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)
Phase: PHASE3
Conditions: Guillain-Barre Syndrome
Sponsor: Alexion Pharmaceuticals, Inc.

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 
Page 2 of 90 
Alexion Confidential 

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. 
Page 3 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
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
Page 4 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
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. 
Page 5 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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 
Page 6 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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 
Page 7 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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 
Page 8 of 90 Alexion 
Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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 
Page 9 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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 
Page 10 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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 
Page 11 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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 
Page 12 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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 
Page 13 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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
Page 14 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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
Page 15 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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 
Page 16 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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. 
Page 17 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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 
● 
Page 18 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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). 
Page 19 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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. 
Page 20 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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. 
Page 21 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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, 
Page 22 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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). 
Page 23 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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. 
Page 24 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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. 
Page 25 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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
Page 26 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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
Page 27 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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). 
Page 28 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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 
Page 29 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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. 
Page 30 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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 
Page 31 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 

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.
Page 32 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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. 
Page 33 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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
Page 34 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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. 
Page 35 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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
Page 36 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 

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. 
Page 37 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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.
Page 38 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 

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. 
Page 39 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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. 
Page 40 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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. 
Page 41 of 90 
Alexion Confidential 
 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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). 
Page 42 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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.
Page 43 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 

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.
Page 44 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 

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
Page 45 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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 
Page 46 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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. 
Page 47 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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). 
Page 48 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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).
Page 49 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 

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. 
Page 50 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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. 
Page 51 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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, 
Page 52 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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. 
Page 53 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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: 
Page 54 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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 
Page 55 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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. 
Page 56 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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. 
Page 57 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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. 
Page 58 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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. 
Page 59 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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. 
Page 60 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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
Page 61 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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.
Page 62 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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).
Page 63 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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. 
Page 64 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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.
Page 65 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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: 
Page 66 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
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.
Page 67 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
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.
Page 68 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
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: 
Page 69 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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. 
Page 70 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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. 
Page 71 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
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.
Page 72 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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 
Page 73 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
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 
Page 74 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
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: 
Page 75 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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 . 
Page 76 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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 
Page 77 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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. 
Page 78 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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. 
Page 79 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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) = 
Page 80 of 90 
Alexion Confidential 

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 
Page 81 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
Page 82 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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 
Page 83 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
Page 84 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
Page 85 of 90 
Alexion Confidential 

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)
Page 86 of 90 
Alexion Confidential 

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
Page 87 of 90 
Alexion Confidential 

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 
Page 88 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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. 
Page 89 of 90 
Alexion Confidential 

Protocol Amendment 1.0 
ECU-GBS-301 
28 Oct 2021 
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. 
Page 90 of 90 
Alexion Confidential