
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19 December 2016 
 
 
 
 
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19 December 2016 
 
 
 
 
Source: http://cssrs.columbia.edu/docs/C-SSRS_1-14-09-Since_Last_Visit.pdf  
*“Since Last Visit” refers to the period since the last visit the C-SSRS scale was administered.  
 
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ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
APPENDIX 10. EUROQOL (EQ-5D) 
Health Questionnaire 
(English version for the United States [US]) 
 
By placing a checkmark in one box in each group below, please indicate which statements best 
describe your own health state today. 
Mobility 
 
I have no problems in walking about 
 
I have some problems in walking about 
 
I am confined to bed 
 
Self-Care 
 
I have no problems with self-care 
 
I have some problems washing or dressing myself 
 
I am unable to wash or dress myself 
 
Usual Activities (e.g. ,work, study, housework,  
family or leisure activities) 
 
I have no problems with performing my usual activities 
 
I have some problems with performing my usual activities 
 
I am unable to perform my usual activities 
 
Pain/Discomfort 
 
I have no pain or discomfort 
 
I have moderate pain or discomfort 
 
I have extreme pain or discomfort 
 
Anxiety/Depression 
 
I am not anxious or depressed 
 
I am moderately anxious or depressed 
 
I am extremely anxious or depressed 
 
 
 
 
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ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
 
To help people say how good or bad a health state is,  
we have drawn a scale (rather like a thermometer) on  
which the best state you can imagine is marked 100 and  
the worst state you can imagine is marked 0. 
We would like you to indicate on this scale how good  
or bad your own health is today, in your opinion. 
Please do this by drawing a line from the box below to 
whichever point on the scale indicates how good or  
bad your health state is today. 
 
 
 
 
9 0 
8 0 
7 0 
6 0 
5 0 
4 0 
3 0 
2 0 
1 0 
100 
Worst 
imaginable 
health state 
0 
Best  
imaginable 
health state 
Your own 
health state 
today 
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ECU-MG-302, Amendment 2 
 
 Alexion Pharmaceuticals, Inc. 
19 December 2016 
 
 
 
APPENDIX 11. COLLECTION OF FOLLOW-UP INFORMATION FROM 
PATIENTS WHO WITHDRAW FROM THE STUDY 
To gain understanding of the patient’s post-treatment disease status, the Sponsor may request 
additional follow-up information. An updated ICF (and/or an ICF Addendum) will be provided 
to all patients describing the reason for collecting follow-up information, the information that 
will be collected, and how the information will be used. The updated ICF (and/or ICF 
Addendum) will also be provided to discontinued patients, subject to IRB/IEC approval. The 
updated ICF (and/or ICF Addendum) will clearly state that the patient has the option to accept or 
reject, and that either decision will have no impact on their medical benefits. Prior to collecting 
any follow-up information, the updated ICF (and/or ICF Addendum) must be signed by the 
patient. 
The Sponsor may obtain patient post-treatment data by querying the patient’s medical records, 
through the study physician or the patient’s current treating physician. The follow-up data to be 
collected from the physician include the following:  
• How has the patient’s MG status changed since they left Study ECU-MG-302 
(better/worse/unchanged); if better or worse, what are the changes 
• What are the patient’s current MG medications and the doses, and MG medication history 
since leaving Study ECU-MG-302 
• Has the patient experienced any exacerbations (Clinical Deteriorations) of MG, or any 
myasthenic crises since leaving Study ECU-MG-302; if so how many times 
• Has the patient experienced any MG-related hospitalizations since leaving Study ECU-
MG-302; if so how many times 
• Has the patient required rescue treatment with IV acetylcholinesterase inhibitors, 
corticosteroids, plasma exchange or IVIg since leaving Study ECU-MG-302; if so how 
many times 
• Has the patient had any assessments using the MG-ADL, QMG, MGC or the 
MG-QOL15 scale; if so, what are the results, and was it administered by the same person 
who did the assessment during the clinical trial 
• Have there been any changes in non-drug therapy. 
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