Clinical trial NCT04752566
Conditions: Guillain-Barre Syndrome
Keywords: Eculizumab Soliris Alexion C5 Inhibition Therapy
Sponsor: Alexion Pharmaceuticals, Inc.
Start date: 2021-03-08; Completion date: 2022-08-03
Enrollment: 57 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a Phase 3, prospective, multicenter, placebo controlled, double blind, randomized study to investigate the efficacy and safety of eculizumab in participants with severe GBS, defined using the Hughes Functional Grade (FG) scale as progressively deteriorating FG3 or FG4/FG5 within 2 weeks from onset of weakness due to GBS.

This study will be conducted only at sites in Japan.

Detailed description:
Eligible participants will be randomized to receive intravenous (IV) infusion of eculizumab or placebo at a 2:1 ratio. All participants will be on concomitant IV immunoglobulin G (Ig) therapy as per standard of care.

Arms: arm 1: Participants will receive eculizumab. arm 2: Participants will receive placebo.
Interventions: intervention 1: Eculizumab intervention 2: Placebo
Intervention descriptions: intervention 1: Eculizumab will be administered via IV infusion once a week for 4 weeks. intervention 2: Placebo will be administered via IV infusion once a week for 4 weeks.

Protocol documents:
Prot_000.pdf: 
0 1 - N o v - 2 0 2 1  |  1 6 : 3 9 : 1 8  E D T
 
 
N C T #: N C T 0 4 7 5 2 5 6 6


Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
INVESTIGATOR’S AGREEMENT 
I have read the study protocol and agree to conduct the study in accordance with this protocol, all 
applicable government regulations, the principles of the ICH E6 Guidelines for Good Clinical 
Practice, and the principles of the World Medical Association Declaration of Helsinki. I also 
agree to maintain the confidentiality of all information received or developed in connection with 
this protocol. 
____________________________________ 
Printed Name of Investigator 
_____________________________________ 
Signature of Investigator 
_______________ 
Date 
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Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
PROTOCOL AMENDMENT SUMMARY OF CHANGES 
DOCUMENT HISTORY 
Document 
Date 
Amendment 1.0 
28 Oct 2021
Original Protocol 
15 Sep 2020
Amendment 1.0 (28 Oct 2021) 
Overall Rationale for the Amendment: 
This amendment has been prepared to incorporate changes made in 4 Administrative Letters and 
to add a Safety Follow-up Phone Call or Visit to allow 8 weeks of follow-up for patients who 
discontinue study drug early or who terminate the study before Week 12. In addition, if 
intravenous immunoglobulin (IVIg) and study drug are administered on the same day, the 
requirement to administer study drug prior to IVIg was removed. Minor editorial updates were 
made for clarification and consistency. 
Section # and Name 
Description of Change 
Brief Rationale 
Throughout the protocol 
Updated amendment number and 
approval date
Administrative change. 
Section 1.1 Synopsis, 
Section 10.12 
Abbreviations 
Updated definition for abbreviation 
“AIDP” to “acute inflammatory 
demyelinating polyradiculopathy.”
Correction. 
Section 1.1 Synopsis, 
Section 6.3.2 Blinding, 
Section 9.6 Independent 
Data Monitoring 
Committee, Section 10.1.5 
Committees Structure 
Removed Independent Data Monitoring 
Committee (IDMC) 
Clarified that there is no IDMC. 
Instead, an interim analysis will be 
performed by the Independent Analysis 
Center (IAC). 
Section 1.3 Schedule of 
Activities, Section 7.2 
Patient 
Discontinuation/Withdrawal 
From the Study 
Added a Safety Follow-up Phone Call 
or Visit after early study drug 
discontinuation or early study 
discontinuation. 
To provide safety follow-up for 
8 weeks after the last dose of study 
drug for patients who discontinue the 
study drug early or who discontinue 
the study prior to Visit 10/Week 12.
Section 1.3 Schedule of 
Activities 
The following footnotes were revised or 
added (bold text): 
b. This is the Early Termination (ET)
Visit for patients who permanently
discontinue the study drug (see Section
7.1) or who permanently discontinue
the study (see Section 7.2).
c. Safety Follow-up Phone Call or
Visit should be conducted 8 weeks
after the last dose of study drug for
patients who discontinue the study
drug or who discontinue the study
prior to V10/W12.
i. In order to maintain good research
practice, it is recommended that all
Updated for clarity and to incorporate 
changes per Administrative Letters 3.0 
and 4.0. 
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Protocol Amendment 1.0 
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28 Oct 2021 
Section # and Name 
Description of Change 
Brief Rationale 
efficacy assessments are performed by 
the same assessor. If 
Screening/Enrollment Visit (V1) and 
Day 1 Visit (V2) are on the same day 
or within 2 days, the efficacy 
assessments will not be repeated, with 
the exception of the Hughes FG 
score. 
k. Targeted physical examination will
be performed when deemed necessary
by the Investigator. A targeted physical
examination will include, at a
minimum, assessments of the skin,
lungs, cardiovascular system, and
abdomen (liver and spleen). If
Screening/Enrollment Visit (V1) and
Day 1 Visit (V2) are on the same day,
the targeted physical examination
will not be repeated if already
performed.
l. If height is unable to be obtained
due to the patient’s medical
condition, measure and record it by
knee height length method. If knee
height length cannot be obtained, the
patient should be asked about their
latest height. If weight is unable to be
obtained due to the patient’s
condition, the patient should be
asked about their latest weight. If
weight is unable to be measured
directly, the Investigator should
measure body weight as soon as
possible. Height and weight, whether
captured directly, indirectly, or
historically, should be recorded.
m. If Screening/Enrollment Visit
(V1) and Day 1 Visit (V2) are on the
same day, vital signs will not be
repeated unless deemed necessary by
the Investigator.
o. If Screening/Enrollment Visit (V1)
and Day 1 Visit (V2) are on the same
day or within 2 days, clinical
laboratory tests for hematology,
chemistry, and urinalysis will not be
repeated for Day 1.
q. Women of childbearing potential
should be enrolled only after a
negative urine or serum pregnancy
test result at Screening. Additional
urine pregnancy testing will be
standard for the protocol unless
serum testing is required by site
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Protocol Amendment 1.0 
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28 Oct 2021 
Section # and Name 
Description of Change 
Brief Rationale 
policies, local regulation, or IRB and 
should be performed per the specified 
time points. A negative test result 
must be verified within 48 hours 
before the first dose of study drug. If 
the Screening/Enrollment Visit (V1) 
and Day 1 Visit (V2) occur within 
48 hours, only 1 pregnancy test is 
required. A pregnancy test may also be 
performed at any visit at the 
Investigator’s discretion.
Section 1.3 Schedule of 
Activities, Section 5.1 
Inclusion Criteria, 
Section 10.2 Appendix 2: 
Clinical Laboratory Tests 
Added text to clarify that women of
childbearing potential should be
enrolled only after a negative urine or
serum pregnancy test result at
Screening and that a negative
pregnancy test result is required within
48 hours before the first dose of study
drug.
To incorporate changes per 
Administrative Letter 1, which 
clarified that a negative urine or serum 
pregnancy test result is required for 
enrollment for women of childbearing 
potential, and to increase by 24 hours 
the timeframe for negative pregnancy 
test results prior to the first dose of 
study drug.
Section 5.1 Inclusion 
Criteria 
Updated inclusion criterion 4 as 
follows: Patients with onset of weakness 
due to GBS less than ≤ 2 weeks before 
screening. 
To enhance clarity. 
Section 6.5.1 Allowed 
Medicine and Therapy 
Removed the requirement for study 
drug administration to occur prior to or 
during the treatment period for 
intravenous immunoglobulin therapy. 
Clarified that if study drug and IVIg are 
given on the same day, they must be 
given at least 1 hour apart.  
No pharmacokinetic reason exists for 
the restriction to require study drug 
administration prior to IVIg, so it was 
removed as a requirement. However, if 
both study drug and IVIg are given on 
the same day, they must be given at 
least 1 hour apart, so that the patient 
can be observed for immediate 
infusion reactions.  
Section 6.5.3 Disallowed 
Testing 
Clarified that measurements of 50% 
hemolytic complement activity and 
other serum complement pathway 
indicators, including anti-ganglioside 
antibody testing, are not allowed prior 
to database lock and study unblinding.
To enhance clarity. 
Section 8.2.6 Nerve 
Conduction Test 
Replaced the word “fibular” with 
“sural” as follows: 
The nerve conduction test measures 
distal latency, compound muscle action 
potential (CMAP) amplitude (proximal, 
distal), CMAP duration (proximal, 
distal), motor nerve conduction 
velocity, and minimum F-wave latency 
of the median, ulnar, fibular, and tibial 
nerves. It also evaluates sensory nerve 
conduction amplitude and velocity of 
the median, ulnar, and fibular sural 
nerves. s 
Correction incorporating change per 
Administrative Letter 2.0. 
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Section # and Name 
Description of Change 
Brief Rationale 
Section 8.6 
Pharmacokinetics 
Removed text stating that 
pharmacokinetic blood samples would 
be collected at unscheduled visits.
Correction 
Section 8.7 
Pharmacodynamics 
Removed text stating that 
pharmacodynamic blood samples would 
be collected at unscheduled visits.
Correction 
Section 9.2 Sample Size 
Determination, Section 9.5 
Interim Analyses 
Replaced the IDMC with the IAC, 
which will perform the interim analysis, 
and specified that details regarding 
statistical power calculations, sample 
size re-estimation, and blinding will be 
included in the Interim Analysis Plan 
(IAP). 
Correction 
Section 10.1.5 Committees 
Structure 
Updated text to specify that details of 
the IAC will be provided in the IAP.
Clarification 
Section 10.2 Appendix 2: 
Clinical Laboratory Tests 
Updated text to clarify central and local 
laboratory sample collection. Specified 
that a fasting glucose test is preferred 
but not required.
Clarification 
Section 10.11 Appendix 11 
Work Productivity and 
Activity Impairment 
Questionnaire 
Updated schedule to administer the 
questionnaire 
To align with the Japanese version of 
the protocol 
Section 10.13 Protocol 
Amendment History 
Added section for protocol amendment 
history 
Administrative change 
Throughout 
Minor grammatical, editorial, and 
document formatting revisions.
Clarification 
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Protocol Amendment 1.0 
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TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
INVESTIGATOR’S AGREEMENT ...............................................................................................2 
PROTOCOL AMENDMENT SUMMARY OF CHANGES ..........................................................3 
TABLE OF CONTENTS .................................................................................................................7 
LIST OF TABLES .........................................................................................................................12 
LIST OF FIGURES .......................................................................................................................12 
1.
PROTOCOL SUMMARY ..........................................................................................13 
1.1. 
Synopsis ......................................................................................................................13 
1.2. 
Schema ........................................................................................................................17 
1.3. 
Schedule of Activities (SoA) ......................................................................................18 
2.
INTRODUCTION ......................................................................................................22 
2.1. 
Study Rationale ...........................................................................................................22 
2.2. 
Background .................................................................................................................23 
2.2.1. 
Unmet Medical Need in Patients With Guillain-Barré Syndrome .............................23 
2.2.2. 
Eculizumab and Complement Inhibition ....................................................................23 
2.3. 
Benefit/Risk Assessment ............................................................................................24 
2.3.1. 
Risk Assessment .........................................................................................................24 
2.3.2. 
Benefit Assessment .....................................................................................................25 
2.3.3. 
Overall Benefit: Risk Conclusion ...............................................................................25 
3.
OBJECTIVES AND ENDPOINTS ............................................................................26 
4.
STUDY DESIGN .......................................................................................................28 
4.1. 
Overall Design ............................................................................................................28 
4.2. 
Scientific Rationale for Study Design ........................................................................28 
4.3. 
Justification for Dose ..................................................................................................29 
4.4. 
End of Study Definition ..............................................................................................30 
5.
STUDY POPULATION .............................................................................................31 
5.1. 
Inclusion Criteria ........................................................................................................31 
5.2. 
Exclusion Criteria .......................................................................................................32 
5.3. 
Lifestyle Considerations .............................................................................................33 
5.4. 
Screen Failures ............................................................................................................33 
6.
STUDY DRUG ...........................................................................................................34 
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6.1. 
Study Drug(s) Administered .......................................................................................34 
6.2. 
Preparation/Handling/Storage/Accountability ............................................................34 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................................35 
6.3.1. 
Randomization ............................................................................................................35 
6.3.2. 
Blinding ......................................................................................................................35 
6.4. 
Study Drug Compliance .............................................................................................36 
6.5. 
Concomitant Therapy .................................................................................................36 
6.5.1. 
Allowed Medicine and Therapy .................................................................................36 
6.5.2. 
Disallowed Medicine and Therapy .............................................................................36 
6.5.3. 
Disallowed Testing .....................................................................................................37 
6.6. 
Dose Modification ......................................................................................................37 
6.7. 
Intervention After the End of the Study .....................................................................37 
7.
DISCONTINUATION OF STUDY DRUG AND PATIENT
DISCONTINUATION/WITHDRAWAL ..................................................................38 
7.1. 
Discontinuation of Study Drug ...................................................................................38 
7.2. 
Patient Discontinuation/Withdrawal From the Study .................................................38 
7.3. 
Lost to Follow-up .......................................................................................................39 
8.
STUDY ASSESSMENTS AND PROCEDURES ......................................................40 
8.1. 
General Assessments and Procedures .........................................................................40 
8.1.1. 
Informed Consent .......................................................................................................40 
8.1.2. 
Medical/Surgical/Social History .................................................................................40 
8.1.3. 
Vaccine and Antibiotic Prophylaxis ...........................................................................40 
8.1.4. 
Inclusion/Exclusion Criteria .......................................................................................41 
8.1.5. 
Study Drug Administration .........................................................................................41 
8.2. 
Efficacy Assessments .................................................................................................41 
8.2.1. 
Hughes Functional Grade Score .................................................................................41 
8.2.2. 
Rasch-built Overall Disability Scale Score ................................................................41 
8.2.3. 
Overall Neuropathy Limitations Scale .......................................................................42 
8.2.4. 
Medical Research Council-SumScore ........................................................................42 
8.2.5. 
Manual Muscle Testing ..............................................................................................42 
8.2.6. 
Nerve Conduction Test ...............................................................................................43 
8.2.7. 
Short Form McGill Pain Questionnaire 2 ...................................................................43 
8.2.8. 
Depression, Anxiety and Stress Scale, Short Form, 21 Questions Score ...................43 
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8.2.9. 
Chalder Fatigue Scale Score .......................................................................................44 
8.2.10. 
European Quality of Life – 5 Dimensions – 5 Levels Score ......................................44 
8.2.11. 
Work Productivity and Activity Impairment Questionnaire ......................................44 
8.3. 
Safety Assessments .....................................................................................................44 
8.3.1. 
Physical Examinations ................................................................................................44 
8.3.2. 
Height and Weight ......................................................................................................45 
8.3.3. 
Vital Signs ..................................................................................................................45 
8.3.4. 
Electrocardiograms .....................................................................................................45 
8.3.5. 
Prior and Concomitant Medication Review ...............................................................45 
8.3.5.1. 
Prior Medications ........................................................................................................46 
8.3.5.2. 
Concomitant Medications and Therapies ...................................................................46 
8.3.6. 
Clinical Safety Laboratory Assessments ....................................................................46 
8.3.7. 
Pregnancy ...................................................................................................................47 
8.3.8. 
Patient Safety Card .....................................................................................................47 
8.4. 
Adverse Events and Serious Adverse Events .............................................................47 
8.4.1. 
Time Period and Frequency for Collecting AE and SAE Information .......................48 
8.4.2. 
Method of Detecting AEs and SAEs ..........................................................................48 
8.4.3. 
Follow-up of AEs and SAEs .......................................................................................48 
8.4.4. 
Regulatory Reporting Requirements for SAEs ...........................................................48 
8.4.5. 
Adverse Events of Special Interest .............................................................................48 
8.5. 
Treatment of Overdose ...............................................................................................49 
8.6. 
Pharmacokinetics ........................................................................................................49 
8.7. 
Pharmacodynamics .....................................................................................................49 
8.8. 
Genetics ......................................................................................................................50 
8.9. 
Biomarkers ..................................................................................................................50 
8.9.1. 
Biomarker Research ....................................................................................................50 
8.9.2. 
Additional Biomarker Research .................................................................................50 
8.10. 
Immunogenicity Assessment ......................................................................................51 
8.11. 
Health Economics Data and Medical Resource Utilization .......................................51 
9.
STATISTICAL CONSIDERATIONS .......................................................................52 
9.1. 
Statistical Hypotheses .................................................................................................52 
9.1.1. 
Primary Hypothesis ....................................................................................................52 
9.1.2. 
Key Secondary Hypotheses ........................................................................................52 
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9.2. 
Sample Size Determination ........................................................................................52 
9.3. 
Populations for Analyses ............................................................................................53 
9.4. 
Statistical Analyses .....................................................................................................53 
9.4.1. 
Enrollment and Disposition ........................................................................................53 
9.4.2. 
Demographics, Baseline Characteristics, Inclusion and Exclusion Criteria, 
and Protocol Deviations ..............................................................................................54 
9.4.3. 
Medical/Surgical History and Physical Examination .................................................54 
9.4.4. 
Prior and Concomitant Medications ...........................................................................54 
9.4.5. 
Efficacy Analyses .......................................................................................................54 
9.4.5.1. 
Primary Endpoint ........................................................................................................54 
9.4.5.2. 
Key Secondary Endpoints ...........................................................................................54 
9.4.5.3. 
Other Secondary and Tertiary/Exploratory Endpoints ...............................................55 
9.4.5.4. 
Multiplicity Adjustment ..............................................................................................55 
9.4.6. 
Safety Analyses ..........................................................................................................56 
9.4.6.1. 
Analysis of Adverse Events ........................................................................................56 
9.4.6.2. 
Analysis of Clinical Laboratory Parameters, Vital Sign Measurements, and 
Electrocardiogram Parameters ....................................................................................56 
9.4.7. 
Analyses of Pharmacokinetic and Pharmacodynamic Parameters .............................56 
9.4.8. 
Analysis of Antidrug Antibodies ................................................................................57 
9.4.9. 
Analysis of Biomarkers ..............................................................................................57 
9.4.10. 
Other Analyses ............................................................................................................57 
9.5. 
Interim Analyses .........................................................................................................57 
9.6. 
Independent Data Monitoring Committee ..................................................................57 
9.7. 
Independent Guillain-Barré Syndrome Variant Determination ..................................57 
10.
SUPPORTING DOCUMENTATION AND OPERATIONAL
CONSIDERATIONS ..................................................................................................58 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations ....................58 
10.1.1. 
Regulatory and Ethical Considerations ......................................................................58 
10.1.2. 
Financial Disclosure ...................................................................................................58 
10.1.3. 
Informed Consent Process ..........................................................................................59 
10.1.4. 
Data Protection ...........................................................................................................59 
10.1.5. 
Committees Structure .................................................................................................59 
10.1.6. 
Dissemination of Clinical Study Data ........................................................................60 
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10.1.7. 
Data Quality Assurance ..............................................................................................60 
10.1.8. 
Source Documents ......................................................................................................60 
10.1.9. 
Study and Site Start and Closure ................................................................................61 
10.1.10. 
Publication Policy .......................................................................................................61 
10.2. 
Appendix 2: Clinical Laboratory Tests .......................................................................63 
10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ........................................................................65 
10.3.1. 
Definition of AE .........................................................................................................65 
10.3.2. 
Definition of SAE .......................................................................................................66 
10.3.3. 
Recording and Follow-up of AE and/or SAE .............................................................66 
10.3.4. 
Reporting of SAEs ......................................................................................................68 
10.4. 
Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information .................................................................................................................69 
10.4.1. 
Definitions ..................................................................................................................69 
10.4.2. 
Contraception Guidance .............................................................................................69 
10.4.2.1. 
Guidance for Female Patients .....................................................................................69 
10.4.2.2. 
Guidance for Male Patients ........................................................................................71 
10.4.3. 
Collection of Pregnancy Information .........................................................................71 
10.4.3.1. 
Male Patients With Partners Who Become Pregnant .................................................72 
10.4.3.2. 
Female Patients Who Become Pregnant .....................................................................72 
10.5. 
Appendix 5: Rasch-built Overall Disability Scale Score ...........................................73 
10.6. 
Appendix 6: Overall Neuropathy Limitation Scale ....................................................75 
10.7. 
Appendix 7: Short Form McGill Pain Questionnaire 2 ..............................................76 
10.8. 
Appendix 8: Depression, Anxiety and Stress Scale, Short Form, 21 
Questions Score ..........................................................................................................77 
10.9. 
Appendix 9: Chalder Fatigue Scale Score ..................................................................80 
10.10. 
Appendix 10: European Quality of Life – 5 Dimensions – 5 Levels Score ...............81 
10.11. 
Appendix 11: Work Productivity and Activity Impairment Questionnaire ................83 
10.12. 
Appendix 12: Abbreviations .......................................................................................86 
10.13. 
Protocol Amendment History .....................................................................................88 
11.
REFERENCES ...........................................................................................................89 
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LIST OF TABLES 
Table 1: 
Schedule of Activities .................................................................................................18 
Table 2: 
Identified Risks of Eculizumab ..................................................................................25 
Table 3: 
Disability Functional Grade Scale ..............................................................................41 
Table 4: 
Medical Research Council Scale ................................................................................42 
Table 5: 
Manual Muscle Testing Score by Medical Research Council System .......................43 
Table 6: 
Analysis Sets ...............................................................................................................53 
Table 7: 
Protocol-Required Laboratory Assessments ...............................................................64 
LIST OF FIGURES 
Figure 1: 
Study Design Schematic .............................................................................................17 
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1.
PROTOCOL SUMMARY
1.1. 
Synopsis
Protocol Title: 
A Phase 3, Prospective, Multicenter, Double-blind, Randomized, Placebo-controlled Study to 
Evaluate the Efficacy and Safety of Eculizumab in Patients With Guillain-Barré Syndrome 
(GBS) 
Short Title: 
A Phase 3 Study to Evaluate the Efficacy and Safety of Eculizumab in Guillain-Barré Syndrome 
Rationale: 
Guillain-Barré syndrome (GBS) is a rare, but potentially fatal neuropathy, with rapid-onset 
muscle weakness caused by the immune system damaging the peripheral nervous system. It is 
preceded in two-thirds of cases by symptoms of infection. The symptoms may develop over 
hours to a few weeks. During the acute phase, the disorder can be life-threatening, with about 
15% of people developing weakness of the breathing muscles and, therefore, requiring 
mechanical ventilation. The syndrome has a progressive, monophasic disease course, usually 
without relapse. It is the most common cause of acute flaccid tetraplegia worldwide with an 
annual global incidence of approximately 1 to 2 per 100,000 person-years.  
Guillain-Barré syndrome is currently classified into 2 major subtypes: 

Acute inflammatory demyelinating form: Acute inflammatory demyelinating
polyradiculopathy (AIDP)

Acute motor axonal variant form: Acute motor axonal neuropathy (AMAN)
The treatment goal in GBS is to interrupt the immune-mediated nerve damage during the acute 
phase of the disease. The standard of care treatments in GBS are plasma exchange (PE) and 
IVIg. 
Eculizumab (h5G1.1-mAb) (SOLIRIS®) is a humanized monoclonal antibody (mAb) derived 
from the murine anti-human complement component 5 (C5) antibody m5G1.1. Eculizumab 
specifically binds C5, thereby inhibiting its cleavage to C5a and C5b during complement 
activation and blocks membrane attack complex (MAC) formation. This strategic blockade of 
the complement cascade at C5 prevents the release of proinflammatory mediators and the 
formation of the cytolytic pore, while preserving the early components of complement activation 
that are essential for the opsonization of microorganisms and clearance of immune complexes. 
The potential efficacy of eculizumab against GBS has been shown in a murine model of Miller 
Fisher syndrome, a variant of GBS. In that model, eculizumab prevented axon-specific 
antiganglioside antibody-induced nerve damage.  
The hypothesis of a causative link between complement activation and GBS pathology was 
further assessed in an Investigator-initiated study conducted in Japan. The efficacy and safety 
results from the Investigator-initiated study support further investigation in this 
Alexion-sponsored Phase 3 controlled clinical study, ECU-GBS-301. In this Phase 3 study, the 
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Protocol Amendment 1.0 
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complement-mediated autoimmunity hypothesis for GBS will be tested in order to confirm the 
results observed in the Investigator-initiated study. 
The primary objective of this Phase 3 study is to evaluate the efficacy of eculizumab in patients 
with GBS. 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To characterize the efficacy of eculizumab in patients 
with Guillain-Barré syndrome (GBS)  

Time to first reaching a Hughes
Functional Grade (FG) score ≤ 1
Key Secondary 
To further characterize the efficacy of eculizumab over 
time in patients with GBS 

Proportion of patients with a Hughes FG
score ≤ 1 at Week 24

Proportion of patients with a Hughes FG
score improvement of ≥ 3 at Week 24

Proportion of patients with a Hughes FG
score ≤1 at Week 8
Other Secondary 
To further characterize the impact of eculizumab on 
medical resource utilization in patients with GBS  

Hospital length of stay (LOS)

Intensive care unit (ICU) stay
 
LOS in the ICU 
 
Proportion of patients admitted to the 
ICU 

Disposition post hospital discharge
To evaluate the effect of eculizumab compared with 
placebo on respiratory function in patients with GBS  

Ventilator support
 
Duration of ventilator support 
 
Proportion of patients requiring 
ventilator support 
To characterize the pharmacokinetic 
(PK)/pharmacodynamic (PD) attributes of eculizumab 
in patients with GBS 

Concentration of eculizumab in serum

Free complement component 5 (C5) in
serum

Hemolytic complement activity in serum
To assess the formation of antidrug antibodies (ADAs) 
in response to eculizumab treatment 

Incidence of ADAs
Safety 
To characterize the overall safety and tolerability of 
eculizumab in patients with GBS 

Incidence of treatment-emergent adverse
events (TEAEs), serious adverse events
(SAEs), and adverse events (AEs) leading
to study drug discontinuation
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Objectives 
Endpoints 
Tertiary/Exploratory 
To characterize the functional status of patients with 
GBS post-acute phase 

Change from baseline in the functional
scales of GBS (Rasch-built Overall
Disability Scale [R-ODS], and Overall
Neuropathy Limitations Scale [ONLS])

Change from baseline in strength
measurements (Medical Research
Council [MRC]-sumscore, and Manual
Muscle Testing [MMT])

Change from baseline in the Hughes FG
score over time
To evaluate the effect of eculizumab compared with 
placebo on pain in patients with GBS 

Change from baseline in the Short Form
McGill Pain Questionnaire 2 (SF-MPQ-2)
scores
To evaluate the effect of eculizumab compared with 
placebo on mood in patients with GBS 

Change from baseline in the Depression,
Anxiety and Stress Scale, Short form, 21
questions (DASS-21) score
To evaluate the effect of eculizumab compared with 
placebo on fatigue in patients with GBS 

Change from baseline in the Chalder
Fatigue Scale (Chalder) score
To evaluate the effect of eculizumab compared with 
placebo on quality of life (QoL) in patients with GBS 

Change from baseline in the European
Quality of Life (EuroQoL) – 5
Dimensions – 5 Levels (EQ-5D-5L) score

Change from baseline in the Work
Productivity and Activity Impairment
(WPAI) score
To evaluate complement, inflammation, and 
neurodegeneration biomarkers in patients with GBS 

Change from baseline in biomarker levels
in blood
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Overall Design 
Study ECU-GBS-301 is a Phase 3, prospective, multicenter, placebo-controlled, double-blind, 
randomized study to investigate the efficacy and safety of eculizumab in patients with severe 
GBS, defined using the Hughes Functional Grade (FG) scale (Plasma Exchange/Sandoglobulin 
Guillain-Barré Syndrome Trial Group, 1997) as progressively deteriorating FG3 or FG4/FG5 
within 2 weeks from onset of weakness due to GBS. Eligible patients will be randomized to 
receive intravenous (IV) infusion of eculizumab or placebo at a 2:1 ratio. All patients will be on 
concomitant IVIg therapy as per standard of care (400 mg/kg body weight daily for 5 days). 
Randomization will be stratified by FG score (progressively deteriorating FG3 or FG4/FG5) and 
diarrhea (present or absent < 4 weeks prior to onset of neurological symptoms). 
An interim analysis is planned for the unblinded sample size re-estimation when approximately 
60% (ie, at least 12 events) of the planned events are observed. 
Disclosure Statement: 
This is a double-blind, randomized, parallel group intervention study with 2 treatment arms 
(eculizumab arm and placebo arm). 
Number of Patients: 
Approximately 57 eligible patients will be randomized in a 2:1 ratio (eculizumab = 38 and 
placebo = 19). 
Intervention Groups and Duration: 
Eligible patients will be randomized in a 2:1 ratio to receive IV eculizumab or placebo. 
Treatment allocation will be blinded to patients, study site, the Sponsor, and the Sponsor’s 
delegates throughout the study. 
Eculizumab will be administered via IV infusion at a dose of 900 mg once a week for 4 weeks. 
A supplemental dose of 600 mg will be given with the first dose on Day 1. 
Placebo will be administered via IV infusion once a week for 4 weeks. Placebo is a matching 
sterile, clear, colorless solution with the same buffer components but without active ingredient, 
in an identical 30 mL vial. A supplemental dose of placebo will be administered with the first 
dose on Day 1 to maintain the blind. 
For each patient, the total duration of study participation will be up to 25 weeks, including the 
Screening Period (up to 1 week), the Treatment Period (4 weeks), and the Follow-up Period 
(20 weeks). Efficacy and safety will be monitored through 24 weeks after the first dose of the 
study drug. The end of the study for each patient is defined as their last visit at Week 24. 
Independent Data Monitoring Committee: No 
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1.2. 
Schema 
Figure 1: 
Study Design Schematic 
Abbreviations: D = day; EOS = end of study; FG = Functional Grade; IVIg = intravenous immunoglobulin; 
n = number of patients in each treatment group; Pbo = placebo; W = week. 
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1.3. 
Schedule of Activities (SoA) 
Table 1: 
Schedule of Activities 
Period 
Screening/
Enrollmenta 
Treatment Period 
Follow-up Period 
ETb 
Safety 
Follow-up 
Phone Call 
or Visitc 
Visit  
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
V13 
Weekd 
W1 
W2 
W3 
W4 
W5 
W6 
W8 
W12 
W16 
W20 
W24
e
Day 
D -7 to D1 
D1f 
D8 
D15 
D22 
D29 
D36 
D43 
D57 
D85 
D113 
D141 
D169 
Time window (day) 
±2 
±2 
±2 
+3
±3 
±3 
±3 
±3 
±3 
±3 
±3 
+3
+3
General assessments/procedures 
Informed consent 
● 
Medical/surgical/social history
●
Confirmation of prior 
meningococcal vaccinationg 
● 
Prophylactic antibioticsg 
Monitor prophylactic antibiotic therapy 
●
Inclusion/exclusion criteria 
● 
Randomization 
●
Study drug administrationh 
● 
● 
● 
● 
Efficacy assessmentsi 
Hughes FG score 
● 
●
●
●
●
●
●
● 
● 
●
●
●
●
●
R-ODS
●
●
●
●
●
●
ONLS 
●
●
●
●
●
● 
●
●
●
MRC-sumscore 
● 
●
●
●
●
●
●
●
●
●
MMT score 
● 
●
●
●
●
●
●
●
●
●
Nerve conduction testj 
● 
● 
SF-MPQ-2 
●
●
●
●
DASS-21 
●
●
●
●
Chalder Fatigue Scale score 
●
●
●
●
EuroQoL-EQ-5D-5L 
●
●
 
●
●
WPAI questionnaire 
●
●
 
●
●
Safety assessments 
Complete physical examination 
● 
 
●
●
Targeted physical examinationk 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Height and weightl 
● 
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Table 1: 
Schedule of Activities 
Period 
Screening/
Enrollmenta 
Treatment Period 
Follow-up Period 
ETb 
Safety 
Follow-up 
Phone Call 
or Visitc 
Visit  
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
V13 
Weekd 
W1 
W2 
W3 
W4 
W5 
W6 
W8 
W12 
W16 
W20 
W24
e
Day 
D -7 to D1 
D1f 
D8 
D15 
D22 
D29 
D36 
D43 
D57 
D85 
D113 
D141 
D169 
Time window (day) 
±2 
±2 
±2 
+3
±3 
±3 
±3 
±3 
±3 
±3 
±3 
+3
+3
Vital signsm 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
12-lead ECG
● 
 
●
●
Review of Patient Safety Cardn 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
● 
Prior medications and 
procedures 
● 
Concomitant therapy 
(including IVIg therapy) and 
physical therapy (including 
inpatient rehabilitation) 
Monitor concomitant therapy and physical therapy (including both inpatient and outpatient 
rehabilitation) 
● 
● 
Hematologyo 
Chemistryo 
Urinalysiso 
● 
● 
● 
● 
● 
● 
● 
● 
Adverse eventsp 
Continuous monitoring 
● 
● 
Pregnancy testq 
● 
● 
● 
● 
● 
● 
● 
● 
Pharmacokinetic and pharmacodynamic assessmentsh 
Eculizumab concentrationr,s 
● 
● 
● 
● 
● 
 
● 
● 
● 
Free C5r,s 
● 
● 
● 
● 
● 
 
● 
● 
● 
Hemolytic 
activationr, s 
● 
● 
● 
● 
● 
 
● 
● 
● 
Biomarker research 
Blood samples (plasma and 
serum) for biomarkerst 
● 
● 
● 
● 
● 
● 
Immunogenicity assessment 
Eculizumab ADA 
●
●
 
●
●
a Enrollment will be complete after obtaining signed informed consent and after eligibility is verified based on the inclusion/exclusion criteria. 
b The end of treatment (ET) Visit should be conducted at the time of early discontinuation of the study drug (see Section 7.1) or early discontinuation from the 
study (see Section 7.2). 
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or Visitc Safety Follow-up Phone Call or Visit should be conducted 8 weeks after the last dose of study drug for patients who discontinue the study drug or who 
discontinue the study prior to V10/W12. 
d Week designators denote end of the week. 
e Week 24 is the end of the study for each patient. The end of study is defined as the date the last patient completes the Week 24 Visit (see Section 4.4). 
f Assessments taken prior to administration of the study drug on Day 1 will be considered as the baseline assessment. 
g Patients will not receive meningococcal vaccinations as part of the study. Patients who are not vaccinated within 3 years of study entry will receive 
prophylactic antibiotic therapy at the time of first dose of study drug and will continue on prophylactic antibiotic therapy throughout the duration of treatment 
and until 8 weeks post the last dose of the study drug. Prophylactic antibiotic therapy is not necessary if patients have documented meningococcal vaccination 
within 3 years of study entry and at least 2 weeks prior to the first dose of the study drug. 
h Study drug infusions will be done in a hospital or clinic setting. Except on the days when blood samples are collected for PK and PD assessments, the study 
drug will be administered after all tests and procedures are complete. On the days of PK and PD assessments, blood samples will be collected predose and 
postdose. Pharmacokinetic/pharmacodynamic assessment results will not be provided to the Investigator until the end of the study. 
i In order to maintain good research practice, it is recommended that all efficacy assessments are performed by the same assessor. If Screening/Enrollment Visit 
(V1) and Day 1 Visit (V2) are on the same day or within 2 days, the efficacy assessments will not be repeated, with the exception of the Hughes FG score. 
j The nerve conduction test is performed at Screening and Week 4 to determine the GBS subtype (AMAN versus AIDP versus “indeterminate”). An independent 
expert assessor for GBS-variant determination will be appointed by Alexion. The assessor will review the clinical history of patients and analyze their nerve 
conduction test results to assign the GBS variants of AIDP, AMAN, and “indeterminate.” 
k Targeted physical examination will be performed when deemed necessary by the Investigator. A targeted physical examination will include, at a minimum, 
assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). If Screening/Enrollment Visit (V1) and Day 1 Visit (V2) are on the 
same day, the Day 1 targeted physical examination will not be repeated if already performed. 
l If height is unable to be obtained due to the patient’s medical condition, measure and record it by knee height length method. If knee height length cannot be
obtained, the patient should be asked about their latest height. If weight is unable to be obtained due to the patient’s condition, the patient should be asked about
their latest weight. If weight is unable to be measured directly, the Investigator should measure body weight as soon as possible. Height and weight, whether
captured directly, indirectly, or historically, should be recorded.
m If Screening/Enrollment Visit (V1) and Day 1 Visit (V2) are on the same day, vital signs will not be repeated unless deemed necessary by the Investigator. 
n The Patient Safety Card is provided to increase patient awareness of the risk of infections, especially meningococcal infection, and promote quick recognition 
and disclosure of any potential signs or symptoms of infection experienced by patients during the course of the study and to inform patients on what actions 
must be taken if they are experiencing signs or symptoms of infection. 
o If Screening/Enrollment Visit (V1) and Day 1 Visit (V2) are on the same day or within 2 days, clinical laboratory tests for hematology, chemistry, and
urinalysis will not be repeated for Day 1 (V2).
p If an AE occurs, the event will be followed up until it has stabilized, or the patient has returned to the state he/she was in before administration of the study 
drug, or the laboratory results return to baseline or normalize. All AEs must be managed and SAEs must be reported according to Section 10.3. 
q Women of childbearing potential should be enrolled only after a negative urine or serum pregnancy test result at Screening. Additional urine pregnancy testing 
will be standard for the protocol unless serum testing is required by site policies, local regulation, or IRB and should be performed per the specified time points. 
A negative test result must be verified within 48 hours before the first dose of study drug. If both the Screening/Enrollment Visit (V1) and Day 1 Visit (V2) 
occur within 48 hours, only 1 pregnancy test is required. A pregnancy test may also be performed at any visit at the Investigator’s discretion. 
r Measurements for eculizumab concentration, free C5, and hemolytic activation will be done at a central laboratory. 
s Blood samples for eculizumab concentration, free C5, and hemolytic activity on Day 1, Day 8, and Day 22 will be collected predose and postdose. Baseline and 
trough blood samples for eculizumab concentration and hemolytic activity will be collected 5 to 90 minutes before infusion of the study drug. Peak blood 
samples for eculizumab concentration and hemolytic activity will be collected 60 minutes (± 10 minutes) after end of infusion of the study drug. 
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t Blood samples for biomarker analyses will be collected predose at designated time points. 
Note: Given the ongoing COVID-19 pandemic, Alexion, in consultation with Investigators and local regulatory agencies, may modify some of the out-patient 
assessments with proper social distancing measures and good clinical and laboratory practices. Samples for planned PK/PD assessments may be collected as 
appropriate following guidance from Alexion. 
Abbreviations: AIDP = acute inflammatory demyelinating polyradiculopathy; AE = adverse event; ADA = antidrug antibody; AMAN = acute motor axonal 
neuropathy; C5 = complement component 5; COVID-19 = coronavirus disease 2019; D = day; DASS = Depression, Anxiety and Stress Scale, Short form, 21 
questions; ECG = electrocardiogram; EDC = electronic data capture; ET = early termination; EuroQoL-EQ-5D-5L = European Quality of 
Life-5-Dimensions-5-Levels; FG = Functional Grade; GBS = Guillain-Barré Syndrome; HCG = human chorionic gonadotropin; IRB = Institutional Review 
Board; IVIg = intravenous immunoglobulin; MMT = Manual Muscle Testing; MRC = Medical Research Council; ONLS = Overall Neuropathy Limitations 
Scale; PD = pharmacodynamic(s); PK = pharmacokinetic(s); QoL = quality of life; R-ODS = Rasch-built Overall Disability Scale; SAE = serious adverse 
event; SF-MPQ-2 = Short Form McGill Pain Questionnaire 2; V = visit; W = week; WPAI = Work Productivity and Activity Impairment. 
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2.
INTRODUCTION
Guillain-Barré syndrome is a rare, but potentially fatal neuropathy, with rapid-onset muscle 
weakness caused by the immune system damaging the peripheral nervous system. It is preceded 
in two-thirds of cases by symptoms of infection. The syndrome has a progressive, monophasic 
disease course, usually without relapse (Leonhard, 2019). It is the most common cause of acute 
flaccid tetraplegia worldwide. The initial symptoms are typically changes in sensation or pain, 
often in the back along with muscle weakness, beginning in the feet and hands, often spreading 
to the arms and upper body, with both sides being involved (Guillain-Barré Syndrome Fact 
Sheet). The symptoms may develop over hours to a few weeks. During the acute phase, the 
disorder can be life-threatening, with about 15% of people developing weakness of the breathing 
muscles and, therefore, requiring mechanical ventilation (Ferri, 2016). The disease has an annual 
global incidence of approximately 1 to 2 per 100,000 person-years. (Leonhard, 2019). 
Guillain-Barré syndrome is currently classified into 2 major subtypes: 

Acute inflammatory demyelinating form: AIDP

Acute motor axonal variant form: AMAN
In Asia and Central and South America, axonal GBS is found in 30% to 65% of patients, while 
in Europe and North America, demyelinating GBS is the major subtype (69% to 90%) 
(Kuwabara, 2013). 
Advances in understanding of the pathophysiology of AMAN have revealed that the binding of 
antibodies against ganglioside antigens and the activation of complement leads to nerve 
conduction block and eventually to axonal degeneration. In particular, the MAC, the terminal 
product of complement activation, could directly cause axonal degeneration in AMAN. 
Activation of complement and deposition of the MAC on Schwann cell membranes have also 
been identified in autopsies of patients with AIDP which suggests that AIDP is caused primarily 
by myelin disruption. However, secondary axonal loss also frequently occurs in AIDP and is the 
main cause of long-lasting disability (Misawa, 2018). 
The treatment goal in GBS is to interrupt the immune-mediated nerve damage during the acute 
phase of the disease. The standard of care treatments in GBS are PE and IVIg (Willison, 2016). 
While PE and IVIg are effective immunotherapies for patients with GBS if given during the first 
few weeks of disease, the prognosis of GBS varies. Approximately 5% of patients die of 
pneumonia, pulmonary embolism, or cardiac arrhythmia attributed to severe respiratory or limb 
muscle weakness and autonomic involvement. Up to 20% of patients cannot walk independently 
a year after disease onset. In addition to incomplete recovery of motor function, many patients 
have a long disease course, often with pain and fatigue, and the long-lasting neurological 
sequelae result in great social and physical loss (Misawa, 2018). 
2.1. 
Study Rationale 
The potential efficacy of eculizumab (SOLIRIS®) against GBS has been shown in a murine 
model of Miller Fisher syndrome, a variant of GBS. In that model, eculizumab prevented 
axon-specific antiganglioside antibody-induced nerve damage (Halstead, 2008). At present, there 
are no animal models of demyelinating GBS. However, autopsy studies involving patients with 
AIDP have shown that C3d and C5b-9 (MAC) are deposited on the Schwann cells, and, 
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therefore, eculizumab may also be an effective treatment for demyelinating GBS (Hafer-Macko, 
1996). 
The hypothesis of a causative link between complement activation and GBS pathology was 
further assessed in an Investigator-initiated study conducted in Japan. In this study, 34 patients 
with GBS were assigned to receive either eculizumab (n = 23) or placebo (n = 11). The primary 
outcome measure did not reach the predefined response rate (lower 90% confidence interval [CI] 
boundary exceeds 50%). At Week 4, the proportion of patients able to walk independently 
(FG ≤ 2) was 61% (90% CI [42 – 78]; n = 14) in the eculizumab group, and 45% (90% CI 
[20 – 73]; n = 5) in the placebo group. However, the secondary endpoint, the proportion of 
patients with an FG score of 0 (healthy) or 1 (able to run) at Week 24, was shown to favor 
eculizumab treatment (74%; 95% CI [52 – 90]; n = 17) over placebo (18%; 95%CI [2 – 52]; 
n = 2) (p=0.004) groups (Misawa, 2018). No deaths or meningococcal infections occurred during 
the study. 
The efficacy and safety results from the Investigator-initiated study support further investigation 
in this Alexion-sponsored Phase 3 controlled study, ECU-GBS-301. In this Phase 3 study, the 
complement-mediated autoimmunity hypothesis for GBS will be tested in order to confirm the 
results observed in the Investigator-initiated study. 
2.2. 
Background 
2.2.1. 
Unmet Medical Need in Patients With Guillain-Barré Syndrome 
The standard treatments for GBS are PE and IVIg. Both treatments are considered in patients 
with disease severity of ≥ FG4 and in patients who are considered to have progressive disease of 
FG3 during the first 2 weeks after onset of neuropathic symptoms (Guillain-Barré syndrome and 
Fisher syndrome treatment guideline, 2013).  
In treatment of severe GBS during the first 2 weeks after onset of neuropathic symptoms, both 
treatments are considered equally effective as monotherapies, and combination treatment with 
IVIg and PE has not been shown to be more effective than each treatment alone (Plasma 
Exchange/Sandoglobulin Guillain-Barré Syndrome Trial Group, 1997). In Japan, IVIg is selected 
as the first treatment in most cases. The approved regimen of IVIg is 400 mg/kg body weight per 
day for 5 days. 
In mild cases, GBS symptoms may spontaneously decrease within several months, leading to a 
perception that GBS is a disease with a benign prognosis. However, in severe cases (peak 
severity of FG3 or more), 16.4% to 23.1% of the patients require assisted ventilation and 
4.1% to 6.3% of the patients die of complications despite treatment with standard of care during 
the acute phase. Recovery takes several months or years, and 13.7% to 16.7% of the patients still 
require aid to walk 1 year after onset. Because of the serious risk of disability, an alternative 
novel therapy that can diminish severe sequelae and expedite recovery is needed  
(Plasma Exchange/Sandoglobulin Guillain-Barré Syndrome Trial Group, 1997). 
2.2.2. 
Eculizumab and Complement Inhibition 
A detailed description of the chemistry, pharmacology, and toxicology data available for 
eculizumab is provided in the Investigator’s Brochure (IB). 
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Eculizumab (h5G1.1-mAb) is a humanized mAb derived from the murine anti-human C5 
antibody m5G1.1. Eculizumab specifically binds C5, thereby inhibiting its cleavage to C5a and 
C5b during complement activation and blocks MAC formation. This strategic blockade of the 
complement cascade at C5 prevents the release of proinflammatory mediators and the formation 
of the cytolytic pore, while preserving the early components of complement activation that are 
essential for the opsonization of microorganisms and clearance of immune complexes. 
Eculizumab has been approved in Japan for the treatment of the following complement-related 
disorders: 

Hemolysis in patients with paroxysmal nocturnal hemoglobinuria (PNH) in 2010.

Thrombotic microangiopathy in patients with atypical hemolytic uremic syndrome
(aHUS) in 2013.

Refractory generalized myasthenia gravis (gMG) in patients whose symptoms cannot
be managed by IVIg or apheresis in 2017.

Neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are
anti-aquaporin-4 (AQP4) antibody-positive in 2019.
The safety, tolerability, pharmacokinetics (PK), and dose-response of eculizumab in these 
conditions have been sufficiently investigated in clinical studies and postmarketing surveillances 
both in Japanese and non-Japanese patients. 
2.3. 
Benefit/Risk Assessment 
Eculizumab was first approved in Japan for the treatment of PNH in April 2010. Eculizumab has 
since been approved in Japan for the treatment of aHUS, refractory gMG, and NMOSD. 
Eculizumab has been well tolerated across indications with a favorable benefit-risk profile. With 
over 10 years of postmarketing experience globally, the safety profile has remained stable. 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events (AEs) of eculizumab may be found in the Investigator’s Brochure. 
2.3.1. 
Risk Assessment 
Identified risks of eculizumab treatment and specific risk mitigation measures are presented in 
Table 2. 
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Table 2: 
Identified Risks of Eculizumab 
Risk of Clinical Significance 
Summary of Data/Rationale 
for Risk 
Mitigation Strategy 
Neisseria meningitidis infection 
Complement component 5 (C5) 
inhibition is known to increase the 
susceptibility to infections caused 
by N. meningitidis. 
Patients who did not receive a 
meningococcal vaccination within 
3 years of study entry will receive 
prophylactic antibiotic therapy at 
the time of first dose of study drug 
and will continue on prophylactic 
antibiotic therapy throughout the 
duration of treatment and until 
8 weeks post the last dose of the 
study drug. Prophylactic antibiotic 
therapy is not necessary if patients 
have documented meningococcal 
vaccination within 3 years of study 
entry and at least 2 weeks prior to 
the first dose of the study drug.
Infusion reactions 
As with all therapeutic proteins, 
administration of eculizumab may 
result in infusion reactions and 
could cause allergic or 
hypersensitivity reactions. 
Infusion reactions have been 
observed in clinical studies and in 
the postmarketing setting. Most 
events of infusion reactions have 
been nonserious.
Monitoring for infusion reactions 
will be conducted as part of routine 
safety assessments for this study. 
2.3.2. 
Benefit Assessment 
The results from a randomized study to assess the relative efficacy of PE and IVIg in patients 
with GBS showed that under the current standard of care, 4.1% to 6.3% of patients with GBS die 
and 13.7% to 16.7% cannot walk unassisted at 1 year after the onset of treatment 
(Plasma Exchange/Sandoglobulin Guillain-Barré Syndrome Trial Group, 1997). About 37.8% of 
patients have substantial difficulty in working and need to change professions due to GBS 
(Rajabally, 2012). 
Based on the results from the Investigator-initiated study in Japan, potential benefits for GBS 
patients treated with eculizumab include clinical recovery and improved mobility compared to 
untreated patients (Misawa, 2018). 
2.3.3. 
Overall Benefit: Risk Conclusion 
Taking into account the measures taken to minimize risk to patients participating in this study, 
the risks identified in association with eculizumab treatment are justified by the anticipated 
benefits that may be afforded to patients with GBS. 
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3.
OBJECTIVES AND ENDPOINTS
Objectives 
Endpoints 
Primary 
To characterize the efficacy of eculizumab in patients 
with Guillain-Barré syndrome (GBS)  

Time to first reaching a Hughes
Functional Grade (FG) score ≤ 1
Key Secondary 
To further characterize the efficacy of eculizumab over 
time in patients with GBS 

Proportion of patients with a Hughes FG
score ≤ 1 at Week 24

Proportion of patients with a Hughes FG
score improvement of ≥ 3 at Week 24

Proportion of patients with a Hughes FG
score ≤1 at Week 8
Other Secondary 
To further characterize the impact of eculizumab on 
medical resource utilization in patients with GBS  

Hospital length of stay (LOS)

Intensive care unit (ICU) stay
 
LOS in the ICU 
 
Proportion of patients admitted to the 
ICU 

Disposition post hospital discharge
To evaluate the effect of eculizumab compared with 
placebo on respiratory function in patients with GBS  

Ventilator support
 
Duration of ventilator support 
 
Proportion of patients requiring 
ventilator support 
To characterize the pharmacokinetic 
(PK)/pharmacodynamic (PD) attributes of eculizumab 
in patients with GBS 

Concentration of eculizumab in serum

Free complement component 5 (C5) in
serum

Hemolytic complement activity in serum
To assess the formation of antidrug antibodies (ADAs) 
in response to eculizumab treatment 

Incidence of ADAs
Safety 
To characterize the overall safety and tolerability of 
eculizumab in patients with GBS 

Incidence of treatment-emergent adverse
events (TEAEs), serious adverse events
(SAEs), and adverse events (AEs) leading
to study drug discontinuation
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Objectives 
Endpoints 
Tertiary/Exploratory 
To characterize the functional status of patients with 
GBS post-acute phase 

Change from baseline in the functional
scales of GBS (Rasch-built Overall
Disability Scale [R-ODS], and Overall
Neuropathy Limitations Scale [ONLS])

Change from baseline in strength
measurements (Medical Research
Council [MRC]-sumscore, and Manual
Muscle Testing [MMT])

Change from baseline in the Hughes FG
score over time
To evaluate the effect of eculizumab compared with 
placebo on pain in patients with GBS 

Change from baseline in the Short Form
McGill Pain Questionnaire 2 (SF-MPQ-2)
scores
To evaluate the effect of eculizumab compared with 
placebo on mood in patients with GBS 

Change from baseline in the Depression,
Anxiety and Stress Scale, Short form, 21
questions (DASS-21) score
To evaluate the effect of eculizumab compared with 
placebo on fatigue in patients with GBS 

Change from baseline in the Chalder
Fatigue Scale (Chalder) score
To evaluate the effect of eculizumab compared with 
placebo on quality of life (QoL) in patients with GBS 

Change from baseline in the European
Quality of Life (EuroQoL) – 5
Dimensions – 5 Levels (EQ-5D-5L) score

Change from baseline in the Work
Productivity and Activity Impairment
(WPAI) score
To evaluate complement, inflammation, and 
neurodegeneration biomarkers in patients with GBS 

Change from baseline in biomarker levels
in blood
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4.
STUDY DESIGN
4.1. 
Overall Design
Study ECU-GBS-301 is a Phase 3, prospective, multicenter, placebo-controlled, double-blind, 
randomized study to investigate the efficacy and safety of eculizumab in patients with severe 
GBS, defined using the Hughes FG scale (Plasma Exchange/Sandoglobulin Guillain-Barré 
Syndrome Trial Group, 1997) as progressively deteriorating FG3 or FG4/FG5 within 2 weeks 
from onset of weakness due to GBS. Eligible patients will be randomized to receive IV infusion 
of eculizumab or placebo at a 2:1 ratio. All patients will be on concomitant IVIg therapy as per 
standard of care (400 mg/kg body weight daily for 5 days). Randomization will be stratified by 
FG score (progressively deteriorating FG3 or FG4/FG5) and diarrhea (present or absent 
< 4 weeks prior to onset of neurological symptoms). 
There will be 3 periods in the study: 

Screening Period: up to 1 week

Treatment Period: 4 weeks

Follow-up Period: 20 weeks
Approximately 57 patients (eculizumab = 38 and placebo = 19) will be randomized. The total 
duration of study participation for each patient will be up to 25 weeks. Efficacy and safety will 
be monitored through 24 weeks after the first dose of the study drug. An interim analysis is 
planned for the unblinded sample size re-estimation when approximately 60% (ie, at least 12 
events) of the planned events are observed. 
Eculizumab will be administered via IV infusion at a dose of 900 mg once a week for 4 weeks. A 
supplemental dose of 600 mg will be given with the first dose on Day 1. 
Placebo will be administered via IV infusion once a week for 4 weeks. Placebo is a matching 
sterile, clear, colorless solution with the same buffer components but without active ingredient, 
in an identical 30 mL vial. A supplemental dose of placebo will be administered with the first 
dose on Day 1 to maintain the blind. 
Treatment allocation will be blinded to patients, study site, the Sponsor, and the Sponsor’s 
delegates throughout the study. 
4.2. 
Scientific Rationale for Study Design 
A double-blind, randomized, placebo-controlled study design is selected to provide the most 
robust evidence of the effectiveness of the intervention on disease progression and safety. 
Randomization minimizes the effects of baseline differences and confounding factors on the 
study population. The use of a placebo comparator allows for the true treatment effect of the 
intervention to be established while also allowing for study management, drug administration, 
and assessments to be conducted similarly between treatment groups, thus minimizing the 
potential for bias. An unequal (2:1) randomization scheme was chosen to decrease the number of 
patients receiving placebo. Patients will continue to receive IVIg therapy as per standard of care 
(400 mg/kg body weight daily for 5 days). 
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To ensure that factors which could affect the course of the disease are equitably distributed 
between treatment groups, a stratification scheme (FG score [progressively deteriorating FG3 or 
FG4/FG5] and diarrhea [present or absent < 4 weeks prior to onset of neurological symptoms]) 
has been implemented. 
Rationale for primary endpoint and key secondary endpoints. 
Hughes FG is a widely accepted evaluation scale for GBS. It comprehensively assesses the level 
of impairment of motor function, which is the main symptom of GBS. A score of FG ≤ 1 
represents a status where only minor symptoms/signs remain and/or the patient has regained the 
ability to run. 
4.3. 
Justification for Dose 
It is crucial to effectively inhibit complement activation and progression of neuropathy in acute 
phase of the GBS (onset to 2 to 4 weeks during which the peak of severity is attained). 
The proposed dosing regimen (ie, 4 weekly doses of 900 mg with a supplemental dose of 600 mg 
on Day 1) is modified from the labeled dosing regimen to account for the influence of extrinsic 
factors including administration of IVIg in patients with GBS. All patients in this study will 
receive IVIg therapy as per standard of care (400 mg/kg body weight daily for 5 days). 
The eculizumab PK is dependent on the neonatal Fc receptor (FcRn) recycling. As stated in the 
Company Core Data Sheet, IVIg treatment is expected to interfere with the endosomal FcRn 
recycling mechanism of mAb and thereby decrease serum eculizumab concentrations. This is 
supported by the following: 

Eculizumab PK data in an open-label study in patients with multifocal motor
neuropathy (Fitzpatrick, 2011), which indicated significantly lower median serum
eculizumab concentration (approximately 30% lower) in patients receiving 1 g/kg
IVIg compared with those not receiving IVIg (Eculizumab Dose Simulations for
Protocol ECU-GBS-301, Report Number: CPR-0023.00).

Eculizumab PK data in the Investigator-initiated study in Japan (Misawa, 2018)
which indicated an approximately 30% lower eculizumab PK exposure resulting from
2 g/kg IVIg treatment (400 mg/kg body weight daily for 5 days), compared to the
eculizumab PK data from the Japanese patients with gMG (Studies ECU-MG-301
and ECU-MG-302) (Eculizumab Dose Simulations for Protocol ECU-GBS-301,
Report Number: CPR-0023.00).
A modeling and simulation approach based on the established exposure-response relationships 
was used to characterize the proposed supplemental dose of 600 mg on Day 1. Based on the 
PK/pharmacodynamic (PD) data from the gMG Phase 3 registration study 
(Study ECU-MG-301), a threshold eculizumab concentration of 116 µg/mL at trough is required 
for ensuring complete terminal complement inhibition (ie, serum free C5 levels < 0.5 µg/mL). 
When hemolytic activity is measured by a validated PD assay, a significant and continuous 
terminal complement inhibition has been confirmed for nearly all patients who reached serum 
eculizumab concentrations that exceed 116 μg/mL. The PK/PD data from the NMOSD Phase 3 
registration study (Study ECU-NMO-301) also confirmed that this threshold concentration led to 
immediate, complete, and sustained inhibition of terminal complement, as demonstrated by 
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serum free C5 < 0.5 µg/mL throughout the entire Treatment Period in nearly all patients. 
Simulations using the established population-PK/PD model of eculizumab confirmed that the 
proposed dosing regimen in patients with GBS is expected to achieve the threshold eculizumab 
concentration at trough for nearly all patients (defined as 97.5 percentile of the population) who 
will be dosed with IVIg regimen (400 mg/kg body weight daily for 5 days) (Eculizumab Dose 
Simulations for Protocol ECU-GBS-301, Report Number: CPR-0023.00). 
Therefore, all patients in the eculizumab treatment arm in this study will receive a total dose of 
1500 mg (900 mg plus 600 mg supplemental dose) on Day 1 followed by 3 weekly doses of 
900 mg. 
4.4. 
End of Study Definition 
A patient is considered to have completed the study if he/she has completed his/her last visit at 
Week 24 as shown in the Schedule of Activities (SoA; Section 1.3). 
The end of the study is defined as the date the last patient completes the last visit at Week 24 as 
shown in the SoA. 
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5.
STUDY POPULATION
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
5.1. 
Inclusion Criteria 
Patients are eligible to be included in the study only if all of the following criteria apply: 
Age 
1. Patients must be ≥ 18 years of age at the time of signing the informed consent form
(ICF).
Type of Patient and Disease Characteristics 
2. Patients who meet the 2019 consensus GBS criteria (Leonhard, 2019).
3. Patients who are able to run prior to onset of GBS symptoms.
4. Patients with onset of weakness due to GBS ≤ 2 weeks before screening.
5. Patients unable to walk unaided for ≥ 5 meters (progressively deteriorating FG3 or FG4
to FG5).
6. Patients who are already on IVIg or deemed eligible for and who will start IVIg.
7. Patients who can start their first dose of study drug before the end of the IVIg treatment
period
8. Patients who have access to physical therapy care and are willing to undergo an
optimized regimen of physical therapy care (including both inpatient and outpatient
rehabilitation) as appropriate.
Sex 
9. Male and female patients are eligible for this study.
10. Female patients of childbearing potential and male patients with female partners of
childbearing potential must follow protocol-specified guidance for avoiding pregnancy
while on treatment and for 5 months after last dose of study drug.
a.
Male patients:
Male patients must agree to use contraception as detailed in the protocol (Section 10.4) during 
the Treatment Period and for at least 5 months after last dose of study drug and refrain from 
donating sperm during this period. 
b. Female patients:
A female patient is eligible to participate if she is not pregnant, not breastfeeding, and meets at 
least 1 of the following conditions: 

Not a woman of childbearing potential (WOCBP).
OR 
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
Is a WOCBP and using an acceptable contraceptive method as described in
Section 10.4 during the Treatment Period and for at a minimum of 5 months after the
last dose of study drug.
 The Investigator should evaluate the effectiveness of the contraceptive method in
relationship to the first dose of study drug. A WOCBP must have a negative 
highly sensitive pregnancy test (urine or serum pregnancy test) at Screening and 
within 48 hours before the first dose of study drug. Additional requirements for 
pregnancy testing during and after study drug administration are described in 
Section 10.4. The Investigator is responsible for review of medical history, 
menstrual history, and recent sexual activity to decrease the risk for inclusion of a 
woman with an early undetected pregnancy. 
Informed Consent 
11. Capable of giving signed informed consent as described in Section 10.1.3 which includes
compliance with the requirements and restrictions listed in the ICF and in this protocol.
5.2. 
Exclusion Criteria 
Patients are excluded from the study if any of the following criteria apply: 
Medical Conditions 
1. Patients with history of peripheral polyneuropathy other than GBS, eg, diabetic (except
for mild sensory disturbance) or severe vitamin B1 deficiency-related peripheral
polyneuropathy.
2. Patients with unresolved N. meningitidis infection or a history of meningococcal
infection.
3. Patients with active systemic infectious diseases determined to be clinically significant by
the Investigator.
4. Patients who are unable to take at least 1 antimicrobial agent used to prevent
N. meningitidis.
5. Hypersensitivity to any ingredient contained in the study drug, including hypersensitivity
to murine proteins.
6. Patients who are known to have or are suspected of having hereditary complement
deficiencies.
7. Any medical or psychological condition that, in the opinion of the Investigator, could
increase the risk to the patient by participating in the study or confound the outcome of
the study.
Prior/Concomitant Therapy 
8. Patients who have previously received or are currently receiving treatment with
complement modulators.
9. Patients who have received rituximab within 12 weeks prior to screening.
10. Patients who are being considered for or are already on plasmapheresis.
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11. Patients who have received immunosuppressive treatment (eg, azathioprine,
cyclosporine, tacrolimus, or > 20 mg prednisolone daily) during the 4 weeks prior to
providing consent.
Prior/Concurrent Clinical Study Experience 
12. Patients who have been administered another investigational product within 30 days or
5 half-lives (whichever is longer) prior to providing consent or are currently participating
in another interventional study.
Other Exclusions 
13. Patients who are unable to comply with study procedures and the treatment regimen.
14. Patients who are pregnant or lactating.
5.3. 
Lifestyle Considerations 
There are no lifestyle restrictions for this study. 
5.4. 
Screen Failures 
Screen failures are defined as patients who consent to participate in the clinical study but are not 
subsequently randomly assigned to study drug. A minimal set of screen failure information is 
required to ensure transparent reporting of screen failure patients to meet the Consolidated 
Standards of Reporting Trials (CONSORT) publishing requirements and to respond to queries 
from regulatory authorities. Minimal information includes demography, screen failure details 
(eg, failed eligibility criteria), and any AEs, including any serious adverse events (SAEs) and any 
related concomitant medication, occurring during the Screening Period. 
Individuals who do not meet the criteria for participation in this study (screen failure) due to a 
reason that is expected to resolve or has resolved, may be rescreened based on discussion and 
agreement between the Investigator and the Medical Monitor. 
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6.
STUDY DRUG
Study drug is defined as any investigational intervention(s), marketed product(s), placebo, or 
medical device(s) intended to be administered to a study patient according to the study protocol. 
6.1. 
Study Drug(s) Administered 
Intervention name 
Eculizumab  
Placebo 
Dose formulation 
Sterile liquid 
Sterile liquid 
Unit dose strength 
Eculizumab is supplied as one 
300 mg/30 mL (10 mg/mL) single-dose 
vial 
Placebo is supplied in an identical 
30 mL vial 
Dosage level 
900 mg once a week for 4 weeks* 
Matching placebo once a week for 
4 weeks
Route of 
administration 
IV infusion 
IV infusion 
Use 
Experimental 
Placebo 
IMP and NIMP 
IMP 
IMP 
Sourcing 
Provided centrally by Alexion or 
contracted manufacturing organization.
Provided centrally by Alexion or 
contracted manufacturing organization.
Packaging and 
labeling 
Study drug will be provided in glass 
vials and stoppered with a butyl rubber 
stopper with an aluminum overseal and 
a flip-off cap. Study drug will be 
supplied in kits and labeled as required 
per country requirement.
Study drug will be provided in glass 
vials and stoppered with a butyl rubber 
stopper with an aluminum overseal and 
a flip-off cap. Study drug will be 
supplied in kits and labeled as required 
per country requirement. 
* A supplemental dose of 600 mg will be given with the first dose on Day 1.
Abbreviations: IMP = investigational medicinal product; IV = intravenous; NIMP = non-investigational medicinal
product. 
6.2. 
Preparation/Handling/Storage/Accountability 
1. The Investigator or designee must confirm appropriate temperature conditions have been
maintained during transit for all study drug received and any discrepancies are reported
and resolved before use of the study drug.
2. Only patients enrolled in the study may receive the study drug and only authorized site
staff may supply or administer the study drug. All study drug must be stored in a secure,
environmentally controlled, and monitored (manual or automated) area in accordance
with the labeled storage conditions with access limited to the Investigator and authorized
site staff.
3. The Investigator, institution, or the head of the medical institution (where applicable) is
responsible for study drug accountability, reconciliation, and record maintenance
(ie, receipt, reconciliation, and final disposition records).
a.
This responsibility includes the reporting of any product complaints to
within 1 business day. A product complaint is
defined as any written, electronic, or oral communication that alleges deficiencies
related to the identity, quality, durability, reliability, usability, safety, effectiveness, or
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performance of a product or clinical trial material and/or its packaging components 
after it is has been released for distribution to an end customer that affects the 
performance of such product. 
4. Further guidance and information for the final disposition of unused study drugs are
provided in the Pharmacy Manual.
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
6.3.1. 
Randomization 
Patients will be randomly allocated on Day 1 to one of two treatment groups after the 
Investigator and Medical Monitor have verified that they are eligible. Patients will be stratified 
by FG score (progressively deteriorating FG3 or FG4/FG5) and diarrhea (present or absent 
< 4 weeks prior to onset of neurological symptoms) and randomized in a 2:1 ratio to either 
eculizumab IV infusion or placebo IV infusion. 
All patients will be centrally randomized using an Interactive Response Technology (IRT) 
system. Before the study is initiated, login information and directions for the IRT system will be 
provided to each site. Study drug will be given IV at the study visits summarized in the SoA 
(Section 1.3). 
6.3.2. 
Blinding 
Patients, study site, the Sponsor, and the Sponsor’s delegates directly associated with the conduct 
of the study will be blinded to patient treatment assignments. The blind will be maintained by 
using identical study drug kits and labels for eculizumab and placebo. The placebo will have an 
identical appearance to that of eculizumab. The randomization code will be maintained by the 
IRT provider. A supplemental dose of placebo will be administered with the first dose on Day 1 
to maintain the blind. 
The IRT will be programmed with blind-breaking instructions. In case of an emergency, the 
Investigator has the sole responsibility for determining if unblinding of a patient’s study drug 
assignment is warranted. Patient safety must always be the first consideration in making such a 
determination. If the Investigator decides that unblinding is warranted, the Investigator should 
make every effort to contact the Medical Monitor prior to unblinding a patient’s study drug 
assignment unless this could delay emergency treatment of the patient. If a patient’s study drug 
assignment is unblinded, the Medical Monitor must be notified within 24 hours after breaking 
the blind. The date and reason that the blind was broken must be recorded in the source 
documentation and electronic case report form (eCRF), as applicable. 
When unblinding is the result of an AE which is unexpected or related and serious, the blind will 
be broken for that specific patient only. The blind with regard to treatment allocation for that 
specific patient will be maintained for all persons (other than the Treating Physician) responsible 
for the ongoing conduct of the study (such as the Management, Medical Monitors, etc.) and those 
responsible for data analysis and interpretation of results at the conclusion of the study, such as 
biometrics personnel. 
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Unblinded information will only be accessible to those who need to be involved in the safety 
reporting to health authorities, PK/PD and biomarker data handling, and/or Institutional Review 
Boards (IRBs). 
6.4. 
Study Drug Compliance 
Patients will be dosed at the site where they will receive study drug directly from the Investigator 
or designee, under medical supervision. The date and time of each dose administered in the 
institution will be recorded in the source documents and recorded in the eCRF. The dose of study 
drug and patient identification will be confirmed at the time of dosing by a member of the study 
site staff other than the person administering the study drug. 
For additional information on study drug compliance and management, refer to the Pharmacy 
Manual. 
6.5. 
Concomitant Therapy 
Any medication or vaccine (including over-the-counter or prescription medicines, vitamins, 
and/or herbal supplements) or other specific categories of interest that the patient is receiving at 
the time of enrollment or receives during the study must be recorded along with: 

Reason for use

Dates of administration including start and end dates

Dosage information including dose and frequency
The Medical Monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
6.5.1. 
Allowed Medicine and Therapy 

Intravenous immunoglobulin therapy as per standard of care (400 mg/kg body weight
daily for 5 days) will be administered. The first dose of study drug will be given
before or during the 5-day course of IVIg therapy.

If IVIg is administered on the same day as the study drug, the study drug and IVIg
must be given at least 1 hour apart, so that the patient can be observed for immediate
infusion reactions.
After discussion with the Medical Monitor, a second treatment of IVIg may be
allowed 4 or more weeks after the first dose of study drug.

Optimized regimen of physical therapy including both inpatient and outpatient
rehabilitation.
6.5.2. 
Disallowed Medicine and Therapy 
The following medications and therapies are prohibited during the study: 

Rituximab

Plasmapheresis
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
Steroid pulse therapy (more than 500 mg/day of methylprednisolone)

Immunosuppressive drugs

Other investigational drugs

Other complement inhibitory agent
6.5.3. 
Disallowed Testing
Eculizumab administration is known to lower 50% hemolytic complement activity (CH50). To 
maintain study blind, measurements of CH50 and other serum complement pathway indicators, 
including anti-ganglioside antibody testing, are not allowed prior to database lock and study 
unblinding. 
If measurement of a serum complement pathway indicator is considered necessary by the 
Investigator, it should be discussed with the Medical Monitor and the procedures described for 
unblinding (see Section 6.3.2) and discontinuation of the patient from the study (see Section 7.2) 
should be followed. 
6.6. 
Dose Modification 
There will be no modification of the planned dose in this study. 
6.7. 
Intervention After the End of the Study 
Not applicable. 
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7.
DISCONTINUATION OF STUDY DRUG AND PATIENT
DISCONTINUATION/WITHDRAWAL
7.1. 
Discontinuation of Study Drug
In rare instances, it may be necessary for a patient to permanently discontinue (definitive 
discontinuation) the study drug. If the study drug is definitively discontinued, the patient should 
remain in the study to be evaluated for safety follow-up. See the SoA (Section 1.3) for data to be 
collected at the time of discontinuation of study drug and follow-up and for any further 
evaluations that need to be completed. 
Patients should be considered for discontinuation from study drug if any of the following occur 
during the study: 

Serious hypersensitivity reaction;

Severe uncontrolled infection;

Use of disallowed medication as defined in Section 6.5;

Pregnancy or planned pregnancy;

The Medical Monitor or the Investigator deems it is necessary for the patient; or

Unblinding of study drug assignment during the Treatment Period.
7.2. 
Patient Discontinuation/Withdrawal From the Study

All efforts should be made to ensure patients are willing to comply with study
participation prior to conducting the screening procedures. The study staff should
notify Alexion and their site monitor of all study withdrawals as soon as possible. The
reason for patient discontinuation must be recorded in the source documents and
eCRF.

A patient may withdraw from the study at any time at his/her own request or may be
withdrawn at any time at the discretion of the Investigator for safety, behavioral,
compliance, or administrative reasons. This is expected to be uncommon.

At the time of discontinuing from the study, if possible, an Early Termination Visit
should be conducted, as shown in the SoA. See SoA (Section 1.3) for data to be
collected at the time of study discontinuation and follow-up and for any further
evaluations that need to be completed.

A Safety Follow-up Phone Call or Visit should be conducted 8 weeks after the last
dose of study drug for patients who discontinue the study drug or who discontinue the
study prior to V10/W12 as shown in the SoA (Section 1.3).

The patient will be permanently discontinued from the study drug and from the study
at that time.

If the patient withdraws consent for disclosure of future information, Alexion may
retain and continue to use any data collected before such a withdrawal of consent.
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
If a patient withdraws from the study, he/she may request destruction of any samples
taken and not tested, and the Investigator must document this in the site study records.
7.3. 
Lost to Follow-up
If a patient fails to return, or is otherwise unavailable, for a scheduled visit within the acceptable 
visit window (Section 1.3), the site study staff must make a reasonable attempt to contact the 
patient to determine the reason for missing the appointment. 
As it is vital to obtain any patient’s missing visit information to ensure the missed appointment 
was not due to an AE, every effort must be made to undertake protocol-specified safety 
follow-up procedures. 
In the exceptional circumstance where a patient cannot or does not come to the study site for 
examination, the patient will be instructed to see his or her local neurologist or physician. In this 
event, if possible, the Treating Physician or designee will contact the local neurologist or 
physician to obtain as much information as possible about the patient’s medical and neurological 
condition, and provide clinical guidance, if needed. The study site will obtain relevant medical 
records as documentation from the local physician’s examination and enter relevant data in the 
AE form as appropriate. 
A patient will be considered lost to follow-up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site. 
The following actions must be taken if a patient fails to return to the site for a required study 
visit: 

The site must attempt to contact the patient and reschedule the missed visit as soon as
possible and counsel the patient on the importance of maintaining the assigned visit
schedule and ascertain whether or not the patient wishes to and/or should continue in
the study.

Before a patient is deemed lost to follow-up, the Investigator or designee must make
every effort to regain contact with the patient (where possible, 3 telephone calls and,
if necessary, a certified letter to the patient’s last known mailing address or local
equivalent methods). These contact attempts should be documented in the patient’s
medical record.

Should the patient continue to be unreachable, he/she will be considered to have
withdrawn from the study.
Discontinuation of specific sites or of the study as a whole are handled as part of Section 10.1.9. 
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8.
STUDY ASSESSMENTS AND PROCEDURES

Study procedures and their timing are summarized in the SoA (Section 1.3). Protocol
waivers or exemptions are not allowed.

Immediate safety concerns should be discussed with the Medical Monitor
immediately upon occurrence or awareness to determine if the patient should
continue or discontinue study drug.

Adherence to the study design requirements, including those specified in the SoA, is
essential and required for study conduct.

All screening evaluations must be completed and reviewed to confirm that potential
patients meet all eligibility criteria. The Investigator will maintain a screening log to
record details of all patients screened and to confirm eligibility or record reasons for
screening failure, as applicable.

Procedures conducted as part of the patient’s routine clinical management (eg, blood
count) and obtained before signing of the ICF may be utilized for screening or
baseline purposes provided the procedures met the protocol-specified criteria and
were performed within the time frame defined in the SoA.
8.1. 
General Assessments and Procedures
8.1.1. 
Informed Consent
The Investigator or qualified designee must obtain a signed and dated ICF from each patient (or 
the patient’s legally authorized representative, as applicable) prior to conducting any study 
procedures as described in Section 10.1.3. All efforts should be made to ensure patients are 
willing to comply with study participation prior to conducting the screening procedures. 
8.1.2. 
Medical/Surgical/Social History 
The Investigator will review and document the patient’s medical/surgical/social history and 
diagnosis at the Screening Visit. Social history will include work status and mobility prior to 
hospitalization. 
8.1.3. 
Vaccine and Antibiotic Prophylaxis 
As with any terminal complement antagonist, the use of eculizumab increases the patient’s 
susceptibility to meningococcal infection (caused by N. meningitidis). 
Patients will not receive meningococcal vaccinations as part of the study. Patients who have not 
received a meningococcal vaccination within 3 years of study entry will receive prophylactic 
antibiotic therapy at the time of first dose of study drug and will continue on prophylactic 
antibiotic therapy throughout the duration of treatment and until 8 weeks post the last dose of the 
study drug. 
Prophylactic antibiotic therapy is not necessary if patients have documented meningococcal 
vaccination within 3 years of study entry and at least 2 weeks prior to the first dose of the study 
drug. 
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8.1.4. 
Inclusion/Exclusion Criteria 
All inclusion (Section 5.1) and exclusion (Section 5.2) criteria must be reviewed by the 
Investigator or qualified designee to ensure the patient qualifies for study participation. 
Both the Investigator and the Sponsor must approve patient eligibility before enrollment. 
8.1.5. 
Study Drug Administration 
Eculizumab or matching placebo will be administered via IV infusion at a dose of 900 mg once a 
week for 4 weeks. A supplemental dose of 600 mg eculizumab or matching placebo will be 
given with the first dose on Day 1. At the scheduled dosing visits (Section 1.3), study drug 
infusion should be performed after all other tests and procedures have been completed, excluding 
the postdose blood sampling for PK and PD assessments. 
Refer to Section 6 for additional information on study drugs including preparation, handling, 
storage, and accountability. For detailed instructions, refer to the Pharmacy Manual. 
8.2. 
Efficacy Assessments 
Planned time points for all efficacy assessments are provided in the SoA (Section 1.3). In order 
to maintain good research practice, it is recommended that all efficacy assessments are 
performed by the same assessor. 
Additional details related to the efficacy assessments are provided in the relevant manuals. 
8.2.1. 
Hughes Functional Grade Score 
Mobility will be evaluated on a 7-point scale as listed in Table 3 (Plasma 
Exchange/Sandoglobulin Guillain-Barré Syndrome Trial Group, 1997). Higher numbers indicate 
more severe impairment. 
Table 3: 
Disability Functional Grade Scale 
Score 
Description 
0 
Healthy, no signs or symptoms of Guillain-Barré syndrome.
1 
Minor signs or symptoms and able to run.
2 
Able to walk 5 m across an open space without assistance.
3 
Able to walk 5 m across an open space with the help of one person and waist-level 
walking-frame, stick, or sticks. 
4 
Chairbound/bedbound: unable to walk as in 3.
5 
Requiring assisted ventilation (for at least part of day or night). 
6 
Dead. 
8.2.2. 
Rasch-built Overall Disability Scale Score 
The Rasch-built Overall Disability Scale (R-ODS) score is a 24-item linearly weighted scale that 
specifically captures activity and social participation limitations in patients with neurological 
conditions like GBS (van Nes, 2011). 
If the patient has difficulty completing the questionnaire due to muscular weakness, a family 
member/caregiver may record the patient’s self-evaluation in the questionnaire. A low score 
indicates more severe symptoms. 
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A copy of the R-ODS scale is provided in Section 10.5. 
8.2.3. 
Overall Neuropathy Limitations Scale 
The Overall Neuropathy Limitations Scale (ONLS) consists of a checklist for interviewing 
patients regarding subjective symptoms in their hands or arms (numbness, tingling, or weakness) 
and legs (difficulty running or climbing stairs, difficulty with walking, etc.). A total score will be 
given as well as a score for each individual limb. A higher score means that symptoms are more 
severe (Graham, 2006). 
A copy of the ONLS scale is provided in Section 10.6. 
8.2.4. 
Medical Research Council-SumScore 
The Medical Research Council (MRC)-sumscore is a summation of the strength of the following 
6 muscle groups tested on both sides (right and left) according to the MRC scale (Table 4) 
(Nerve Injuries Committee, MRC Memorandum No. 45, 1976 and Kleyweg, 1991). 

Abduction of the arm

Flexion of the forearm

Extension of the wrist

Flexion of the leg

Extension of the knee

Dorsal flexion of the foot
Table 4: 
Medical Research Council Scale 
Grade 
Description 
0 
No visible contraction 
1 
Visible contraction without movement of the limb (not existent for hip 
flexion)
2 
Movement of the limb but not against gravity 
3 
Movement against gravity over (almost) the full range 
4 
Movement against gravity and resistance 
5 
Normal  
The assessment will give the ‘MRC-sumscore’ ranging from 0 (paralysis) to 60 (normal 
strength). The patient is investigated in sitting posture and/or lying supine. 
8.2.5. 
Manual Muscle Testing 
The Manual Muscle Testing (MMT) evaluates the muscle strength of major muscles in the body: 
both sides of deltoid, biceps brachii, wrist extension, iliopsoas, quadriceps muscle, and tibialis 
anterior muscle as well as neck anteflexion. Assessment of muscle strength is based on the 
5 parameters listed in Table 5 and the grade of each muscle is totaled into a final score  
(based on Nerve Injuries Committee, MRC Memorandum No. 45, 1976). 
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Table 5: 
Manual Muscle Testing Score by Medical Research Council System 
Grade 
Description 
0 
No contraction 
1 
Flicker or trace of contraction 
2 
Active movement, with gravity eliminated  
3 
Active movement against gravity 
4 
Active movement against gravity and resistance 
5 
Normal power 
8.2.6. 
Nerve Conduction Test 
The nerve conduction test is performed at Screening and Week 4 to determine the GBS subtype 
(AMAN versus AIDP versus ‘indeterminate’). 
The nerve conduction test measures distal latency, compound muscle action potential (CMAP) 
amplitude (proximal, distal), CMAP duration (proximal, distal), motor nerve conduction 
velocity, and minimum F-wave latency of the median, ulnar, fibular, and tibial nerves. It also 
evaluates sensory nerve conduction amplitude and velocity of the median, ulnar, and sural 
nerves. The tests for each individual patient should be conducted on one side of the body, and 
that side should remain the same throughout the study period. 
An independent expert assessor for GBS-variant determination will be appointed by Alexion to 
review the clinical history of patients and analyze their nerve conduction test results 
(Section 9.7). 
8.2.7. 
Short Form McGill Pain Questionnaire 2 
The Short Form McGill Pain Questionnaire 2 (SF-MPQ-2), a shorter version of the McGill Pain 
Questionnaire, is a multidimensional measure of perceived pain in adults with chronic pain. The 
SF-MPQ-2 includes visual analogue and verbal rating scales of pain intensity as well as 15 pain 
descriptors that are each rated on a 4-point verbal scale (Dworkin, 2019). 
A copy of the SF-MPQ-2 questionnaire is provided in Section 10.7. 
8.2.8. 
Depression, Anxiety and Stress Scale, Short Form, 21 Questions Score 
The Depression, Anxiety and Stress Scale, Short form, 21 questions (DASS-21) is a 42-item 
self-report instrument designed to measure the negative emotional states of depression, anxiety 
and stress (DASS, Psychology Foundation of Australia, 2018). 
Each of the 3 DASS scales contains 14 items, divided into subscales of 2 to 5 items with similar 
content. 

The Depression scale assesses dysphoria, hopelessness, devaluation of life,
self-deprecation, lack of interest/involvement, anhedonia, and inertia.

The Anxiety scale assesses autonomic arousal, skeletal muscle effects, situational
anxiety, and subjective experience of anxious affect.
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
The Stress scale is sensitive to levels of chronic nonspecific arousal. It assesses
difficulty relaxing, nervous arousal, and being easily upset/agitated,
irritable/over-reactive, and impatient.
Patients are asked to use 4-point severity/frequency scales to rate the extent to which they have 
experienced each state over the past week. Scores for Depression, Anxiety and Stress are 
calculated by summing the scores for the relevant items. 
A copy of the DASS-21 questionnaire is provided in Section 10.8. 
8.2.9. 
Chalder Fatigue Scale Score 
The Chalder Fatigue Scale (Chalder) measures subjective symptoms of fatigue and covers 
physical fatigue (eg, lack energy, feel weak, less muscle strength, need to rest), and mental 
fatigue (eg, concentration, memory). It contains 11 items to produce a global score and 
2 domains of physical and mental fatigue (Cella, 2010). 
A copy of the Chalder score is provided in Section 10.9. 
8.2.10. 
European Quality of Life – 5 Dimensions – 5 Levels Score 
The 5 Dimensions – 5 Levels (EQ-5D-5L) is a well-known and widely used health status 
instrument. It was developed by the European Quality of Life (EuroQoL) Group in the 1980s to 
provide a concise, generic instrument that could be used to measure, compare, and value health 
status across disease areas (Devlin, 2017). 
A copy of the EuroQoL-EQ-5D-5L questionnaire is provided in Section 10.10. 
8.2.11. 
Work Productivity and Activity Impairment Questionnaire 
The Work Productivity and Activity Impairment (WPAI) questionnaire is used to measure the 
effect of general health and symptom severity on work productivity and regular activities. 
Function-related endpoints are assessed as part of this questionnaire which allow a measure of 
the economic impact of relative differences in either the safety or efficacy of therapeutic 
interventions (Reilly, 1993). 
A copy of the WPAI questionnaire is provided in Section 10.11. 
8.3. 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA (Section 1.3). 
8.3.1. 
Physical Examinations 

A complete physical examination will include, at a minimum, assessments of the
cardiovascular, respiratory, gastrointestinal, and neurological systems.

A targeted physical examination will include, at a minimum, assessments of the skin,
lungs, cardiovascular system, and abdomen (liver and spleen).

Investigators should pay special attention to clinical signs related to previous serious
illnesses.
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
For consistency, all efforts should be made to have the physical examination
performed by the same qualified study staff at each study visit.

Additional physical examinations can be performed as medically indicated during the
study at the Investigator’s discretion.
8.3.2. 
Height and Weight

Body weight will be measured in kilograms

Height will be measured in centimeters.
8.3.3. 
Vital Signs

Vital signs will be measured at every visit and will include assessments of systolic
and diastolic blood pressure (mm Hg), temperature (°C), respiratory rate (RR), and
heart rate (HR) (beats/minute). Vital signs will be obtained after the patient has been
supine or seated for at least 5 minutes.

Blood pressure and pulse measurements will be assessed with a completely
automated device. Manual techniques will be used only if an automated device is not
available. Ideally, the same arm for each patient should be used for measurements.

Blood pressure and pulse measurements should be preceded by at least 5 minutes of
rest for the patient in a quiet setting without distractions (eg, television, cell phones).
8.3.4. 
Electrocardiograms

A single 12-lead electrocardiogram (ECG) will be obtained as outlined in the SoA
(Section 1.3) using an ECG machine that automatically calculates the HR and
measures PR, QRS, interval between the start of the Q wave and the end of the
T wave in an ECG (QT), and corrected QT interval (QTc) intervals.

Patients must be supine for approximately 5 to 10 minutes before ECG collection and
remain supine but awake during ECG collection.

The Investigator or designee will be responsible for reviewing the ECG to assess
whether the ECG is within normal limits and determine the clinical significance of
the results. These assessments will be recorded on the eCRF.
8.3.5. 
Prior and Concomitant Medication Review
It is important for Investigators or a qualified designee to review each medication and therapy 
the patient is taking before starting the study and at each visit (Section 1.3). 
Any medication or vaccine (including over-the-counter or prescription medicines, vitamins, 
and/or herbal supplements) or other specific categories of interest that the patient is receiving at 
the time of enrollment or receives during the study must be recorded along with: 

Reason for use

Dates of administration including start and end dates

Dosage information including dose and frequency
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The Medical Monitor should be contacted if there are any questions regarding concomitant or 
prior medications and therapy. 
8.3.5.1. 
Prior Medications 
Prior medications and/or vaccines and procedures (any therapeutic intervention, such as 
surgery/biopsy or physical therapy) that the patient took or underwent within 30 days before the 
start of screening or during the Screening Period before the first dose of eculizumab, as well as 
any meningococcal vaccine administered within the last 3 years prior to study entry, will be 
recorded in the patient’s eCRF. Additionally, all medications or therapies ever used for GBS 
before the first dose of eculizumab must be collected. 
8.3.5.2. 
Concomitant Medications and Therapies 
Use of concomitant medications and therapies (Section 6.5) will be evaluated during the study. 
At each visit, patients should be questioned about any new medication or therapies or changes to 
concomitant medications and therapies since the last visit. Concomitant medications and 
therapies should be recorded in the source documents and the patient’s eCRF. 
Any changes in concomitant medications also will be recorded in the patient’s source 
document/medical chart and eCRF. When possible, concomitant medications will be recorded 
from the first infusion of study drug until the patient has discontinued or completed the study. 
Antibiotics administered for prophylaxis of meningococcal infection will also be recorded. 
8.3.6. 
Clinical Safety Laboratory Assessments 

See Section 10.2 for the list of clinical laboratory tests to be performed and the SoA
(Section 1.3) for the timing and frequency.

The Investigator must review the laboratory report, document this review, and record
any clinically relevant changes occurring during the study in the AE section of the
eCRF. The laboratory reports must be filed with the source documents. Clinically
significant abnormal laboratory findings are those which are not associated with the
underlying disease, unless judged by the Investigator to be more severe than expected
for the patient’s condition.

All laboratory tests with values considered clinically significantly abnormal during
participation in the study or within 8 weeks after the last dose of study drug should be
repeated until the values return to normal or baseline or are no longer considered
clinically significant by the Investigator or Medical Monitor.
 If such values do not return to normal/baseline within a period of time judged
reasonable by the Investigator, the etiology should be identified, and Alexion 
notified. 
 All protocol-required laboratory assessments, as defined in Section 10.2, must be 
conducted in accordance with the Laboratory Manual and the SoA. 
 If laboratory values from non-protocol-specified laboratory assessments 
performed at the institution’s local laboratory require a change in patient 
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management or are considered clinically significant by the Investigator (eg, SAE 
or AE or dose modification), then the results must be recorded in the eCRF. 
8.3.7. 
Pregnancy 

Pregnancy data from female patients and female spouses/partners of male patients will be
collected at the time points specified in the SoA (Section 1.3). Any female patient who
becomes pregnant while participating in the study will be discontinued from the study
drug. If a pregnancy is reported, the Investigator must immediately inform the Medical
Monitor within 24 hours of awareness of the pregnancy and follow the procedures
outlined in Section 10.4.

For all Alexion products, both in development or post approval, exposure during
pregnancy must be recorded and the pregnancy followed, until the outcome of the
pregnancy is known (ie, spontaneous miscarriage, elective termination, normal birth, or
congenital abnormality), even if the patient discontinues the study drug or withdraws
from the study. The corresponding infant must be followed up with for 3 months
postpartum.

Pregnancy is not considered as an AE (Section 10.4.3) unless there is a suspicion that the
study drug may have interfered with the effectiveness of a contraceptive medication.
However, complications of pregnancy and abnormal outcomes of pregnancy are AEs and
may meet the criteria for an SAE (eg, ectopic pregnancy, spontaneous abortion,
intrauterine fetal demise, neonatal death, or congenital anomaly) (Section 8.4). Elective
abortions without complications should not be reported as AEs.
8.3.8. 
Patient Safety Card 
A Patient Safety Card will be provided to the patients to carry with them at all times. The card is 
provided to increase patient awareness of the risk of infections, especially meningococcal 
infection, and promote quick recognition and disclosure of any potential signs or symptoms of 
infection experienced by patients during the course of the study and to inform patients on what 
actions must be taken if they are experiencing signs or symptoms of infection. 
At each visit, the study staff will ensure that the patient has the Patient Safety Card (Section 1.3). 
8.4. 
Adverse Events and Serious Adverse Events 
The definitions of AEs and SAEs can be found in Section 10.3. 
Adverse events will be reported to the Investigator or qualified designee by the patient (or, when 
appropriate, by a caregiver, surrogate, or the patient’s legally authorized representative). 
The Investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up AEs that are serious, considered related to the study drug or study procedures, or that caused 
the patient to discontinue the study drug (see Section 7). 
Procedures for recording, evaluating, reporting, and follow-up of AEs and SAEs are outlined in 
Section 10.3. 
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8.4.1. 
Time Period and Frequency for Collecting AE and SAE Information 
All AEs and SAEs will be collected from the signing of the ICF until the last Follow-up Visit. 
All SAEs will be recorded and reported to Alexion or designee immediately and under no 
circumstance should this exceed 24 hours, as indicated in Section 10.3. The Investigator will 
submit any updated SAE data to Alexion within 24 hours of it being available. 
Investigators are not obligated to actively seek AE or SAE data after the conclusion of study 
participation. However, if the Investigator learns of any SAE, including a death, at any time after 
a patient has been discharged from the study, and he/she considers the event to be reasonably 
related to the study drug or study participation, the Investigator must promptly notify Alexion. 
8.4.2. 
Method of Detecting AEs and SAEs 
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Section 10.3. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the patient is the preferred method to inquire about AE 
occurrences. 
8.4.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow up on each 
patient at subsequent visits/contacts. All SAEs will be followed up until resolution, stabilization, 
the event is otherwise explained, or the patient is lost to follow-up (as defined in Section 7.3). 
Further information on follow-up procedures is provided in Section 10.3. 
8.4.4. 
Regulatory Reporting Requirements for SAEs  

Prompt notification of an SAE by the Investigator to Alexion is essential so that legal
obligations and ethical responsibilities towards the safety of patients and the safety of
a study drug under clinical investigation are met.

Alexion has a legal responsibility to notify both the local regulatory authority and
other regulatory agencies about the safety of a study drug under clinical investigation.
Alexion will comply with country-specific regulatory requirements relating to safety
reporting to the regulatory authority, IRBs, and Investigators.

Suspected unexpected serious adverse reactions (SUSARs) must be reported
according to local regulatory requirements and Alexion policy and forwarded to
Investigators as necessary.

An Investigator who receives an Investigator safety report describing an SAE or other
specific safety information (eg, summary or listing of SAEs) from Alexion will
review and then file it along with the Investigator’s Brochure and will notify the IRB,
if appropriate according to local requirements.
8.4.5. 
Adverse Events of Special Interest 
Meningococcal infections will be collected as adverse events of special interest (AESIs). 
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8.5. 
Treatment of Overdose 
For this study, any dose of study drug greater than that specified in the protocol will be 
considered an overdose. 
Alexion does not recommend specific treatment for an overdose. 
Overdoses are medication errors that are not considered AEs unless there is an untoward medical 
occurrence resulting from the overdose. Overdose must be reported by the Investigator within 
24 hours to Alexion regardless of its association with or without an AE. 
In the event of an overdose, the Investigator/treating physician should: 
1. Contact the Medical Monitor immediately.
2. Closely monitor the patient for any AE/SAE.
3. Obtain a plasma sample for PK analysis if requested by the Medical Monitor (determined
on a case-by-case basis).
4. Document the quantity of the excess dose as well as the duration of the overdose in the
eCRF.
Decisions regarding dose interruptions or modifications will be made by the Investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the patient. 
8.6. 
Pharmacokinetics 

Blood samples for determination of serum drug concentrations will be collected
before and after infusion of study drug at the time points specified in the SoA
(Section 1.3).

The predose blood sample may be drawn through the venous access created for the
dose infusion, prior to infusion of the dose. The postdose blood samples will be
drawn from the patient’s opposite non-infused arm.

Blood samples at a non-dosing visit can be collected at any time.

Instructions for the collection and handling of biological samples will be provided by
Alexion. The actual date and time (24-hour clock time) of each sample will be
recorded on the eCRF and the central laboratory requisition form.

Study drug concentration information that may unblind the study will not be reported
to investigative sites or blinded personnel until the study has been unblinded.
Additional information on sample collection, including blood volume requirements, is provided 
in the Laboratory Manual. 
8.7. 
Pharmacodynamics 

Blood samples for PD (free C5 and hemolytic complement activity) will be collected
before and after infusion of study drug at the time points specified in the SoA
(Section 1.3).
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
The predose blood sample may be drawn through the venous access created for the
dose infusion, prior to infusion of the dose. The postdose blood samples will be
drawn from the patient’s opposite non-infused arm.

Blood samples at a non-dosing visit can be collected at any time.

Instructions for the collection and handling of biological samples will be provided by
Alexion. The actual date and time (24-hour clock time) of each sample will be
recorded on the eCRF and the central laboratory requisition form.

Pharmacodynamic assessments that may unblind the study will not be reported to
investigative sites or blinded personnel until the study has been unblinded.
Additional information on sample collection, including blood volume requirements, is provided 
in the Laboratory Manual. 
8.8. 
Genetics 
Genetics are not evaluated in this study. 
8.9. 
Biomarkers 
All biomarker assessments that may unblind the study will not be reported to investigative sites 
or blinded personnel until the study has been unblinded. 
8.9.1. 
Biomarker Research 
Blood sample (plasma and serum) for biomarker research will be collected predose from all 
patients at the time points specified in the SoA (Section 1.3). Refer to the Laboratory Manual for 
details on sample collection, including blood volume requirements. 
Biomarkers to be measured may include, but are not limited to, assessments of the following: 

Complement pathway dysregulation eg, C5b-9, C5a, etc.

Neurodegeneration eg, neurofilament light chain (NfL), glial fibrillary acidic protein
(GFAP).

Neuroinflammation, eg, proinflammatory cytokines (interleukin-6 [IL-6], tumor
necrosis factor alpha [TNF-α]), autoantibodies, etc.
8.9.2. 
Additional Biomarker Research
Remaining samples from PK, PD, immunogenicity, and biomarker testing will be stored for 
additional biomarker research and may be evaluated after the study is completed. Analyses may 
be performed on biomarkers thought to play a role in GBS activity/progression or treatment 
response to eculizumab. These samples may also be used to develop methods, prognostics and/or 
companion diagnostic assays related to the study drug target, disease process, pathways 
associated with disease state, other complement-related diseases, and/or mechanism of action of 
the study drug. 
Samples may be stored for a maximum duration according to local regulations following the last 
patient’s last visit for the study at a facility selected by Alexion to enable further analyses. 
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8.10. 
Immunogenicity Assessment 
Antidrug antibodies to eculizumab will be evaluated in serum samples collected from all patients 
according to the SoA (Section 1.3). Additionally, serum samples should also be collected at the 
Early Termination Visit from patients who discontinued study drug or were withdrawn from the 
study. These samples will be tested by Alexion or designee. 
Serum samples will be screened for antibodies binding to eculizumab and the titer of confirmed 
positive samples will be reported. Other analyses may be performed to further characterize the 
immunogenicity of eculizumab. 
The detection and characterization of antibodies to eculizumab will be performed using a 
validated assay method by or under the supervision of Alexion. Samples collected for detection 
of antibodies to study drug will also be evaluated for eculizumab serum concentration to enable 
interpretation of the antibody data. Antibodies may be further characterized and/or evaluated for 
their ability to neutralize the activity of the study drug(s). 
8.11. 
Health Economics Data and Medical Resource Utilization 
Health Economics and Outcomes Research (HEOR) measures the societal impact of the disease 
on patients. 
In this study, the overall health-related quality of life (QoL) of patients with GBS will be 
assessed using the EuroQoL-EQ-5D-5L questionnaire (Section 8.2.10). The EQ-5D-5L is the 
preferred EQ-5D version of the questionnaire in Japan. 
In addition, the impact of the disease on patient working status will be assessed using the WPAI 
questionnaire (Section 8.2.11). 
Copies of the EQ-5D-5L and WPAI questionnaires are provided in Section 10.10 and 
Section 10.11, respectively. 
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9.
STATISTICAL CONSIDERATIONS
Statistical methods described in this section will be further detailed in a separate statistical 
analysis plan (SAP). The SAP will be developed and finalized prior to the database lock. 
Statistical analyses will include tabulations of summary data, inferential analyses, by-patient 
listings and figures. Inference from efficacy analyses will be based on a 2-sided Type I error 
(α) = 5% unless stated otherwise. The summary statistics for continuous variables will include, 
but not be limited to, the number of patients, mean, standard deviation, minimum, median, and 
maximum. For categorical variables, frequencies and percentages will be presented. 
All efficacy analyses will be based on the Full Analysis Set (FAS). Supplemental per protocol 
analyses for primary and secondary efficacy endpoints will be performed based on the Per 
Protocol Set (PPS) in the same manner as done for the FAS. Safety analyses will be performed 
on the Safety Set (SS). 
The baseline value for analysis and reporting will be based on the last non-missing measurement 
on or prior to the first dose of study drug unless stated otherwise. 
Analyses will be performed using the Statistical Analysis System (SAS®) software Version 9.4 
or higher. 
9.1. 
Statistical Hypotheses 
9.1.1. 
Primary Hypothesis 
The primary null hypothesis is that the effect of eculizumab is no different than placebo in time 
to initially or first reach an FG score ≤ 1. The alternative hypothesis is that there is a treatment 
difference from placebo in favor of eculizumab based on time to initially or first reach an FG 
score ≤ 1. 
9.1.2. 
Key Secondary Hypotheses 
The null hypotheses associated with the key secondary objectives are that eculizumab is no 
different than placebo for the respective endpoints; the alternative hypotheses are described 
below: 

Proportion of patients with an FG score ≤ 1 at Week 24: The alternative hypothesis is
that there is a treatment difference from placebo in favor of eculizumab in the
proportion of patients with an FG score ≤ 1 at Week 24.

Proportion of patients with an FG score improvement ≥ 3 at Week 24: The alternative
hypothesis is that there is a treatment difference from placebo in favor of eculizumab
in the proportion of patients with an FG score improvement ≥ 3 at Week 24.

Proportion of patients with an FG score ≤ 1 at Week 8: The alternative hypothesis is
that there is a treatment difference from placebo in favor of eculizumab in the
proportion of patients with an FG score ≤ 1 at Week 8.
9.2. 
Sample Size Determination
The sample size for this study is based on results from the Investigator-initiated study in Japan 
(Misawa, 2018). Assuming a 2:1 randomization of patients with GBS to eculizumab and placebo, 
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a drop-out rate of approximately 10%, a cumulative probability of response at 24 weeks of 70% 
for eculizumab and 20% for placebo (corresponding to a true hazard ratio of 5.4), one-sided 
Type I error of 0.025, a fixed Follow-up Period of 24 weeks for each patient with approximately 
an average enrollment rate of 1 patient per week, a total sample size of 57 patients with 
approximately a total of 19 events (responders) would provide at least 90% power using a 
log-rank test for the primary endpoint, time to first reaching an FG score ≤ 1. 
The total sample size of 57 patients (assuming a dropout rate of approximately 10%) will provide 
at least 90% power to detect a treatment difference of 50% in favor of eculizumab for the first 
key secondary endpoint FG score ≤ 1 at Week 24 assuming a placebo response rate of 20%; and 
at least 85% power to detect a treatment difference of 43% in favor of eculizumab for the second 
key secondary endpoint FG improvement of ≥ 3 at Week 24 assuming a placebo response rate of 
27%; and approximately 85% power to detect a treatment difference of 40% in favor of 
eculizumab for the third key secondary endpoint FG score  ≤ 1 at Week 8 assuming a placebo 
response rate of 20%. 
An interim analysis is planned for the unblinded sample size re-estimation when approximately 
60% (ie, at least 12 events) of the planned events are observed. The sample size will be increased 
to a maximum of 72 patients to generate a maximum of approximately 32 events using a 
conditional power approach. Further details will be provided in the Interim Analysis Plan (IAP). 
The sample size calculation was performed in EAST 6.5 using the Logrank test for the primary 
endpoint, and two-sample test for the difference in proportions with unpooled variance estimate 
for the key secondary endpoints. 
9.3. 
Populations for Analyses 
The analysis sets are defined in Table 6. 
Table 6: 
Analysis Sets 
Analysis set 
Description 
Full Analysis Set (FAS) 
All patients who receive at least 1 dose of study drug and have a baseline FG 
score and at least 1 postbaseline FG score. Patients will be analyzed according 
to the treatment group assigned by randomization.
Safety Set (SS) 
All patients who receive at least 1 dose of study drug. Patients will be 
analyzed according to the study drug they actually received. 
Per Protocol Set (PPS) 
All FAS patients without any major protocol deviations. 
Pharmacokinetic Analysis Set 
(PKAS) 
All patients who receive at least 1 dose of eculizumab and who have at least 
1 postdose PK sample.
Abbreviations: FG = Functional Grade; PK = pharmacokinetic(s).
9.4. 
Statistical Analyses 
9.4.1. 
Enrollment and Disposition 
The number of patients screened, screen failed, and randomized will be presented. Enrollment 
information will be presented by stratification factor and treatment group. Number of patients 
discontinued and reasons for discontinuation will be summarized. 
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9.4.2. 
Demographics, Baseline Characteristics, Inclusion and Exclusion Criteria, and 
Protocol Deviations 
All demographic information and baseline characteristics will be reported by treatment group 
and overall. No statistical test will be performed for homogeneity among treatment groups. The 
number and percentage of patients not meeting specific inclusion or exclusion criteria will be 
summarized. Similar summaries will be provided for major protocol deviations based on 
prespecified categories. 
9.4.3. 
Medical/Surgical History and Physical Examination 
The medical and surgical history will be summarized by System Organ Class (SOC) and 
Preferred Term using the Medical Dictionary for Regulatory Activities (MedDRA) Version 20.1 
or higher. Complete and targeted physical examination findings will also be summarized. 
9.4.4. 
Prior and Concomitant Medications 
For analysis and reporting purpose, any medication started prior to first dose of study drug will 
be considered as prior medication and any medication taken by a patient that overlaps with the 
infusion of study drug will be considered as concomitant medication. All prior and concomitant 
medications including GBS-specific medications during the study, if any, will be summarized. 
9.4.5. 
Efficacy Analyses 
9.4.5.1. 
Primary Endpoint 
The primary null hypothesis is that the effect of eculizumab is no different than placebo in time 
to reach an FG score ≤ 1. The alternative hypothesis is that there is a treatment difference from 
placebo in favor of eculizumab based on time to reach an FG score ≤ 1. 
The comparison of the treatment groups for the primary endpoint time to first reaching an FG 
score ≤ 1 will use a stratified Logrank test. Confidence intervals (95% CIs) will be presented for 
the estimated proportion of patients reaching the defined endpoint at various timepoints based on 
complementary log-log transformation. Hazard ratio and cumulative probability of improvement 
over 24 weeks from a stratified Cox proportional hazards model will be summarized with 
95% CI. Kaplan-Meier curves for both treatment groups will be produced. The randomization 
stratification variables will be used in these analyses. 
The study will be considered to have met its primary efficacy objective if the null hypothesis is 
rejected at a 2-sided statistically significant level of 0.05 in favor of eculizumab. (See 
Section 9.4.5.4 for Type 1 error control due to the interim analysis for sample size re-estimation.) 
Patients who are discontinued prematurely without a response or complete 24-week Follow-up 
Period without a response will be censored for this analysis. Further details will be provided in 
the SAP. 
9.4.5.2. 
Key Secondary Endpoints 
Hypothesis testing comparing eculizumab treatment with placebo treatment for the key 
secondary efficacy analyses will be performed using a closed testing procedure with the 
following rank order: 
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1. Proportion of patients with an FG score ≤ 1 at Week 24
2. Proportion of patients with an FG improvement of  ≥ 3 at Week 24
3. Proportion of patients with an FG score ≤ 1 at Week 8
The hypothesis testing will proceed from highest rank (1: Proportion of patients with an FG 
score ≤ 1 at Week 24) to lowest rank (3: Proportion of patients with an FG score ≤ 1 at Week 8). 
The comparison of the treatment groups for the key secondary endpoints will be based on a 
logistic regression model with treatment and randomization stratification factors as covariates. 
The p-value and 95% CI of the Odds Ratio will be presented. In addition, the difference in the 
proportion of patients with response (FG score ≤ 1) and the 95% CI of the difference between the 
treatment groups, as well as the number and proportion of patients with response for each 
treatment will be presented. 
Patients who discontinued prematurely from the study without a response will be considered as a 
non-responder in this analysis. Further details will be provided in the SAP. 
9.4.5.3. 
Other Secondary and Tertiary/Exploratory Endpoints 
Analyses of other secondary and tertiary/exploratory endpoints are supportive in nature with 
p-values and 95% CIs presented for descriptive purposes only.
The mixed-effects model with repeated measures will be used for the tertiary/exploratory 
efficacy endpoints involving change from baseline over time using all available longitudinal 
data. The model will include the appropriate endpoint at each prespecified time point as the 
response variable, fixed categorical effects of treatment, study visit, and treatment-by-study visit 
interaction, as well as fixed covariate of baseline value and the randomization stratification 
variables. The treatment effect will be evaluated via contrast for the treatment-by-visit term at 
Week 24 and other timepoints of interest. An unstructured covariance matrix will be used to 
model the correlations among repeated measurements within each patient. Other covariance 
structures will be implemented if a convergence issue occurs (details to be provided in the SAP). 
The Kenward-Rogers method will be used to estimate the denominator degrees of freedom. 
In addition, summary statistics will be provided for all secondary and tertiary/exploratory 
endpoints. Missing data will not be imputed. 
Further details will be provided in the SAP. 
9.4.5.4. 
Multiplicity Adjustment 
The primary hypothesis will be tested with a 2-sided Type 1 error of 0.05.  
An unblinded interim analysis on at least 12 events (approximately 60% of the planned events) 
will be conducted for only the sample size re-estimation based on the conditional power. The 
Cui, Hung, Wang (CHW) method will be used for controlling the Type 1 error rate due to the 
interim analysis. Further details will be provided in the SAP. 
Hypothesis testing associated with the key secondary endpoints will proceed only if the null 
hypothesis associated with the primary endpoint is rejected and will proceed from the highest 
rank (1: Proportion of patients with an FG score ≤ 1 at Week 24 to the lowest rank 3: Proportion 
of patients with an FG score ≤ 1 at Week 8). If statistical significance is not achieved at an 
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endpoint (2-sided p-value ≤0.05), then the endpoint of lower rank will not be considered to be 
statistically significant. Confidence intervals and p-values will be presented for all key secondary 
efficacy endpoints for descriptive purposes, regardless of the outcome of the closed testing 
procedure. Further details will be provided in the SAP. 
9.4.6. 
Safety Analyses 
The safety and tolerability of eculizumab versus placebo in GBS patients will be assessed based 
on AEs, clinical laboratory findings, physical examination findings, vital sign findings, and ECG 
abnormalities. 
9.4.6.1. 
Analysis of Adverse Events 
The analysis and reporting of AEs will be based on treatment-emergent adverse events (TEAEs), 
defined as AEs with onset on or after the first dose of study drug. The incidence of TEAEs will 
be summarized by SOC and Preferred Term, with additional summaries showing severity, 
relationship to study drug, TEAEs leading to study drug discontinuation, and TEAEs resulting in 
death. Summaries of treatment-emergent serious adverse events (TESAEs) will also be 
summarized by SOC and Preferred Term, with an additional summary showing relationship to 
study drug. These summaries will be presented by treatment group. 
9.4.6.2. 
Analysis of Clinical Laboratory Parameters, Vital Sign Measurements, and 
Electrocardiogram Parameters 
Laboratory measurements as well as their changes from baseline and shift from baseline, if 
applicable, will be summarized descriptively. Electrocardiograms, including ECG interpretation 
of HR, PR, QRS, QT, and QTc intervals, and vital signs will also be summarized using 
descriptive analyses. 
9.4.7. 
Analyses of Pharmacokinetic and Pharmacodynamic Parameters 
Individual serum concentration data for all patients who receive at least 1 dose of the study drug 
and have at least 1 postdose PK sample will be used to derive PK parameters for eculizumab. 
Graphs of mean serum concentration-time profiles will be constructed. Graphs of serum 
concentration-time profiles for individual patients may also be provided. Actual dose 
administration and sampling times will be used for all calculations. Descriptive statistics will be 
calculated for serum concentration data at each sampling time, as appropriate. Assessment of 
population-PK may be considered using data from this study or in combination with data from 
other studies. 
Pharmacodynamic analyses will be performed for all patients who receive at least 1 dose of 
eculizumab and who have evaluable PD data. 
Descriptive statistics will be presented for all eculizumab PD endpoints at each sampling time. 
The PD effects of eculizumab will be evaluated by assessing the absolute values and changes and 
percentage changes from baseline in free C5 serum concentrations over time, as appropriate. 
Assessments of eculizumab PK/PD relationships may be explored using data from this study or 
in combination with data from other studies. 
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9.4.8. 
Analysis of Antidrug Antibodies 
For assessment of immunogenicity, the presence of confirmed positive ADAs will be 
summarized. Additionally, following confirmation of positive ADAs, samples will be assessed 
for ADA titer and presence of neutralizing antibodies. 
9.4.9. 
Analysis of Biomarkers 
Biomarker testing, data and analyses will be performed after study completion and may not be 
included in the clinical study report. For biomarker analyses, summary statistics will be 
presented for observed values, change, and percentage change from baseline. 
9.4.10. 
Other Analyses 
Any other analyses will be detailed in the SAP. 
9.5. 
Interim Analyses 
An interim analysis for the unblinded sample size re-estimation to a maximum 72 patients to 
generate a maximum of 32 events will be performed by the Independent Analysis Center (IAC) 
when approximately 60% (ie, at least 12 events) of the planned events are observed, using the 
conditional power approach. Details of the conditional power calculations and the sample size re-
estimation will be prespecified in the IAP. 
The planned interim analysis for the unblinded sample size re-estimation will be performed by 
the IAC. Details of the IAC membership, roles and responsibilities as well as the calculations for 
the unblinded interim sample size re-estimation will be provided in the IAP. 
To maintain study integrity and to prevent the potential introduction of bias, all study team 
members will remain blinded until the final analysis. Details of this process will be documented 
in the IAP. 
9.6. 
Independent Data Monitoring Committee 
There will be no independent data monitoring committee. 
9.7. 
Independent Guillain-Barré Syndrome Variant Determination 
An independent expert assessor for GBS-variant determination will be appointed by Alexion. 
The assessor will review the clinical history of patients and analyze their nerve conduction test 
results from Screening and Week 4 to assign the GBS variants of AIDP, AMAN, and 
“indeterminate”. 
The specific electrophysiologic criteria for GBS-variant determination and the specific 
responsibilities of the assessor will be described in the GBS Variant Determination Charter. 
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10.
SUPPORTING DOCUMENTATION AND OPERATIONAL
CONSIDERATIONS
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
Regulatory and Ethical Considerations 

This study will be conducted in accordance with the protocol and with the following:
 Consensus ethical principles derived from international guidelines including the
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
 Applicable International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) 
Guidelines 
 Applicable laws and regulations 

The protocol, protocol amendments, ICF, IB, and other relevant documents
(eg, advertisements) must be submitted to an IRB by the Investigator and reviewed
and approved by the IRB before the study is initiated.

Any amendments to the protocol will require IRB approval before implementation of
changes made to the study design, except for changes necessary to eliminate an
immediate hazard to study patients.

The Investigator will be responsible for the following:
 Providing written summaries of the status of the study to the IRB annually or
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB 
 Notifying the IRB of SAEs or other significant safety findings as required by IRB 
procedures 
 Providing oversight of the conduct of the study at the site and adherence to 
requirements of ICH guidelines, the IRB, and all other applicable regulations. 
10.1.2. 
Financial Disclosure 
Investigators and Sub-Investigators will provide Alexion with sufficient, accurate financial 
information as requested to allow Alexion to submit complete and accurate financial certification 
or disclosure statements to the appropriate regulatory authorities. Investigators are responsible 
for providing information on financial interests during the course of the study and for 1 year after 
completion of the study. 
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10.1.3. 
Informed Consent Process 

It is the responsibility of the Investigator to obtain signed (written or electronic
signature) informed consent from all study patients prior to any study-related
procedures including screening assessments.

The Investigator or his/her representative will explain the nature of the study
(including but not limited to the objectives, potential benefits and risks,
inconveniences, and the patient’s rights and responsibilities) to the patient or his/her
legally authorized representative, defined according to local and country regulations
where the study is taking place, and answer all questions regarding the study.

Patients must be informed that their participation is voluntary. Patients or their legally
authorized representative will be required to sign a statement of informed consent or a
certified translation if applicable, that meets the requirements of local regulations,
ICH guidelines, where applicable, and the IRB or study center.

The medical record must include a statement that signed (written or electronic)
informed consent was obtained before the patient was screened in the study and the
date the written consent was obtained. The authorized person obtaining the informed
consent must also sign the ICF.

Patients must be reconsented to the most current version of the ICF during their
participation in the study.

A copy of the signed (written or electronic) ICF documentation (ie, a complete set of
patient information sheets and fully executed signature pages) must be provided to the
patient or the patient’s legally authorized representative, as applicable. This document
may require translation into the local language. Signed (written or electronic) consent
forms must remain in each patient’s study file and must be available for verification
at any time.
Patients who are rescreened are required to sign a new ICF (see Section 5.4). 
10.1.4. 
Data Protection 

Patients will be assigned a unique identifier by Alexion. Any patient records or
datasets that are transferred to Alexion will contain the identifier only; patient names
or any information which would make the patient identifiable will not be transferred.

Patients must be informed that their personal study-related data will be used by
Alexion in accordance with local data protection law. The level of disclosure must
also be explained to the patients who will be required to give consent for their data to
be used as described in the informed consent.

Patients must be informed that their medical records may be examined by Clinical
Quality Assurance auditors or other authorized personnel appointed by Alexion, by
appropriate IRB members, and by inspectors from regulatory authorities.
10.1.5. 
Committees Structure 
Details of the IAC will be provided in the IAP. 
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10.1.6. 
Dissemination of Clinical Study Data 
Study-related information and study results may be posted on publicly accessible clinical trial 
databases (eg, the US website https://www.clinicaltrials.gov/ and the Japan Registry of Clinical 
Trials https://jrct.niph.go.jp/), as appropriate, and in accordance with national, regional, and local 
regulations. 
10.1.7. 
Data Quality Assurance 

All patient data relating to the study will be recorded on printed or eCRF unless
transmitted to Alexion or designee electronically (eg, laboratory data). The
Investigator is responsible for verifying that data entries are accurate and correct by
physically or electronically signing the eCRF.

The Investigator must maintain accurate documentation (source data) that supports
the information entered in the eCRF.

The Investigator must permit study-related monitoring, audits, IRB review, and
regulatory agency inspections and provide direct access to source data documents.

Alexion or designee is responsible for the data management of this study including
quality checking of the data.

Study monitors will perform ongoing source data verification to confirm that data
entered into the eCRF by authorized site personnel are accurate, complete, and
verifiable from source documents; that the safety and rights of patients are being
protected; and that the study is being conducted in accordance with the currently
approved protocol and any other study agreements, ICH GCP, and all applicable
regulatory requirements.

Records and documents, including signed ICFs, pertaining to the conduct of this
study must be retained by the Investigator for 2 years after the last marketing
application approval, or if not approved, 2 years following the discontinuance of the
study drug, unless local regulations or institutional policies require a longer retention
period. No records may be destroyed during the retention period without the written
approval of Alexion. No records may be transferred to another location or party
without written notification to Alexion.
10.1.8. 
Source Documents 
Source documents provide evidence for the existence of the patient and substantiate the integrity 
of the data collected. The Investigator or designee will prepare and maintain adequate and 
accurate source documents (eg, medical records, ECGs, AE and concomitant medication 
reporting, and raw data collection forms) designed to record all observations and other pertinent 
data for each patient. 
Data reported on the eCRF that are transcribed from source documents must be consistent with 
the source documents or the discrepancies must be explained. The Investigator may need to 
request previous medical records or transfer records, depending on the study. Also, current 
medical records must be available. Source documents are filed at the Investigator’s site. 
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10.1.9. 
Study and Site Start and Closure 
The study start date is the date on which the first patient is consented. 
Alexion reserves the right to close the study site or terminate the study at any time for any reason 
at the sole discretion of Alexion. Study sites will be closed after the study is completed or 
following the decision to close or terminate the study. A study site is considered closed when all 
patients have completed the end of study or the Early Termination Visit, all data have been 
collected and entered into electronic data capture (EDC) system, all required documents and 
study supplies have been collected, and a study-site closure visit has been performed. 
The Investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by Alexion or Investigator may include but are not 
limited to: 

Failure of the Investigator to comply with the protocol, the requirements of the IRB
or local health authorities, Alexion’s procedures, or GCP guidelines

Inadequate recruitment of patients by the Investigator

Discontinuation of further study drug development
If the study is prematurely terminated or suspended, Alexion shall promptly inform the 
Investigators, the IRBs, the regulatory authorities, and any contract research organization(s) used 
in the study of the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The Investigator shall promptly inform the patient and should assure appropriate 
patient therapy and/or follow-up. 
10.1.10. 
Publication Policy 

Where possible, primary manuscripts reporting results of the primary efficacy
endpoint or the final results will be submitted for publication within 12 to 18 months
of the primary evaluation date or end of study, whichever is earlier.

Investigators who participate as authors in manuscripts derived from
Alexion-sponsored studies will agree to the prerequisites as outlined in the Alexion
author engagement agreement prior to engaging in manuscript development.

The Investigator agrees to submit proposals for new manuscripts (whether or not the
proposed analyses are derived from protocol-specified endpoints) to Alexion for
review and consideration. All manuscripts or abstracts emanating from approved
proposals are to be submitted to Alexion for review before submission to the
journal/society. This allows Alexion to protect proprietary information and to provide
comments.
 The proprietary nature of some development work may preclude publication. In
some cases, it may be necessary to delay a publication to allow Alexion to ensure 
protection of intellectual property. 

In general, primary publications, including congress and journal publications,
containing the protocol-specified results of a study should occur prior to the
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publication of individual study site results or case reports. Alexion’s policy prohibits 
duplicate publication, whereby the same results must not be published in multiple 
peer-reviewed journal manuscripts. 
 Encore congress publications may be appropriate to allow communication of 
research findings to relevant audience and geographical regions. 

Alexion will comply with the requirements for publication of study results. In
accordance with standard editorial and ethical practice, Alexion will generally
support publication of multicenter studies only in their entirety and not as individual
site data. In this case, a Coordinating Investigator will be designated by mutual
agreement.

Authorship will be determined by mutual agreement and in line with International
Committee of Medical Journal Editors authorship requirements and per the Alexion
Publication Policy.
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10.2. 
Appendix 2: Clinical Laboratory Tests 

The tests detailed in Table 7 will be performed by the central laboratory.

Local laboratory results are only required if the central laboratory results are not
available in time for either study drug infusion and/or response evaluation. If a local
sample is required, it is important that the sample for central analysis is also obtained
for inclusion of results in EDC. (If a local sample is used, the sample does not need to
have been collected at the same time as the central laboratory sample. In other words,
if a local sample collected as part of routine clinical management is used, a second
local sample does not need to be collected at the same time as the central analysis
sample.) Additionally, if the local laboratory results are used to make either a study
drug decision or response evaluation, the results must be entered into the eCRF.

Protocol-specific requirements for inclusion or exclusion of patients are detailed in
Section 5 of the protocol.

Additional tests may be performed at any time during the study as determined
necessary by the Investigator or required by local regulations.

Pregnancy testing: Women of childbearing potential should only be enrolled after a
negative urine or serum pregnancy test result at Screening. Additional urine
pregnancy testing will be standard for the protocol unless serum testing is required by
site policies, local regulation, or IRB and should be performed per the time points
specified in the SoA (Section 1.3).
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Table 7: 
Protocol-Required Laboratory Assessments 
Laboratory 
Assessments 
Parameters 
Hematology 
Platelet count
Red blood cell count
Hemoglobin
Hematocrit
Red blood cell (RBC) indices (MCV, MCH, %reticulocytes)
White blood cell (WBC) count with differential (neutrophils, lymphocytes, monocytes,
eosinophils, basophils)
Clinical 
chemistry 
Alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT)
Alkaline phosphatase
Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT)
Blood urea nitrogen (BUN)
Calcium
Creatinine
Glucose (fasting preferred)
Potassium
Sodium
Total and direct bilirubin
Total protein
Routine 
urinalysis 
Specific gravity
pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase
by dipstick
Microscopic examination (if blood or protein is abnormal)
Other 
screening tests 
Follicle-stimulating hormone and estradiol (as needed in women of non-childbearing
potential only)
Highly sensitive serum or urine human chorionic gonadotropin (HCG) pregnancy test
(as needed for women of childbearing potential)
Investigators must document their review of each laboratory safety report. 
Clinical laboratory tests listed in Table 7 will not unblind the Investigator. However, testing C5 
levels would result in unblinding. 
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10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
10.3.1. 
Definition of AE 
AE Definition 

An AE is any untoward medical occurrence in a patient, temporally associated with the use of study drug,
whether or not considered related to the study drug.

Note: An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory
finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug.
Events Meeting the AE Definition  

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other safety
assessments (eg, ECG, radiological scans, vital signs measurements), including those that worsen from
baseline, considered clinically significant in the medical and scientific judgment of the Investigator (ie, not
related to progression of underlying disease).

Exacerbation of a chronic or intermittent pre-existing condition including either an increase in frequency
and/or intensity of the condition.

New conditions detected or diagnosed after study drug administration even though it may have been present
before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study drug or a concomitant
medication. Overdose per se will not be reported as an AE/SAE unless it is an intentional overdose taken
with possible suicidal/self-harming intent. Such overdoses should be reported regardless of sequelae.

“Lack of efficacy” or “failure of expected pharmacological action” per se will not be reported as an AE or
SAE. Such instances will be captured in the efficacy assessments. However, the signs, symptoms, and/or
clinical sequelae resulting from lack of efficacy will be reported as AE or SAE if they fulfil the definition of
an AE or SAE.
Events Not Meeting the AE Definition  

Medical or surgical procedure (eg, endoscopy, appendectomy): The condition that leads to the procedure is
the AE. Situations in which an untoward medical occurrence did not occur (eg, hospitalization for elective
surgery if planned before the signing the ICF, admissions for social reasons or for convenience).

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.

A medication error (including intentional misuse, abuse, and overdose of the product) or use other than what
is defined in the protocol is not considered an AE unless there is an untoward medical occurrence as a result
of a medication error.

Cases of pregnancy that occur during maternal or paternal exposure to study drug are to be reported within
24 hours of Investigator/site awareness. Data on fetal outcome and breastfeeding will be collected for
regulatory reporting and safety evaluation.

Any clinically significant abnormal laboratory findings or other abnormal safety assessments which are
associated with the underlying disease, unless judged by the Investigator to be more severe than expected for
the patient’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of the disease/disorder being
studied, unless more severe than expected for the patient’s condition.
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10.3.2. 
Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (eg, hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease). 
An SAE is defined as any untoward medical occurrence that, at any dose: 
1.
Results in death
2.
Is life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which the patient was at risk of
death at the time of the event. It does not refer to an event, which hypothetically might have caused death, if it
was more severe.
3.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the patient has been detained (usually involving at least an overnight
stay) at the hospital or emergency ward for observation and/or treatment that would not have been appropriate in
the physician’s office or outpatient setting. Complications that occur during hospitalization are AEs. If a
complication prolongs hospitalization or fulfills any other serious criteria, the event is serious. When in doubt as
to whether “hospitalization” occurred or was necessary, the AE should be considered serious.
Hospitalization for elective treatment of a pre-existing condition that did not worsen from baseline is not
considered an AE.
4.
Results in persistent disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct normal life functions.

This definition is not intended to include experiences of relatively minor medical significance such as
uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma (eg, sprained ankle)
which may interfere with or prevent everyday life functions but do not constitute a substantial disruption.
5.
Is a congenital anomaly/birth defect
6.
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE 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 patient or may require medical or surgical intervention to
prevent one of the other outcomes listed in the above definition. These events should usually be considered
serious.

Examples of such events include invasive or malignant cancers, 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.
10.3.3. 
Recording and Follow-up of AE and/or SAE 
Recording of AE and/or SAE 

When an AE/SAE occurs, it is the responsibility of the Investigator to review all documentation (eg, hospital
progress notes, laboratory reports, and diagnostics reports) related to the event.

The Investigator will then record all relevant AE/SAE information in the eCRF.

It is not acceptable for the Investigator to send photocopies of the patient’s medical records to Alexion or
designee in lieu of completion of the AE/SAE eCRF page.

There may be instances when copies of medical records for certain cases are requested by Alexion or
designee. In this case, all patient identifiers, with the exception of the patient number, will be redacted on
the copies of the medical records before submission to Alexion or designee.

The Investigator will attempt to establish a diagnosis of the event based on signs, symptoms, and/or other
clinical information. Whenever possible, the diagnosis (not the individual signs/symptoms) will be
documented as the AE/SAE.
Assessment of Intensity 
The Investigator will make an assessment of intensity for each AE and SAE reported during the study and assign 
it to one of the following categories from National Cancer Institute Common Terminology Criteria for Adverse 
Events (CTCAE) v5.0, published 27 Nov 2017: 
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28 Oct 2021 

Grade 1: Mild (awareness of sign or symptom, but easily tolerated)

Grade 2: Moderate (discomfort sufficient to cause interference with normal activities)

Grade 3: Severe (incapacitating, with inability to perform normal activities)

Grade 4: Life-threatening

Grade 5: Fatal
Assessment of Causality 

The Investigator is obligated to assess the relationship between the study drug and each occurrence of each
AE or SAE. An Investigator causality assessment must be provided for all AEs (both nonserious and
serious). This assessment must be recorded in the eCRF and on any additional forms, as appropriate. The
definitions for the causality assessments are as follows:
 
Not related: There is no reasonable possibility the study drug caused the AE. 

The AE has a more likely alternative etiology; it may be due to underlying or
concurrent illness, complications, concurrent treatments, or effects of another
concurrent drug.

The event does not follow a reasonable temporal relationship to administration of the
study drug.
 
Related: There is a reasonable possibility the study drug caused the AE. 

The AE has a temporal relationship to the administration of the study drug.

The event does not have a likely alternative etiology.

The event corresponds with the known pharmaceutical profile of the study drug.

There is improvement on discontinuation and/or reappearance on rechallenge.

The Investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, as well as the
temporal relationship of the event to study drug administration will be considered and investigated.

The Investigator will also consult the Investigator’s Brochure (IB) and/or Product Information, for marketed
products, in his/her assessment.

For each AE/SAE, the Investigator must document in the medical notes that he/she has reviewed the
AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred, and the Investigator has minimal information to
include in the initial report to Alexion or designee. However, it is very important that the Investigator
always make an assessment of causality for every event before the initial transmission of the SAE data to
Alexion or designee.

The Investigator may change his/her opinion of causality in light of follow-up information and send an SAE
follow-up report with the updated causality assessment.

The causality assessment is one of the criteria used when determining regulatory reporting requirements.
Follow-up of AEs and SAEs 

The Investigator is obligated to perform or arrange for the conduct of supplemental measurements and/or
evaluations as medically indicated or as requested by Alexion or designee to elucidate the nature and/or
causality of the AE or SAE as fully as possible. This may include additional laboratory tests or
investigations, histopathological examinations, or consultation with other health care professionals.

If a patient dies during participation in the study or during a recognized follow-up period, the Investigator
will provide Alexion or designee with a copy of any post-mortem findings including histopathology.

New or updated information will be recorded in the originally completed eCRF.

The Investigator will submit any updated SAE data to Alexion or designee within 24 hours of receipt of the
information.
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28 Oct 2021 
10.3.4. 
Reporting of SAEs  
SAE Reporting to Alexion or Designee via an Electronic Data Collection Tool 

All SAEs will be recorded and reported to Alexion or designee immediately and within 24 hours of
awareness.

The primary mechanism for reporting an SAE to Alexion or designee will be the electronic data collection
tool.

If the electronic system is unavailable at the time that the Investigator or site becomes aware of an SAE,
the site will use the paper Contingency Form for SAE reporting via fax or email. Facsimile transmission or
email may be used in the event of electronic submission failure.
 
Email:
or Fax: 

The site will enter the SAE data into the EDC system as soon as it becomes available.

When further information becomes available, the EDC should be updated within 24 hours with the new
information and an updated SAE report should be submitted to Alexion Global Drug Safety (GDS).

After the study is completed at a given site, the electronic data collection tool will be taken off-line to
prevent the entry of new data or changes to existing data.

If a site receives a report of a new SAE from a study patient or receives updated data on a previously
reported SAE after the electronic data collection tool has been taken off-line, then the site can report this
information on a paper SAE form or to the Alexion Medical Monitor by telephone.
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28 Oct 2021 
10.4. 
Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information 
10.4.1. 
Definitions 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below). 
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study drug, additional evaluation should be considered. 
Women in the following categories are not considered WOCBP 
1. Premenarchal
2. Premenopausal female with one of the following:

Documented hysterectomy

Documented bilateral salpingectomy

Documented bilateral oophorectomy
For individuals with permanent infertility due to an alternate medical cause other than the above, 
(eg, Mullerian agenesis, androgen insensitivity), Investigator discretion should be applied to 
determining study entry. 
Note: Documentation can come from the site personnel’s: review of the patient’s medical 
records, medical examination, or medical history interview. 
3. Postmenopausal female

A postmenopausal state is defined as no menses for 12 months without an alternative
medical cause.
 A high follicle-stimulating hormone (FSH) level in the postmenopausal range
may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the absence 
of 12 months of amenorrhea, confirmation with more than 1 FSH measurement is 
required. 

Females on HRT and whose menopausal status is in doubt will be required to use one
of the non-estrogen hormonal highly effective contraception methods if they wish to
continue their HRT during the study. Otherwise, they must discontinue HRT to allow
confirmation of postmenopausal status before study enrollment.
10.4.2. 
Contraception Guidance 
10.4.2.1. Guidance for Female Patients 
Female patients of non-childbearing potential are exempt from contraception requirements. 
Non-childbearing potential for female patients is defined as any of the following: 
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1. Prior to first menses
2. Postmenopausal, as documented by amenorrhea for at least 1 year prior to the Day 1 Visit
and FSH serum levels consistent with postmenopausal status
3. Permanent sterilization at least 6 weeks prior to the Day 1 Visit:
4. Hysteroscopic sterilization
5. Bilateral tubal ligation or bilateral salpingectomy
6. Hysterectomy
7. Bilateral oophorectomy
Female patients of childbearing potential must use a highly effective method of contraception, 
including at least one of the following: 
1. Intrauterine device (without copper) in place for at least 6 weeks.
2. Progestogen-only hormonal contraception (either oral, injectable, or implantable) for at least
6 weeks.
3. Intrauterine progestogen releasing system for at least 6 weeks.
4. Bilateral tubal occlusion for at least 6 weeks.
5. Combined (estrogen- and progestogen-containing) hormonal contraception (either oral,
intravaginal, or transdermal) for at least 6 weeks. Estrogen-containing hormonal
contraception is acceptable only if it has been used for at least 6 weeks immediately prior to
the Day 1 Visit. Estrogen-containing hormonal contraception may not be initiated during the
study period.
6.
Surgical sterilization of the male partner (medical assessment of azoospermia is required if
vasectomy was performed within the prior 6 months).
7. Sexual abstinence for female patients:
a.
Sexual abstinence is considered a highly effective method only if defined as refraining from
heterosexual intercourse. In this study, abstinence is only acceptable if consistent with the
patient’s preferred and usual lifestyle. Abstinent female patients who wish to initiate a highly
effective method of contraception during the study must refrain from heterosexual
intercourse for at least 5 months after last dose of study drug.
a.
Periodic abstinence (eg, calendar, symptothermal, or post-ovulation methods) is not
considered a highly effective method of contraception for female patients.
Other methods of contraception that are not considered highly effective for female patients: 
1. Barrier methods, such as male or female condoms, diaphragm, or cervical cap, used alone or
in combination, are not acceptable.
2. Spermicides or spermicidal sponges, used alone or in combination with barrier methods, are
not acceptable.
Withdrawal (coitus interruptus) is not acceptable. 
Lactational amenorrhea is not acceptable. 
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Female patients must not donate ova from the Day 1 Visit until 5 months after the last dose of 
study drug. 
10.4.2.2. Guidance for Male Patients 
Contraception is the responsibility of the heterosexually active male patients, regardless of his 
female partner’s method of contraception. 
Male patients who have had a vasectomy > 6 months prior must use a condom during 
heterosexual intercourse. Male patients who have had a vasectomy < 6 months prior must use a 
condom and spermicide during heterosexual intercourse. 
Male patients who have not had a vasectomy must use a condom and spermicide during 
heterosexual intercourse. 
10.4.2.2.1. Sexual Abstinence for Male Patients 
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse. In this study, abstinence is only acceptable if consistent with the 
patient’s preferred and usual lifestyle. Abstinent male patients who become heterosexually active 
must use a condom and spermicide during intercourse. 
Periodic abstinence (eg, calendar, symptothermal, or post-ovulation methods for a female 
partner) is not considered a highly effective method of contraception for male patients. 
Male patients must not donate sperm from the Day 1 Visit until 5 months after the last dose of 
study drug. 
10.4.3. 
Collection of Pregnancy Information 
Pregnancy data will be collected during this study for all female patients and female 
spouses/partners of male patients. Exposure during pregnancy (also referred to as exposure in 
utero) can be the result of either maternal exposure or transmission of study drug via semen 
following paternal exposure. If a female patient or a male patient’s female partner becomes 
pregnant during the conduct of this study, the Investigator must submit the “Pregnancy Reporting 
and Outcome/Breastfeeding” form to Alexion Global Drug Safety (GDS) via facsimile or email. 
When the outcome of the pregnancy becomes known, the form should be updated and submitted 
to Alexion GDS. If additional follow-up is required, the Investigator will be requested to provide 
the information. 
Exposure of an infant to study drug during breastfeeding must also be reported (via the 
“Pregnancy Reporting and Outcome Form/Breastfeeding”) and any AEs experienced by the 
infant must be reported to Alexion GDS or designee via email or facsimile. 
Pregnancy is not regarded as an AE unless there is a suspicion that the study drug may have 
interfered with the effectiveness of a contraceptive medication. However, complications of 
pregnancy and abnormal outcomes of pregnancy are AEs and may meet the criteria for an SAE 
(eg, ectopic pregnancy, spontaneous abortion, intrauterine fetal demise, neonatal death, or 
congenital anomaly). Elective abortions without complications should not be reported as AEs. 
Any female patient who becomes pregnant while participating in the study will be discontinued 
from study drug. 
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28 Oct 2021 
10.4.3.1. Male Patients With Partners Who Become Pregnant 

The Investigator will attempt to collect pregnancy information on any male patient’s
female partner who becomes pregnant while the male patient is in this study. This
applies only to male patients who receive the study drug.

After obtaining the necessary signed informed consent from the pregnant female
partner directly, the Investigator will record pregnancy information on the appropriate
Pregnancy Outcome/Breastfeeding form and submit it to Alexion within 24 hours of
learning of the partner’s pregnancy. The female partner will also be followed to
determine the outcome of the pregnancy. Information on the status of the mother and
child will be forwarded to Alexion. Generally, the follow-up will be no longer than
3 months following the estimated delivery date. Any termination of the pregnancy
will be reported regardless of fetal status (presence or absence of anomalies) or
indication for the procedure.
10.4.3.2. Female Patients Who Become Pregnant 

The Investigator will collect pregnancy information on any female patient who
becomes pregnant while participating in this study. The initial Information will be
recorded on the appropriate form and submitted to Alexion within 24 hours of
learning of a patient’s pregnancy.

The patient will be followed up to determine the outcome of the pregnancy. The
Investigator will collect follow-up information on the patient and the neonate, and the
information will be forwarded to Alexion. Generally, follow-up will not be required
for longer than 3 months beyond the estimated delivery date. Any termination of
pregnancy will be reported, regardless of fetal status (presence or absence of
anomalies) or indication for the procedure.

While pregnancy itself is not considered to be an AE or SAE, any pregnancy
complication or elective termination of a pregnancy for medical reasons will be
reported as an AE or SAE. A spontaneous abortion (occurring at < 22 weeks
gestational age) or still birth (occurring at > 22 weeks gestational age) is always
considered to be an SAE and will be reported as such. Any post-study pregnancy
related SAE considered reasonably related to the study drug by the Investigator will
be reported to Alexion as described in Section 8.4.4. While the Investigator is not
obligated to actively seek this information in former study patients, he or she may
learn of an SAE through spontaneous reporting.
Any female patient who becomes pregnant while participating in the study will
discontinue study drug, and each pregnancy will be followed up to term and Alexion
notified regarding the outcome.
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10.5. 
Appendix 5: Rasch-built Overall Disability Scale Score 
RODS for GBS - CIDP - MGl.llSP 
INSTRUCTIONS: This is a questlio11111aire abol!Jrt the relationslnip b,etw ee1111 d aily actlivitlies and 
yom health. Youir answers give informatlion abourl how your polyneumpathy affects yo ur daily 
and sociial actlivitiies and to what degree you are able to perform your usu.d actJivitiies. 
Answer ,each questlion by marking the conect box ("x''). If you ar;e not sme abou~ your ability 
to pertorm a task, you arest1ill requ:ested to mark a11 answer that comes as alose as possitile 
to your Judged ability to complete su:ch a task. A!II qu:es11ioli1JS should be oompleted. You can 
o nly choose o ne answer to each q ues11ion. If yoursitua1Jio11 fluduates, your alliswershol!Jld be 
based on how you usuaJJy perform the task. 
If you need assistance or you are using sped al devices to p,erform the act1iviity, you are 
r,equest,ed to mark "possible, but with some difficulty ". In case you never perform the activity 
due to yo ur poly neumpathy mark "not possitile". 
Are you able to 
Task 
1. 
read a 
newspaper/book? 
2. 
eat? 
3. 
brush yo u1r teeth? 
4. 
wash upper body? 
5. 
sit 01111 a toilet? 
6. 
make a sandwich? 
7. 
dress uip p,er body? 
8. 
wash lower body? 
9. 
mov e a chair? 
10. 
tum a key in a lock? 
11. 
go to the g en;eral 
p ract1i1ii oner? 
12. 
take a shower? 
13. do the diishes? 
Mark Ute best option with "x" 
N1ot 
Possible, 
Possible, 
possible 
but with 
without 
to 
some 
any 
perfor01 
difficulty 
difficulty 
[iO]I 
[1]1 
D I 
CJ 
CJ 
ll 
CJ 
CJ 
CJ 
CJ 
CJ 
D I 
CJ 
CJ 
[2)1 
CJ 
CJ 
CJ 
i=i 
CJ 
i=i 
CJ 
CJ 
CJ 
CJ 
CJ 
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Protocol Amendment 1.0 
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28 Oct 2021 
14. 
do the shopping? 
CJ 
CJ 
15. catch an object (e.g., 
I 
ball)? 
1'6. 
bend and pick up an 
ob ject? 
17. walk one f light of stairs? 
CJ 
CJ 
18. travel by public 
trans po rtati on? 
1'9. walk and avoid 
D I 
obstacles? 
20. 
walk 01..1tdoors < 1 km? 
CJ 
CJ 
21. carry and put down a 
D I 
heavy object? 
22. 
dance? 
CJ 
CJ 
23. stand for homs? 
CJ 
CJ 
24. 
ruin? 
CJ 
CJ 
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Protocol Amendment 1.0 
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28 Oct 2021 
10.6. 
Appendix 6: Overall Neuropathy Limitation Scale 
N-2.me: 
D.ate: 
Overall Neuropalhy limitafioris Scale (ONLS ) 
lris1rncfio ris: f h.?eJ<amU71E'r ihoiJld q=oon and ol>:-€rvelbepatient in ordar to dat€'1mi""'the a ""'"'rs tothe followingq=lior,;. Note 
siho111d ,t,,, made of a "'i otf>er <f150rd;ar other !f>a n :penjpl>eral ,..uropathy whidh lfimits furiclion at th.? foot of the p age_ 
ARMSCAIE 
l>oes th e patient have a ny symptoms in, thei: hands or arms.. eg lin.g lin.g , rtumb ness or wealon.ess? 
Yes 
fd •oo•, please go to lags" !&11cinl 
ls the patient a ffected in th.ei: ab.ty to: 
wash a rTtd brush their hair 
Not affected 
Affected but oot 
Tum a key in a lkx::1' 
Use a k,nife a nd fork together {or ~poon, if lk,nife a nd for~ oot used) 
Do or uooo buttons or ,u,; 
Dress the 1.1pper pa rt of their body e>:eludir,g buttons or , ip; 
If a ll these fuoctioru are preverrrtedcanthe patEnt 
ma ke purposeful movements with tlreir b , nds or a nm5'? 
A,m Grade 
O=: ND.nm.a1 
prie,vented 
1: Mioor~mptomsinone or both a r,m bllrtoot affectir,g ar,y of the luoctioru lfi;tcd 
SCORE: 
2,; Disa bifrty in one or both a nms affe,cting b!JI not pre-venting • .B'I' of !be ; uoctioru ftsted 
3=0k3bifrty in 0111e or both arm!> preventirrig at ieas.t oDe burt not all f1.1111,cttO:ru.: lrBted 
4= Disa bifrty in both a rms pre-venting ., II furiclions lftsted b!JI purpo*lul movement S'lill :possi~e 
5: Disabifrty in both a nmspre-veotir,g aJI pu~p.0*fu1 mO\/ements 
IEGSCAIE 
Does the patiel\t base <frfficulty r unning or <flmbii,g stairs? 
Does the patiel\t lliaoe cfrffrculty with walk1ing? 
Do-:s thsir gaiUoo'.k abnonm,3f? 
How do they mobiTi;;e for about 10 metres fie 33 feet)? 
Wli!ho!JI aid 
Wim """ stick or <rut<h or holding to somrore's a nm 
Wlthtvi'O stK:ks. or orutd~s-or oo,es:tick or 
crutch hokfJng onto somrore's a nm or Ira me 
with a Yoihee.lohair 
If they ,usea ,,nee.ldlliair, caothey stand a nd wa'lk 1 metre 
with the haslP of one :persoo? 
vi,,, 
No 
Not a ppfica~e 
Not appf1tal>e 
If they canoot walk as a~e a rethiey able to make some pu~p.0*fUI 
mO\/eome'Ots of their egs, eg reposition egs in bed? 
Does the patiel\t use a nkle fool orthasesJbraoes? tplease <ir<leJ 
If yes: fplease cirnleJ right/left 
leg grade 
O=Wa1kii11Jg/climbimg stairs/runniBg not affected 
1:walk1ir,g/ cfim bing stairs/rum•in;:: is affected, bllrl gait does not look aboorma l 
SCORE: 
2,; Walks indapendaJ>tiy b!JI gait looks a'bnorm , I 
5: l,e,qr:rires unilateral •upport to wa lk 10 m"tres (stick, ,ir,g!e <rutch, one a rm J 
4:;: Reqi:iires bil3teral:;iupport to walk :l!.O me,tres. {:sfi:::ks, cin.rtoh:s, cin:m:h alld arm, fnme~ 
5: 1,e,qr:rires wheek:hair to traoel 10 m"tresb!JI able to sta nd a nd wa lk 1metre w:it~ the help of one pe,rson 
6:Rest nicted to Yo'heelclliair, uoobe to staoo and walk 1 metnewith th.? helP of one pe,rson, btJt a'~e to make 
some purpose-fiJ 12<-gmov·ements. 
7: Rest nicted to w heelcllia ir or bed most of th.? day, uoo be to ma'ke a "'i pu~p.0*fu1 movements of th.? egs 
o verall Naaunopathy Limitalioo sala=a rm scale (,a r,ge o to !;J+leg scae {,angeo to 7J; 
{range: o (no <frsa'bifrtyJ to 12 {ma ~imum <frsa biTrtylJ 
TOTAi SCORE: __ 
ls th.ere a ny disorder, oth.er th.on, p eripheral n.eurapathy. w hich affects the above fu n.clian• 
Yes 
N:o 
If yes., please describe: 
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10.7. 
Appendix 7: Short Form McGill Pain Questionnaire 2 
Tt.s Qll9StJ 
d 
ttJ 
·11 
you 
o 
2. Shoottnlil a 
3. Stabb Ing p 
111 
. Shup, pain 
5. Cramplr191 p n 
8. Gnawrlijl, pain 
d1I r 
llil 
put e 
rCM.Jgh e 
··· 
e l 
I d ;ngtl'le 
I< 
r(l~O 
1 2: J 3: 1 4 1 ,s 1 ,s 1 1 1 a I s 11.0 
-1 o , 1: 2· l 3: I 1 
6, I 
16 I 1 1 a I e 11
10 
_,y_ p,=iblrJ 
-1 o 
1 2: 1 3, I .4 1 ,s I ,s 11 ., I e I 9 I 1:0 
WCltlfili','OS5' 
2· 
3: 
.4 
5 
6 
7 
8 
9 
0 
1 2· 1 3 I .4 i' 1s I 1s 11 , 
I a I 9 110 womr~ 
1 2 1 3, 1.,1 1 15 1 16- 11 1 I e 1 9 110 woralfl"SS.'~ 
2· 
3 
4 
5 
16 
1 
8 
9 
0 Yltll8l~ 
8. Ach ng pain 
wne o 
9. Heavy pain 
OOD;/ 1 o CI] 2: 1 3: I .4 1 s 1 16 I 1 I e I s 110 l !'SJ~ 
r.ooeJ ,0 
I 2 I 3: I ,4 I 5 I 18 I 7 I 8 I 9 110 Jw=I~ 
11. $plit(ing pain 
I ,o 
I 2 I 3 I 4 I s I 13. It 7 I e I 9 1110 
12. Til'ii~,.exha1:.1sling ~ ·0 
1 
2: 
3: 
__!_ 
16: 
7 
8 
9 
10 
'i/DJ'3J 
131. Sld!eni I 
14. Feuful 
15,, Plllill,'hing-oruel 
non,., 
10 
11 I 2 
3: 
4 
6, 
16, 
7 
8 
9 
110 
,_ 0 
1 
2: 
;J: 
.4 
,5 
ilj: It i 
8 
9 
110 
WO!&! ~bfe 
8 
9 
110 worsJ~, 
8 
9 
0 
womj~"bJg 
fl. Cold,lreez:in.g, pain 
-
·O 
2. 
3 
4 
,s 
,s It 1 
a 
9 to worsi 
18. Pltrc ng 
19. Pain ca.us. di by 
lgl'lt touc 
20. lkhlng 
211. Till I ng or 'pims 
:and niHdlH' 
22. N 
2· 
3: 
,4 
15 
16 
7 
8 
9 
fO 
/»'It o 
2: 
3: 
4 
:5 
10; 
1 
e 
9 
10 I YIMJl~M 
r,(11)9 .o 
11 
2: ] 3: 
4 
5, 
16 
, 
e 
1 
1il!'li I 
...._·0 ....... _1 ........ _2 ........ 
1 _;J_: .._4 ....... _16___.__'6_
1 _ 1 __ 
,_. _.__9_· ...._'il_O_.I 
4 
16 
7 
9 
aR, 
ci~ic.ii ti1a 
D !MIIIY:e 
li!oll . 
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10.8. 
Appendix 8: Depression, Anxiety and Stress Scale, Short Form, 21 
Questions Score 
Name: 
Date:: 
Please read each statement and circle a number 0, l , 2 or J which indicates bow much the 
statement applied to you olr,er t.h.e p.ast week. There are no right or wrong answers. Do not 
spend too much rune on any :statement 
The rating scale i:s as follows: 
0 
Did not apply to me .it all 
1 
Applied to me to some degree, or some of the time 
2 
Applied to me to a considerable degree or a good part of time 
3 
Applied to me very much or most of the time 
1 (s) 
I found it hard to wind down 
0 
1 
2 
2(a) 
I was aware of drynei:s of my mouth 
0 
1 
2 
3 (d) 
I coull:ln 't seem to experience .my positive feeling at al'l 
0 
1 
2 
4(a) 
I expo...rienced breathing difficulty (e.g. excei;:sivel.y rapid breathing, 
0 
1 
2 
breathlessnes:;: in the absence of physiel!] exertion) 
5 (d) 
I found it difficult to work up the initiative to do thing,; 
0 
1 
2 
6 (·) 
I tended to over-react to situ~tious 
0 
1 
2 
7 (a) 
I expo...rienced trembling (e.g. in the hllllds) 
0 
1 
2 
8 (s) 
I felt fu--..t I Wli!:l: u:sing a lot of nervous energy 
0 
1 
2 
9(a) 
I Wli!:l: worried about situ~onas in which I might patnic and m,ake a fool of 0 
1 
2 
myseH' 
lO(d) I felt that I h~ nothing to look forward to 
0 
1 
2 
11 (:s) I found mysellf getting agitated 
0 
1 
2 
12(:s) I found it difficult to rel.lax 
0 
1 
2 
13 (d) I feit down-hearted and blue 
0 
1 
2 
14(:s) 
I Wli!:l: intolerant of anything th'<llt kept me from getting on ,,rith " hat I 
0 
1 
2 
WlilS doing 
15 (a) I feit I Wail clo.ie to panic 
0 
1 
2 
16(d) I ,,r;a;; un'<llhle to become enthu:smtic about anything 
0 
1 
2 
17 (d) 
I felt I wa.m 't ui orth much a;, a person 
0 
1 
2 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
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18 (s) 
I felt thcait I wa;; rather touchy 
0 
1 
2 
19 (a) 
I waai &"\ are of the ..ction of my heart in the ab-.i!ence of phy~ical 
0 
1 
2 
exertion (e.g. ·en'ile of heart rate increase,, heart missing a beat) 
20(a) 
I felt scared without any good rea,;on 
0 
1 
2 
21 (d) 
I felt thcait llife waai meainingl'~s 
0 
1 
2 
DA.SS-21 Scoring Instrudions 
TheDASS-21 should not be used to replace aface toface clinical intervie1,1.,•_ Ifyou are 
experiencing significant emotional difficulties you should contact your GP for a refenal to 
a qualified. professional. 
Depr,ession, A.n.xiety and Str,ess Scale - 21 Items ,(DASS-21) 
The Depression, Anxiety and Stress Scale - 21 Items (DASS-21) ts ase! of three self-report 
scales cksigned to measure the emotional states of depression, araiety and stress. 
Each of the three DASS-21 scales contains 7 ttems, divickd into subscales with similar 
content. The depression scale assesses dJ sphoria., hopelessness, devaluation of life, self-
deprecation, lack of interest I involvem.mt, a.nhedonia and inertia. The araiety scale 
assesses auionomic arousal, skBletal muscle effects, situational anxiety, and subjecttve 
experience of araious affect. The stress scale is sensitive to levels of chronic non- specific 
arousal. It assesses difficulty relaxing, nervous arousal, and being easilJ, upset I agitated., 
irritable I over-reactive and impatient. Scores for depression, anxtet; and stress are 
calculated by SWtmting the scores for the relevant items. 
3 
3 
3 
3 
The DASS-21 is based on a dimensional rather than a categorical conception of 
psychological disorder. The assumption on which the DASS-21 development was based ( and 
which was coJJfirmed. by the research data) is that the differences between the depression, 
anxiety and the stress ex.pertenced. by normal subjects and clinical populations are 
essentiallJ, differences of degree. The DASS-21 therefore has no direct implications for the 
allocation of patients to discrete diagnostic categories postulated in classificatory systems 
such as the DSM and ICD. 
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Protocol Amendment 1.0 
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Recommended cui-off scores for conventtonal severity la.be.ls (normal, mm:krate, severe) 
are a.sfollows: 
'1:,,'f'ote.- Scores on the DASS-21 wtll n€12d to be multiphed by 2 to calculate the final score. 
Deiness:io111 
A11Kiety 
Stress 
Nmmal 
o-9 
0-7 
0-14 
Mild 
10-B 
8-9 
15-18 
Moderate-
14-20 
10-14 
19-25, 
S,e-1,1e-r,e-
21-27 
15-19 
2fr 33, 
Extremely S,e-1,1e-re 
28+ 
20+ 
34+ 
Lovibond, S.H. & Lovibond, P.F. (1.9-951. Manual for t he Depression Anxiety & Stress S,cales. (2rd Ed.)S1i1dne-y: 
P-s1i1chology Foundation. 
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Protocol Amendment 1.0 
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10.9. 
Appendix 9: Chalder Fatigue Scale Score 
We would like to hww more about any pro bl.ems you have had with feeling tired, weak or lacking in 
energy in the last month. Pl.ease answer ALL the questions by ticking the answer which applies to 
you most closely. lf you have been feeling tired for a long while, then compare yourself to how 
youfelt whenyou were last well Please tick only one box per line. 
Less tho.n 
no more tlian 
more th.an usual 
m.ucli 
11W re tho.n 
usual 
nsnal 
usual 
Do you have problems with ti.redness? 
Do you need to rest more? 
Do you feel sleepy or drowsy? 
Do you have problems starting things? 
Do you lack energy? 
Do you have less 
strength m your 
muscles? 
Do you feel weak? 
Do you have difficulties concentrating? 
Do you make slips of 
the tongue when 
speaking? 
Do you find it more 
difficult to find the right 
word? 
bett£r /Jr.an 
no worse /Jr.an 
~•,me tlian usual m.uclr worse tho.n 
usual 
nsnal 
usual 
how is your memory? 
This scale can be scored "bimodally" with columns representing 0, 0, 1 & 1 and a range from Oto 11 
with a total of 4 or more qualifying ft "caseness ". Alternatively, it can be scored in "Likert" styl.e 0, 
1, 2& 3 with a range from Oto 33. Mean "bimodal" score for CFS sufferers was9.14 (SD2.73) and 
foracommunitysampl.e 3.27 (SD 3 . 21). Mean "Likert" scorewas24.4 (SD 5..8) and 14.2 (SD 4..6). 
Total (0-33) = 
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Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
10.10. 
Appendix 10: European Quality of Life – 5 Dimensions – 5 Levels 
Score 
Under each heading, pleas,e tick the ONE box that best desaibes your health TODAY. 
MOJBDLITY 
I have no problems in walking abolit 
I have slight problems in walking about 
I have moderate problems in walking about 
I have severe problems in walking about 
I am unable to walk about 
SELF-CARE 
I have no problems washing or dressing myself 
I have slight problems washing or dressing myself 
I have moderate problems washing or dressing myself 
I have s,evere problems washing or dressing myself 
I am unable to wash or dress myself 
USUAL ACinlJTIES 
(e.g. work, study, housework, family or leisure 
activities) 
I have no problems doing my usual activities 
I have slight problems doing my usual activities 
I have moderate problems doing my us.ual a.ctivfties 
I have s,evere problems doing my usual a.ctivities 
I am unable to do my usual a.ctiviti:es 
PAIN I DISCOMFORT 
I have no pain or discomfort 
I have slight pain or dis.comfort 
I have moderate pain or dis,comfort 
I have s,evere pain or discomfort 
I have extr,eme pain or dis.comfort 
ANXIETY / DEPRESSION 
I am not anxious or depress,ed 
I am slightly anxious or depress,ed 
I am moderately anxious or depress,ed 
I am severely anxious or depress,ed 
I am ,extremely anxious or depress,ed 
a 
a 
a 
a 
a 
a 
.a 
a 
a 
a 
a 
a 
a 
a 
a 
a 
a 
a 
a 
a 
a 
a 
a 
a 
a 
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10.11. 
Appendix 11: Work Productivity and Activity Impairment 
Questionnaire 
HEOR questions for the ECU-GBS study 
At Visit 2 (Day 1): 
Question 0a: Are you currently employed (working for pay)?  _____ NO ___ YES 
(“NO” answer covers unemployed, retired and housewife/husband patients) 
If YES, check “YES” and then ask 
Question 0b: Do you work full time in this paid job (40 hours by week)? ___NO__ YES 
If NO, check “NO” and then ask 
Question 0c: How many hours per week are you currently employed (working for 
pay)?  _____ HOURS 
If NO to question 0a, check “NO” and then ask 

Question 0d: Are you living in a retirement home or nursing home (use
correct wording for Japan) _____ NO ___ YES
(YES answered expected to come from some retired elderly patients or
disabled patients not working)

And skip to question 6 of the WPAI questionnaire at Visit 7 (Week 5),
Visit 13 (Week 24), and ET.
At Visits 7, 13, and ET (Week 5, Week 24, and ET): 
Ask the full WPAI questions to patients who answered “YES” to the Question 0 
“currently employed” 
Ask only the question 6 of the WPAI questionnaire to the ones who answered “NO” to 
the Question 0  
Official English WPAI questionnaire available on next page 
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Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
10.12. 
Appendix 12: Abbreviations 
Abbreviations 
Definition 
ADA(s) 
antidrug antibody (ies)
AE 
adverse event 
AESI 
adverse event of special interest
AIDP 
acute inflammatory demyelinating polyradiculopathy
aHUS 
atypical hemolytic uremic syndrome
AMAN 
acute motor axonal neuropathy
AQP4 
anti-aquaporin-4 
C5 
complement component 5
Chalder 
Chalder Fatigue Scale 
CH50 
50% hemolytic complement activity
CI 
confidence interval 
CIOMS 
Council for International Organizations of Medical Sciences
CMAP 
compound muscle action potential
CONSORT 
Consolidated Standards of Reporting Trials
CTCAE 
Common Terminology Criteria for Adverse Events
DASS-21 
Depression, Anxiety and Stress Scale, Short form, 21 questions
CHW 
Cui, Hung, Wang  
ECG 
electrocardiogram  
EDC 
electronic data capture
eCRF 
electronic case report form
EuroQoL 
European Quality of Life
EQ-5D-5L 
5 Dimensions – 5 Levels
ET 
end of treatment 
FAS 
Full Analysis Set 
FcRn 
neonatal Fc receptor 
FG 
Functional Grade 
FSH 
follicle-stimulating hormone
GBS 
Guillain-Barré syndrome
GCP 
Good Clinical Practice
GDS 
Global Drug Safety 
gMG 
generalized myasthenia gravis
GFAP 
glial fibrillary acidic protein
HEOR 
Health Economics and Outcomes Research
HR 
heart rate 
HRT 
hormonal replacement therapy
IB 
Investigator’s Brochure
IAC 
Independent Analysis Center
IAP 
Interim Analysis Plan 
ICF 
informed consent form
ICH 
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for 
Human Use 
ICU 
intensive care unit 
IL-6 
interleukin-6 
IRB 
Institutional Review Board
IV 
intravenous(ly) 
IVIg 
intravenous immunoglobulin
IRT 
Interactive Response Technology
LOS 
length of stay 
mAb(s) 
monoclonal antibody(ies)
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Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
Abbreviations 
Definition 
MAC 
membrane attack complex
MedDRA 
Medical Dictionary for Regulatory Activities
MMT 
Manual Muscle Testing
MRC 
Medical Research Council
NfL 
neurofilament light chain
NMOSD 
neuromyelitis optica spectrum disorders
ONLS 
Overall Neuropathy Limitations Scale
PD 
pharmacodynamic(s) 
PE 
plasma exchange 
PK 
pharmacokinetic(s) 
PNH 
paroxysmal nocturnal hemoglobinuria
PPS 
Per Protocol Set 
QoL 
quality of life 
QT 
interval between the start of the Q wave and the end of the T wave in an ECG 
QTc 
corrected QT interval 
R-ODS
Rasch-built Overall Disability Scale
RR 
respiratory rate 
SAE 
serious adverse event 
SAP 
statistical analysis plan
SAS® 
Statistical Analysis System (software)
SF-MPQ-2 
Short Form McGill Pain Questionnaire 2 
SoA 
Schedule of Activities 
SOC 
System Organ Class 
SS 
Safety Set 
SUSAR 
suspected unexpected serious adverse reaction
TEAE 
treatment-emergent adverse event
TESAE 
treatment-emergent serious adverse event
TNF-α 
tumor necrosis factor alpha 
WOCBP 
Woman/women of childbearing potential
WPAI 
Work Productivity and Activity Impairment
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Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
10.13. 
Protocol Amendment History 
The protocol amendment summary of changes table for the current amendment is located 
directly before the Table of Contents. 
DOCUMENT HISTORY 
Document 
Type of Amendment 
(Global or 
Country-specific) 
Date 
Summary of Key Changes in the 
Amendment 
Original 
protocol 
Not applicable 
15 Sep 2020 
Not applicable 
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Protocol Amendment 1.0 
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11.
REFERENCES
Cella M, Chalder T. Measuring fatigue in clinical and community settings. J Psychosom Res. 
2010; 69(1): 17-22. 
Depression Anxiety Stress Scales (DASS). Psychology Foundation of Australia. 2018. Link: 
http://www2.psy.unsw.edu.au/dass//. Accessed: 06 April 2020. 
Devlin NJ and Brooks R. EQ-5D and the EuroQol Group: Past, Present and Future. Appl Health 
Econ Health Policy. 2017;15(2):127-137. 
Dworkin RH, Turk DC, Revicki DA, et al. Development and initial validation of an expanded 
and revised version of the Short-form McGill Pain Questionnaire (SF-MPQ-2). Pain. 2009; 
144(1-2): 35-42. 
Ferri F. Ferri’s Clinical Advisor 2017: 5 Books in 1. 1st ed. Elsevier Health Sciences. ISBN 
9780323448383; 2016. p. 529. 
Fitzpatrick AM, Mann CA, Barry S, Brennan K, Overell JR, Willison HJ. An open label clinical 
trial of complement inhibition in multifocal motor neuropathy. J Peripher Nerv Syst. 
2011;16(2):84-91. 
Graham RC, Hughes RA. A modified peripheral neuropathy scale: The Overall Neuropathy 
Limitations Scale psychiatry. Neurol Neurosurg Psychiatry. 2006;77(8):973-976. 
Guillain-Barré syndrome and Fisher syndrome treatment Guideline 2013. 
https://www.neurology-jp.org/guidelinem/gbs.html. 
Guillain-Barré Syndrome Fact Sheet. https://www.ninds.nih.gov/Disorders/Patient-Caregiver-
Education/Fact-Sheets/Guillain-Barr%C3%A9-Syndrome-Fact-Sheet. 
Hafer-Macko CE, Sheikh KA, Li CY, et al. Immune attack on the Schwann cell surface in acute 
inflammatory demyelinating polyneuropathy. Ann Neurol. 1996;39:625–635. 
Halstead SK, Zitman FMP, Humphreys PD, et al. Eculizumab prevents anti-ganglioside antibody 
mediated neuropathy in a murine model. Brain. 2008;131:1197–1208. 
Kleyweg RP, van der Meché FG, Schmitz PI. Interobserver agreement in the assessment of 
muscle strength and functional abilities in Guillain-Barré syndrome. Muscle Nerve. 
1991;14(11):1103-1109. 
Kuwabara S, Yuki N. Axonal Guillain-Barré syndrome: concepts and controversies. Lancet 
Neurol. 2013;12:1180-1188. 
Leonhard SE, Mandarakas MR, Gondim FAA, et al. Diagnosis and management of 
Guillain-Barré syndrome in ten steps. Nat Rev Neurol. 2019;15(11):671–683. 
Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work productivity and 
activity impairment instrument. Pharmacoeconomics. 1993;4(5):353-365. 
Misawa S, Kuwabara S, Sato Y, et al. Safety and efficacy of eculizumab in Guillain-Barré 
syndrome: A multicentre, double-blind, randomized phase 2 trial. Lancet Neurol. 
2018:17(6):519-529. 
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Nerve injuries committee. Aids to the examination of the peripheral nervous system. Medical 
Research Council Memorandum No.45 (superseding War Memorandum No. 7). 1976;1-62. 
(Used with the permission of the Medical Research Council UK). 
Plasma Exchange/Sandoglobulin Guillain-Barré Syndrome Trial Group. Randomised trial of 
plasma exchange, intravenous immunoglobulin, and combined treatments in Guillain-Barré 
syndrome. Lancet. 1997;349(9047):225-230.  
Rajabally YA, Uncini A. Outcome and its predictors in Guillain-Barré syndrome. J Neurol 
Neurosurg Psychiatry. 2012;83(7):711-718. 
van Nes SI, Vanhoutte EK, van Doorn PA, et al. Rasch-built Overall Disability Scale (R ODS) 
for immune-mediated peripheral neuropathies. Neurology. 2011;76(4):337-345. 
Willison HJ, Jacobs BC, van Doorn PA. Guillain-Barré syndrome. Lancet. 
2016;388(10045):717-727. 
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SAP_001.pdf: 
Statistical Analysis Plan 
Version 2.0 
ECU-GBS-301 
30 June 2022 
TITLE PAGE 
STATISTICAL ANALYSIS PLAN 
Final Analysis 
Version Number: Final 2.0 
Protocol Title: A Phase 3, Prospective, Multicenter, Double-blind, Randomized, 
Placebo-Controlled Study to Evaluate the Efficacy and Safety of Eculizumab in Patients 
With Guillain-Barré Syndrome (GBS) 
Protocol Number: ECU-GBS-301 
Protocol Amendment Number: Not applicable 
Compound: Eculizumab (SOLIRIS®) 
Short Title: A Phase 3 Study to Evaluate the Efficacy and Safety of Eculizumab in 
Guillain-Barré Syndrome 
Sponsor Name: Alexion Pharma GK 
Legal Registered Address:  
Ebisu First Square 
1-18-14 Ebisu, Shibuya-ku
Tokyo 150-0013, Japan
Author: 
 
Version Date: 30 June 2022 
Page 1 of 57 
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NCT #: NCT04752566


Statistical Analysis Plan 
Version 2.0 
ECU-GBS-301 
30 June 2022 
TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
VERSION HISTORY ......................................................................................................................6 
APPROVAL SIGNATURES...........................................................................................................7 
1.
INTRODUCTION ........................................................................................................8 
1.1. 
Objectives and Endpoints .............................................................................................8 
1.2. 
Study Design .................................................................................................................9 
2.
STATISTICAL HYPOTHESES ................................................................................12 
2.1. 
Primary Hypothesis ....................................................................................................12 
2.2. 
Key Secondary Hypotheses ........................................................................................12 
2.3. 
Multiplicity Adjustment..............................................................................................12 
3.
SAMPLE SIZE DETERMINATION .........................................................................13 
4.
ANALYSIS SETS ......................................................................................................14 
5.
STATISTICAL ANALYSES .....................................................................................15 
5.1. 
General Considerations ...............................................................................................15 
5.2. 
Study Patients .............................................................................................................15 
5.2.1. 
Disposition of Patients ................................................................................................15 
5.2.2. 
Protocol Deviations ....................................................................................................16 
5.2.3. 
Demographics and Medical History ...........................................................................17 
5.2.3.1. 
Demographics .............................................................................................................17 
5.2.3.2. 
Disease Characteristics ...............................................................................................18 
5.2.3.3. 
Medical History ..........................................................................................................18 
5.2.4. 
Prior and Concomitant Medications/Nonpharmacologic Therapies ...........................18 
5.3. 
Primary Endpoint Analysis .........................................................................................19 
5.3.1. 
Primary Endpoint ........................................................................................................19 
5.3.2. 
Main Analytical Approach .........................................................................................19 
5.3.3. 
Sensitivity Analysis ....................................................................................................20 
5.3.3.1. 
Sensitivity Analysis to Handle Missing Primary Endpoint ........................................20 
5.3.3.2. 
Sensitivity Analysis: Unstratified Analyses for Primary Endpoint ............................21 
5.3.4. 
Supplementary Analyses ............................................................................................21 
5.4. 
Secondary Endpoints Analysis  ..................................................................................21 
5.4.1. 
Key Secondary Endpoints ...........................................................................................21 
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ECU-GBS-301 
30 June 2022 
5.4.2. 
Definition of Endpoints ..............................................................................................21 
5.4.3. 
Main Analytical Approach .........................................................................................22 
5.4.3.1. 
Proportion of Patients With a Hughes FG Score  1 at Week 24 ...............................22 
5.4.3.2. 
Proportion of Patients With a Hughes FG Sco
 3 at 
Week 24 ......................................................................................................................22 
5.4.3.3. 
Proportion of Patients With a Hughes FG Score  1 at Week 8 .................................23 
5.4.4. 
Sensitivity Analyses to Handle Missing Data ............................................................23 
5.4.5. 
Supplementary Analyses ............................................................................................24 
5.4.6. 
Other Secondary Endpoints ........................................................................................25 
5.4.6.1. 
Medical Resource Utilization .....................................................................................25 
5.4.6.2. 
Respiratory Support ....................................................................................................26 
5.5. 
Exploratory Endpoints Analysis .................................................................................27 
5.5.1. 
Functional Status Postacute Phase ..............................................................................27 
5.5.1.1. 
Rasch-Built Overall Disability Scale ..........................................................................27 
5.5.1.2. 
Overall Neuropathy Limitations Scale .......................................................................28 
5.5.1.3. 
Medical Research Council Sum Score .......................................................................28 
5.5.1.4. 
Manual Muscle Testing ..............................................................................................29 
5.5.1.5. 
Hughes FG Scores Over Time ....................................................................................29 
5.5.2. 
Pain, Mood, and Fatigue .............................................................................................30 
5.5.2.1. 
Short Form McGill Pain Questionnaire 2 ...................................................................30 
5.5.2.2. 
Depression, Anxiety, and Stress Scale - Short Form 21 Questions ............................30 
5.5.2.3. 
The Chalder Fatigue Scale ..........................................................................................31 
5.5.3. 
Quality of Life ............................................................................................................31 
5.5.3.1. 
European Quality of Life  5 Dimensions  5 Levels ................................................31 
5.5.3.2. 
Work Productivity and Activity Impairment ..............................................................32 
5.5.4. 
Biomarkers ..................................................................................................................33 
5.6. 
Safety Analyses ..........................................................................................................33 
5.6.1. 
Extent of Exposure .....................................................................................................33 
5.6.2. 
Adverse Events ...........................................................................................................33 
5.6.2.1. 
Overall Summary of AEs ............................................................................................34 
5.6.2.2. 
AEs and SAEs by SOC and PT ..................................................................................34 
5.6.2.3. 
AEs and SAEs by SOC, PT, and Relationship ...........................................................35 
5.6.2.4. 
AEs by SOC, PT, and Toxicity Grade ........................................................................35 
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Statistical Analysis Plan 
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5.6.2.5. 
Other Significant Adverse Events ..............................................................................35 
5.6.3. 
Additional Safety Assessments...................................................................................35 
5.6.3.1. 
Analyses for Laboratory Tests ....................................................................................35 
5.6.3.2. 
Vital Signs ..................................................................................................................36 
5.6.3.3. 
Physical Examinations ................................................................................................36 
5.6.3.4. 
Electrocardiogram .......................................................................................................36 
5.6.3.5. 
Other Safety Parameters of Special Interest ...............................................................36 
5.7. 
Other Analyses ............................................................................................................36 
5.7.1. 
Other Variables and/or Parameters .............................................................................36 
5.7.1.1. 
Nerve Conduction Test ...............................................................................................36 
5.7.1.2. 
Immunogenicity ..........................................................................................................36 
5.7.1.3. 
Pharmacokinetic and Pharmacodynamic Analyses ....................................................36 
5.7.2. 
Subgroup Analyses .....................................................................................................37 
5.8. 
Interim Analyses .........................................................................................................38 
6.
SUPPORTING DOCUMENTATION ........................................................................39 
6.1. 
Appendix 1: List of Abbreviations .............................................................................39 
6.2. 
Appendix 2: Changes to Protocol-Planned Analyses .................................................40 
6.2.1. 
Changes From Protocol to SAP V1.0 .........................................................................40 
6.2.2. 
Changes From SAP V1.0 to SAP V2.0 ......................................................................40 
6.3. 
Appendix 3: Technical Specifications for Derived Variables ....................................45 
6.3.1. 
Definition of Baseline Values .....................................................................................46 
6.3.2. 
Change From Baseline ................................................................................................46 
6.3.3. 
Visit Window ..............................................................................................................46 
6.3.4. 
Definitions of Durations .............................................................................................46 
6.3.4.1. 
Duration of Ventilation Support .................................................................................46 
6.3.4.2. 
Duration of Hospitalization ........................................................................................46 
6.3.4.3. 
Duration of ICU ..........................................................................................................46 
6.3.5. 
Definition of mEGOS .................................................................................................47 
6.3.6. 
Derivation of Treatment-Emergent Adverse Events for Missing or 
Incomplete Date of Onset ...........................................................................................47 
6.3.7. 
Derivation of Prior and Concomitant Medication for Missing or Incomplete 
Dates ...........................................................................................................................48 
6.3.8. 
EQ-5D-5L Calculations ..............................................................................................49 
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Statistical Analysis Plan 
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30 June 2022 
6.3.9. 
WPAI Calculations .....................................................................................................51 
6.3.9.1. 
WPAI Scoring and Calculations .................................................................................51 
6.4. 
Appendix 4: Additional Details on Statistical Methods .............................................52 
6.4.1. 
SAS Code for Key Efficacy Endpoints Analyses .......................................................52 
6.4.1.1. 
SAS Code for the Primary Efficacy Endpoint ............................................................52 
6.4.1.2. 
SAS Code for the Key Secondary Efficacy Endpoints ...............................................52 
6.4.1.3. 
SAS Code for the Multiple Imputations .....................................................................53 
6.4.2. 
SAS Code for Exploratory Endpoints Analyses .........................................................54 
6.5. 
Details of Statistical Analyses to Address COVID-19 Impacts .................................54 
6.5.1. 
Patients Who Were Impacted by COVID-19 .............................................................54 
6.5.2. 
Efficacy Assessments .................................................................................................54 
6.5.3. 
COVID-19-Related Analyses .....................................................................................54 
7.
REFERENCES ...........................................................................................................56 
LIST OF TABLES 
Table 1: 
Objectives and Endpoints .............................................................................................8 
Table 2: 
Randomization Strata ....................................................................................................9 
Table 3: 
Analysis Sets ...............................................................................................................14 
Table 4: 
Protocol Deviation Categories ....................................................................................16 
Table 5: 
Definition of Key Secondary Endpoints .....................................................................22 
Table 6: 
Definition of Key Secondary Endpoints for Sensitivity Analysis 1 ...........................23 
Table 7: 
Summary of Analyses of Primary and Key Secondary Endpoints .............................24 
Table 8: 
Subgroup Analysis for Efficacy..................................................................................37 
Table 9: 
Modified Erasmus GBS Outcome Scores ...................................................................47 
Table 10: EQ-5D-5L Scoring ......................................................................................................50 
LIST OF FIGURES 
Figure 1: 
Study Design Schematic .............................................................................................11 
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Statistical Analysis Plan 
Version 2.0 
ECU-GBS-301 
30 June 2022 
VERSION HISTORY 
This statistical analysis plan (SAP) for Study ECU-GBS-301 is based on protocol amendment 
1.0, dated 28 Oct 2021. 
SAP Version
Version Date 
Change 
Rationale 
1 
02 Dec 2021 
Not applicable 
Original version 
2 
30 Jun 2022 
See Section 6.2 
(Appendix 2) for 
detailed changes. 
The definition of treatment-emergent adverse event 
was made consistent with the protocol in SAP 
Version 2.0. 
The Pharmacokinetic Analysis Set was revised to 
include patients who received placebo. 
The Pharmacodynamic Analysis Set was added. 
Efficacy analyses to assess the impact of 
Coronavirus Disease 2019 were revised using the 
while-on-treatment strategy. 
Subgroup analyses on treatment-emergent adverse 
event were added. 
Multiple imputations using linear regression model 
were used to predict missing Functional Grade 
scores after discontinuation. 
As a sensitivity analysis, baseline observation 
carried forward was used to impute the missing 
values for patients who discontinued the study. This 
reflects the worst-case scenario.  
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APPROVAL SIGNATURES 
Date 
Date 
 
Date 
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1.
INTRODUCTION
This statistical analysis plan (SAP) describes the statistical methods for the final analysis for 
Study ECU-GBS-301. Standard data presentation instructions and table, figure, and listing 
specifications are contained in the data presentation plan in a separate document.  
All data collected in this protocol except for the exploratory biomarker data will be included for 
the final database lock and statistical analysis. The statistical analysis of biomarker data will be 
provided in a separate document. 
This SAP is finalized before database lock and study unblinding. 
The planned interim analysis for sample size re-estimation is provided in a separate interim 
analysis plan (IAP). 
1.1. 
Objectives and Endpoints 
The objectives and endpoints for this study are provided in Table 1. 
Table 1: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To characterize the efficacy of eculizumab in patients 
with GBS 
Time to first reaching a Hughes FG score  1 
Key Secondary 
To further characterize the efficacy of eculizumab over 
time in patients with GBS 
Proportion of patients with a Hughes FG 
score  1 at Week 24 
Proportion of patients with a Hughes FG score 
 3 at Week 24 
Proportion of patients with a Hughes FG 
score  1 at Week 8 
Other Secondary 
To further characterize the impact of eculizumab on 
medical resource utilization in patients with GBS 
Hospital LOS 
ICU stay 
o
LOS in the ICU
o
Proportion of patients admitted to the
ICU
Disposition post hospital discharge 
To evaluate the effect of eculizumab compared with 
placebo on respiratory function in patients with GBS 
Ventilator support 
o
Duration of ventilator support
o
Proportion of patients requiring
ventilator support
To characterize the PK/PD attributes of eculizumab in 
patients with GBS 
Concentration of eculizumab in serum 
Free C5 in serum 
Hemolytic complement activity in serum 
To assess the formation of ADAs in response to 
eculizumab treatment 
Incidence of ADAs 
Safety 
To characterize the overall safety and tolerability of 
eculizumab in patients with GBS 
Incidence of TEAEs, SAEs, and AEs leading 
to study drug discontinuation 
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Table 1: 
Objectives and Endpoints 
Objectives 
Endpoints 
Tertiary/Exploratory 
To characterize the functional status of patients with 
GBS postacute phase 
Change from Baseline in the functional scales 
of GBS (R-ODS and ONLS) 
Change from Baseline in strength 
measurements (MRC-SS and MMT) 
Change from Baseline in the Hughes FG score 
over time 
To evaluate the effect of eculizumab compared with 
placebo on pain in patients with GBS 
Change from Baseline in the SF-MPQ-2 score 
To evaluate the effect of eculizumab compared with 
placebo on mood in patients with GBS 
Change from Baseline in the DASS-21 score 
To evaluate the effect of eculizumab compared with 
placebo on fatigue in patients with GBS 
Change from Baseline in the Chalder score 
To evaluate the effect of eculizumab compared with 
placebo on QoL in patients with GBS 
Change from Baseline in the EQ-5D-5L score 
Change from Baseline in the WPAI score 
To evaluate complement, inflammation, and 
neurodegeneration biomarkers in patients with GBS 
Change from Baseline in biomarker levels in 
blood 
Abbreviations: ADA = antidrug antibody; AE = adverse event; C5 = complement component 5; 
Chalder = Chalder Fatigue Scale; DASS -21 = Depression, Anxiety, and Stress Scale, Short Form, 
21 Questions; EQ-5D-5L = European Quality of Life  5 Dimensions  5 Levels; FG = Functional Grade; 
GBS = Guillain-Barré syndrome; ICU = intensive care unit; LOS = length of stay; MMT = Manual Muscle 
Testing; ONLS = Overall Neuropathy Limitations Scale; PD = pharmacodynamic; PK = pharmacokinetic; 
QoL = quality of life; R-ODS = Rasch-Built Overall Disability Scale; SAE = serious adverse event; 
SF-MPQ-2 = Short Form McGill Pain Questionnaire 2; TEAE = treatment-emergent adverse event; 
WPAI = Work Productivity and Activity Impairment 
1.2. 
Study Design 
Study ECU-GBS-301 is a Phase 3, prospective, multicenter, placebo-controlled, double-blind, 
randomized study to investigate the efficacy and safety of eculizumab in patients with severe 
Guillain-Barré syndrome (GBS), defined using the Hughes Functional Grade (FG) score 
(Plasma Exchange/Sandoglobulin Guillain-Barré Syndrome Trial Group, 1997) as progressively 
deteriorating FG3 or FG4/FG5 within 2 weeks from onset of weakness due to GBS. Eligible 
GBS patients will be randomized in a 2:1 ratio to either eculizumab intravenous (IV) infusion or 
placebo IV infusion within each stratum as defined in Table 2. All patients will be on 
concomitant IV immunoglobulin (IVIg) therapy per standard of care (400 mg/kg body weight 
daily for 5 days). 
Table 2: 
Randomization Strata 
Strata 
FG Score 
Diarrhea 
Progressively Deteriorating FG3 vs Stable 
or Progressively Deteriorating FG4/5 
Present vs Absent < 4 Weeks Prior to 
Onset of Neurological Symptoms 
1 
Progressively deteriorating FG3 
Present 
2 
Progressively deteriorating FG3 
Absent 
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Table 2: 
Randomization Strata 
Strata 
FG Score 
Diarrhea 
Progressively Deteriorating FG3 vs Stable 
or Progressively Deteriorating FG4/5 
Present vs Absent < 4 Weeks Prior to 
Onset of Neurological Symptoms 
3 
Stable or progressively deteriorating FG4/5 
Present 
4 
Stable or progressively deteriorating FG4/5 
Absent 
Abbreviations: FG = Functional Grade; vs = versus 
There will be 3 periods in the study as follows: 
Screening Period: up to 1 week 
Treatment Period: 4 weeks 
Follow-up Period: 20 weeks 
Approximately 57 patients (eculizumab = 38 and placebo = 19) will be randomized. The total 
duration of study participation for each patient will be up to 25 weeks. Efficacy and safety will 
be monitored through 24 weeks after the first dose of the study drug. An interim analysis is 
planned for the unblinded sample size re-estimation when approximately 60% (ie, at least 
12 events) of the planned events (FG score  1) are observed. 
Eculizumab will be administered via IV infusion at a dose of 900 mg once per week for 4 weeks. 
A supplemental dose of 600 mg will be given with the first dose on Day 1. 
Placebo will be administered via IV infusion once per week for 4 weeks. Placebo is a matching 
sterile, clear, colorless solution with the same buffer components but without active ingredient, 
in an identical 30-mL vial. A supplemental dose of placebo will be administered with the first 
dose on Day 1 to maintain the blind. 
delegates throughout the study. 
There is no data monitoring committee for this study, but an independent analysis center (IAC) 
will be established for the interim analysis. 
The final statistical analysis will occur when the last patient has completed the 20-week 
Follow-up Period and the last scheduled visit or prematurely discontinued from the study and 
when the database is locked. 
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Figure 1: 
Study Design Schematic 
Abbreviations: D = day; EOS = end of study; FG = Functional Grade; IVIg = intravenous immunoglobulin; 
N = number of patients randomized; n = number of patients in each treatment group; Pbo = placebo; W = week 
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2.
STATISTICAL HYPOTHESES
2.1. 
Primary Hypothesis
The primary null hypothesis is that the effect of eculizumab is no different from placebo in time 
to first reaching a Hughes FG score  1. The alternative hypothesis is that there is a treatment 
difference from placebo in favor of eculizumab based on time to first reaching a Hughes FG 
score  1. 
2.2. 
Key Secondary Hypotheses 
The null hypothesis associated with the key secondary objectives is that eculizumab is no 
different from placebo for the respective endpoints. The alternative hypotheses are described as 
follows: 
Proportion of patients with a Hughes FG score  1 at Week 24: The alternative 
hypothesis is that there is a treatment difference from placebo in favor of eculizumab 
in the proportion of patients with an FG score  1 at Week 24. 
Proportion of patients with a Hughes FG score improvement of  3 at Week 24: The 
alternative hypothesis is that there is a treatment difference from placebo in favor of 
eculizumab in the proportion of patients with an FG score improvement of  3 at 
Week 24. 
Proportion of patients with a Hughes FG score  1 at Week 8: The alternative 
hypothesis is that there is a treatment difference from placebo in favor of eculizumab 
in the proportion of patients with an FG score  1 at Week 8. 
2.3. 
Multiplicity Adjustment 
The primary hypothesis will be tested with a 2-sided type 1 error of 0.05. 
Hypothesis testing associated with the key secondary endpoints will proceed only if the null 
hypothesis associated with the primary endpoint is rejected and will proceed from the highest 
rank ([1] proportion of patients with a Hughes FG score  1 at Week 24) to the lowest rank 
([3] proportion of patients with a Hughes FG score  1 at Week 8). If statistical significance is 
not achieved at an endpoint (2-sided p  0.05), then the endpoint of lower rank will not be 
considered to be statistically significant. Confidence intervals (CIs) and p-values will be 
presented for all key secondary efficacy endpoints for descriptive purposes, regardless of the 
outcome of the closed testing procedure.  
An unblinded interim analysis on at least 12 events (FG score  1; approximately 60% of the 
planned events) will be conducted for only the sample size re-estimation based on the conditional 
power. Details are provided in a separate IAP. The method by Gao et al (Gao, 2008) will be used 
for controlling the type 1 error rate due to the interim analysis.  
Further details are provided in Sections 5.8 and 6.2.1. 
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3.
SAMPLE SIZE DETERMINATION
The sample size for this study is based on results from the Investigator-initiated study in Japan 
(Misawa, 2018). Assuming a 2:1 randomization of patients with GBS to eculizumab and placebo, 
a dropout rate of approximately 10%, a cumulative probability of response at 24 weeks of 70% 
for eculizumab and 20% for placebo (corresponding to a true hazard ratio of 5.4), 1-sided type 1 
error of 0.025, and a fixed Follow-up Period of 24 weeks for each patient with approximately an 
average enrollment rate of 1 patient per week, a total sample size of 57 patients with 
approximately a total of 19 events (responders) would provide at least 90% power using a 
log-rank test for the primary endpoint, time to first reaching a Hughes FG score  1. 
The total sample size of 57 patients (assuming a dropout rate of approximately 10%) will provide 
at least 90% power to detect a treatment difference of 50% in favor of eculizumab for the first 
key secondary endpoint FG score  1 at Week 24, assuming a placebo response rate of 20%; at 
least 85% power to detect a treatment difference of 43% in favor of eculizumab for the second 
key secondary endpoint FG improvement of  3 at Week 24, assuming a placebo response rate of 
27%; and approximately 85% power to detect a treatment difference of 40% in favor of 
eculizumab for the third key secondary endpoint FG score  1 at Week 8, assuming a placebo 
response rate of 20%. 
An interim analysis is planned for the unblinded sample size re-estimation when approximately 
60% (ie, at least 12 events) of the planned events (FG score  1) are observed. The sample size 
will be increased to a maximum of 72 patients to generate a maximum of approximately 
32 events using a conditional power approach. Further details will be provided in the IAP. 
The sample size calculation was performed in EAST 6.5 using the log-rank test for the primary 
endpoint and 2-sample test for the difference in proportions with unpooled variance estimate for 
the key secondary endpoints. 
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4.
ANALYSIS SETS
The analysis sets are defined in Table 3. 
Table 3: 
Analysis Sets 
Analysis Set 
Description 
FAS 
All randomized patients who received at least 1 dose of study drug and have a 
baseline FG score and at least 1 postbaseline FG score. Patients will be 
analyzed according to the treatment group assigned by randomization. 
SS 
All patients who received at least 1 dose of study drug. Patients will be 
analyzed according to the study drug they actually received. For a participant 
to be analyzed according to the treatment they actually received, they would 
have to receive that treatment for the entire duration of the study treatment 
period.
PPS 
All FAS patients without any major protocol deviations. 
PKAS 
All patients who received at least 1 dose of study drug and who have at least 
1 postdose PK sample. 
PDAS 
All patients who received at least 1 dose of study drug and who have at least 
1 postdose PD sample. 
Abbreviations: FAS = Full Analysis Set; FG = Functional Grade; PD = pharmacodynamic; 
PDAS = Pharmacodynamic Analysis Set; PK = pharmacokinetic; PKAS = Pharmacokinetic Analysis Set; 
PPS = Per Protocol Set; SS = Safety Set 
In general, all efficacy analyses will be based on the Full Analysis Set (FAS). Supplemental 
per-protocol analyses for the primary efficacy endpoint will be performed based on the Per 
Protocol Set (PPS) in the same manner as done for the FAS. Safety analyses will be performed 
on the Safety Set (SS). 
Further details on addressing Coronavirus Disease 2019 (COVID-19) impacts are provided in 
Section 6.5. 
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5.
STATISTICAL ANALYSES
5.1. 
General Considerations
Statistical analyses will include tabulations of summary data, inferential analyses, by-patient 
listings, and figures. Inference from efficacy analyses will be based on a 2-sided type 1 error 
 = 0.05 unless stated otherwise. 
The summary statistics for continuous variables will include, but will not be limited to, the 
number of patients, mean, standard deviation, minimum, median, and maximum. For categorical 
variables, frequencies and percentages will be presented. 
The baseline value for analysis and reporting will be based on the last nonmissing measurement 
on or prior to the first dose of the study drug unless stated otherwise. 
Analyses will be performed using the Statistical Analysis System (SAS®) software version 9.4 or 
higher. 
Alexion will be responsible for collecting data, reviewing and validating all the information in 
the electronic case report forms (CRFs), performing statistical analysis, and generating the final 
clinical report. 
The Alexion Quantitative Sciences Department will perform the statistical analysis of the data 
derived from this study. 
Medications will be coded using the World Health Organization (WHO) Drug Dictionary 
(March 2021 or higher). Therapies will be coded using Medical Dictionary for Regulatory 
Activities (MedDRA; version 24.0 or higher).  
Adverse events (AEs) will be coded by primary system organ class (SOC) and preferred term 
(PT) using MedDRA (version 24.0 or higher).  
The impacts of COVID-19 on the planned analyses are described in Section 6.5. 
5.2. 
Study Patients 
5.2.1. 
Disposition of Patients 
The number of patients screened, the number of screen failures and the reasons for screen 
failures, the number of patients randomized and treated in the study, the number of patients who 
completed the study, and the number of patients who discontinued from the study and the 
reasons for discontinuation will be tabulated. The number and percentage of patients included in 
the FAS, the SS, and the PPS and excluded from these same populations will be presented.  
Summary statistics of study duration will also be provided for all randomized patients. The study 
duration (weeks) will be calculated as 
, rounded to 
1 decimal. The last date on study is the visit date of Week 24 for patients who have completed 
the study, or the date of discontinuation for patients who discontinued the study early. 
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The number of patients who discontinued from the study will also be provided for the following 
time periods: 
The 4-week Treatment Period 
The 20-week Follow-up Period 
The number and percentage of patients within each stratum will be summarized by treatment 
group. 
5.2.2. 
Protocol Deviations 
The number and percentage of patients with important protocol deviations for the categories 
provided in Table 4 will be summarized by treatment group and overall using the FAS 
population. 
Table 4: 
Protocol Deviation Categories 
1.
Eligibility and entry criteria
2.
Investigational product
3.
Concomitant medication
4.
Informed consent
5.
Laboratory assessment
6.
Visit schedule
7.
Study procedure/tests
8.
Randomization
9.
Safety reporting
10. Source document
11. Other
All protocol deviations will also be provided at the patient level using data listings. 
For the purpose of defining the PPS, patients have met any of the following important protocol 
deviation criteria will be considered for exclusion from the PPS: 
Patients with unscheduled readministration of IVIg within 4 weeks of first dose of 
study drug 
Patients with plasma exchange 
Patients who took < 3 doses of study drug  
Patients who took < 4 doses of IVIg  
Patients who were incorrectly stratified for randomization 
Patients with deviation from the following inclusion criteria: 
o
#2 Patients who meet the 2019 consensus GBS criteria
o
#3 Patients who are able to run prior to onset of GBS symptoms
o
#4 Patients with onset of weakness due to GBS < 2 weeks before Screening
o
#5
 5 meters (progressively deteriorating 
FG3 or FG4 to FG5)
o
#6 Patients who are already on IVIg or deemed eligible for and who will start
IVIg
o
#7 Patients who can start their first dose of the study drug before the end of the
IVIg treatment period
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Patients with deviation from the following exclusion criteria: 
o
#8 Patients who have previously received or are currently receiving treatment
with complement modulators
o
#9 Patients who have received rituximab within 12 weeks prior to Screening
o
Patients who have received plasmapheresis
o
#11 Patients who have received immunosuppressive treatment (eg, azathioprine,
cyclosporine, tacrolimus, or > 20mg prednisolone daily) during the 4 weeks prior
to providing consent
Patients who took any of the protocol-prohibited medications/procedures during the 
study: 
o
Rituximab
o
Plasmapheresis
o
Steroid pulse therapy (> 500 mg/day of methylprednisolone)
o
Immunosuppressive drugs
o
Other investigational drugs
o
Other complement inhibitory agent
The list of patients identified to be excluded from the PPS will be documented in the final data 
review meeting minutes before database lock. 
The COVID-19-related important protocol deviations will also be identified and provided in data 
summaries and listings (see Section 6.5). 
5.2.3. 
Demographics and Medical History 
All demographic and baseline characteristics information including baseline GBS disease 
characteristics and background therapy will be summarized using the FAS population. Medical 
history will be summarized using the FAS population. Summary statistics will be presented by 
treatment group and overall. 
The same summaries will also be provided for the SS if it differs from the FAS. 
5.2.3.1. 
Demographics 
The following demographic variables will be summarized: 
Age (years)  
Sex 
Race and ethnicity 
Baseline weight (kilograms) 
Baseline height (centimeters) 
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5.2.3.2. 
Disease Characteristics 
The following GBS disease characteristics will be summarized by treatment group and overall: 
Baseline FG stratification (progressively deteriorating FG3, stable, or progressively 
deteriorating FG4/FG5) 
Diarrhea < 4 weeks prior to onset of neurological symptoms (present or absent) 
Days since GBS onset calculated as follows: (Date of first dose  Date of GBS 
onset + 1) 
o
< Median days since GBS onset
o
Median days since GBS onset
Baseline Medical Research Council sum score (MRC-SS; see Section 5.5.1.3) 
o
< Median baseline MRC-SS
o
Median baseline MRC-SS
Baseline modified Erasmus GBS outcome score (mEGOS; see Section 6.3.5) 
o
< Median mEGOS
o
Median mEGOS
Days since IVIg calculated as follows: (Date of first dose  Date of first IVIg 
dose + 1) 
o
One to 3 days since IVIg
o
Four to 5 days since IVIg
GBS subtype (acute inflammatory demyelinating neuropathy [AIDP], acute motor 
axonal neuropathy [AMAN], and indeterminate) 
5.2.3.3. 
Medical History 
Baseline medical history information (ie, number [percentage] of patients who have a medical 
history) will be summarized by SOC and PT for the FAS population. By-patient listings will be 
created for medical history. 
5.2.4. 
Prior and Concomitant Medications/Nonpharmacologic Therapies 
Prior medications or therapies are defined as medications taken or therapies received by patients 
prior to the first dose in the study. Concomitant medications or therapies are defined as 
medications taken or therapies received by patients during the study on or after the first dose.  
Summaries will be performed on the FAS population. The number (percentage) of patients using 
prior and concomitant medications will be summarized based on the WHO Anatomical 
Therapeutic Chemical Level 3 class code and generic name.  
By-patient listings of all reported medications will be produced. 
If prohibited medications as defined by clinical review are used by patients in this study, then a 
listing of those patients and the respective prohibited medication(s) will be produced. 
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Any antibiotic details, meningococcal vaccination status, and IVIg details will also be provided 
in patient data listings. 
Nonpharmacologic therapies and procedures will be summarized by SOC and PT for each 
treatment group. 
5.3. 
Primary Endpoint Analysis 
The FAS will be used for the analysis of the primary endpoint. The PPS will also be used as a 
supplemental analysis of the primary endpoint. 
The details of the statistical analyses of the primary endpoint are provided in the following 
sections and in Table 7.  Further details of addressing COVID-19 impacts are provided in 
Section 6.5. 
5.3.1. 
Primary Endpoint 
The primary endpoint is the time to first reaching a Hughes FG score  1. 
An event will be considered as achieving an FG score  1. Time (days) to first event (FG 
score  1) will be calculated as follows: 
For patients who have experienced an event, the date when the first event was reported will be 
used in the calculation. Patients who have not experienced any event by Week 24 of the 
Follow-up Period will be censored at the last visit, and patients who discontinued prematurely 
without ever achieving an event will be censored at the date of early discontinuation.  
Additional sensitivity analyses of handling missing data will be provided in Section 5.3.3. 
5.3.2. 
Main Analytical Approach 
Treatment comparison in the primary endpoint will be performed via the log-rank test stratified 
by the 4 randomization strata as defined in Section 5.2.1.  
The study will be concluded as positive if the 2-sided p-value from the log-rank test is less than 
the final alpha level adjusted for the interim analysis in favor of eculizumab (section to interim 
analysis.).  If the final sample size is not increased due to unblinded interim analysis, the final 
alpha will be 0.05 (2-sided). Further details are in Section 6.4.1.1. 
In addition, to estimate the hazard ratio, a stratified Cox proportional hazard model will be used 
with time to event as the dependent variable, treatment group as the fixed effect in the model, 
stratified by randomization strata. In this analysis, the baseline hazard function will be allowed to 
 (Efron, 1977). Firth 
adjustment (Firth, 1993) is applied if no event observed in a treatment group and stratum. 
The estimated hazard ratio (eculizumab versus placebo) and the 95% CI of the hazard ratio from 
the stratified Cox proportional hazard model will be presented. An estimated hazard ratio greater 
than 1 will be indicative of benefit favoring eculizumab versus placebo, if statistically 
significant. 
In addition, a Kaplan-Meier curve will be presented for the cumulative proportion of patients 
reaching the response (FG score  1); the 95% CIs of the proportion based on complementary 
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log-log transformation will be presented over the 24-week period, along with the 25th percentile, 
50th percentile (median), 75th percentile of time to event (days), and the 95% CIs of the 25th, 
50th, and 75th percentiles of time to event will also be summarized for each treatment group.  
5.3.3. 
Sensitivity Analysis 
5.3.3.1. 
Sensitivity Analysis to Handle Missing Primary Endpoint 
To assess the robustness of the primary analysis of this endpoint in terms of handling missing 
data, the following sensitivity analyses will also be performed: 
1. Sensitivity Analysis 1: In this sensitivity analysis, if the last FG score prior to
discontinuation 
 1, then no imputation will be done and the observed time to first
event will be used for analysis. If the last FG score prior to discontinuation is > 1, then
the baseline FG score will be carried forward (baseline observation carried forward
[BOCF]) for all visits after discontinuation. Based on this imputation, the censoring time
will be derived as Week 24 for these patients.
2. Sensitivity Analysis 2: In this sensitivity analysis, if the last FG score prior to
 1, then the last FG score will be carried forward (last observation 
carried forward [LOCF]) for all visits after discontinuation in order to have a complete 
response profile for the responders. The time-to-event for such patients will still be based 
on the first observed FG response. The intermittent missing FG scores will be imputed 
based on the LOCF approach. If the last FG score prior to discontinuation is > 1, then 
missing FG scores will be imputed using a multiple imputation approach, assuming that 
data are missing at random (MAR). The missing FG scores for patients will be imputed at 
each post-discontinuation visit. Imputation will be implemented using a linear regression 
model and the monotone method with the treatment group and randomization strata as the 
fixed effects and the baseline FG score as covariate. A score of 0 will be assigned if the 
imputed score is <0; A score of 5 will be assigned if the imputed score is >5. Based on 
this imputation the time-to-event and censoring time will be rederived for these patients. 
3. Sensitivity Analysis 3: In this sensitivity analysis, if the last FG score prior to
 1, then the last FG score will be carried forward (LOCF) for all visits 
after discontinuation in order to have a complete response profile for the responders. The 
time-to-event for such patients will still be based on the first observed FG response. The 
intermittent missing FG scores will be imputed based on the LOCF approach. If the last 
FG score prior to discontinuation is > 1, then missing FG scores will be imputed using a 
multiple imputation approach, assuming that data are missing not at random (MNAR). 
The missing FG scores for patients will be imputed at each post-discontinuation visit 
based on the placebo patients who continue to that visit. Imputation will be implemented 
using a linear regression model and the monotone method with the treatment group and 
randomization strata as the fixed effects and the baseline FG score as covariate. A score 
of 0 will be assigned if the imputed score is <0; A score of 5 will be assigned if the 
imputed score is >5. Based on this imputation, the time-to-event and censoring time will 
be rederived for these patients. The same analyses as described in Section 5.3.2 will be 
performed on the imputed data. Further details, including the SAS program code, are 
described in Section 6.4.1.3.  
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5.3.3.2. 
Sensitivity Analysis: Unstratified Analyses for Primary Endpoint 
Sensitivity Analysis 4: As a sensitivity analysis to assess the impact of stratification, the 
2 treatment groups will be compared using an unstratified log-rank test. The hazard ratio together 
with the associated 95% CI obtained using the unstratified Cox regression model will also be 
presented. 
5.3.4. 
Supplementary Analyses 
Supplemental analyses will be performed on the primary endpoint based on the PPS. 
5.4. 
Secondary Endpoints Analysis  
The analysis of the secondary endpoints will be performed on the FAS. Detailed analyses are 
described in the following sections and in Table 7. 
If the primary endpoint is statistically significant, the hypothesis testing of the key secondary 
endpoints will be performed in a hierarchical order as described in Section 2.3. 
5.4.1. 
Key Secondary Endpoints 
The key secondary endpoints are described in Table 1 and are as follows: 
Proportion of patients with a Hughes FG score  1 at Week 24 
 3 at Week 24 
Proportion of patients with a Hughes FG score  1 at Week 8 
5.4.2. 
Definition of Endpoints 
The definitions of each key secondary endpoints are provided in Table 5. 
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Table 5: 
Definition of Key Secondary Endpoints 
Endpoint 
Definition 
A Hughes FG score  1 at Week 24 
If a patient has an FG score  1 prior to or at Week 24, then the 
patient is considered a responder; otherwise, patients discontinued 
prior to Week 24 or with an FG score > 1 at Week 24 are 
nonresponders. 
A Hughes FG 
 3 at 
Week 24 
If a patient has a change from Baseline in FG score (value at 
Week 24  b
3, then the patient is considered a 
responder. Discontinued patients will be considered 
nonresponders. 
A Hughes FG score  1 at Week 8 
If a patient has an FG score  1 prior to or at Week 8, then the 
patient is considered a responder; otherwise, patients discontinued 
prior to Week 8 or with an FG score > 1 at Week 8 are 
nonresponders. 
Note: An FG score  1 is considered not reversible once it is achieved during the study. 
Abbreviation: FG = Functional Grade 
5.4.3. 
Main Analytical Approach 
5.4.3.1. 
Proportion of Patients With a Hughes FG Score  1 at Week 24 
The analysis will be performed on the FAS population using the definition from Table 5. 
The treatment comparison for this endpoint will be performed with a logistic regression model, 
with response (Yes and No) as the dependent variable and treatment group and randomization 
strata as the fixed effects. Firth adjustment (Firth, 1993) is applied if convergence of the logistic 
regression model cannot be achieved due to complete separation. The p-value, the estimated 
odds ratio (OR) of response between eculizumab and placebo, and the 2-sided 95% CI of the OR 
from the logistic regression model will be presented. The p-value from this analysis will be used 
for multiplicity adjustment. 
As an additional analysis, a Mantel-Haenszel (MH) test will be performed to compare the 
2 proportions between eculizumab and placebo, stratified by randomization strata. The p-value, 
the estimated difference in the 2 proportions, and the 2-sided 95% CI of the difference using the 
MH stratum weights (Mantel, 1959) and the Sato variance estimator will be presented. 
In addition, the difference in the proportion of patients with a response, p-value, and the 95% CI 
of the difference between the treatment groups, as well as the number and proportion of patients 
with a response for each treatment, will be presented. 
5.4.3.2. 
 3 at 
Week 24 
The analysis will be performed on the FAS population using the definition from Table 5. 
The treatment comparison in this endpoint will be performed with the same analysis methods as 
described in Section 5.4.3.1.  
 1, 2, 3, 4, 
and 5 over time will also be presented for each treatment group. 
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5.4.3.3. 
Proportion of Patients With a Hughes FG Score  1 at Week 8 
The analysis will be performed on the FAS population using the definition from Table 5. 
The treatment comparison in this endpoint will be performed with the same analysis methods as 
described in Section 5.4.3.1.  
5.4.4. 
Sensitivity Analyses to Handle Missing Data 
To assess the robustness of the main analyses of those key secondary endpoints in terms of 
handling of missing data, the following sensitivity analyses will also be performed: 
Sensitivity Analysis 1: This sensitivity analysis is applicable only to the first and the third key 
secondary endpoints. 
In this analysis, if a patient died during the study, he/she is considered a nonresponder.  
Table 6: 
Definition of Key Secondary Endpoints for Sensitivity Analysis 1 
Endpoint 
Definition 
A Hughes FG score  1 at Week 24 
If a patient has an FG score  1 at or prior to Week 24, then the 
patient is considered a responder for this endpoint if the patient 
does not discontinue the study due to death; otherwise, 
discontinued patients will be considered nonresponders. 
A Hughes FG score  1 at Week 8 
If a patient has an FG score  1 at or prior to Week 8, then the 
patient is considered a responder for this endpoint if the patient 
does not discontinue due to death before Week 8; otherwise, 
patients discontinued prior to Week 8 will be considered 
nonresponders. 
Abbreviation: FG = Functional Grade 
Sensitivity Analysis 2: 
 1, then the last FG score 
will be carried forward (LOCF) for all visits after discontinuation in order to have a complete 
response profile for the responders. The intermittent missing FG scores will be imputed based on 
the last observation carried forward (LOCF) approach. If the last FG score prior to 
discontinuation is > 1, then missing FG scores will be imputed using a multiple imputation 
approach, assuming that data are MAR. The missing FG scores for patients will be imputed at 
each post-discontinuation visit. Imputation will be implemented using a linear regression model 
and the monotone method with the treatment group and randomization strata as the fixed effects 
and the baseline FG score as covariate. A score of 0 will be assigned if the imputed score is <0; 
A score of 5 will be assigned if the imputed score is >5.  
Sensitivity Analysis 3: In this sensitivity analysis, if the last FG score prior to early 
 1, then the last FG score will be carried forward (LOCF) for all visits after 
discontinuation in order to have a complete response profile for the responders. The intermittent 
missing FG scores will be imputed based on the last observation carried forward (LOCF) 
approach. If the last FG score prior to discontinuation is > 1, then missing FG scores will be 
imputed using a multiple imputation approach, assuming that data are missing not at random 
(MNAR). The missing FG scores for patients will be imputed at each post-discontinuation visit 
based on the placebo patients who continue to that visit. The missing FG scores for patients will 
be imputed at each post-discontinuation visit. Imputation will be implemented using a linear 
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regression model and the monotone method with the treatment group and randomization strata as 
the fixed effects and the baseline FG score as covariate. A score of 0 will be assigned if the 
imputed score is <0; A score of 5 will be assigned if the imputed score is >5. 
The same analyses as described in Section 5.4.3.1 will be performed on the imputed data. 
In addition, the number and proportion of patients with an FG score  1, as well as each category 
of FG scores over time, will also be presented for each group. 
5.4.5. 
Supplementary Analyses 
Supplemental analyses will be performed on the key secondary endpoints based on the PPS. 
Analysis described in Section 5.4.3.1 to Section 5.4.3.3 will be conducted using the PPS. 
Table 7: 
Summary of Analyses of Primary and Key Secondary Endpoints 
Endpoint 
Analysis 
Population 
Method 
Missing Data Handling 
Primary 
Time to first reaching a 
Hughes FG score  1 
Primary 
FAS 
Stratified log-rank test and 
stratified Cox proportional 
hazard model 
Patients who discontinued early 
without achieving FG  1 will be 
censored at the time of 
discontinuation. 
Sensitivity 1 
FAS 
Stratified log-rank test and 
stratified Cox proportional 
hazard model 
Time to event after discontinuation 
will be based on BOCF for patients 
whose last FG score > 1. The 
censoring time will be derived as 
Week 24 for these patients. 
Sensitivity 2 
FAS 
Stratified log-rank test and 
stratified Cox proportional 
hazard model 
Time to event after discontinuation 
will be based on MAR multiple 
imputation as described in 
Section 5.3.3 for patients whose last 
FG score > 1. 
Sensitivity 3 
FAS 
Stratified log-rank test and 
stratified Cox proportional 
hazard model 
Time to event after discontinuation 
will be based on MNAR multiple 
imputation as described in 
Section 5.3.3 for patients whose last 
FG score > 1. 
Sensitivity 4 
FAS 
Unstratified log-rank test 
and unstratified Cox 
proportional hazard model 
Patients who discontinued early 
without achieving FG  1 will be 
censored at the time of 
discontinuation. 
Supplemental 
PPS 
Stratified log-rank test and 
stratified Cox proportional 
hazard model 
Patients who discontinued early 
without achieving FG  1 will be 
censored at the time of 
discontinuation. 
Secondary 
First: Proportion of 
patients with a Hughes 
FG score  1 at 
Week 24 
Third: Proportion of 
patients with a Hughes 
FG score  1 at Week 8 
Primary 
FAS 
Logistic regression 
See Table 5 for details. 
Supportive 
FAS 
Stratified CMH 
Sensitivity 1 
FAS 
Logistic regression and 
stratified CMH 
Patients who died during the study 
are nonresponders. 
Sensitivity 2
FAS 
Logistic regression and 
stratified CMH 
MAR-based multiple imputation for 
patients whose last FG score > 1 
prior to discontinuation as 
described in Section 5.4.4; 
otherwise, the patients are 
considered as responders. 
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Table 7: 
Summary of Analyses of Primary and Key Secondary Endpoints 
Endpoint 
Analysis 
Population 
Method 
Missing Data Handling 
Sensitivity 3 
FAS 
Logistic regression and 
stratified CMH 
MNAR-based multiple imputation 
for patients whose last FG score > 1 
prior to discontinuation as 
described in Section 5.4.4; 
otherwise, the patients are 
considered as responders. 
Supplemental
PPS 
Logistic regression and 
stratified CMH  
See Table 5 for details. 
Second: Proportion of 
patients with a Hughes 
FG score improvement 
 3 at Week 24 
Primary 
FAS 
Logistic regression 
See Table 5 for details. 
Supportive 
FAS 
Stratified CMH 
Sensitivity 1 
FAS 
Logistic regression and 
stratified CMH 
MAR-based multiple imputation for 
patients whose last FG score > 1 
prior to discontinuation as 
described in Section 5.4.4; 
otherwise, LOCF imputation. 
Sensitivity 2 
FAS 
Logistic regression and 
stratified CMH 
MNAR-based multiple imputation 
for patients whose last FG score > 1 
prior to discontinuation as 
described in Section 5.4.4; 
otherwise, LOCF imputation. 
Supplemental 
PPS 
Logistic regression and 
stratified CMH  
See Table 5 for details. 
Abbreviations: BOCF = baseline observation carried forward; CMH = Cochran-Mantel-Haenszel; FAS = Full Analysis Set; 
FG = Functional Grade; LOCF = last observation carried forward; MAR = missing at random; MNAR = missing not at 
random; PPS = Per Protocol Set 
5.4.6. 
Other Secondary Endpoints 
There is no formal statistical hypothesis testing for any of the endpoints in this section, and only 
summary statistics are provided. In some cases, nominal p-values and 95% CIs are also presented 
for hypothesis-generating purposes. 
5.4.6.1. 
Medical Resource Utilization 
Analysis of medical resource utilization will be based on the FAS population for index 
hospitalizations. 
The number and proportion of patients (n [%]) will be presented in each treatment group for the 
following: 
Any index hospitalizations during the study 
When hospitalized: 
o
Type of hospitalization
Hospitalization without intensive care unit (ICU) stay 
ICU stay 
o
Disposition post hospital discharge
Discharged to rehabilitation hospital/facility 
Discharged to nursing home 
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Discharged to home 
Summary statistics will also be provided for each treatment group among those hospitalized for 
each type of hospitalization and overall: 
Number of hospitalizations without ICU 
Number of ICU admissions  
Number of hospitalizations including ICU 
Total length of stay (LOS; days) of each type of hospitalizations calculated as 
follows: 
o
Date of discharge  Date of admission + 1
o
If the hospitalization is still ongoing, then the date of the last visit will be used in
place of the date of discharge.
Total LOS (days) in the hospitalizations without ICU  
Total LOS (days) in ICU 
Total LOS (days) in the hospitalizations including ICU 
The treatment effect on total LOS of hospitalizations including ICU will be evaluated based on 
an ANCOVA model with LOS of hospitalizations as the dependent variable and the following 
list of independent variables as fixed effects: treatment group and randomization strata. The 
model-estimated mean difference in LOS between eculizumab and placebo and the 95% CI of 
the difference will be presented. 
5.4.6.2. 
Respiratory Support 
The respiratory support data are collected on the CRF page, and the statistical analysis will be 
based on the FAS population. 
Only respiratory support received during the index hospitalization period will be analyzed. 
The number and proportion of patients (n [%]) will be presented in each treatment group for the 
following: 
Any respiratory support (Yes and No) during the index hospitalization period 
Method of support among those who received respiratory support 
o
Supplemental oxygen without intubation
o
Noninvasive mechanical ventilation
o
Intubation with mechanical ventilation
Summary statistics will be provided for each treatment group among those who received 
respiratory support: 
Duration of respiratory support calculated as follows: 
o
End date  Start date + 1
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o
If respiratory support is ongoing, then the date of the last visit will be used in
place of the end date
o
The duration of respiratory support will be summarized by method of respiratory
support (for example, Noninvasive mechanical ventilation).
5.5. 
Exploratory Endpoints Analysis  
For each exploratory endpoint in this section, the FAS population will be used in the statistical 
analysis. All data collected will be provided in patient data listings. 
Unless otherwise stated, missing item data for each questionnaire will not be imputed. 
Analyses of exploratory endpoints are supportive in nature, with 95% CIs and p-values presented 
for hypothesis-generating purposes only. 
5.5.1. 
Functional Status Postacute Phase 
5.5.1.1. 
Rasch-Built Overall Disability Scale 
The Rasch-Built Overall Disability Scale (R-ODS) score is a 24-item linearly weighted 
self-administered scale that specifically captures activity and social participation limitations in 
patients with neurological conditions such as GBS (van Nes, 2011). If a patient has difficulty 
completing the questionnaire due to muscular weakness, a family member/caregiver may record 
-evaluation in the questionnaire.
Each item/activity on the scale is score
-evaluation of their usual
ability to perform a task as follows: 0 = not possible to perform,
 = possible but with some 
difficulty,
 = possible without any difficulty.  
The patient total score equals the sum of individual item scores and ranges from 0 to 48. A 
patient total score indicates higher limitations in activities of daily living for patients. If a patient 
did not complete all 24 items, then the total score will be set to missing. 
Changes in R-ODS score from Baseline at each visit will be analyzed using a restricted 
maximum likelihood-based repeated measures approach (ie, MMRM [Mallinckrodt, 2008]) and 
all available longitudinal data. The model will include fixed effects for baseline R-ODS score, 
randomization strata, treatment group, visit, and visit-by-treatment group interaction. The 
treatment effect will be evaluated via contrast for the treatment-by-visit term at each visit. An 
unstructured covariance structure will be used to model the correlations among repeated 
measures within each patient. If the model fails to converge, the following structures will be 
tested, 
first-order autoregressive, compound symmetry, and Toeplitz. The Kenward-Roger 
approximation will be used to estimate denominator degrees of freedom.  
The model-estimated mean difference in change from Baseline in R-ODS score between 
eculizumab and placebo and the 95% CI of the difference will be presented. 
In addition, summary statistics of R-ODS scores and changes from Baseline in R-ODS scores at 
each visit will also be presented for each treatment group. 
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5.5.1.2. 
Overall Neuropathy Limitations Scale 
The Overall Neuropathy Limitations Scale (ONLS) consists of a checklist for interviewing 
patients regarding current subjective symptoms in their hands or arms (numbness, tingling, or 
weakness) and legs (difficulty with running or climbing stairs, difficulty with walking, etc.). The 
ONLS is completed by clinicians who ask and observe/examine enrolled patients to determine 
their ability to perform specific arm- or leg-related activities. 
(ranging from 0 to 5), 
from 0 to 7). 
Score
Interpretation for the Arm 
Interpretation for the Leg 
0 
Normal 
Walking/climbing stairs/running is not affected 
1 
Minor symptoms in 1 or both arms but not 
affecting any of the functions listed 
Walking/climbing stairs/running is affected, but gait 
does not look abnormal 
2 
Disability in 1 or both arms affecting but not 
preventing any of the functions listed 
Walks independently but gait looks abnormal 
3 
Disability in 1 or both arms preventing at 
least 1 but not all functions listed 
Requires unilateral support to walk 10 meters (stick, 
single crutch, and 1 arm) 
4 
Disability in both arms preventing all 
functions listed but purposeful movement 
still possible 
Requires bilateral support to walk 10 meters (sticks, 
crutches, crutch and arm, and frame) 
5 
Disability in both arms preventing all 
purposeful movements 
Requires wheelchair to travel 10 meters but able to 
stand and walk 1 meter with the help of 1 person 
6 
Not applicable (NA) 
Restricted to wheelchair, unable to stand and walk 
1 meter with the help of 1 person, but able to make 
some purposeful leg movements 
7 
NA 
Restricted to wheelchair or bed most of the day and 
unable to make any purposeful movements of the legs 
and leg 
scores, which 
arms and 12 meaning maximum disability. A higher patient total ONLS score indicates higher 
Graham, 2006). 
If a clinician did not complete all items, then the total ONLS score will be set to missing. 
The statistical analysis of the changes from Baseline in total ONLS score will be performed 
using the same method as described in Section 5.5.1.1. 
5.5.1.3. 
Medical Research Council Sum Score 
The MRC-SS is a summation of the strength score of 6 peripheral muscle groups on each 
 (12 muscle groups in total per patient) as evaluated and scored by a clinician 
according to the MRC-SS scale described in the table below (Medical Research Council 
Memorandum No. 45, 1976; Kleyweg, 1991). The peripheral muscles that will be tested in this 
study on both sides of the body are those responsible for the following movements: 
Abduction of the arm 
Flexion of the forearm 
Extension of the wrist 
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Flexion of the leg 
Extension of the knee 
Dorsal flexion of the foot 
-SS ranges from 0 to 60 (ie, 12 muscle groups, each scored from 0 to 5). A
lower patient MRC-SS indicates lower peripheral muscle strength. If a clinician did not complete 
all 12 items, then the total MRC-SS will be set to missing. 
Score 
Description 
0 
No visible contraction 
1 
Visible contraction without movement of the limb (not existent for hip flexion) 
2 
Movement of the limb but not against gravity 
3 
Movement against gravity over (almost) the full range 
4 
Movement against gravity and resistance 
5 
Normal 
The statistical analysis of the changes from Baseline in MRC-SS will be performed using the 
same method as described in Section 5.5.1.1. 
5.5.1.4. 
Manual Muscle Testing 
The Manual Muscle Testing (MMT) evaluates the muscle strength of the following major 
muscles in the body: deltoid, biceps brachii, wrist extension, iliopsoas, quadriceps muscle, and 
tibialis anterior muscle (each on both sides of the body), as well as neck anteflexion. The 
strength of each muscle group will be graded according to the table below, and the grade of each 
muscle will be totaled into a patient
 total score (Medical Research Council Memorandum 
No. 45, 1976), which will range from 0 to 65. A lower patient total MMT score indicates lower 
muscle strength while the maximum score of 65 indicates normal muscle strength in the 
13 muscle groups assessed. If a clinician did not complete all items, then the total MMT score 
will be set to missing. 
Grade 
Description 
0 
No contraction 
1 
Flicker or trace of contraction 
2 
Active movement, with gravity eliminated 
3 
Active movement against gravity 
4 
Active movement against gravity and resistance 
5 
Normal power 
The statistical analysis of the changes from Baseline in total MMT score will be performed using 
the same method as described in Section 5.5.1.1. 
5.5.1.5. 
Hughes FG Scores Over Time 
The number and percentage of patients with various levels of FG score improvement from 
Baseline at each visit will be tabulated for each treatment group.  
The statistical analysis of change from Baseline in Hughes FG score at each visit will be 
performed with the same model described in Section 5.5.1.1. 
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5.5.2. 
Pain, Mood, and Fatigue 
5.5.2.1. 
Short Form McGill Pain Questionnaire 2 
The Short Form McGill Pain Questionnaire 2 (SF-MPQ-2) is a multidimensional measure of 
perceived neuropathic and non-neuropathic pain in adults with chronic pain. The SF-MPQ-2 is a 
self-administered questionnaire and includes 22 pain descriptor items that are each rated on a 
rating scale of 0 to 10, as experienced by the patient over the week prior to completing the 
questionnaire (Dworkin, 2009).  
The patient  total SF-MPQ-2 score will be calculated as the mean of all item ratings for the 
patient. Similarly, subscale scores for the 4 dimensions will be calculated as the mean of the 
corresponding item ratings for each dimension for the patient, as indicated in the table below. 
If a patient did not complete all items, then the total SF-MPQ-2 score will be set to missing. 
Similarly, if a patient did not complete all items for a subscale score, then that subscale score 
will be set to missing. A lower score indicates lower pain intensity, with 0 indicating no pain and 
10 indicating worst possible pain. The scale is subdivided into 4 dimensions as follows: 
Dimension 
Number 
of Items 
Items Belonging to the Dimension 
Value 
Range 
Continuous pain 
6 
Throbbing, cramping, gnawing, aching, 
heavy, and tender pain 
Total score for the 
6 items ÷ 6 
0 10 
Intermittent pain 
6 
Shooting, stabbing, sharp, splitting, 
electric-shock, and piercing pain 
Total score for the 
6 items ÷ 6 
0 10 
Neuropathic pain 
6 
Hot-burning, cold-freezing, caused-by-
light-touch, itching, tingling, and 
numbness pain 
Total score for the 
6 items ÷ 6 
0 10 
Affective descriptors 
4 
Tiring-exhausting, sickening, fearful, 
and punishing-cruel pain 
Total score for the 
4 items ÷ 4 
0 10 
The statistical analyses of changes from Baseline in total SF-MPQ-2 score, as well as the 
subscale scores, will be performed using the same method as described in Section 5.5.1.1. 
5.5.2.2. 
Depression, Anxiety, and Stress Scale - Short Form 21 Questions 
The Depression, Anxiety, and Stress Scale Short Form, 21 Questions (DASS-21) is an 
instrument set of 3 self-report scales designed to measure the emotional states of depression, 
anxiety, and stress (Depression Anxiety Stress Scales [DASS]). Each of the 3 DASS-21 scales 
contains 7 items and is divided into subscales of items with similar content as follows: 
The depression scale assesses dysphoria, hopelessness, devaluation of life, 
self-deprecation, lack of interest/involvement, anhedonia, and inertia: items 3, 5, 10, 
13, 16, 17, and 21 
The anxiety scale assesses autonomic arousal, skeletal muscle effects, situational 
anxiety, and subjective experience of anxious affect: items 2, 4, 7, 9, 15, 19, and 20 
The stress scale is sensitive to levels of chronic nonspecific arousal. It assesses 
difficulty relaxing; nervous arousal; and being easily upset/agitated, 
irritable/overreactive, and impatient: items 1, 6, 8, 11, 12, 14, and 18 
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Patients are asked to use a 4-point severity/frequency scale to rate the extent to which they have 
experienced each of the 21 states over the week prior to completing the questionnaire. The 
severity/frequency points are scored as follows: 
Severity/Frequency Point 
Score 
Did not apply to me at all 
0 
Applied to me to some degree or some of the time 
1 
Applied to me to a considerable degree or a good part of time 
2 
Applied to me very much or most of the time 
3 
Patient scores for each subscale (depression, anxiety, and stress) will be calculated by summing 
the scores for the corresponding items indicated above. If a patient did not complete all items for 
a DASS-21 scale, then the score will be set to missing for that scale. The summed scores for each 
subscale will be multiplied by 2 for statistical analyses. 
The statistical analyses of changes from Baseline in DASS-21 scale scores will be performed 
using the same method as described in Section 5.5.1.1. 
In addition, the number and proportion of patients in each of the following categories for each 
DASS-21 scale score will be tabulated over time for each treatment group: 
Depression 
Anxiety 
Stress 
Normal 
0 9 
0 7 
0 14 
Mild 
10 13 
8 9 
15 18 
Moderate 
14 20 
10 14 
19 25 
Severe 
21 27 
15 19 
26 33 
Extremely severe 
 28 
 20 
 34 
5.5.2.3. 
The Chalder Fatigue Scale 
The Chalder Fatigue Scale (Chalder) is a self-report instrument that measures subjective 
symptoms of fatigue and covers 7 physical fatigue dimensions and 4 mental fatigue dimensions 
(eg, concentration and memory). It contains 11 items to produce a global score and 2 domains of 
physical and mental fatigue (Cella, 2010). Patients use a 4-point Likert scale to indicate on each 
of the 11 fatigue dimensions measured how they felt during the month prior to responding to the 
questionnaire or, if feeling tired for longer than a month, in comparison to the last time they felt 
well. These points are (scores in parentheses) as follows: less/better than usual (0), no 
more/worse than usual (1), more/worse than usual (2), and much more/worse than usual (3). An 
individual patient score is then calculated by summing the scores of all items and ranges from 
0 to 33, where 0 indicates much less fatigue and 33 indicates much more fatigue than usual. If a 
patient did not complete all 11 items, then the total score will be set to missing. 
The statistical analyses of changes from Baseline in total Chalder score will be performed using 
the same method as described in Section 5.5.1.1.  
5.5.3. 
Quality of Life 
5.5.3.1. 
European Quality of Life  5 Dimensions  5 Levels 
The European Quality of Life (EuroQoL)  5 Dimensions  5 Levels (EQ-5D-5L) is a widely 
used self-report 2-part health status instrument. It was developed by the EuroQoL Group to 
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provide a concise, generic instrument that could be used to measure, compare, and value health 
status across disease areas (Devlin, 2017). The instrument is used to measure health status at the 
time of completing the questionnaire. 
The descriptive system section of the EQ-5D questionnaire produces a 5-digit health state profile 
that represents the level of reported problems (of the following 5 levels [scores in brackets]: no 
[1], slight [2], moderate [3], severe [4], or unable to/extreme problems [5]) on each of the 
5 dimensions of health (mobility, self-care, usual activities, pain/discomfort, and 
anxiety/depression). For example, the EQ-5D-5L health state 21143 represents a patient who 
indicates slight problems on the mobility dimension, no problems on the self-care and usual 
activities dimensions, severe pain or discomfort dimension, and moderate problems on the 
anxiety/depression dimension. These health states should be converted into a single utility value 
or score as described in Section 6.3.8. 
own assessment of their health status on a scale from 0 to 100, where 100 indicates the best 
health you can imagine and 0 indicates the worst health you can imagine. 
The statistical analyses of the changes from Baseline in EQ-5D-5L utility score and the VAS 
score will be performed using the same method as described in Section 5.5.1.1.  
Additionally, the number and proportion of patients will be tabulated at each level for each 
dimension in each treatment over time. 
5.5.3.2. 
Work Productivity and Activity Impairment 
The Work Productivity and Activity Impairment (WPAI) is a frequently used questionnaire 
related to work productivity and activity impairment (Reilly, 1993). For people who are able to 
answer themselves, this patient-reported activity/outcome questionnaire has 6 questions and is 
self-administered.  
The WPAI analyzes the impact of a disease or condition, such as GBS, on working status, 
absenteeism and presenteeism, and regular activities of daily life. 
The number and proportion of patients with each level of employment status (employed and not 
employed), as well as shift changes from Baseline at each visit, will be tabulated for each 
treatment group.  
Summary statistics will be provided for the following items for each treatment group at each post 
Baseline timepoint (see Section 6.3.9 for further details about calculations): 
If employed: 
o
Number of hours worked
o
Number of hours missed from work due to GBS
o
Number of hours missed from work due to other reasons
o
Total number of hours missed from work
o
Percentage of work time missed due to health
o
Percentage of impairment while working due to health
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o
Percentage of overall work impairment due to health
 Percentage of activity impairment due to health 
If not employed: 
o
Ability affected by GBS to do daily activities
o
Percentage of activity impairment due to health
All data will be provided in patient data listings. 
Further details of score calculations and statistical analyses will be provided in Section 6.3.9. 
5.5.4. 
Biomarkers 
Statistical analysis of biomarker data for this study will be provided in a separate document. 
5.6. 
Safety Analyses 
All safety analyses will be conducted on the SS population. No formal hypothesis testing is 
planned.  
Further details of addressing COVID-19 impacts are provided in Section 6.5. 
5.6.1. 
Extent of Exposure 
Treatment duration will be summarized by treatment group for the SS population. 
Summary statistics will be provided for treatment duration (days) and total dose (milligrams) for 
each treatment group.  
The number and percentage of patients with the following treatment compliance (%) will be 
presented for each treatment group: 100%, 75%, 50%, 25%, and 0%. 
Treatment duration will be calculated only for patients randomized and treated as the time in 
days from the first dose date of the study drug until the last dose date of study drug (ie, treatment 
duration (days) = Last dose date  First dose date + 1). 
Treatment compliance will be calculated as follows: (actual number of doses taken/planned 
number of doses) × 100.  
In addition, IVIg treatment, as well as study drug exposure data, will be provided in patient data 
listings. 
5.6.2. 
Adverse Events 
For the purpose of this SAP, the following types of AEs will be noted: 
Pretreatment adverse events (PTAEs) and pretreatment serious adverse events 
(PTSAEs): 
o
PTAEs and PTSAEs are defined as the AEs and serious adverse events (SAEs),
respectively, that occur between the signing of informed consent and the first dose
of the study drug.
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Treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse 
events (TESAEs): 
o
TEAEs and TESAEs are defined as the AEs and SAEs, respectively, with onset
on or after the first dose of the study drug.
All statistical summaries of AEs/SAEs with onset on or after the first dose of the study drug will 
be provided for each treatment group for the following time periods: 
First dose to Day 85 (Week 12) 
After Day 85 
Overall (first dose to end of study) 
The PTAEs/PTSAEs will be summarized by treatment group only. 
5.6.2.1. 
Overall Summary of AEs 
An overview of AEs with onset on or after the first dose of the study drug will be presented, 
showing the number of AEs and the number and percentage (n [%]) of patients who: 
Experienced any AE 
Discontinued study drug due to an AE 
Experienced an AE considered related to study drug 
Experienced an AE considered not related to study drug 
Experienced an AE considered related to antibiotics 
Experienced an AE considered not related to antibiotics 
Experienced an AE by each toxicity grade: Grades 1 to 5 
Experienced an AE leading to death 
These statistics will also be prepared for all SAEs, except toxicity grade. 
5.6.2.2. 
AEs and SAEs by SOC and PT 
The number of AEs/SAEs with onset on or after the first dose of the study drug and the number 
and percentage of patients with events will be presented by both SOC and PT and by PT alone. 
Patients will be counted once in each SOC and PT.  
Percentages will be based on the total number of patients in the SS in each treatment group. The 
SOCs will be listed alphabetically, and PTs within each SOC will be listed in order of decreasing 
frequency of occurrence (percentage) overall. A summary table will also be produced for events 
 5% of patients in either treatment group. Another table will be produced for 
 2 patients in either treatment group. 
The number of nonserious AEs and the number and percentage of patients with nonserious 
events will be presented by SOC and PT. 
The incidence of AEs/SAEs leading to study drug discontinuation and death will be summarized. 
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Summary of event rate (per 100 patient-years [PY]) of AEs/SAEs by SOC and PT will also be 
provided for each treatment group. Total PY is defined as the sum of study duration 
(days)/365.25 for all patients. For event rate tables, the rate per 100 PY will be calculated as 
follows:  
Event Rate = 100 × Total number of events/Total PY 
Detailed listings of patients who experienced AEs/SAEs will be presented. These listings will 
include period (pretreatment, first dose to Day 85 [Week 12], and after Day 85 to end of the 
study), seriousness, toxicity grade, and relationship to treatment, as well as action taken 
regarding study treatment, other action taken, and patient outcome. A separate listing of patients 
who discontinued from the study due to an AE/SAEs will also be provided, as well as AEs/SAEs 
resulting in death. 
5.6.2.3. 
AEs and SAEs by SOC, PT, and Relationship 
Summaries of AEs and SAEs with onset on or after the first dose of the study drug by 
relationship (related versus not related) to study drug will be provided by treatment group. 
Similar summaries of AEs and SAEs with onset on or after the first dose of the study drug by 
relationship (related versus not related) to antibiotics will be provided by treatment group. 
5.6.2.4. 
AEs by SOC, PT, and Toxicity Grade 
Summaries of AEs with onset on or after the first dose of the study drug by worst toxicity grade 
(Grades 1 to 5) will be provided by treatment group. 
5.6.2.5. 
Other Significant Adverse Events 
A by-patient listing of AEs of special interest (meningococcal infections) will be provided. 
The listing will include periods (first dose to Day 85 [Week 12] and after Day 85 to end of study) 
in which the AE occurs. 
5.6.3. 
Additional Safety Assessments 
Other safety parameters will be summarized by treatment group for all patients in the SS 
population with data available.  
For the purpose of statistical analysis, the data collected on scheduled visits will be used for 
summary statistics, and the data collected on scheduled and unscheduled visits will be used for 
shift tables. 
5.6.3.1. 
Analyses for Laboratory Tests 
Each laboratory parameter will be summarized by treatment group and visit, as applicable. 
Changes from Baseline will be presented. An overall shift table will also be summarized by visit. 
All laboratory values will be classified as normal, below normal, or above normal based on 
normal ranges.  
Summary statistics will be based on central laboratory data. Data from the local laboratory will 
be provided in data listings only. 
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5.6.3.2. 
Vital Signs 
Vital signs (systolic blood pressure, diastolic blood pressure, temperature, respiratory rate, and 
heart rate [HR]) and changes from Baseline in vital signs will be summarized by treatment group 
and visit. 
Body weight (kilograms) and height (centimeters) at Baseline will be provided in data listings 
only. 
5.6.3.3. 
Physical Examinations 
Number (%) of patients with abnormal physical examinations will be summarized by treatment 
group at each visit. Listings will also be produced. 
5.6.3.4. 
Electrocardiogram 
Electrocardiogram (ECG) results will be summarized by treatment group and visit. Descriptive 
statistics will be presented for each ECG parameter (including HR, PR interval, QRS interval, 
QT interval, and RR interval values) and for change from Baseline. Listings of ECG results will 
be produced. 
5.6.3.5. 
Other Safety Parameters of Special Interest 
Urine and serum pregnancy tests will be summarized in by-patient listings. 
5.7. 
Other Analyses 
5.7.1. 
Other Variables and/or Parameters 
Other parameters will be summarized by treatment group. All data will be presented in 
by-patient listings. 
5.7.1.1. 
Nerve Conduction Test  
The nerve conduction test is performed at Screening and Week 4 to determine the GBS subtype 
(AMAN versus AIDP versus indeterminate ) for FAS. 
By-patient listings of nerve conduction test will be produced for all patients in the FAS. 
5.7.1.2. 
Immunogenicity 
For assessment of immunogenicity, the presence of confirmed positive antidrug antibodies 
(ADAs) will be summarized for all patients in SS by treatment group and visit. A by-patient 
listing showing ADA results by visit will include positive/negative ADA, and for confirmed 
positive ADA samples, the ADA titer and the presence of neutralizing antibodies will also be 
assessed. 
5.7.1.3. 
Pharmacokinetic and Pharmacodynamic Analyses 
Blood samples will be collected to evaluate eculizumab concentrations over time. Descriptive 
statistics of eculizumab concentration data will be presented for patients in the Pharmacokinetic 
Analysis Set (PKAS) at each scheduled time point. 
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PD analysis will be performed for all participants in Pharmacodynamic Analysis Set (PDAS). 
Blood samples will also be collected to evaluate free complement component 5 (C5) 
concentrations, as well as hemolytic complement activity in serum. Descriptive statistics will be 
presented by treatment group and for each scheduled sampling time point. Free C5 
concentrations and hemolytic complement activity in serum will be evaluated by assessing the 
absolute values and the changes and the percent changes from Baseline as appropriate. Boxplots 
by visit will also be provided, as appropriate. 
By-patient listings of eculizumab concentrations, free C5 concentrations, and hemolytic 
complement activity in serum will be produced.  
5.7.2. 
Subgroup Analyses 
All subgroup analyses will assess the consistency of the treatment effect across different levels 
for the following subgroups: 
Randomization stratification factors: 
o
FG scores: progressively deteriorating FG3 and FG4/FG5
o
Diarrhea: present or absent (< 4 weeks prior to onset of neurological symptoms)
Age group (< 60 years and  60 years) 
Sex (male and female) 
Days since GBS onset (< median and  median) 
Baseline MRC-SS (< median and  median) 
Baseline mEGOS (< median and  median; see Section 6.3.5) 
Days since IVIg (One to 3 days since IVIg and Four to 5 days since IVIg) 
GBS subtype (acute inflammatory demyelinating neuropathy [AIDP], acute motor 
axonal neuropathy [AMAN], and indeterminate) 
TEAE analysis will be summarized by SOC and PT for the following subgroups (no p-values 
will be produced for these subgroup analyses). 
Sex (male and female) 
Age group (< 
 60 years) 
Baseline weight category (< median,  median) 
For subgroup analyses of categorical endpoints, a logistic regression model or proportional 
hazard model using the Firth correction (Firth, 1993) will be used to obtain a p-value for the 
treatment-by-subgroup interaction. 
The detailed statistical analyses for each subgroup are summarized in Table 8. 
Table 8: 
Subgroup Analysis for Efficacy 
Endpoint 
Analysis for Each Subgroup 
Time to first FG  1 
Number of events in each treatment group 
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Table 8: 
Subgroup Analysis for Efficacy 
Endpoint 
Analysis for Each Subgroup 
Median time (days) to first event (95% CI1) in each treatment group 
Hazard ratio (95% CI2) (eculizumab vs placebo)  
An FG score  1 at Week 24 
Number (percentage) of patients with response in each treatment group 
Odds ratio (95% CI3) in response (eculizumab vs placebo) 
Difference (95% CI4) in percentages of response between the 2 treatment 
groups  
An FG 
 3 at 
Week 24 
Number (percentage) of patients with response in each treatment group 
Odds ratio (95% CI3) in response (eculizumab vs placebo) 
Difference (95% CI4) in percentages of response between the 2 treatment 
groups 
An FG score  1 at Week 8 
Number (percentage) of patients with response in each treatment group 
Odds ratio (95% CI3) in response (eculizumab vs placebo) 
Difference (95% CI4) in percentages of response between the 2 treatment 
groups 
195% CI will be calculated using the Kaplan-Meier method. 
295% CI will be calculated using the stratified Cox proportional hazard model with treatment-by-subgroup 
interaction term. 
395% CI will be calculated using the logistic model containing the treatment-by-subgroup interaction term. 
495% CI will be calculated using Miettinen and Nurminen method (Miettinen, 1985). 
Abbreviations: CI = confidence interval; FG = Functional Grade; vs = versus 
5.8. 
Interim Analyses 
A preplanned interim analysis for a sample size increase will be performed by an IAC when, 
approximately, the first12 events (FG score  1) are observed. The sample size will be increased 
to 72 patients if the conditional power at the interim analysis falls within the prespecified 
promising zone. Details are provided in a separate IAP.  
As described in Section 6.2.1, to control the study-level type 1 error due to the unblinded interim 
sample size increase, Gao et al
Gao, 2008) will be used for the adjusted final critical 
value as follows: 
where 
with 
 being the target number of events from the original sample size, the number 
of events after the sample size increase, and the number of events observed at the interim 
analysis, respectively. 
Note:  
1. If the sample size is not increased,
. 
2. 
if interim analysis occurs. 
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6.
SUPPORTING DOCUMENTATION
6.1. 
Appendix 1: List of Abbreviations
Abbreviations 
Definition 
ADA 
antidrug antibody 
AE 
adverse event 
AIDP 
acute inflammatory demyelinating neuropathy 
AMAN 
acute motor axonal neuropathy 
BOCF 
Baseline observation carried forward 
C5 
complement component 5 
Chalder 
Chalder Fatigue Scale 
CHW 
Cui, Hung, and Wang 
CI 
confidence interval 
COVID-19 
Coronavirus Disease 2019 
CRF 
case report form 
DASS-21 
Depression, Anxiety, and Stress Scale, Short Form, 21 Questions 
ECG 
electrocardiogram 
EQ-5D-5L 
European Quality of Life  5 Dimensions  5 Levels 
EuroQoL 
European Quality of Life 
FAS 
Full Analysis Set 
FG 
Functional Grade 
GBS 
Guillain-Barré syndrome 
HR 
heart rate 
IAC 
independent analysis center 
IAP 
interim analysis plan 
ICU 
intensive care unit 
IV 
intravenous 
IVIg 
intravenous immunoglobulin 
LOCF 
last observation carried forward 
LOS 
length of stay 
MAR 
missing at random 
MedDRA 
Medical Dictionary for Regulatory Activities 
mEGOS 
modified Erasmus GBS outcome score 
MH 
Mantel-Haenszel 
MMT 
Manual Muscle Testing 
MNAR 
missing not at random 
MRC-SS 
Medical Research Council Sum Score 
NA 
not applicable 
ONLS 
Overall Neuropathy Limitations Scale 
OR 
odds ratio 
PDAS 
Pharmacodynamic Analysis Set 
PKAS 
Pharmacokinetic Analysis Set 
PPS 
Per Protocol Set 
PT 
preferred term 
PTAE 
pretreatment adverse event 
PTSAE 
pretreatment serious adverse event 
PY 
patient-years 
QT 
interval between the start of the Q wave and the end of the T wave in an ECG 
R-ODS
Rasch-Built Overall Disability Scale 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
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Abbreviations 
Definition 
SAS® 
Statistical Analysis System (software) 
SF-MPQ-2 
Short Form McGill Pain Questionnaire 2 
SOC 
system organ class 
SS 
Safety Set 
TEAE 
treatment-emergent adverse event 
TESAE 
treatment-emergent serious adverse event 
VAS 
visual analog scale 
WHO 
World Health Organization 
WPAI 
Work Productivity and Activity Impairment 
6.2. 
Appendix 2: Changes to Protocol-Planned Analyses 
6.2.1. 
Changes From Protocol to SAP V1.0 
The protocol states that the Cui, Hung, and Wang (CHW) method (Cui, 1999) will be used for 
controlling the type 1 error due to the interim analysis. This has been changed to the Gao et al
method (Gao, 2008). As demonstrated by Gao et al (Gao, 2008), in a 2-stage design with only 
1 interim analysis, Gao et al
type 1 error and is equivalent to the method 
proposed by CHW. The type 1 error control is also further demonstrated in the simulations as 
provided in the IAP. 
6.2.2. 
Changes From SAP V1.0 to SAP V2.0 
The following table summarizes the changes in the planned analyses compared to the SAP 
version 1.0. 
Section Number and Name 
Description of Changes 
Brief Rationale 
4 ANALYSIS SETS 
Analysis Sets 
The following text has been changed: 
PKAS: All patients who received at least 1 dose of 
study drug and who have at least 1 postdose PK 
sample. 
The following text has been added: 
PDAS: All patients who received at least 1 dose of 
study drug and who have at least 1 postdose PD 
sample. 
PKAS is defined to include 
placebo-treated patients. 
PDAS is used to perform PD 
analysis.  
5.2.2 Protocol Deviations 
The following text has been changed: 
For the purpose of defining the PPS, patients have 
met any of the following important protocol 
deviation criteria will be considered for exclusion 
from the PPS: 
The following text has been added: 
#2 Patients who meet the 2019 
consensus GBS criteria 
Update criteria being used for 
exclusion from PPS 
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Section Number and Name 
Description of Changes 
Brief Rationale 
5.3.1 Primary Endpoint  
The following text has been deleted: 
A sensitivity analysis will be performed by 
censoring at the last FG assessment date in case 
the last observed date is later than the last FG 
assessment for patients without ever achieving an 
event at their last visit on study. 
Not meaningful given the FG 
scores are available at the last 
observed date. 
5.3.2 Main Analytical Approach  
The following text has been deleted: 
If the proportional hazard assumption used for the 
primary analysis method cannot be supported by 
graphical methods, an analysis using the 
restricted mean survival time method will be 
performed (Guo, 2019). 
To clarify the single analysis 
approach for the primary 
endpoint. 
5.3.3.1 Sensitivity Analysis 1 
The following text has been added:  
If the last FG score prior to discontinuation is 
> 1, then the baseline FG score will be carried
forward (baseline observation carried forward
[BOCF]) for all visits after discontinuation.
BOCF is used as the worst-
case scenario. 
5.3.3.1 Sensitivity Analysis 2  
The following text has been added:  
The time-to-event for such patients will still be 
based on the first observed FG response. The 
intermittent missing FG scores will be imputed 
based on the LOCF approach. If the last FG score 
prior to discontinuation is > 1, then missing FG 
scores will be imputed using a multiple imputation 
approach, assuming that data are missing at 
random (MAR). The missing FG scores for 
patients will be imputed at each 
post-discontinuation visit. Imputation will be 
implemented using a linear regression model and 
the monotone method with the treatment group 
and randomization strata as the fixed effects and 
the baseline FG score as covariate. A score of 0 
will be assigned if the imputed score is <0; A 
score of 5 will be assigned if the imputed score is 
>5. Based on this imputation, the time-to-event
and censoring time will be rederived for these
patients.
Actual value of FG scores is 
imputed. 
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Section Number and Name 
Description of Changes 
Brief Rationale 
5.3.3.1 Sensitivity Analysis 3 
The following text has been added: 
The intermittent missing FG scores will be 
imputed based on the LOCF approach. If the last 
FG score prior to discontinuation is > 1, then 
missing FG scores will be imputed using a 
multiple imputation approach, assuming that data 
are missing not at random (MNAR). The missing 
FG scores for patients will be imputed at each 
post-discontinuation visit based on the placebo 
patients who continue to that visit. Imputation will 
be implemented using a linear regression model 
and the monotone method with the treatment 
group and randomization strata as the fixed 
effects and the baseline FG score as covariate. A 
score of 0 will be assigned if the imputed score is 
<0; A score of 5 will be assigned if the imputed 
score is >5. Based on this imputation, the time-to-
event and censoring time will be rederived for 
these patients. 
Actual value of FG scores is 
imputed. 
5.3.4 Supplementary Analyses  
The following text has been added: 
Supplemental analyses will be performed on the 
primary endpoint based on the PPS. 
PPS on the primary endpoint 
is planned as supplementary 
analysis. 
5.4.3.1 Proportion of Patients With a 
Hughes FG Score 
1 at Week 24 
The following text has been revised from: 
The treatment comparison in this endpoint will be 
performed with a logistic regression model, with 
response (Yes and No) as the dependent variable, 
treatment group as the fixed effect, and 
stratification factors at randomization 
(progressively deteriorating FG3 or FG4/FG5 
and diarrhea present or absent < 4 weeks prior to 
onset of neurological symptoms) as stratification 
factors.  
to: 
The treatment comparison in this endpoint will be 
performed with a logistic regression model, with 
response (Yes and No) as the dependent variable 
and treatment group and randomization strata as 
the fixed effects. Firth adjustment (Firth, 1993) is 
applied if convergence of the logistic regression 
model cannot be achieved due to complete 
separation. 
Clarify the randomization 
strata is used in the model. 
Add Firth adjustment if 
convergence cannot be 
achieved. 
5.4.4 Sensitivity Analyses to Handle 
Missing Data 
The following texts have been added: 
To assess the robustness of the main analyses of 
those key secondary endpoints in terms of 
handling of missing data, the following sensitivity 
analyses will also be performed: 
Sensitivity Analysis 1: This sensitivity analysis is 
applicable only to the first and the third key 
secondary endpoints. 
In this analysis, if a patient died during the study, 
he/she is considered a nonresponder.   
Add sensitivity analysis to 
handle deaths during the 
study. 
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Section Number and Name 
Description of Changes 
Brief Rationale 
5.4.6.1 Medical Resource Utilization 
The following text has been added:  
The treatment effect on total LOS of hospital 
and/or ICU will be evaluated based on an 
ANCOVA model with LOS of hospitalizations as 
the dependent variable and the following list of 
independent variables as fixed effects: treatment 
group and randomization strata. The 
model-estimated mean difference in length of stay 
between eculizumab and placebo and the 95% CI 
of the difference will be presented. 
Add statistical analysis for 
total LOS of hospitalization. 
5.4.6.2 Ventilator Support 
Ventilator support is changed to respiratory 
support. 
5.5.1.5 Hughes FG Scores Over Time 
The following text has been added to replace the 
shift analysis:  
The number and proportion of patients with 
various levels of FG score improvement from 
Baseline at each visit will be tabulated for each 
treatment group.  
The following text has been deleted:  
The statistical analysis of change from Baseline of 
an FG score at Week 24 will be performed with a 
nonparametric ANOVA approach. 
The new analysis is more 
clinically meaningful. The 
treatment effect will be 
evaluated by a more powerful 
method (MMRM). 
5.5.3.2 Work Productivity and Activity 
Impairment 
The following text has been added: 
The number and proportion of patients with each 
level of employment status (employed and not 
employed), as well as shift changes from Baseline 
at each visit, will be tabulated for each treatment 
group. 
The following text has been deleted: 
The number and percent of patients with the 
following categories will be tabulated for each 
treatment group at each timepoint: 
Employment status (employed and 
not employed) 
o
If status =
Hours worked 
Hours missed from 
work due to GBS 
Hours missed from 
work due to other 
reasons 
Work Productivity and 
Activity Impairment 
questionnaire at baseline does 
not contain hours missed due 
to GBS and due to other 
reasons.  
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Section Number and Name 
Description of Changes 
Brief Rationale 
5.6 Safety Analyses 
The definition of TEAE has been revised as 
follows: 
TEAEs and TESAEs are defined as the AEs and 
SAEs, respectively, with onset on or after the first 
dose of the study drug. 
The following text replaces the analyses by period 
of first 12 weeks, 12-24 weeks, and overall: 
All statistical summaries of AEs/SAEs with onset 
on or after the first dose of the study drug will be 
provided for each treatment group for the 
following time periods: 
First dose to Day 85 (Week 12) 
After Day 85 
Overall (first dose to end of study) 
Clarification of analysis 
method. 
5.6.3.3 Physical Examinations 
The shift analysis has been deleted, and the 
following text has been added: 
Abnormal physical examinations will be 
summarized by treatment group at each visit. 
Listings will also be produced. 
Shift analysis is not deemed 
necessary. 
5.7.1.1 Nerve Conduction Test 
The following text has been added: 
The nerve conduction test is performed at 
Screening and Week 4 to determine the GBS 
subtype (AMAN versus AIDP versus 
indeterminate ) for FAS. 
By-patient listings of nerve conduction test will be 
produced for all patients in the FAS. 
Add the listing of nerve 
conduction test. 
5.7.1.2 Immunogenicity 
The original analysis that summarized patient 
randomized and treated with eculizumab has been 
deleted. 
Summarize by treatment 
group. 
5.7.2 Subgroup Analysis 
The following subgroup analyses for TEAE has 
been added: 
TEAE analysis will be summarized by SOC and 
PT for the following subgroups (no p-values will 
be produced for these subgroup analyses): 
Sex (male and female) 
Age group (< 
 60 years) 
Baseline weight category (< median, 
 median) 
The following text has been added: 
For subgroup analyses of categorical endpoints, a 
logistic regression model or proportional hazard 
model using the Firth correction (Firth, 1993) will 
be used to obtain a p-value for the 
treatment-by-subgroup interaction. 
New analysis. 
Subgroup analysis using the 
model along with 
treatment-by-subgroup 
interaction term. 
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Section Number and Name 
Description of Changes 
Brief Rationale 
6.3.3 Visit Window 
The following is the definition of Analysis Day 1: 
SAP V1                    
SAP V2 
Visit Day Window (Days) 
Visit Day Window 
(Days) 
First row: 4 
 1 
Second row: [4, 12)  
[2, 12) 
Last row: [155, 183) 
155 
Days after Day 1 are mapped 
to next visit. 
6.5.2 Efficacy Assessments 
The following text has been deleted: 
The planned analyses in Sections 5.3 and 5.4 will 
be repeated with the efficacy data from patients 
impacted by the following COVID-19-related 
assessments handled using the hypothetical 
strategy as follows: 
Efficacy assessments for patients who had 
COVID-19-related SAE will be excluded from the 
planned analysis from the date of the event up to 
2 weeks from resolution of the SAE. 
Efficacy assessments for patients who had a 
change in the GBS concomitant treatment due to 
COVID-19 will be excluded from the planned 
analysis until the dose returns to baseline levels. 
Efficacy assessments for patients who missed 
1 dose of study drug due to COVID-19-related 
disruptions will not be excluded from the planned 
analysis. 
Efficacy assessment for patients who missed 2 or 
more sequential doses of study drug due to 
COVID-19 will be excluded from the planned 
analysis up to 2 weeks from initiating study drug 
administration. 
Missing efficacy assessment due to COVID-19 
will be handled as MAR.  
The following text has been added: 
The planned analyses in Sections 5.3 and 5.4 will 
be repeated with the efficacy data to assess the 
impact of COVID-19 using the while-on-treatment 
strategy as follows: 
a.
Efficacy assessments for patients who
had COVID-19 impact will be censored
at the date when patients had first
COVID-19-related events or
disruptions.
This strategy is used to evaluate the treatment 
effect prior to the occurrence of the intercurrent 
COVID-19 events. 
Analyses have been 
streamlined. 
Throughout the document 
Editorial changes 
Editorial changes 
6.3. 
Appendix 3: Technical Specifications for Derived Variables 
The following derived data will be calculated prior to analysis. For all dates (except AE and 
medication dates), in cases where only the month and year are provided for a date, the day for the 
date will be imputed as 15. Missing month will be imputed as June.  
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6.3.1. 
Definition of Baseline Values 
Baseline is defined as the last available assessment on or before the first dose for all patients. 
6.3.2. 
Change From Baseline 
Change from Baseline will be calculated as follows: 
Change from Baseline = assessment value  baseline assessment value 
6.3.3. 
Visit Window 
For the purpose of statistical analysis, data collected on the scheduled visits from the protocol 
and CRFs will be used.  
In case of an early discontinuation visit, an unscheduled, or out of window  visit, an analysis 
visit will be assigned, where necessary, according to the table below using the number of days 
from the first dose as calculated below: 
Visit day = Date of visit  Date of first dose + 1 
Visit Day Window (Days) 
Analysis Day 
Analysis Visit 
1 
1 
Day 1 
(2, 12) 
8 
Week 1 
(12, 19) 
15 
Week 2 
(19, 26) 
22 
Week 3 
(26, 33) 
29 
Week 4 
(33, 40) 
36 
Week 5 
(40, 50) 
43 
Week 6 
(50, 71) 
57 
Week 8 
(71, 99) 
85 
Week 12 
(99, 127) 
113 
Week 16 
(127, 155) 
141 
Week 20 
 155 
169 
Week 24 
6.3.4. 
Definitions of Durations 
6.3.4.1. 
Duration of Ventilation Support 
Number of days on ventilation = End date  Start date + 1 
6.3.4.2. 
Duration of Hospitalization 
Number of days in the hospital = Date of discharge  Date of admission + 1 
If ongoing  then the date of the last visit will be used for the date of discharge. 
Note that the admission date could happen before first dose date. 
6.3.4.3. 
Duration of ICU  
Number of days in ICU = Date of discharge from ICU  Date of admission into ICU + 1 
If ongoing  then the date of the last visit will be used for the date of discharge. 
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6.3.5. 
Definition of mEGOS 
The baseline value of mEGOS will be calculated as the total sum of scores assigned to the 
prognostic factors according to the following table, with the mEGOS ranging from 0 to 9. The 
MRC-SS collected at the earliest date of Screening or Day 1 will be used. If the date of MRC-SS 
is 4 or more days after hospital admission, then the baseline value of mEGOS is set to missing. 
Table 9: 
Modified Erasmus GBS Outcome Scores 
Prognostic Factors 
Score 
Age at onset 
 40 
0 
41 60 
1 
> 60
2 
Preceding diarrhea 
Absent 
0 
Present 
1 
MRC-SS (within 3 days after admission to hospital, on the 
earliest date of Screening or Day 1) 
51 60 
0 
41 50 
2 
31 40 
4 
0 30 
6 
Walgaard, 2011 
Abbreviations: GBS = Guillain-Barré Syndrome; MRC-SS = Medical Research Council sum score 
6.3.6. 
Derivation of Treatment-Emergent Adverse Events for Missing or Incomplete 
Date of Onset 
The analysis of AEs is described in Section 5.6.2. 
If the start date of an AE is partially or completely missing and the end (stop) date and time of 
the AE do not indicate that it occurred prior to the first dose, then the determination of 
treatment-emergent status will be based on the following: 
If the start year is after the year of the first dose, then the AE is treatment emergent. 
If the start year is the same as the year of the first dose and: 
o
If the start month is missing, then the AE is treatment emergent.
o
If the start month is present and is the same as or after the month of the first dose,
then the AE is treatment emergent.
If the start date is completely missing, then the AE is treatment emergent. 
If both start and end dates of AEs are completely missing, no imputation will be performed, and 
those AEs will be considered treatment emergent. 
If the start date is partial: 
1. If only the day is missing:
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1.1. If the month/year of the start date is the same as those of the first study drug 
administration date, then the missing day will be imputed as the smaller nonmissing 
value of (day of first study drug administration, day of the AE end date). 
1.2. 
.
2. If both day and month are missing:
2.1. If the year of the AE start date coincides with the year of the first study drug
administration date, the partial start date will be set as the first study drug date. If this 
leads to a date after the AE end date, then the missing day and month of the AE start 
date will be imputed as the day and month of the AE end date. 
2.2. If the year of the AE start date is different from the year of the first study drug 
administration date, the missing day and month of the AE start date will be imputed as 
.
If the stop date is partial: 
1. If only the day is missing:
1.1. The missing day will be imputed as the last of the month, adjusting for the leap year.
2. If both day and month are missing:
2.1. If the year of the AE end date coincides with the maximum of (the year of first study
drug administration date or the year of the last study drug administration), then the 
missing month will be imputed as the month of the corresponding study drug 
administration date (first or last) and the missing day will be imputed as the last of the 
month adjusting for the leap year.  
2.2. 
.
AEs with missing relationship will be assumed to be related to study treatment. AEs with 
missing toxicity grade will be summarized as a separate category. 
6.3.7. 
Derivation of Prior and Concomitant Medication for Missing or Incomplete 
Dates 
If both start and end dates of medications are completely missing, no imputation will be 
performed, and those medications will be considered both prior and concomitant medications. 
If the end date is partial: 
1. If only the day is missing:
1.1. If the year and month coincide with those of the last study drug administration date, then
the end of medication will be set to the last study drug administration date. 
1.2. If the year and month do not coincide with those of the last study drug administration 
date, then the missing day will be imputed as the last day of the month considering leap 
year and month in consideration. 
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2. If both day and month are missing:
2.1. If the year coincides with that of the last study drug administration date, then missing
month and day will be imputed as the month and day of the last study drug 
administration. 
2.2. If the year does not coincide with that of the last study drug administration date, then the 
,
If the start date is partial: 
1. If only the day is missing:
1.1. If the year coincides with that of the first study drug administration date, then do the
following:
1.2. If the month does not coincide with that of the first study drug administration date, then
.  
1.3. If the month coincides with that of the first study drug administration date: 
1.3.1. If the end date is greater than the first study drug administration date, then impute 
the missing day as the day of the first study drug administration date. 
1.3.2. If the end date is less than or equal to the first study drug administration date, then 
impute the missing day as the day of the end date of medication. 
1.4. If the year and the month do not coincide with those of the first dose date, then impute 
.
2. If both day and month are missing:
2.1. If the year does not coincide with that of the first study drug administration date, then
.  
2.2. If the year coincides with that of the first study drug administration date: 
2.2.1. If the end date is greater than the first study drug administration date, then impute 
the missing day and month as those of the first study drug administration. 
2.2.2. If the end date is less than or equal to the first study drug administration date, then 
impute the missing day and month as those of the end date of the medication. 
2.3. If the start date is completely missing, the missing start date will be set as the earlier of 
the first study drug administration date and end of the medication date. 
For meningococcal vaccination, the missing end date will not be imputed. 
6.3.8. 
EQ-5D-5L Calculations 
The EQ-5D-5L is a widely used self-report 2-part health status instrument. It was developed by 
the EuroQoL Group to provide a concise, generic instrument that could be used to measure, 
compare, and value health status across disease areas (Devlin, 2017). The instrument is used to 
measure health status at the time of completing the questionnaire. 
The descriptive system section of the EQ-5D questionnaire produces a 5-digit health state profile 
that represents the level of reported problems (of the following 5 levels [scores in brackets]: no 
[1], slight [2], moderate [3], severe [4], or unable to/extreme problems [5]) on each of the 
5 dimensions of health (mobility, self-care, usual activities, pain/discomfort, and 
anxiety/depression). For example, the EQ-5D-5L health state 21143 represents a patient who 
indicates slight problems on the mobility dimension, no problems on the self-care and usual 
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activities dimensions, severe pain or discomfort dimension, and moderate problems on the 
anxiety/depression dimension. These health states should be converted into a single utility value 
or score using 1 of the standard EQ-5D-5L value sets. 
An EQ-5D-5L utility score is derived by applying a formula that attaches values (weights) to 
each of the levels in each dimension. The score is calculated by deducting the appropriate 
absolute weights from 1, the value for full health (ie, state 11111), and rounding the result to 
3 decimals. For this purpose, as patients are currently recruited from Japan, the value set for 
Japan below will be used.  
Important note for programming: The utility score should be calculated for each patient and at 
each time point using the weights of the value set from Table 10. Each level of answer from the 
questionnaire corresponds to a weight from Table 10, except for the level 1 answers for which 
the weight is 0. Below are examples of how to calculate utility scores from the answers to the 
EQ-5D-5L questionnaire. 
For an EQ-5D-5L health state reported as 21143, the equation for calculating the utility score is 
as follows: 
Of note, the utility score of the health state (11111) = 1  0.06924 (intercept) = 0.939076 is 
presenting the value of perfect health in the general population in Japan and therefore cannot be 
equal to 1. Similarly, the worst possible utility score (health state 55555) is negative:  0.025449. 
Table 10: 
EQ-5D-5L Scoring 
Domain 
Value 
Weight 
Intercept weight 
- 
-0.060924 
Mobility 
2 
-0.063865
3 
-0.112618
4 
-0.179043
5 
-0.242916
Self-care 
2 
-0.043632
3 
-0.076660
4 
-0.124265
5 
-0.159659
Usual activities 
2 
-0.050407
3 
-0.091131
4 
-0.147929
5 
-0.174786
Pain/discomfort 
2 
-0.044545
3 
-0.068178
4 
-0.131436
5 
-0.191203
Anxiety/depression 
2 
-0.071779
3 
-0.110496
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Table 10: 
EQ-5D-5L Scoring 
Domain 
Value 
Weight 
4 
-0.168171
5 
-0.195961
Abbreviation: EQ-5D-5L = European Quality of Life  5 Dimensions  5 Levels 
6.3.9. 
WPAI Calculations 
The WPAI is the most used questionnaire related to work productivity and activity impairment 
asked in the general population or in patients with different diseases. This is a self-administered 
questionnaire (a patient-reported activity/outcome questionnaire). 
6.3.9.1. 
WPAI Scoring and Calculations 
The WPAI includes 6 questions. Unemployed patients only answer Question 6.  
Employment status (STATUS): 
o
STATUS = employed  if Q1 = YES or Q1 = NO or missing and hours missed or
worked > 0.
o
STATUS = not employed  if Q1 = missing and hours missed and worked = 0.
Hours missed 
o
If hours worked = 0, then productivity while at work is NA.
o
If the line or box is slashed through or there is a response of NA, code as 0. If the
respondent enters a range of hours, enter the midpoint. If the respondent records
+  after the number of hours, ignore the +  Hours are usually rounded to
1 decimal.
Missing or unreadable response 
Responses from other assessments should not be used to eliminate missing data. For 
example, if a patient indicates that he works 40 hours at 1 assessment but leaves that 
question blank on a subsequent assessment, the blank response is coded missing. 
Productivity and regular activity questions 
If the words at the end of the scale are circled, enter the corresponding number (ie, a 
0  or 10 ). If 2 responses are circled, enter the midpoint, and round off to the 
nearest integer. 
WPAI outcomes are expressed as impairment percentages, with higher numbers indicating 
greater impairment and less productivity (ie, worse outcomes) as follows: 
Questions: 
o
Q1 = currently employed
o
Q2 = hours missed due to health problems
o
Q3 = hours missed due to other reasons
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o
Q4 = hours actually worked
o
Q5 = degree health affected productivity while working
o
Q6 = degree health affected regular activities
Scores: 
o
Multiply scores by 100 to express in percentages
o
Percentage of work time missed due to health: Q2/(Q2 + Q4)
o
Percentage of impairment while working due to health: Q5/10
o
Percentage of overall work impairment due to health:
Q2/(Q2 + Q4) + [(1 - (Q2/(Q2 + Q4)) )× (Q5/10)]
o
Percentage of activity impairment due to health: Q6/10
6.4. 
Appendix 4: Additional Details on Statistical Methods 
6.4.1. 
SAS Code for Key Efficacy Endpoints Analyses 
The SAS codes in this section are provided as a general guidance and may be slightly different 
from the actual codes used in the final analysis. 
6.4.1.1. 
SAS Code for the Primary Efficacy Endpoint 
The primary endpoint will be performed using a stratified log-rank test. The basic SAS code for 
this is as follows: 
PROC LIFETEST data=<dataset name>; 
     TIME <time >*<status (0)>;    (0 =censored data; 1=event data) 
     STRATA <strata >/GROUP=<treatment group >; 
RUN; 
The supportive analysis will be performed using a stratified Cox proportional hazard model. The 
basic SAS code for this is as follows: 
PROC PHREG data=<dataset name>; 
     CLASS <treatment group>*<status (0)>=<treatment group>/ties=efron; 
STRATA <strata > ; 
            RUN; 
6.4.1.2. 
SAS Code for the Key Secondary Efficacy Endpoints 
The statistical analyses of the key secondary efficacy endpoints as described in Section 5.4.1 will 
be performed using a logistic regression. The basic SAS code for this is as follows: 
PROC LOGISTIC DATA=<dataset name>; 
     CLASS <treatment group> <strata > ; 
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MODEL <response>=<treatment group> <strata >/ dist=bin link=logit; 
            RUN; 
The supportive analysis will be performed using the randomization-based Cochran-MH 
approach. The basic SAS code is the following: 
PROC FREQ DATA=<dataset name>; 
TABLES <strata > **<treatment group>*<resp>/cmh commonriskdiff(test=mh); 
            RUN; 
6.4.1.3. 
SAS Code for the Multiple Imputations 
For the sensitivity analyses described in Section 5.3.3, missing data will be imputed using a 
multiple imputation approach. 
The sensitivity analysis 2 assumes that data are MAR. The basic SAS code is as follows: 
PROC MI DATA=<data set name> OUT=<output data> seed=1306528 
NIMPUTE=100; 
CLASS <treatment group> <strata > ; 
VAR <treatment group>  <strata >  <resp>; 
MONOTONE REG (/details); 
          RUN; 
The sensitivity analysis 3 assumes that data are MNAR. The basic SAS code is as follows: 
PROC MI DATA=<data set name> OUT=<output data> seed=1306528 
NIMPUTE=100; 
CLASS <treatment group> <strata > ; 
VAR   <strata >  <resp>; 
MONOTONE REG (<resp>=<treatment group>  <strata> /details); 
MNAR MODEL (<resp>/modelobs=(<treatment group>=<placebo variable value>)); 
          RUN; 
For each sensitivity analysis, the imputed datasets will then be analyzed by imputation using the 
analysis method for each endpoint as described in Table 7, and the PROC MIANALYZE 
procedure will be used to generate valid statistical inferences for each endpoint. The basic SAS 
code is as follows: 
PROC MIANALYZE DATA=<data set name>; 
MODELEFFECTS <estimated treatment effect>; 
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STDERR <estimated standard error >; 
            RUN; 
Transformations are needed depending on the nature of the statistics to be summarized. For 
example, Wilson-Hilferty transformation is needed for the Chi-square test statistics. 
6.4.2. 
SAS Code for Exploratory Endpoints Analyses 
For some exploratory endpoints, the analysis of changes over time involves an MMRM analysis. 
The basic SAS code for this analysis is as follows: 
PROC MIXED DATA=<data set name> METHOD=reml; 
     CLASS <patient id> <visit> <treatment group> <strata > ; 
     MODEL <change> =<treatment group> <visit> <treatment group*visit> <strata > 
<base>/ddfm=kr solution; 
    REPEATED <visit>/type=un subject=<patient id>; 
    LSMEANS <treatment group>*<visit>/CL DIFF; 
RUN; 
6.5. 
Details of Statistical Analyses to Address COVID-19 Impacts 
6.5.1. 
Patients Who Were Impacted by COVID-19 
Patients who were impacted by COVID-19 as follows will be identified: 
a.
Patients who had a COVID-19-related AE
b. Patients who missed 2 consecutive scheduled doses of study drug due to
COVID-19-related disruptions
c.
Patients who terminated early due to COVID-19-related disruptions
d. Patients who received concomitant treatments for COVID-19 that could be used as
GBS medication
6.5.2. 
Efficacy Assessments 
The planned analyses in Sections 5.3 and 5.4 will be repeated with the efficacy data to assess the 
impact of COVID-19 using the while-on-treatment strategy as follows: 
a.
Efficacy assessments for patients who had COVID-19 impact will be censored at the
date when patients had their first COVID-19-related events or disruptions.
This strategy is used to evaluate the treatment effect prior to the occurrence of the intercurrent 
COVID-19 events. 
6.5.3. 
COVID-19-Related Analyses 
The following analyses will be included to address COVID-19-related impact on the data: 
a.
A summary of patient disposition will include COVID-19-related screen failure
reasons and COVID-19-related discontinuations/withdrawals.
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b. A summary of the number and percentage of patients with pretreatment and
treatment-emergent known exposure to COVID-19 will be provided using SS.
c.
A summary of COVID-19-related important protocol deviations will be provided.
d. A summary of the number and percentage of patients who missed a study visit and/or
who had a modified study visit, along with the reasons (COVID-19 related/not), will
be provided by treatment group and visit using the FAS. For patients who had a
modified study visit, the method for the different assessments will be summarized.
e.
A summary of the total number and percentage of patients with COVID-19-related
missed doses, the reason for missed doses, and the total number of missed doses will
be provided. Similarly, the total number of patients with any COVID-19-related
unscheduled infusions, the reason for unscheduled infusions, and the total number of
unscheduled doses will be provided.
f.
The primary and key secondary efficacy endpoint analyses will be repeated using the
while-on-treatment strategy on FAS.
g. A summary table of AEs with onset on or after the first dose of the study drug by
SOC and PT will be provided for patients who had COVID-19 related AEs using the
SS.
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7.
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