Prospective, Single-Arm, Multicenter Study to Evaluate the Efficacy, Safety, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Eculizumab in Complement Inhibitor Treatment-Naïve Pediatric and Adult Participants With Atypical Hemolytic Uremic Syndrome (aHUS) in China
Phase: PHASE3
Conditions: Atypical Hemolytic Uremic
Sponsor: Alexion Pharmaceuticals, Inc.

Protocol Amendment 2
ECU-aHUS-302
26 Apr 2023
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Alexion Confidential
TITLE PAGE
Protocol Title: Prospective, Single-Arm, Multicenter Study to Evaluate the Efficacy, Safety, 
Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Eculizumab in Complement 
Inhibitor Treatment-Naïve Pediatric and Adult Participants with Atypical Hemolytic Uremic 
Syndrome (aHUS) in China
Protocol Number: ECU-aHUS-302
Compound: Eculizumab
Study Phase: 3b
Short Title: Single-Arm Study of Eculizumab in Pediatric and Adult Participants with Atypical 
Hemolytic Uremic Syndrome (aHUS) in China
Sponsor Name: Alexion Europe SAS
Legal Registered Address: 103-105 rue Anatole France, 92300 Levallois-Perret, France
Regulatory Agency Identifier Number(s): Not assigned
Original Protocol: 30 Nov 2021
Protocol Amendment 1: 20 Jun 2022
Protocol Amendment 2: 26 Apr 2023
Sponsor Signatory:
Alexion Pharmaceuticals, Inc.
Date
Medical Monitor Name and Contact Information can be found in the study contact list.

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NCT #: NCT05876351

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INVESTIGATOR’S AGREEMENT 
I have read the study protocol amendment and agree to conduct the study in accordance with this 
protocol amendment, all applicable government regulations, the principles of the International 
Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use 
(ICH) E6 Guideline for Good Clinical Practice (GCP), 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 amendment. 
 
 
 
 
____________________________________ 
Printed Name of Investigator 
 
_____________________________________ 
Signature of Investigator 
 
 
_______________ 
Date 
 

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TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
INVESTIGATOR’S AGREEMENT ...............................................................................................2 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................8 
1. 
PROTOCOL SUMMARY ..........................................................................................16 
1.1. 
Synopsis ......................................................................................................................16 
1.2. 
Schema ........................................................................................................................20 
1.3. 
Schedule of Activities .................................................................................................21 
2. 
INTRODUCTION ......................................................................................................38 
2.1. 
Study Rationale ...........................................................................................................38 
2.2. 
Background .................................................................................................................38 
2.3. 
Benefit/Risk Assessment ............................................................................................39 
2.3.1. 
Risk Assessment .........................................................................................................39 
2.3.1.1. 
Coronavirus Disease 2019 ..........................................................................................40 
2.3.2. 
Benefit Assessment .....................................................................................................40 
2.3.3. 
Overall Benefit: Risk Conclusion ...............................................................................40 
3. 
OBJECTIVES, ESTIMANDS, AND ENDPOINTS ..................................................41 
3.1. 
Primary Estimand .......................................................................................................42 
3.2. 
Secondary Estimands ..................................................................................................43 
3.3. 
Tertiary/Exploratory Estimands ..................................................................................43 
4. 
STUDY DESIGN .......................................................................................................44 
4.1. 
Overall Design ............................................................................................................44 
4.2. 
Scientific Rationale for Study Design ........................................................................44 
4.3. 
Justification for Dose ..................................................................................................45 
4.4. 
End of Study Definition ..............................................................................................45 
5. 
STUDY POPULATION .............................................................................................46 
5.1. 
Inclusion Criteria ........................................................................................................46 
5.2. 
Exclusion Criteria .......................................................................................................47 
5.3. 
Lifestyle Considerations .............................................................................................49 
5.4. 
Screen Failures ............................................................................................................49 
6. 
STUDY INTERVENTION ........................................................................................51 
6.1. 
Study Intervention Administered ................................................................................51 

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6.1.1. 
Study Intervention(s) Packaging and Labeling ...........................................................51 
6.2. 
Preparation/Handling/Storage/Accountability ............................................................52 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................................52 
6.4. 
Study Intervention Compliance ..................................................................................52 
6.5. 
Concomitant Therapy .................................................................................................53 
6.5.1. 
Allowed Medicine and Therapy .................................................................................53 
6.5.2. 
Disallowed Medicine and Therapy .............................................................................54 
6.5.3. 
Vaccination .................................................................................................................55 
6.6. 
Dose Modification ......................................................................................................55 
6.7. 
Intervention After the End of the Study .....................................................................56 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL .......................................57 
7.1. 
Discontinuation of Study Intervention........................................................................57 
7.1.1. 
Temporary Discontinuation ........................................................................................57 
7.2. 
Participant Discontinuation/Withdrawal from the Study ...........................................57 
7.3. 
Lost to Follow-up .......................................................................................................58 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................59 
8.1. 
Efficacy Assessments .................................................................................................59 
8.1.1. 
Laboratory Assessments for Efficacy Estimands/Endpoints ......................................59 
8.1.2. 
Kidney Function Parameters .......................................................................................59 
8.1.3. 
Other Disease-related Laboratory Parameters ............................................................60 
8.2. 
Safety Assessments .....................................................................................................60 
8.2.1. 
Physical Examinations ................................................................................................60 
8.2.2. 
Vital Signs ..................................................................................................................61 
8.2.3. 
Electrocardiograms .....................................................................................................61 
8.2.4. 
Clinical Safety Laboratory Assessments ....................................................................61 
8.2.5. 
Pregnancy ...................................................................................................................62 
8.2.6. 
Participant Safety Card ...............................................................................................62 
8.3. 
Adverse Events and Serious Adverse Events .............................................................62 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE Information .......................63 
8.3.2. 
Method of Detecting AEs and SAEs ..........................................................................63 
8.3.3. 
Follow-up of AEs and SAEs .......................................................................................63 
8.3.4. 
Regulatory Reporting Requirements for SAEs ...........................................................63 

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8.3.5. 
Adverse Events of Special Interest (AESI) ................................................................64 
8.4. 
Treatment of Overdose ...............................................................................................64 
8.5. 
Pharmacokinetics ........................................................................................................64 
8.6. 
Pharmacodynamics .....................................................................................................64 
8.7. 
Genetics ......................................................................................................................65 
8.8. 
Biomarkers ..................................................................................................................65 
8.9. 
Immunogenicity Assessments ....................................................................................65 
8.9.1. 
ADA Variables ...........................................................................................................65 
8.10. 
Health Economics Data and/or Medical Resource Utilization ...................................65 
8.11. 
Other Assessments and Procedures ............................................................................66 
8.11.1. 
Informed Consent .......................................................................................................66 
8.11.2. 
Demographics .............................................................................................................66 
8.11.3. 
Inclusion and Exclusion Criteria ................................................................................66 
8.11.4. 
Medical History and aHUS History ............................................................................66 
8.11.5. 
Prior and Concomitant Medications Review ..............................................................67 
8.11.5.1. 
Prior Medications ........................................................................................................67 
8.11.5.2. 
Concomitant Medications ...........................................................................................67 
8.11.6. 
Study Intervention Administration .............................................................................67 
9. 
STATISTICAL CONSIDERATIONS .......................................................................69 
9.1. 
Statistical Hypotheses .................................................................................................69 
9.2. 
Sample Size Determination ........................................................................................69 
9.3. 
Populations for Analyses ............................................................................................69 
9.4. 
Statistical Analyses .....................................................................................................69 
9.4.1. 
Efficacy Analyses .......................................................................................................70 
9.4.1.1. 
Analyses of Primary Efficacy Estimand(s) and Endpoint ..........................................70 
9.4.1.2. 
Analyses of Secondary Efficacy Estimand(s) and/or Endpoint(s) .............................70 
9.4.1.3. 
Multiplicity Adjustment..............................................................................................70 
9.4.1.4. 
Analyses of Exploratory Estimand(s) and/or Endpoint(s) ..........................................70 
9.4.2. 
Safety Analyses ..........................................................................................................71 
9.4.3. 
Other Analyses ............................................................................................................71 
9.4.3.1. 
PK/PD .........................................................................................................................71 
9.4.3.2. 
Immunogenicity ..........................................................................................................71 
9.5. 
Interim Analyses .........................................................................................................71 

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9.6. 
Data Monitoring Committee .......................................................................................72 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................73 
10.1. 
Regulatory, Ethical, and Study Oversight Considerations .........................................73 
10.1.1. 
Regulatory and Ethical Considerations ......................................................................73 
10.1.2. 
Financial Disclosure ...................................................................................................73 
10.1.3. 
Informed Consent Process ..........................................................................................74 
10.1.4. 
Data Protection ...........................................................................................................74 
10.1.5. 
Dissemination of Clinical Study Data ........................................................................75 
10.1.6. 
Data Quality Assurance ..............................................................................................75 
10.1.7. 
Source Documents ......................................................................................................76 
10.1.8. 
Study and Site Start and Closure ................................................................................76 
10.1.9. 
Publication Policy .......................................................................................................77 
10.1.10. 
Good Clinical Practice Compliance............................................................................78 
10.2. 
Clinical Laboratory Tests ...........................................................................................79 
10.3. 
Adverse Events: Definitions and Procedures for Recording, Evaluating, 
Follow-up, and Reporting ...........................................................................................81 
10.3.1. 
Definition of AE .........................................................................................................81 
10.3.2. 
Definition of SAE .......................................................................................................82 
10.3.3. 
Recording and Follow-Up of AE and/or SAE ............................................................82 
10.3.4. 
Reporting of SAEs ......................................................................................................84 
10.4. 
Contraceptive Guidance and Collection of Pregnancy Information ...........................85 
10.4.1. 
Definitions ..................................................................................................................85 
10.4.2. 
Contraception Guidance .............................................................................................86 
10.4.2.1. 
Guidance for Female Participants ...............................................................................86 
10.4.2.2. 
Guidance for Male Participants ..................................................................................87 
10.4.3. 
Collection of Pregnancy Information .........................................................................87 
10.4.3.1. 
Male Participants with Partners Who Become Pregnant ............................................88 
10.4.3.2. 
Female Participants Who Become Pregnant ...............................................................88 
10.5. 
COVID-19 Risk Assessment ......................................................................................90 
10.6. 
Protocol Amendment History .....................................................................................92 
10.7. 
Abbreviations ..............................................................................................................93 
11. 
REFERENCES ...........................................................................................................95 

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LIST OF TABLES 
Table 1: 
Eculizumab Induction and Maintenance Dosing by Weight Cohorta .........................19 
Table 2: 
Schedule of Activities: Screening and Treatment Period, Weight Cohorts 
≥ 40 kg, 30 to < 40 kg, and 20 to < 30 kg ...................................................................21 
Table 3: 
Schedule of Activities: Treatment Period (Continued) to End of Study, 
Weight Cohorts ≥ 40 kg, 30 to < 40 kg, and 20 to < 30 kg ........................................24 
Table 4: 
Schedule of Activities: Screening and Treatment Period, Weight Cohort 10 
to < 20 kg ....................................................................................................................27 
Table 5: 
Schedule of Activities: Treatment Period (Continued) to End of Study, 
Weight Cohort 10 to < 20 kg ......................................................................................30 
Table 6: 
Schedule of Activities: Screening, Treatment Period, and End of Study, 
Weight Cohort 5 to < 10 kg ........................................................................................33 
Table 7: 
Risk Assessment .........................................................................................................39 
Table 8: 
Mapping of Objectives to Estimands and Endpoints ..................................................41 
Table 9: 
Study Intervention ......................................................................................................51 
Table 10: Estimated Glomerular Filtration Rate Category/Stage in Chronic Kidney 
Disease ........................................................................................................................60 
Table 11: 97.5th Percentile Serum Creatinine Reference Intervals ............................................66 
Table 12: Eculizumab Induction and Maintenance Dosing by Weight Cohorta .........................68 
Table 13: Populations for Analyses ............................................................................................69 
Table 14: Protocol-Required Safety Laboratory Assessments ...................................................80 
Table 15: Potential Risks and Mitigation Measures due to COVID-19 .....................................90 
Table 16: Abbreviations and Specialist Terms ...........................................................................93 
 
LIST OF FIGURES 
Figure 1: 
ECU-aHUS-302 Study Design Schematic..................................................................20 

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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
Amendment 2 
Overall Rationale for the Amendment: 
The primary reason for this amendment was to clarify activities to be followed when a change in 
weight causes a participant to move to a different weight cohort during the study period. 
Additionally, updates to estimand descriptions for endpoints were also made. 
Section # and Title 
Description of Change 
Brief Rationale 
Title Page 
Added updated protocol amendment 
number. 
Administrative 
Throughout 
Updated definition of ED Visit to 
early discontinuation from the study. 
For clarity 
1.1 – Synopsis (Objectives, 
Estimands, and Endpoints) 
 
3 - Objectives, Estimands, and 
Endpoints 
 
3.1 Primary Estimand 
Updated definition of “Population” in 
“Estimands and Endpoints” for the 
primary endpoint of efficacy 
assessment as follows (strikethrough 
[deleted], bold [added]): 
 
Chinese participants with aHUS 
who are eligible to be enrolled in 
the study, based on the inclusion 
and exclusion criteria Participants in 
the FAS (defined in Section 9.3). 
To align the definition of population 
with ICH E9(R1) 
1.1 – Synopsis (Objectives, 
Estimands, and Endpoints) 
 
3 - Objectives, Estimands, and 
Endpoints 
 
3.2 - Secondary Estimands 
Updated definition of “Population” in 
“Estimands and Endpoints” for the 
secondary endpoint of safety 
assessment as follows (strikethrough 
[deleted], bold [added]): 
 
Chinese participants with aHUS 
who are eligible to be enrolled in 
the study, based on the inclusion 
and exclusion criteriaParticipants in 
the Safety Set (defined in 
Section 9.3). 
To align the definition of population 
with ICH E9(R1) 

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Section # and Title 
Description of Change 
Brief Rationale 
1.1 – Synopsis (Objectives, 
Estimands, and Endpoints) 
 
3 - Objectives, Estimands, and 
Endpoints 
 
3.2 - Secondary Estimands 
Updated “Population” and “Summary 
measure” definitions for PK 
assessment as follows (strikethrough 
[deleted], bold [added]): 
 
Population: Chinese participants 
with aHUS who are eligible to be 
enrolled in the study, based on the 
inclusion and exclusion 
criteria.Participants in the PK 
Analysis Set (defined in Section 9.3). 
 
Summary measure: Mean serum 
eculizumab concentrations at all 
scheduled visitsSerum eculizumab 
concentrations at all available study 
visits. 
To align the definition of population 
with ICH E9(R1). 
1.1 – Synopsis (Objectives, 
Estimands, and Endpoints) 
 
3 - Objectives, Estimands, and 
Endpoints 
 
3.2 - Secondary Estimands 
Updated “Population”, “Variable”, 
and “Summary measure” definitions 
for PD assessment as follows 
(strikethrough [deleted], bold 
[added]): 
 
Population: Chinese participants 
with aHUS who are eligible to be 
enrolled in the study, based on the 
inclusion and exclusion 
criteria.Participants in the PD 
Analysis Set (defined in Section 9.3). 
 
Variable: Mean cChanges in serum 
free and total C5 complement 
component 5 concentrations over time 
(Section 3.23.2). 
 
Summary measure: Mean changes in 
serum free and total C5 
concentrations at all scheduled 
visitsMean change in serum free and 
total complement component 5 
concentrations from baseline over 
time at all study visits. 
To align the definition of population 
with ICH E9(R1). 

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Section # and Title 
Description of Change 
Brief Rationale 
1.1 – Synopsis (Objectives, 
Estimands, and Endpoints) 
 
3 - Objectives, Estimands, and 
Endpoints 
 
3.2 - Secondary Estimands 
Updated “Population”, “Variable”, 
and “Summary measure” definitions 
for immunogenicity assessment as 
follows (strikethrough [deleted], bold 
[added]): 
 
Population: Chinese participants 
with aHUS who are eligible to be 
enrolled in the study, based on the 
inclusion and exclusion 
criteria.Participants in the Safety Set 
(defined in Section 9.3). 
 
Variable: ADA response category 
Proportion of participants who 
develop ADA and neutralizing 
antibodies (Section 3.2). 
 
Summary measure: Proportion of 
ADA positive participants 
Proportion of participants at all study 
visits with ADA positive and 
neutralizing antibody titers. 
To align the definition of population 
with ICH E9(R1). 
1.1 - Synopsis (Overall Design) 
 
4.1 - Overall Design 
Revised text on prophylactic 
antibiotics as follows: 
 
Participants who are vaccinated less 
than 14 days2 weeks prior to 
receiving the first dose of eculizumab 
will receive treatment with 
appropriate prophylactic antibiotics 
until 14 days2 weeks after the 
vaccination. 
For internal document consistency.  
1.1 - Synopsis (Intervention 
Groups and Duration) 
 
1.3 - Schedule of Activities 
(Table 2, Table 3, Table 4, 
Table 5, and Table 6) 
 
8.11.6 - Study Intervention 
Administration 
Added a footnote to Table 1 and 
Table 12, and added note for weight 
assessment in Table 2, Table 3, 
Table 4, Table 5, and Table 6 to 
indicate that participants will be 
weighed prior to dosing at each study 
visit as eculizumab dosing will be 
based on the weight assessment at 
that specific visit. 
Also added that participants will not 
need to be weighed at each study visit 
if eculizumab is permanently 
discontinued.  
To reiterate that weight must be 
measured prior to other assessments 
to determine eculizumab dose. 
 
 
 
 
 
To reiterate that if eculizumab is 
permanently discontinued and the 
participant remains in the study, for 
the rest of the scheduled visits, the 
schedule of activities will not need to 
be adjusted based on weight. 
1.3 - Schedule of Activities 
(Table 2, Table 4, and Table 6) 
Updated Day 0 to Day -1 in the Study 
Day Visit Window.  
For clarity 

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Section # and Title 
Description of Change 
Brief Rationale 
1.3 - Schedule of Activities 
(Table 2, Table 4, and Table 6) 
Deleted assessment of “LDH 
isozymes”. 
Updated as only total LDH is 
measured in the study and not the 
individual isoenzymes 
1.3 - Schedule of Activities 
(Table 2, Table 3, Table 4, 
Table 5, and Table 6) 
Added “Dialysis requirement status”. 
For internal document consistency 
1.3 - Schedule of Activities 
(Table 2, Table 3, Table 4, 
Table 5, and Table 6) 
Added the note “Clinical laboratory 
measurements will be collected 
predose on dosing days and not from 
a heparinized line” for “Hematology 
including coagulation”. 
For internal document consistency 
1.3 - Schedule of Activities 
(Table 2, Table 3, Table 4, 
Table 5, and Table 6) 
 
8.11.6 - Study Intervention 
Administration 
Added footnote for “Administration 
of Study Intervention” and text in 
“Study Intervention Administration” 
section to indicate schedule of 
activities to be followed if a change in 
weight cohort occurs during the study 
period. 
Also added that if eculizumab is 
permanently discontinued and the 
participant remains in the study, for 
the rest of the scheduled visits, the 
SoA will not need to be adjusted 
based on weight. 
Added to provide clarity on schedule 
of activities to be followed when a 
change in weight causes a participant 
to move to a different weight cohort 
during the study period.  
1.3 - Schedule of Activities 
(Table 3, Table 5, and Table 6) 
Merged table column for “ED” with 
“Treatment Period”. 
For clarity 
3.1 - Primary Estimand 
Added “(composite strategy for 
intercurrent events)” to the 
description of the primary estimand.  
Added to specify the strategy for 
handling the intercurrent events. 
3.2 - Secondary Estimands 
Added “Treatment policy will be 
applied for the predefined intercurrent 
events, where all data collected will 
be used in the analyses as if there is 
no occurrence of any intercurrent 
event” to the description of the 
secondary estimands. 
 
Added “For the definition of 
estimands, the population will be the 
same as in the primary objective 
(variables are presented in Table 8); 
the handling of intercurrent events for 
main analyses will apply treatment 
policy strategy, and the summary 
measures and all the other details will 
be provided in the SAP.” 
Added to specify the strategy for 
handling the intercurrent events. 

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Section # and Title 
Description of Change 
Brief Rationale 
4.4 - End of Study Definition 
Revised definition of end of study for 
participants who will and will not 
receive continued access to 
eculizumab after completing study 
treatment.  
For flexibility and clarity when a 
change in weight causes a participant 
to move to a different weight cohort 
during the study period.  
5.1 - Inclusion Criteria 
Revised criterion #1 (strikethrough 
[deleted]): 
Age 
- 
Participants of any age 
weighing ≥ 5 kg. 
To reduce redundancy 
5.1 - Inclusion Criteria 
Revised criterion #2 (strikethrough 
[deleted], bold [added]): 
Evaluation of Inclusion Criteria 3a 2a 
and 3b 2b may be based on local 
laboratory results within 28 days prior 
to the start of the Screening Period or 
laboratory results obtained during the 
Screening Period from a local or 
central laboratory. 
[…] 
If a participant is found to not meet 
the eligibility criteria for serum 
creatinine (Inclusion Criterion 3c2c) 
based on central laboratory results, 
they must not be enrolled into the 
study; if the participant has received 
the first dose of eculizumab, the 
participant must be withdrawn from 
the study and may be replaced. A 
central laboratory result for Inclusion 
Criterion 3c 2c may not be available 
prior to first dose; results received 
after the first dose indicating that 
eligibility is not satisfied could lead to 
discontinuation and replacement of 
the participant. 
[…] 
To correct typos 
5.1 - Inclusion Criteria 
Revised criterion #5 to add reference 
to Section 6.5.3.  
For clarity 

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Section # and Title 
Description of Change 
Brief Rationale 
6.5.3 - Vaccination 
Added the following: 
x 
Participants must be 
administrated prophylactic 
antibiotics for prevention of 
meningococcal infection, if 
study intervention 
administration occurs before 
the vaccination 
administration. 
x 
Participants who 
permanently discontinue 
study intervention before 
vaccination against 
meningococcal infection 
must be administered 
prophylactic antibiotics for 
at least 8 weeks or be 
vaccinated for 
meningococcal infection. 
To clarify that prophylactic 
antibiotics must be administered to 
participants who have started 
treatment with the study intervention 
but did not receive the vaccination. 
 
 
 
To clarify vaccination requirements if 
there is permanent discontinuation of 
study intervention.  
7.1 - Discontinuation of Study 
Intervention 
Revised text as follows (strikethrough 
[deleted], bold [added]): 
If the study intervention is 
definitively permanently 
discontinued, the participant should, 
if at all possible, remain in the study 
to be evaluated for safetyall 
assessments described in the SoA 
(Section 1.3). 
If study intervention is definitively 
permanently discontinued, and the 
participant remains in the study, 
the participant should be asked to 
return for an ED Visit and have a the 
Safety Follow-up Phone Call 8 weeks 
after the last dose of study 
intervention. 
Refer to the SoA (Section 1.3) for 
data to be collected at the time of 
discontinuation of study intervention 
and follow-up and for any further 
evaluations that need to be completed. 
[…] 
Data collected at the time of study 
intervention discontinuation and 
follow up and for any further 
evaluations that need to be completed 
are provided in the SoA (Section 1.3). 
Clarified assessments to be 
performed when there is permanent 
discontinuation of study intervention, 
and the participant remains in the 
study. 

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Section # and Title 
Description of Change 
Brief Rationale 
7.1 - Discontinuation of Study 
Intervention 
Moved the following paragraph from 
Section 7.1 to Section 7.2: 
“If it is determined at any point that a 
participant’s Screening data do not 
satisfy ADAMTS13 negative testing 
(< 5% activity, Exclusion Criterion 1) 
or Shiga toxin negative testing 
(Exclusion Criterion 2) after receiving 
at least 1 dose of study intervention, 
the participant will be discontinued 
from the study and may be replaced. 
ED procedures described in the SoA 
(Section 1.3) will be performed, if 
possible, on participants who are 
terminated early from the study, and 
AEs will be collected through the 
8-week Safety Follow-up Phone Call 
(Section 1.3).” 
Updated as the text describes 
discontinuation from the study.  
7.2 Participant 
Discontinuation/Withdrawal 
from the Study 
Revised text as follows (bold 
[added]): 
• 
At the time of discontinuing 
from the study, if possible, an ED 
Visit should be conducted, as shown 
in the SoA (Section 1.3). 
Additionally, participants should 
have the 8-week Safety Follow-up 
Phone Call. Refer to the SoA for data 
to be collected at the time of study 
discontinuation and follow up and for 
any further evaluations that need to be 
completed. 
[…] 
• 
The 8-week Safety 
Follow-up Phone Call will not be 
required if a participant withdraws 
consent. 
To clarify when the 8-week Safety 
Follow-up Phone Call needs to be 
performed.  
8.2.1 - Physical Examinations 
Clarified that weight must be 
recorded prior to dosing at every 
study visit, however, if eculizumab is 
permanently discontinued weight will 
not need to be measured at each study 
visit.  
For clarity.  
8.6 - Pharmacodynamics 
Revised text as follows (strikethrough 
[deleted]): 
 
Serum and urine samples will be 
collected for measurement of C5 
(serum) as specified in the SoA 
(Section 1.3). 
Updated as C5 is measured through 
serum and only serum samples are 
collected in the study.  
8.11.4 - Medical History and 
aHUS History 
Added “emergency room visits” to 
the documentation of aHUS medical 
history.  
Added as this information is collected 
in the CRF 

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Section # and Title 
Description of Change 
Brief Rationale 
8.11.5.1 - Prior Medications 
Updated the timeframe for usage of 
prior medications before the start of 
Screening or during the Screening 
Period before the first dose of 
eculizumab from 30 days to 28 days. 
For internal document consistency 
9.4.3.1 - PK/PD 
Added “total C5” to list of PD data 
collected. 
Updated the following statement 
(strikethrough [deleted], bold 
[added]): 
The relationship between PK 
exposure and PD (serum free C5 
concentration) willresponse may be 
explored. 
For clarity 
10.6 - Protocol Amendment 
History 
Added details on Protocol 
Amendment 1. 
Administrative 
Throughout 
Headers updated with amendment 
number and date. 
Administrative 
Throughout 
Corrected grammar, syntax, 
abbreviations, and formatting. 
For clarity and to maintain internal 
document consistency 
Note: […] indicates additional unchanged text. 
Abbreviations: ADA = antidrug antibody; ADAMTS13 = a disintegrin and metalloproteinase with a 
thrombospondin type 1 motif; AE = adverse event; aHUS = atypical hemolytic uremic syndrome; 
C5 = complement component 5; CRF = case report form; ED = early discontinuation from the study; 
ICH = International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use; 
LDH = lactate dehydrogenase; PD = pharmacodynamic(s); PK = pharmacokinetic(s); SAP = statistical analysis 
plan; SoA = Schedule of Activities 

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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: 
Prospective, Single-Arm, Multicenter Study to Evaluate the Efficacy, Safety, Pharmacokinetics, 
Pharmacodynamics, and Immunogenicity of Eculizumab in Complement Inhibitor 
Treatment-Naïve Pediatric and Adult Participants with Atypical Hemolytic Uremic Syndrome 
(aHUS) in China 
Short Title: 
Single-Arm Study of Eculizumab in Pediatric and Adult Participants with Atypical Hemolytic 
Uremic Syndrome (aHUS) in China 
Rationale: 
Atypical hemolytic uremic syndrome (aHUS) is a rare and life-threatening disease characterized 
by complement-mediated thrombotic microangiopathy (TMA). The annual incidence of aHUS in 
the United States and European Union is 1 to 2 cases per million. Such published data are not yet 
available in China; however, case reports from 5 major medical centers in China suggest the 
estimated annual incidence of aHUS in China is similar. aHUS is associated with sometimes 
fatal manifestations of the nervous system, cardiovascular, gastrointestinal, and renal systems. 
TMA in patients with aHUS occurs because of impaired regulation of the alternative 
complement pathway involving complement component 5 (C5). Eculizumab (SOLIRIS®) is a 
humanized monoclonal antibody (mAb) that specifically binds to C5 and is the standard of care 
treatment for aHUS. The therapeutic efficacy and safety of eculizumab in the treatment of aHUS 
has been demonstrated in 3 pivotal clinical studies for registration and has since been supported 
by subsequent postmarketing evidence. This postapproval study, agreed as a condition of 
approval in China, will be conducted in participants with aHUS who are being treated with 
eculizumab in China. 

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Objectives, Estimands, and Endpoints 
Objectives 
Estimands and Endpoints 
Primary 
To assess the efficacy of eculizumab in 
the treatment of participants with aHUS 
x 
Population: Chinese participants with aHUS who are eligible to be 
enrolled in the study, based on the inclusion and exclusion criteria. 
x 
Variable: Complete TMA Response during the 26-week Treatment 
Period (Section 3.1). 
x 
Treatment: Eculizumab 
x 
ICE: 
o 
ICE1: premature discontinuation of study intervention 
o 
ICE2: initiation of disallowed therapy or medicine 
All participants who meet response criteria after ICE1 or ICE2 
will be considered as nonresponders thereafter. 
x 
Summary measure: The proportion of complete TMA responders 
overall along with 95% CIs. 
Secondary 
To characterize the safety and tolerability 
of eculizumab in participants with aHUS 
x 
Population: Chinese participants with aHUS who are eligible to be 
enrolled in the study, based on the inclusion and exclusion criteria. 
x 
Variable: Incidence of TEAEs and SAEs (Section 3.2). 
x 
Treatment: Eculizumab 
x 
ICE: 
o 
ICE1: premature discontinuation of study intervention 
o 
ICE2: initiation of disallowed therapy or medicine 
All data after ICE1 or ICE2 will be included. 
x 
Summary measure: Number and percentage of participants with 
TEAEs and SAEs and number of events by System Organ Class and 
Preferred Term. 
To characterize the pharmacokinetics of 
eculizumab in participants with aHUS 
x 
Population: Chinese participants with aHUS who are eligible to be 
enrolled in the study, based on the inclusion and exclusion criteria. 
x 
Variable: Serum eculizumab concentrations over time 
(Section 3.2). 
x 
Treatment: Eculizumab 
x 
ICE: 
o 
ICE1: premature discontinuation of study intervention 
o 
ICE2: initiation of disallowed therapy or medicine 
All data after ICE1 or ICE2 will be used. 
x 
Summary measure: Mean serum eculizumab concentrations at all 
scheduled visits. 
To characterize the pharmacodynamics of 
eculizumab in participants with aHUS 
x 
Population: Chinese participants with aHUS who are eligible to be 
enrolled in the study, based on the inclusion and exclusion criteria. 
x 
Variable: Changes in serum free and total C5 concentrations 
over time (Section 3.2). 
x 
Treatment: Eculizumab 
x 
ICE: 
o 
ICE1: premature discontinuation of study intervention 
o 
ICE2: initiation of disallowed therapy or medicine 
All data after ICE1 or ICE2 will be used. 
x 
Summary measure: Mean changes in serum free and total C5 
concentrations at all scheduled visits. 

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Objectives 
Estimands and Endpoints 
To characterize the immunogenicity of 
eculizumab in participants with aHUS 
x 
Population: Chinese participants with aHUS who are eligible to be 
enrolled in the study, based on the inclusion and exclusion criteria. 
x 
Variable: ADA response category. 
x 
Treatment: Eculizumab 
x 
ICE: 
o 
ICE1: premature discontinuation of study intervention 
o 
ICE2: initiation of disallowed therapy or medicine 
All data after ICE1 or ICE2 will be used. 
x 
Summary measure: Proportion of ADA positive participants. 
Additional Secondary 
To evaluate the efficacy of eculizumab 
and characterize TMA by additional 
measures  
x 
Time to Complete TMA Response 
x 
Dialysis requirement status over time 
x 
Observed value and change from baseline in estimated glomerular 
filtration rate (eGFR) at all scheduled visits 
x 
Chronic kidney disease (CKD) stage classified as improved, stable 
(no change), or worsened at all scheduled visits compared to 
baseline 
x 
Observed value and change from baseline in hematologic parameters 
(platelets, LDH, hemoglobin) at all scheduled visits 
x 
Increase in hemoglobin of ≥ 20 g/L from baseline through Week 26 
To characterize the safety profile of 
eculizumab by additional safety measures 
x 
Changes from baseline in vital signs and laboratory parameters at 
scheduled visits 
Abbreviations: ADA = antidrug antibody; aHUS = atypical hemolytic uremic syndrome; C5 = complement 
component 5; CI = confidence interval; ICE = intercurrent event; LDH = lactate dehydrogenase; SAE = serious 
adverse event; TEAE = treatment-emergent adverse event; TMA = thrombotic microangiopathy 
Overall Design 
This is a Phase 3b, open-label, single-arm, multicenter study to evaluate the efficacy and safety 
of eculizumab in participants with aHUS in China. The study will be conducted in participants of 
any age who weigh ≥ 5 kg and who previously have not been treated with complement 
inhibitors. The study consists of an up to 7-day Screening Period and a 26-week Treatment 
Period. An 8-week Safety Follow-up Phone Call will be required only for participants who 
discontinue eculizumab treatment during the study or for participants who will not receive 
continued access to eculizumab after completing study treatment. Approximately 25 eligible 
participants in China will be enrolled. 
After providing informed consent/assent, participants will be screened for eligibility for the study 
during the 7-day Screening Period. If all inclusion criteria and none of the exclusion criteria are 
met, participants will be enrolled and vaccinated against Neisseria meningitidis if not already 
vaccinated within the period of active coverage specified by the vaccine manufacturer. 
Participants who are vaccinated less than 2 weeks prior to receiving the first dose of eculizumab 
will receive treatment with appropriate prophylactic antibiotics until 2 weeks after the 
vaccination. 
During the 26-week Treatment Period, participants will receive eculizumab by intravenous (IV) 
administration based on body weight cohorts presented in Table 1. 
Participants who discontinue eculizumab treatment at any time during the study will have an 
Early Discontinuation from Study (ED) Visit at the time of discontinuation and a Safety 
Follow-up Phone Call 8 weeks after the last dose of eculizumab. 

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Participants who will not receive continued access to eculizumab after completing the 
End-of-Study (EOS) Visit will also have an 8-week Safety Follow-up Phone Call. 
Participants who complete study treatment and will receive continued access to eculizumab after 
the study will not have an 8-week Safety Follow-up Phone Call. 
Clinical measures and laboratory tests will be performed to assess safety, clinical, and 
biochemical parameters associated with aHUS. 
Disclosure Statement: This is an open-label, single-arm, treatment study. 
Number of Participants: Approximately 25 participants will be enrolled and treated. 
Note: “Enrolled” means a participant’s agreement to participate in a clinical study following 
completion of the informed consent/assent process and satisfying inclusion/exclusion criteria. 
Potential participants who are screened for the purpose of determining eligibility for the study, 
but do not participate in the study, are not considered enrolled, unless otherwise specified by the 
protocol. 
Intervention Groups and Duration: 
Eculizumab will be administered by IV infusion according to body weight as described in 
Table 1. 
Table 1: 
Eculizumab Induction and Maintenance Dosing by Weight Cohorta 
Body Weight 
Induction 
Maintenance 
≥ 40 kg 
900 mg weekly × 4 doses 
1200 mg at Day 29; then 1200 mg every 2 weeks 
30 to <40 kg 
600 mg weekly × 2 doses 
900 mg at Day 15; then 900 mg every 2 weeks 
20 to < 30 kg 
600 mg weekly × 2 doses 
600 mg at Day 15; then 600 mg every 2 weeks 
10 to < 20 kg 
600 mg weekly × 1 dose 
300 mg at Day 8; then 300 mg every 2 weeks 
5 to < 10 kg  
300 mg weekly × 1 dose 
300 mg at Day 8; then 300 mg every 3 weeks 
a Participants will be weighed at each study visit as eculizumab dosing will be based on the weight assessment. 
The total duration of study participation for each participant will be up to 35 weeks, including 
the Screening Period (up to 7 days), Treatment Period (26 weeks), and Safety Follow-up Phone 
Call (8 weeks). 
Data Monitoring Committee: No.

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1.2.
Schema
Figure 1:
ECU-aHUS-302 Study Design Schematic
a The Safety Follow-up Phone Call is required for any participant who discontinues eculizumab early or for any participant who 
will not receive continued access to eculizumab after completing study treatment.

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1.3. 
Schedule of Activities 
Table 2: 
Schedule of Activities: Screening and Treatment Period, Weight Cohorts ≥ 40 kg, 30 to < 40 kg, and 20 to 
< 30 kg 
Study Period 
Screening 
Treatment Perioda 
Notes 
Study Day 
Visit Window (days) 
-7 to -1 
1 
8 
± 1 
15 
± 1 
22 
± 1 
29 
± 1 
43 
± 2 
57 
± 2 
71 
± 2 
85 
± 2 
99 
± 2 
End of Week 
-1 
Day 1 
1 
2 
3 
4 
6 
8 
10 
12 
14 
General Assessments/Procedures 
Informed consent/assent 
X 
 
 
 
 
 
 
 
 
 
 
Refer to Section 8.11.1. 
Inclusion/exclusion 
X 
X 
 
 
 
 
 
 
 
 
 
Refer to Section 8.11.3. 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
Refer to Section 8.11.2. 
Medical and aHUS history 
X 
 
 
 
 
 
 
 
 
 
 
Refer to Section 8.11.4. 
Prior medications 
X 
 
 
 
 
 
 
 
 
 
 
Refer to Section 8.11.5. 
Weight 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Participants must be weighed prior to dosing 
as eculizumab dosing will be based on the 
weight assessment at each visit. 
Participant will not need to be weighed at 
each study visit if eculizumab is 
permanently discontinued.  
Heightb 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Confirmation or administration 
of meningococcal vaccination 
X 
 
 
 
 
 
 
 
 
 
 
Participants must be vaccinated against 
meningococcal infection and revaccinated 
during the study if needed (Section 6.5.3). 
Hib and Streptococcus 
pneumoniae vaccination 
X 
 
 
 
 
 
 
 
 
 
 
For pediatric participants only. Refer to 
Section 6.5.3. 
HIV test 
X 
 
 
 
 
 
 
 
 
 
 
Test includes HIV-1 and HIV-2. Refer to 
Section 8.2.4. 
Direct Coombs testc 
X 
 
 
 
 
 
 
 
 
 
 
Refer to Section 8.2.4. 
ADAMTS13 test 
X 
 
 
 
 
 
 
 
 
 
 
Refer to Section 8.2.4. 
ST-HUS test 
X 
 
 
 
 
 
 
 
 
 
 
Refer to Section 8.2.4. 
Pregnancy testd 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
Female participants of childbearing potential 
only (Section 8.2.5). 
Follicle-stimulating hormone 
X 
 
 
 
 
 
 
 
 
 
 
Postmenopausal females only (Section 8.2.4 
and Section 10.4.1). 
Safety and Efficacy Assessments 
Full physical examination 
X 
 
 
 
 
 
 
 
 
 
 
Refer to Section 8.2.1. 
Abbreviated physical 
examination 
 
X 
 
 
X 
 
X 
 
X 
 
X 
Refer to Section 8.2.1. 

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Table 2: 
Schedule of Activities: Screening and Treatment Period, Weight Cohorts ≥ 40 kg, 30 to < 40 kg, and 20 to 
< 30 kg 
Study Period 
Screening 
Treatment Perioda 
Notes 
Study Day 
Visit Window (days) 
-7 to -1 
1 
8 
± 1 
15 
± 1 
22 
± 1 
29 
± 1 
43 
± 2 
57 
± 2 
71 
± 2 
85 
± 2 
99 
± 2 
End of Week 
-1 
Day 1 
1 
2 
3 
4 
6 
8 
10 
12 
14 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Refer to Section 8.2.2. 
ECG 
X 
 
 
 
 
 
 
 
 
 
 
Refer to Section 8.2.3. 
Chemistry 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
Clinical laboratory measurements will be 
collected predose on dosing days and not 
from a heparinized line. Refer to 
Section 8.2.4. 
Dialysis requirement status 
X 
Continuous monitoring 
Refer to Section 8.1.2. 
Hematology including 
coagulation 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
Clinical laboratory measurements will be 
collected predose on dosing days and not 
from a heparinized line. Refer to 
Section 8.2.4. 
Urinalysis and urine chemistry 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
Refer to Section 8.2.4. 
Participant Safety Carde 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Refer to Section 8.2.6. 
Concomitant medications 
 
Continuous monitoring 
Refer to Section 8.11.5. 
Adverse events 
 
Continuous monitoring 
Refer to Section 8.3. 
PK/PD/ADA Assessments 
PK/PD samplingf 
 
B/P 
T/P 
 
 
T/P 
 
 
 
T/P 
 
Refer to Section 8.5 and Section 8.6. 
ADA/NAb blood sample 
 
B 
 
 
 
 
 
 
 
T 
 
Refer to Section 8.9. 
Administration of Study Interventiong 
Eculizumab infusion (mg) 
20 to < 30 kg 
 
600 
600 
600 
NA 
600 
600 
600 
600 
600 
600 
Administered after all other required 
tests/procedures. Refer to Section 8.11.6. 
Eculizumab infusion (mg) 
30 to < 40 kg 
 
600 
600 
900 
NA 
900 
900 
900 
900 
900 
900 
Administered after all other required 
tests/procedures. Refer to Section 8.11.6. 
Eculizumab infusion (mg) 
≥ 40 kg 
 
900 
900 
900 
900 
1200 
1200 
1200 
1200 
1200 
1200 
Administered after all other required 
tests/procedures. Refer to Section 8.11.6. 
a An ED Visit and Safety Follow-up Phone Call are required for any participant who discontinues the study during the Treatment Period. Refer to Table 3 for assessments at the 
ED Visit and Safety Follow-up Phone Call. 
b For adult participants (≥ 18 years of age), height will be collected only at Screening. 
c Eligibility may be determined using results from test carried out as standard of care for the treatment of the current TMA prior to a participant giving informed consent/assent. In 
these cases, informed consent/assent will be provided prior to collecting the data for the study. 
d For female participants of childbearing potential, a serum pregnancy test should be performed at Screening and the last study visit, and at other timepoints as determined by the 
Investigator. A urine pregnancy test should be performed at all other timepoints. 
e Instruct the participant to carry safety card at all times and bring to scheduled visits. 

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f PK/PD baseline (B) and trough (T) samples are to be taken within 90 minutes before eculizumab infusion. Peak (P) samples are to be taken within 90 minutes after completion of 
eculizumab infusion. 
g Based on the result of weight assessment prior to dosing, a participant may be attributed to a different weight cohort from the previous visit due to weight gain or weight loss. 
The schedule of activities from this point on will follow the criteria described in Section 8.11.6. 
Abbreviations: ADA = antidrug antibody; ADAMTS13 = a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; aHUS = atypical hemolytic uremic 
syndrome; B = baseline; ECG = electrocardiogram; ED = early discontinuation from the study; Hib = Haemophilus influenzae type b; HIV = human immunodeficiency virus; 
NA = not applicable; NAb = neutralizing antibody; P = peak; PD = pharmacodynamics; PK = pharmacokinetics; ST-HUS = Shiga toxin-related hemolytic uremic syndrome; 
T = trough; TMA = thrombotic microangiopathy 
 

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Table 3: 
Schedule of Activities: Treatment Period (Continued) to End of Study, Weight Cohorts ≥ 40 kg, 30 to < 40 kg, 
and 20 to < 30 kg 
Study Period or Visit 
Treatment Period 
 
Notes 
Study Day 
Visit Window (days) 
113 
± 2 
127 
± 2 
141 
± 2 
155 
± 2 
169/ 
EOT 
± 2 
183/ 
EOSa 
± 2 
EDb 
Safety Follow-up 
Phone Call/EOSc 
(8 weeks after last 
dose) 
± 3 
 
End of Week 
16 
18 
20 
22 
24 
26 
 
 
General Assessments/Procedures 
Weight 
X 
X 
X 
X 
X 
X 
X 
 
Participants must be weighed prior to 
dosing as eculizumab dosing will be 
based on the weight assessment at 
each visit. Participant will not need to 
be weighed at each study visit if 
eculizumab is permanently 
discontinued. 
Heightd 
X 
X 
X 
X 
X 
X 
X 
 
 
Pregnancy teste 
 
X 
 
X 
 
X 
X 
 
Female participants of childbearing 
potential only (Section 8.2.5). 
Safety and Efficacy Assessments 
Abbreviated physical 
examination 
X 
X 
 
X 
 
X 
X 
 
Refer to Section 8.2.1. 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
 
Refer to Section 8.2.2.  
ECG 
 
 
 
 
 
X 
X 
 
Refer to Section 8.2.3.  
Chemistry 
X 
X 
 
X 
 
X 
X 
 
Clinical laboratory measurements 
will be collected predose on dosing 
days and not from a heparinized line 
(Section 8.2.4). 
Dialysis requirement status 
X 
Continuous monitoring 
 
Refer to Section 8.1.2. 
Hematology including 
coagulation 
X 
X 
 
X 
 
X 
X 
 
Clinical laboratory measurements 
will be collected predose on dosing 
days and not from a heparinized line. 
Refer to Section 8.2.4. 
Urinalysis and urine chemistry 
X 
X 
 
X 
 
X 
X 
 
Refer to Section 8.2.4. 
Review safety cardf 
X 
X 
X 
X 
X 
X 
X 
X 
Refer to Section 8.2.6. 
Concomitant medications 
Continuous monitoring 
X 
X 
Refer to Section 8.11.5. 
Adverse events 
Continuous monitoring 
X 
X 
Refer to Section 8.3. 
PK/PD/ADA Assessments 

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Table 3: 
Schedule of Activities: Treatment Period (Continued) to End of Study, Weight Cohorts ≥ 40 kg, 30 to < 40 kg, 
and 20 to < 30 kg 
Study Period or Visit 
Treatment Period 
 
Notes 
Study Day 
Visit Window (days) 
113 
± 2 
127 
± 2 
141 
± 2 
155 
± 2 
169/ 
EOT 
± 2 
183/ 
EOSa 
± 2 
EDb 
Safety Follow-up 
Phone Call/EOSc 
(8 weeks after last 
dose) 
± 3 
 
End of Week 
16 
18 
20 
22 
24 
26 
 
 
PK/PD samplingg 
 
 
T/P 
 
 
T 
X 
 
Refer to Section 8.5 and Section 8.6. 
PK/PD sample at an ED Visit may be 
collected at any time. 
ADA/NAb blood sample 
 
 
 
 
 
T 
X 
 
Refer to Section 8.9. ADA sample at 
an ED Visit may be collected at any 
time. 
Administration of Study Interventionh 
Eculizumab infusion (mg) 
20 to < 30 kg 
600 
600 
600 
600 
600 
 
 
 
Administered after all other required 
tests/procedures. Refer to 
Section 8.11.6. 
Eculizumab infusion (mg) 
30 to < 40 kg 
900 
900 
900 
900 
900 
 
 
 
Administered after all other required 
tests/procedures. Refer to 
Section 8.11.6. 
Eculizumab infusion (mg) 
≥ 40 kg 
1200 
1200 
1200 
1200 
1200 
 
 
 
Administered after all other required 
tests/procedures. Refer to 
Section 8.11.6. 
Table 3: 
Schedule of Activities: Treatment Period (Continued) to End of Study, Weight Cohorts ≥ 40 kg, 30 to < 40 kg, 
and 20 to < 30 kg 
a For weight cohorts ≥ 40 kg, 30 to < 40 kg, and 20 to < 30 kg, the Day 183 Visit will be the EOS Visit for participants who complete study treatment and who will receive 
continued access to eculizumab after the study. Refer to the Safety Follow-up Phone Call (footnote c) for participants who complete study treatment but who will not receive 
continued access to eculizumab after the study. 
b An ED Visit is required at the time of withdrawal for any participant who discontinues the study during the Treatment Period. Also refer to the Safety Follow-up Phone Call 
(footnote c). 
c The Safety Follow-up Phone Call is required for any participant who discontinues eculizumab early during the Treatment Period; the Safety Follow-up Phone Call will be the 
EOS Visit for participants who discontinue eculizumab early. The Safety Follow-up Phone Call is also required for any participant who has completed the Day 183 Visit but who 
will not receive continued access to eculizumab after the study; the Safety Follow-up Phone Call will be the EOS Visit for these participants. The Safety Follow-up Phone Call 
should occur 8 weeks after the last dose of eculizumab. Other means of verbal communication, such as videoconferencing, are acceptable for the Safety Follow-up Phone Call. 
d For adult participants (≥ 18 years of age), height will be collected only at Screening. 
e For female participants of childbearing potential, a serum pregnancy test should be performed at Screening and the last study visit, and at other timepoints as determined by the 
Investigator. A urine pregnancy test should be performed at all other timepoints. 

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f Instruct the participant to carry safety card at all times and bring to scheduled visits. 
g PK/PD Trough (T) samples are to be taken within 90 minutes before eculizumab infusion. Peak (P) samples are to be taken within 90 minutes after completion of eculizumab 
infusion. 
h Based on the result of weight assessment prior to dosing, a participant may be attributed to a different weight cohort from the previous visit due to weight gain or weight loss. 
The schedule of activities from this point on will follow the criteria described in Section 8.11.6. 
Abbreviations: ADA = antidrug antibody; ECG = electrocardiogram; ED = early discontinuation from the study; EOS = end of study; EOT = end of treatment; NAb = neutralizing 
antibody; P = peak; PD = pharmacodynamics; PK = pharmacokinetics; T = trough 
 
 

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Table 4: 
Schedule of Activities: Screening and Treatment Period, Weight Cohort 10 to < 20 kg 
Study Period 
Screening 
Treatment Perioda 
Notes 
Study Day 
Visit Window (days) 
-7 to -1 
1 
8 
± 1 
22 
± 2 
36 
± 2 
50 
± 2 
64 
± 2 
78 
± 2 
92 
± 2 
106 
± 2 
120 
± 2 
End of Week 
-1 
Day 1 
1 
3 
5 
7 
9 
11 
13 
15 
17 
General Assessments/Procedures 
Informed consent/assent 
X 
 
 
 
 
 
 
 
 
 
 
Refer to Section 8.11.1. 
Inclusion/exclusion 
X 
X 
 
 
 
 
 
 
 
 
 
Refer to Section 8.11.3. 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
Refer to Section 8.11.2. 
Medical and aHUS history 
X 
 
 
 
 
 
 
 
 
 
 
Refer to Section 8.11.4. 
Prior medications 
X 
 
 
 
 
 
 
 
 
 
 
Refer to Section 8.11.5. 
Weight 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Participants must be weighed prior to dosing 
as eculizumab dosing will be based on the 
weight assessment at each visit. Participant 
will not need to be weighed at each study 
visit if eculizumab is permanently 
discontinued. 
Heightb 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Confirmation or administration 
of meningococcal vaccination 
X 
 
 
 
 
 
 
 
 
 
 
Participants must be vaccinated against 
meningococcal infection and revaccinated 
during the study if needed (Section 6.5.3). 
Hib and Streptococcus 
pneumoniae vaccination 
X 
 
 
 
 
 
 
 
 
 
 
For pediatric participants only. Refer to 
Section 6.5.3. 
HIV test 
X 
 
 
 
 
 
 
 
 
 
 
Test includes HIV-1 and HIV-2. Refer to 
Section 8.2.4. 
Direct Coombs testc 
X 
 
 
 
 
 
 
 
 
 
 
Refer to Section 8.2.4. 
ADAMTS13 test 
X 
 
 
 
 
 
 
 
 
 
 
Refer to Section 8.2.4. 
ST-HUS test 
X 
 
 
 
 
 
 
 
 
 
 
Refer to Section 8.2.4. 
Pregnancy testd 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
Female participants of childbearing 
potential only (Section 8.2.5). 
Follicle-stimulating hormone 
X 
 
 
 
 
 
 
 
 
 
 
Postmenopausal females only (Section 8.2.4 
and Section 10.4.1). 
Safety and Efficacy Assessments 
Full physical examination 
X 
 
 
 
 
 
 
 
 
 
 
Refer to Section 8.2.1. 
Abbreviated physical 
examination 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Refer to Section 8.2.1. 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Refer to Section 8.2.2  
ECG 
X 
 
 
 
 
 
 
 
 
 
 
Refer to Section 8.2.3  

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Table 4: 
Schedule of Activities: Screening and Treatment Period, Weight Cohort 10 to < 20 kg 
Study Period 
Screening 
Treatment Perioda 
Notes 
Study Day 
Visit Window (days) 
-7 to -1 
1 
8 
± 1 
22 
± 2 
36 
± 2 
50 
± 2 
64 
± 2 
78 
± 2 
92 
± 2 
106 
± 2 
120 
± 2 
End of Week 
-1 
Day 1 
1 
3 
5 
7 
9 
11 
13 
15 
17 
Chemistry 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
Clinical laboratory measurements will be 
collected predose on dosing days and not 
from a heparinized line (Section 8.2.4). 
Dialysis requirement status 
Continuous monitoring 
Refer to Section 8.1.2. 
Hematology including 
coagulation 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
Clinical laboratory measurements will be 
collected predose on dosing days and not 
from a heparinized line. Refer to 
Section 8.2.4. 
Urinalysis and urine chemistry 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
Refer to Section 8.2.4. 
Participant Safety Carde 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Refer to Section 8.2.6. 
Concomitant medications 
 
Continuous monitoring 
Refer to Section 8.11.5. 
Adverse events 
 
Continuous monitoring 
Refer to Section 8.3. 
PK/PD/ADA Assessments 
PK/PD samplingf 
 
B/P 
T/P 
 
T/P 
 
 
 
T/P 
 
 
Refer to Section 8.5 and Section 8.6. 
ADA/NAb blood sample 
 
B 
 
 
 
 
 
 
T 
 
 
Refer to Section 8.9. 
Administration of Study Interventiong 
Eculizumab infusion (mg) 
10 to < 20 kg 
 
600 
300 
300 
300 
300 
300 
300 
300 
300 
300 
Administered after all other required 
tests/procedures. Refer to Section 8.11.6. 
a An ED Visit and Safety Follow-up Phone Call are required for any participant who discontinues the study during the Treatment Period. Refer to Table 5 for assessments at the 
ED Visit and Safety Follow-up Phone Call. 
b For adult participants (≥ 18 years of age), height will be collected only at Screening. 
c Eligibility may be determined using results from test carried out as standard of care for the treatment of the current TMA prior to a participant giving informed consent/assent. In 
these cases, informed consent/assent will be provided prior to collecting the data for the study. 
d For female participants of childbearing potential, a serum pregnancy test should be performed at Screening and the last study visit, and at other timepoints as determined by the 
Investigator. A urine pregnancy test should be performed at all other timepoints. 
e Instruct the participant to carry safety card at all times and bring to scheduled visits. 
f PK/PD baseline (B) and trough (T) samples are to be taken within 90 minutes before eculizumab infusion. Peak (P) samples are to be taken within 90 minutes after completion of 
eculizumab infusion. 
g Based on the result of weight assessment prior to dosing, a participant may be attributed to a different weight cohort from the previous visit due to weight gain or weight loss. 
The schedule of activities from this point on will follow the criteria described in Section 8.11.6. 
Abbreviations: ADA = antidrug antibody; ADAMTS13 = a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; aHUS = atypical hemolytic uremic 
syndrome; B = baseline; ECG = electrocardiogram; ED = early discontinuation from the study; Hib = Haemophilus influenzae type b; HIV = human immunodeficiency virus; 
NAb = neutralizing antibody; P = peak; PD = pharmacodynamics; PK = pharmacokinetics; ST-HUS = Shiga toxin-related hemolytic uremic syndrome; T = trough; 
TMA = thrombotic microangiopathy 
 

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Table 5: 
Schedule of Activities: Treatment Period (Continued) to End of Study, Weight Cohort 10 to < 20 kg 
Study Period or Visit 
Treatment Period 
 
Notes 
Study Day 
Visit Window (days) 
134 
± 2 
148 
± 2 
162 
± 2 
176/ 
EOT 
± 2 
190/ 
EOSa 
± 2 
EDb 
Safety 
Follow-up 
Phone 
Call/EOSc 
(8 weeks after 
last dose)  
± 3 
End of Week 
19 
21 
23 
25 
27 
 
 
General Assessments/Procedures 
Weight 
X 
X 
X 
X 
X 
X 
 
Participants must be weighed prior to 
dosing as eculizumab dosing will be 
based on the weight assessment at 
each visit. Participant will not need to 
be weighed at each study visit if 
eculizumab is permanently 
discontinued. 
Heightd 
X 
X 
X 
X 
X 
X 
 
 
Pregnancy teste 
X 
 
X 
 
X 
X 
 
Female participants of childbearing 
potential only (Section 8.2.5). 
Safety and Efficacy Assessments 
Abbreviated physical examination 
X 
 
X 
 
X 
X 
 
Refer to Section 8.2.1. 
Vital signs 
X 
X 
X 
X 
X 
X 
 
Refer to Section 8.2.2. 
ECG 
 
 
 
 
X 
X 
 
Refer to Section 8.2.3. 
Chemistry 
X 
 
X 
 
X 
X 
 
Clinical laboratory measurements 
will be collected predose on dosing 
days and not from a heparinized line 
(Section 8.2.4). 
Dialysis requirement status 
Continuous monitoring 
 
Refer to Section 8.1.2. 
Hematology including coagulation 
X 
 
X 
 
X 
X 
 
Clinical laboratory measurements 
will be collected predose on dosing 
days and not from a heparinized line. 
Refer to Section 8.2.4. 
Urinalysis and urine chemistry 
X 
 
X 
 
X 
X 
 
Refer to Section 8.2.4. 
Review safety cardf 
X 
X 
X 
X 
X 
X 
X 
Refer to Section 8.2.6. 
Concomitant medications 
Continuous monitoring 
X 
X 
Refer to Section 8.11.5. 
Adverse events 
Continuous monitoring 
X 
X 
Refer to Section 8.3. 
PK/PD/ADA Assessments 

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Table 5: 
Schedule of Activities: Treatment Period (Continued) to End of Study, Weight Cohort 10 to < 20 kg 
Study Period or Visit 
Treatment Period 
 
Notes 
Study Day 
Visit Window (days) 
134 
± 2 
148 
± 2 
162 
± 2 
176/ 
EOT 
± 2 
190/ 
EOSa 
± 2 
EDb 
Safety 
Follow-up 
Phone 
Call/EOSc 
(8 weeks after 
last dose)  
± 3 
End of Week 
19 
21 
23 
25 
27 
 
 
PK/PD samplingg 
 
T/P 
 
T 
 
X 
 
Refer to Section 8.5 and Section 8.6. 
PK/PD sample at an ED Visit may be 
collected at any time. 
ADA/NAb blood sample 
 
 
 
T 
 
X 
 
Refer to Section 8.9. ADA sample at 
an ED Visit may be collected at any 
time. 
Administration of Study Interventionh 
Eculizumab infusion (mg) 
10 to < 20 kg 
300 
300 
300 
300 
 
 
 
Administered after all other required 
tests/procedures. Refer to 
Section 8.11.6. 
a For weight cohort 10 to < 20 kg, the Day 190 Visit will be the EOS Visit for participants who complete study treatment and who will receive continued access to eculizumab 
after the study. Refer to the Safety Follow-up Phone Call (footnote c) for participants who complete study treatment but who will not receive continued access to eculizumab 
after the study. 
b An ED Visit is required at the time of withdrawal for any participant who discontinues the study during the Treatment Period. Also refer to the Safety Follow-up Phone Call 
(footnote c). 
c The Safety Follow-up Phone Call is required for any participant who discontinues eculizumab early during the Treatment Period; the Safety Follow-up Phone Call will be the 
EOS Visit for participants who discontinue eculizumab early. The Safety Follow-up Phone Call is also required for any participant who has completed the Day 190 Visit but who 
will not receive continued access to eculizumab after the study; the Safety Follow-up Phone Call will be the EOS Visit for these participants. The Safety Follow-up Phone Call 
should occur 8 weeks after the last dose of eculizumab. Other means of verbal communication, such as videoconferencing, are acceptable for the Safety Follow-up Phone Call. 
d For adult participants (≥ 18 years of age), height will be collected only at Screening. 
e For female participants of childbearing potential, a serum pregnancy test should be performed at Screening and the last study visit, and at other timepoints as determined by the 
Investigator. A urine pregnancy test should be performed at all other timepoints. 
Table 5: 
Schedule of Activities: Treatment Period (Continued) to End of Study, Weight Cohort 10 to < 20 kg 
f Instruct the participant to carry safety card at all times and bring to scheduled visits. 
g PK/PD Trough (T) samples are to be taken within 90 minutes before eculizumab infusion. Peak (P) samples are to be taken within 90 minutes after completion of eculizumab 
infusion. 
h Based on the result of weight assessment prior to dosing, a participant may be attributed to a different weight cohort from the previous visit due to weight gain or weight loss. 
The schedule of activities from this point on will follow the criteria described in Section 8.11.6. 
Abbreviations: ADA = antidrug antibody; ECG = electrocardiogram; ED = early discontinuation from the study; EOS = end of study; EOT = end of treatment; NAb = neutralizing 
antibody; P = peak; PD = pharmacodynamics; PK = pharmacokinetics; T = trough 

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Table 6: 
Schedule of Activities: Screening, Treatment Period, and End of Study, Weight Cohort 5 to < 10 kg 
Study Period or Visit 
Screening 
Treatment Period 
 
Notes 
Study Day 
Visit Window (days) 
-7 to -1 
1 
8 
± 1 
29 
± 2 
50 
± 2 
71 
± 2 
92 
± 2 
113 
± 2 
134 
± 2 
155 
± 2 
176/ 
EOT 
± 2 
197/ 
EOSa 
± 2 
EDb 
Safety 
Follow-up 
Phone 
Call/EOSc 
(8 weeks 
after last 
dose) 
± 3 
End of Week 
-1 
Day 1 
1 
4 
7 
10 
13 
16 
19 
22 
25 
28 
 
 
General Assessments/Procedures 
Informed consent/assent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Refer to 
Section 8.11.1. 
Inclusion/exclusion 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Refer to 
Section 8.11.3. 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Refer to 
Section 8.11.2. 
Medical and aHUS history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Refer to 
Section 8.11.4. 
Prior medications 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Refer to 
Section 8.11.5. 
Weight 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Participants must be 
weighed prior to 
dosing as eculizumab 
dosing will be based 
on the weight 
assessment at each 
visit. Participant will 
not need to be 
weighed at each 
study visit if 
eculizumab is 
permanently 
discontinued. 
Heightd 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Confirmation or 
administration of 
meningococcal 
vaccination 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Participants must be 
vaccinated against 
meningococcal 
infection and 

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Table 6: 
Schedule of Activities: Screening, Treatment Period, and End of Study, Weight Cohort 5 to < 10 kg 
Study Period or Visit 
Screening 
Treatment Period 
 
Notes 
Study Day 
Visit Window (days) 
-7 to -1 
1 
8 
± 1 
29 
± 2 
50 
± 2 
71 
± 2 
92 
± 2 
113 
± 2 
134 
± 2 
155 
± 2 
176/ 
EOT 
± 2 
197/ 
EOSa 
± 2 
EDb 
Safety 
Follow-up 
Phone 
Call/EOSc 
(8 weeks 
after last 
dose) 
± 3 
End of Week 
-1 
Day 1 
1 
4 
7 
10 
13 
16 
19 
22 
25 
28 
 
 
revaccinated during 
the study if needed 
(Section 6.5.3). 
Hib and Streptococcus 
pneumoniae vaccination 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
For pediatric 
participants only. 
Refer to 
Section 6.5.3. 
HIV test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Test includes HIV-1 
and HIV-2. Refer to 
Section 8.2.4. 
Direct Coombs teste 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Refer to 
Section 8.2.4. 
ADAMTS13 test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Refer to 
Section 8.2.4. 
ST-HUS test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Refer to 
Section 8.2.4. 
Pregnancy testf 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Female participants 
of childbearing 
potential only 
(Section 8.2.5). 
Follicle-stimulating 
hormone 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Postmenopausal 
females only 
(Section 8.2.4 and 
Section 10.4.1). 
Safety and Efficacy Assessments 
Full physical examination 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Refer to 
Section 8.2.1. 
Abbreviated physical 
examination 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Refer to 
Section 8.2.1. 

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Table 6: 
Schedule of Activities: Screening, Treatment Period, and End of Study, Weight Cohort 5 to < 10 kg 
Study Period or Visit 
Screening 
Treatment Period 
 
Notes 
Study Day 
Visit Window (days) 
-7 to -1 
1 
8 
± 1 
29 
± 2 
50 
± 2 
71 
± 2 
92 
± 2 
113 
± 2 
134 
± 2 
155 
± 2 
176/ 
EOT 
± 2 
197/ 
EOSa 
± 2 
EDb 
Safety 
Follow-up 
Phone 
Call/EOSc 
(8 weeks 
after last 
dose) 
± 3 
End of Week 
-1 
Day 1 
1 
4 
7 
10 
13 
16 
19 
22 
25 
28 
 
 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Refer to 
Section 8.2.2  
ECG 
X 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
Refer to 
Section 8.2.3  
Chemistry 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Clinical laboratory 
measurements will be 
collected predose on 
dosing days and not 
from a heparinized 
line (Section 8.2.4). 
Dialysis requirement 
status 
Continuous monitoring 
 
Refer to 
Section 8.1.2. 
Hematology including 
coagulation 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Clinical laboratory 
measurements will be 
collected predose on 
dosing days and not 
from a heparinized 
line. Refer to 
Section 8.2.4. 
Urinalysis and urine 
chemistry 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Refer to 
Section 8.2.4. 
Participant Safety Cardg 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Refer to 
Section 8.2.6. 
Concomitant medications 
 
Continuous monitoring 
X 
X 
Refer to 
Section 8.11.5. 
Adverse events 
 
Continuous monitoring 
X 
X 
Refer to Section 8.3. 
PK/PD/ADA Assessments 
PK/PD blood samplesh 
 
B/P 
 
 
 
T/P 
 
 
 
T/P 
 
 
X 
 
Refer to Section 8.5 
and Section 8.6. 

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Table 6: 
Schedule of Activities: Screening, Treatment Period, and End of Study, Weight Cohort 5 to < 10 kg 
Study Period or Visit 
Screening 
Treatment Period 
 
Notes 
Study Day 
Visit Window (days) 
-7 to -1 
1 
8 
± 1 
29 
± 2 
50 
± 2 
71 
± 2 
92 
± 2 
113 
± 2 
134 
± 2 
155 
± 2 
176/ 
EOT 
± 2 
197/ 
EOSa 
± 2 
EDb 
Safety 
Follow-up 
Phone 
Call/EOSc 
(8 weeks 
after last 
dose) 
± 3 
End of Week 
-1 
Day 1 
1 
4 
7 
10 
13 
16 
19 
22 
25 
28 
 
 
PK/PD sample at an 
ED Visit may be 
collected at any time. 
ADA/NAb blood sample 
 
B 
 
 
 
 
 
 
 
T 
 
 
X 
 
Refer to Section 8.9. 
ADA sample at an 
ED Visit may be 
collected at any time. 
Administration of Study Interventioni 
Eculizumab infusion (mg) 
 
300 
300 
300 
300 
300 
300 
300 
300 
300 
300 
 
 
 
Administered after 
all other required 
tests/procedures. 
Refer to 
Section 8.11.6. 
a For weight cohort 5 to < 10 kg, the Day 197 Visit will be the EOS Visit for participants who complete study treatment and who will receive continued access to eculizumab after 
the study. Refer to the Safety Follow-up Phone Call (footnote c) for participants who complete study treatment but who will not receive continued access to eculizumab after the 
study. 
b An ED Visit is required at the time of withdrawal for any participant who discontinues the study during the Treatment Period. Also refer to the Safety Follow-up Phone Call 
(footnote c). 
c The Safety Follow-up Phone Call is required for any participant who discontinues eculizumab early during the Treatment Period; the Safety Follow-up Phone Call will be the 
EOS Visit for participants who discontinue eculizumab early. The Safety Follow-up Phone Call is also required for any participant who has completed the Day 197 Visit but who 
will not receive continued access to eculizumab after study participation; the Safety Follow-up Phone Call will be the EOS Visit for these participants. The Safety Follow-up 
Phone Call should occur 8 weeks after the last dose of eculizumab. Other means of verbal communication, such as videoconferencing, are acceptable for the Safety Follow-up 
Phone Call. 
d For adult participants (≥ 18 years of age), height will be collected only at Screening. 
Table 6: 
Schedule of Activities: Screening, Treatment Period, and End of Study, Weight Cohort 5 to < 10 kg 
e Eligibility may be determined using results from test carried out as standard of care for the treatment of the current TMA prior to a participant giving informed consent/assent. In 
these cases, informed consent/assent will be provided prior to collecting the data for the study. 

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f For female participants of childbearing potential, a serum pregnancy test should be performed at Screening and the last study visit, and at other timepoints as determined by the 
Investigator. A urine pregnancy test should be performed at all other timepoints. 
g Instruct the participant to carry the safety card at all times and bring to scheduled visits. 
h PK/PD baseline (B) and trough (T) samples are to be taken within 90 minutes before eculizumab infusion. Peak (P) samples are to be taken within 90 minutes after completion of 
eculizumab infusion. 
i Based on the result of weight assessment prior to dosing, a participant may be attributed to a different weight cohort from the previous visit due to weight gain or weight loss. 
The schedule of activities from this point on will follow the criteria described in Section 8.11.6. 
Abbreviations: ADA = antidrug antibody; ADAMTS13 = a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; aHUS = atypical hemolytic uremic 
syndrome; B = baseline; ECG = electrocardiogram; ED = early discontinuation from the study; EOS = end of study; EOT = end of treatment; Hib = Haemophilus influenzae type 
b; HIV = human immunodeficiency virus; NAb = neutralizing antibody; P = peak; PD = pharmacodynamics; PK = pharmacokinetics; ST-HUS = Shiga toxin-related hemolytic 
uremic syndrome; T = trough; TMA = thrombotic microangiopathy 

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2. 
INTRODUCTION 
2.1. 
Study Rationale 
Eculizumab has been approved in China for the treatment of aHUS in children and adult patients. 
The therapeutic efficacy and safety of eculizumab has been demonstrated in 3 global pivotal 
clinical trials conducted at study sites outside of China for registration and has since been 
supported by subsequent postmarketing evidence (Socié, 2019). This postapproval study, agreed 
as a condition of approval in China, will be conducted in Chinese participants with aHUS being 
treated in China. 
In addition to safety and efficacy evaluation, the study is intended to characterize the population 
pharmacokinetic (PK), pharmacodynamic (PD), and immunogenicity of eculizumab in this 
patient population. Drug safety information will be collected continuously to support the safety 
profile. 
2.2. 
Background 
aHUS is TMA most often caused by mutations in genes encoding proteins involved in the 
alternative pathway of complement (APC) or by autoantibodies against APC regulatory proteins 
(Noris, 2010), although pathologic gene mutations or autoantibodies are only identified in at 
most 50% to 60% of patients (Fakhouri, 2017; Schaefer, 2018). Patients with aHUS are at risk 
for life-threatening manifestations of disease resulting from endothelial damage, including 
thrombocytopenia, intravascular hemolysis, acute renal failure, and extrarenal tissue damage. 
Importantly, approximately 20% of patients experience extrarenal manifestations of disease, 
including central nervous system, cardiac, gastrointestinal, distal extremity, and severe systemic 
organ involvement (Brodsky, 2015; Loirat, 2011). 
aHUS is a rare and life-threatening disease with an annual incidence in the United States and 
European Union of 1 to 2 cases per million (Constantinescu, 2004; Salvadori, 2013). 
TMA occurs in patients with aHUS because of dysregulation of the APC involving C5. Chronic, 
uncontrolled terminal complement activation, specifically, activation of C5 and dysregulation of 
complement activity, is central to the pathogenesis of aHUS and the devastating manifestations 
of this disease. As a result, the targeted blockade of C5, with selective inhibition of generation of 
C5a and terminal complement complex (C5b-9), represents an important therapeutic mechanism 
of treatment. 
Eculizumab is a humanized mAb that specifically binds to C5 and is the standard of care 
treatment for aHUS. Before the availability of eculizumab, mortality rates among patients with 
aHUS were as high as 15% during the acute progressing phase of the disease (Noris, 2010; 
Sellier-Leclerc, 2007). Up to 50% of patients progressed to end-stage kidney disease (ESKD), 
often within a year of disease onset, and required dialysis or kidney transplant to sustain life. 
Eculizumab has no known off-target interactions with other proteins in vitro or in vivo. In 
addition, eculizumab is predicted to be effectorless, having no detectable binding to complement 
C1q or most Fcγ receptors (FcγR I, IIb/c IIIa, IIIb) and more than 10-fold weaker binding than 
an immunoglobulin G1 (IgG1) isotype to FcγR IIa. Upon binding to the complement protein C5, 

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eculizumab blocks cleavage to C5a and C5b by C5 convertase, which prevents generation of 
C5b-9. These attributes underlie the established safety and therapeutic efficacy profile of 
eculizumab as demonstrated in the clinical studies and supported by subsequent postmarketing 
experiences. 
2.3. 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events (AEs) of eculizumab may be found in the Soliris Package Insert. 
2.3.1. 
Risk Assessment 
Table 7: 
Risk Assessment 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for 
Risk 
Mitigation Strategy 
Identified Risks 
Meningococcal infection 
The use of eculizumab is known to 
increase the patient’s susceptibility 
to Neisseria meningitidis infection. 
Participants must be vaccinated 
against all available serotypes of 
N meningitidis (A, C, Y, W135, and B 
if available). Prophylactic antibiotics 
will be required for participants (if 
initiated on eculizumab less than 
2 weeks after the start of vaccination 
series). Each participant will be 
provided with a Participant Safety 
Card with signs and symptoms of 
meningococcal infection, instructions 
on when to contact a healthcare 
provider, and relevant contact 
information. The Participant Safety 
Card will be reviewed at each visit 
(Schedule of Activities, Section 1.3). 
Other infections 
Children treated with eculizumab 
may be at increased risk of 
developing serious infections due to 
Streptococcus pneumoniae and 
Haemophilus influenzae type b 
(Hib). 
Participants < 18 years of age must 
also be vaccinated against Hib and 
S pneumoniae according to national 
and local vaccination schedule 
guidelines, prior to, or at the time of, 
receiving the first dose of eculizumab. 
Infusion-related reaction 
As with all therapeutic proteins, 
administration of eculizumab may 
result in infusion reactions, 
including anaphylaxis or other 
hypersensitivity reactions. Most 
infusion reactions that occurred in 
patients receiving eculizumab were 
nonserious and did not required 
discontinuation of eculizumab. 
Participants with known 
hypersensitivity to eculizumab, 
murine proteins, or to any of the 
excipients will be excluded. Treatment 
with eculizumab will be discontinued 
in participants who experience serious 
hypersensitivity reactions (see 
Section 7). 
Potential Risks 
Immunogenicity 
Therapeutic proteins, including 
humanized monoclonal antibodies 
like eculizumab, may be associated 
with immunogenicity responses. 
Infrequent antibody responses have 
Presence of antidrug antibodies will 
be assessed. Blood samples will be 
collected to test for presence and titer 
of antidrug antibodies to eculizumab 
in serum prior to study intervention 

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Table 7: 
Risk Assessment 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for 
Risk 
Mitigation Strategy 
been detected in eculizumab-treated 
patients across all clinical studies. 
In paroxysmal nocturnal 
hemoglobinuria placebo-controlled 
studies, low antibody responses 
have been reported with a 
frequency (3.4%) similar to that of 
placebo (4.8%). 
administration as indicated in the 
Schedule of Activities (Section 1.3). 
2.3.1.1. 
Coronavirus Disease 2019 
The coronavirus disease 2019 (COVID-19) pandemic is active in many countries at the time of 
this original protocol. Given this unique circumstance, specific consideration has been given to 
the risks and benefits of the study as they relate to COVID-19 (see Section 10.5). 
2.3.2. 
Benefit Assessment 
Eculizumab is a recombinant, humanized mAb that binds to complement protein C5 and delivers 
rapid, sustained, and specific inhibition of C5 activation and the terminal complement cascade. 
Eculizumab has been shown to be an effective therapy for the treatment of aHUS. 
Five single-arm studies (4 prospective studies: C08-002A/B [NCT00844545 and 
NCT00844844], C08-003A/B [NCT00838513 and NCT00844428], C10-003 [NCT01193348], 
and C10-004 [NCT01194973] and 1 retrospective study C09-001r [NCT01770951]) evaluated 
the safety and efficacy of eculizumab for the treatment of aHUS. Reduction in terminal 
complement activity was observed after commencement of eculizumab. Eculizumab reduced 
signs of complement-mediated TMA activity, as shown by an increase in mean platelet counts 
from baseline. 
2.3.3. 
Overall Benefit: Risk Conclusion 
Eculizumab has a cumulative patient-year exposure of 62341 at the time of this original protocol 
and has been well tolerated. Considering the measures taken to minimize risk to participants who 
will take part in this study, the potential risks identified in association with eculizumab are 
balanced by the anticipated benefits that may be afforded to participants with aHUS. In addition, 
eculizumab remains the standard of care for aHUS. 

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3. 
OBJECTIVES, ESTIMANDS, AND ENDPOINTS 
Mapping of objectives to estimands and endpoints is provided in Table 8. 
Table 8: 
Mapping of Objectives to Estimands and Endpoints 
Objectives 
Estimands and Endpoints 
Primary 
To assess the efficacy of eculizumab in 
the treatment of participants with aHUS 
x 
Population: Chinese participants with aHUS who are eligible to 
be enrolled in the study, based on the inclusion and exclusion 
criteria. 
x 
Variable: Complete TMA Response during the 26-week 
Treatment Period (Section 3.1). 
x 
Treatment: Eculizumab 
x 
ICE: 
o 
ICE1: premature discontinuation of study intervention 
o 
ICE2: initiation of disallowed therapy or medicine 
All participants who meet response criteria after ICE1 or 
ICE2 will be considered as nonresponders thereafter. 
x 
Summary measure: The proportion of complete TMA 
responders overall along with 95% CIs. 
Secondary 
To characterize the safety and tolerability 
of eculizumab in participants with aHUS 
x 
Population: Chinese participants with aHUS who are eligible to 
be enrolled in the study, based on the inclusion and exclusion 
criteria. 
x 
Variable: Incidence of TEAEs and SAEs (Section 3.2). 
x 
Treatment: Eculizumab 
x 
ICE: 
o 
ICE1: premature discontinuation of study intervention; 
o 
ICE2: initiation of disallowed therapy or medicine 
All data after ICE1 or ICE2 will be included. 
x 
Summary measure: Number and percentage of participants with 
TEAEs and SAEs and number of events by System Organ Class 
and Preferred Term. 
To characterize the pharmacokinetics of 
eculizumab in participants with aHUS 
x 
Population: Chinese participants with aHUS who are eligible to 
be enrolled in the study, based on the inclusion and exclusion 
criteria. 
x 
Variable: Serum eculizumab concentrations over time 
(Section 3.2). 
x 
Treatment: Eculizumab 
x 
ICE: 
o 
ICE1: premature discontinuation of study intervention 
o 
ICE2: initiation of disallowed therapy or medicine 
All data after ICE1 or ICE2 will be used. 
x 
Summary measure: Mean serum eculizumab concentrations at 
all scheduled visits. 

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Table 8: 
Mapping of Objectives to Estimands and Endpoints 
Objectives 
Estimands and Endpoints 
To characterize the pharmacodynamics of 
eculizumab in participants with aHUS 
x 
Population: Chinese participants with aHUS who are eligible to 
be enrolled in the study, based on the inclusion and exclusion 
criteria. 
x 
Variable: Changes in serum free and total C5 
concentrations over time (Section 3.2). 
x 
Treatment: Eculizumab 
x 
ICE: 
o 
ICE1: premature discontinuation of study intervention 
o 
ICE2: initiation of disallowed therapy or medicine 
All data after ICE1 or ICE2 will be used. 
x 
Summary measure: Mean changes in serum free and total C5 
concentrations at all scheduled visits. 
To characterize the immunogenicity of 
eculizumab in participants with aHUS 
x 
Population: Chinese participants with aHUS who are eligible to 
be enrolled in the study, based on the inclusion and exclusion 
criteria. 
x 
Variable: ADA response category (Section 3.2). 
x 
Treatment: Eculizumab 
x 
ICE: 
o 
ICE1: premature discontinuation of study intervention 
o 
ICE2: initiation of disallowed therapy or medicine 
All data after ICE1 or ICE2 will be used. 
x 
Summary measure: Proportion of ADA positive participants. 
Additional Secondary 
To evaluate the efficacy of eculizumab 
and characterize TMA by additional 
measures  
x 
Time to Complete TMA Response 
x 
Dialysis requirement status over time 
x 
Observed value and change from baseline in estimated 
glomerular filtration rate (eGFR) at all scheduled visits 
x 
Chronic kidney disease (CKD) stage classified as 
improved, stable (no change), or worsened at all scheduled 
visits compared to baseline 
x 
Observed value and change from baseline in hematologic 
parameters (platelets, LDH, hemoglobin) at all scheduled 
visits 
x 
Increase in hemoglobin of ≥ 20 g/L from baseline through 
Week 26 
To characterize the safety profile of 
eculizumab by additional safety measures 
x 
Changes from baseline in vital signs and laboratory 
parameters at scheduled visits 
Abbreviations: ADA = antidrug antibody; aHUS = atypical hemolytic uremic syndrome; C5 = complement 
component 5; CI = confidence interval; ICE = intercurrent event; LDH = lactate dehydrogenase; SAE = serious 
adverse event; TEAE = treatment-emergent adverse event; TMA = thrombotic microangiopathy 
3.1. 
Primary Estimand 
The primary objective of the study is to assess the efficacy of eculizumab in the treatment of 
participants with aHUS in China. 
The estimand corresponding to the primary objective is defined as follows: 

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The proportion of participants with Complete TMA Response during the 26-week Treatment 
Period without premature discontinuation of study intervention or the initiation of disallowed 
therapy or medicine (composite strategy for intercurrent events). Population for this analysis 
includes Chinese participants with aHUS who are eligible to be enrolled in the study, based on 
the inclusion and exclusion criteria. 
3.2. 
Secondary Estimands 
Secondary objectives of the study are to characterize the safety and tolerability of eculizumab, 
PK and PD of eculizumab, and immunogenicity of eculizumab in participants with aHUS in 
China during the 26-week Treatment Period. 
The estimands corresponding to these secondary objectives are as follows. Populations for 
analysis are Chinese participants with aHUS who are eligible to be enrolled in the study, based 
on the inclusion and exclusion criteria. Treatment policy will be applied for the predefined 
intercurrent events, where all data collected will be used in the analyses as if there is no 
occurrence of any intercurrent event. 
x Number and percentage of participants in the Safety Set with treatment-emergent 
adverse events (TEAEs) and serious adverse events (SAEs) and number of events. 
x Mean serum eculizumab concentrations at all scheduled visits. 
x Mean changes in serum free and total C5 concentrations at all scheduled visits. 
x Proportion of antidrug antibody (ADA) positive participants. 
Additional secondary objectives are presented in Table 8. For the definition of estimands, the 
population will be the same as in the primary objective (variables are presented in Table 8); the 
handling of intercurrent events for main analyses will apply treatment policy strategy, and the 
summary measures and all the other details will be provided in the Statistical Analysis Plan 
(SAP). 
3.3. 
Tertiary/Exploratory Estimands 
Not applicable. 

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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a Phase 3b, open-label, single-arm, multicenter study to evaluate the efficacy and safety 
of eculizumab in participants with aHUS in China. The study will be conducted in participants of 
any age who weigh ≥ 5 kg and who previously have not been treated with complement 
inhibitors. Up to 25 eligible participants in China will be enrolled. 
The study consists of an up to 7-day Screening Period and a 26-week Treatment Period. An 
8-week Safety Follow-up Phone Call will be required only for participants who discontinue 
eculizumab treatment during the study or for participants who will not receive continued access 
to eculizumab after completing study treatment. The study schematic is provided in Section 1.2. 
After providing informed consent/assent, participants will be screened for eligibility for the study 
during the 7-day Screening Period. If all inclusion criteria and none of the exclusion criteria are 
met, participants will be enrolled and vaccinated against N meningitidis if not already vaccinated 
within the period of active coverage specified by the vaccine manufacturer. Participants who are 
vaccinated less than 2 weeks prior to receiving the first dose of eculizumab will receive 
treatment with appropriate prophylactic antibiotics until 2 weeks after the vaccination. 
During the 26-week Treatment Period, participants will receive eculizumab by IV administration 
based on body weight cohorts presented in Table 12. 
Participants who discontinue eculizumab treatment at any time during the study will have an ED 
Visit at the time of discontinuation from the study and a Safety Follow-up Phone Call 8 weeks 
after the last dose of eculizumab. 
Participants who will not receive continued access to eculizumab after completing the EOS Visit 
will also have a Safety Follow-up Phone Call 8 weeks after the last dose of eculizumab. 
Participants who complete study treatment and will receive continued access to eculizumab after 
the study (see Section 6.7) will not have an 8-week Safety Follow-up Phone Call. 
Clinical measures and laboratory tests will be performed to assess safety, clinical, and 
biochemical parameters associated with aHUS. 
4.2. 
Scientific Rationale for Study Design 
This postapproval study has been designed to assess the efficacy and safety of eculizumab in 
pediatric and adult participants with aHUS in China. Eculizumab is currently the standard of care 
for aHUS. The safety and effectiveness of eculizumab for the treatment of aHUS have been 
established in pediatric patients. 
Based on past human experience and cumulative clinical study safety data of eculizumab in 
paroxysmal nocturnal hemoglobinuria, aHUS, myasthenia gravis, and neuromuscular optica 
syndrome, eculizumab has been shown to be well tolerated and safe, and exposure to eculizumab 
in humans has not raised any unexpected safety concerns. The use of eculizumab in pediatric 
patients for this indication is supported by evidence from 4 adequate and well-controlled clinical 
studies assessing the safety and effectiveness of eculizumab for the treatment of aHUS. The 

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assessments included in this protocol are consistent with those used in other studies with 
eculizumab. 
4.3. 
Justification for Dose 
The weight-based dosages of eculizumab in this study (Section 6.1) are based on label 
recommendations (Soliris Package Insert) and have been well established in global pivotal 
Phase 3 studies. The selection of the eculizumab dose regimen for patients with aHUS is based 
on targeting immediate, complete, and sustained inhibition of terminal complement in patients 
with aHUS. 
4.4. 
End of Study Definition 
Participants who will receive continued access to eculizumab after completing study treatment: 
x A participant is considered to have completed the study if the participant completes 
the last scheduled procedure in their last recorded weight cohort as shown in the 
Schedule of Activities (SoA; Section 1.3). 
Participants who will NOT receive continued access to eculizumab after completing study 
treatment: 
x A participant is considered to have completed the study if the participant completes 
the last scheduled procedure in their last recorded weight cohort and completes the 
Safety Follow-up Phone Call shown in the SoA (Section 1.3). 
A participant is considered to have terminated early from the study if the participant is 
discontinued from the study after enrollment (defined as completion of the informed 
consent/assent process and satisfying inclusion/exclusion criteria) and prior to completing the 
study, as specified above. A participant who terminates the study during the Treatment Period 
will complete the ED Visit and the Safety Follow-up Phone Call as shown in the SoA 
(Section 1.3). 
The end of the study is defined as the date the last participant completes the last visit (including 
follow-up) as shown in the SoA (Section 1.3). 

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5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
Age 
1. Participants of any age. 
Type of Patient and Disease Characteristics 
2. Complement treatment naïve with evidence of TMA, including thrombocytopenia, 
evidence of hemolysis, and kidney injury, based on the following laboratory findings: 
a. Platelet count < 150000/μL during the Screening Period or within 28 days prior to the 
start of the Screening Period, and 
b. Lactate dehydrogenase (LDH) ≥ 1.5 × upper limit of normal (ULN) during the 
Screening Period or within 28 days prior to the start of the Screening Period, and 
hemoglobin ≤ lower limit of normal (LLN) for age and gender during the Screening 
Period or ≤ 28 days prior to the start of the Screening Period, and 
c. Serum creatinine level ≥ ULN in adults (≥ 18 years of age), or ≥ 97.5th percentile for 
age (Section 8.11.3) at Screening in children (< 18 years of age) (participants who 
require dialysis for < 3 months are also eligible) 
Note: Evaluation of Inclusion Criteria 2a and 2b may be based on local laboratory results 
within 28 days prior to the start of the Screening Period or laboratory results obtained 
during the Screening Period from a local or central laboratory. If a local laboratory is 
used to define eligibility, additional samples will be collected during the Screening 
Period for LDH, platelet count, hemoglobin, and serum creatinine and tested at the 
central laboratory. If a participant is found to not meet the eligibility criteria for serum 
creatinine (Inclusion Criterion 2c) based on central laboratory results, they must not be 
enrolled into the study; if the participant has received the first dose of eculizumab, the 
participant must be withdrawn from the study and may be replaced. A central laboratory 
result for Inclusion Criterion 2c may not be available prior to first dose; results received 
after the first dose indicating that eligibility is not satisfied could lead to discontinuation 
and replacement of the participant. 
3. Among participants with a kidney transplant: 
a. Known history of aHUS prior to current kidney transplant, or 
b. If no known history of aHUS, persistent evidence of TMA at least 4 days after 
modifying the immunosuppressive regimen (eg, suspending or reducing the dose) of 
calcineurin inhibitor (CNI; eg, cyclosporine, tacrolimus) or mammalian target of 
rapamycin inhibitor (mTORi; eg, sirolimus, everolimus) 
4. Among participants with onset of TMA postpartum, persistent evidence of TMA for 
> 3 days after the day of childbirth. 

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5. To reduce the risk of meningococcal infection (N meningitidis), all participants must be 
vaccinated against N meningitidis if not already vaccinated within the time period of 
active coverage specified by the vaccine manufacturer. Participants must be vaccinated at 
least 14 days prior to receiving the first dose of eculizumab or be vaccinated and receive 
treatment with appropriate antibiotics until 14 days after the vaccination (Refer to 
Section 6.5.3). 
6. Participants < 18 years of age must have been vaccinated against Haemophilus influenzae 
type b (Hib) and Streptococcus pneumoniae according to local vaccination schedule 
guidelines. 
7. In participants receiving treatment with medications known to cause TMA, persistent 
evidence of TMA at least 4 days after modifying the excluded medication (eg, 
gemcitabine, CNI [eg, cyclosporine, tacrolimus], or mTORi [eg, sirolimus, everolimus]). 
Weight 
8. Body weight ≥ 5 kg. 
Sex 
9. Male and/or female. 
10. Female participants of childbearing potential and male participants must follow 
protocol-specified contraception guidance as described in Section 10.4. 
Informed Consent 
11. Capable of giving signed informed consent or assent as described in Section 10.1.3 which 
includes compliance with the requirements and restrictions listed in the informed consent 
or assent form and in this protocol. 
5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
Medical Conditions 
1. Known familial or acquired ADAMTS13 (a disintegrin and metalloproteinase with a 
thrombospondin type 1 motif, member 13) deficiency (activity < 5%). (Note: Participants 
with pending ADAMTS13 test results who meet all other criteria may be enrolled and 
allowed to receive the Day 1 dose. If results return positive for activity < 5%, the 
participant will be withdrawn [Section 7.2]). 
2. Shiga toxin-related hemolytic uremic syndrome (ST-HUS) as demonstrated by local 
guidelines. (Note: Participants with pending ST-HUS test results who meet all other 
criteria may be enrolled and allowed to receive the Day 1 dose. If results return positive, 
the participant will be withdrawn [Section 7.2]). 
3. Positive direct Coombs test which, in the judgment of the Investigator, is indicative of a 
clinically significant immune-mediated hemolysis not due to aHUS. 
4. Known human immunodeficiency virus (HIV) infection. 
5. Unresolved meningococcal disease. 

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6. Confirmed diagnosis of ongoing sepsis defined as positive blood cultures within 7 days 
prior to the start of Screening and untreated with antibiotics. 
7. Presence or suspicion of active and untreated systemic infection that, in the opinion of the 
Investigator, confounds an accurate diagnosis of aHUS or impedes the ability to manage 
the aHUS disease. 
8. Heart, lung, small bowel, pancreas, or liver transplant. 
9. Among participants with a kidney transplant, acute kidney dysfunction within 4 weeks of 
transplant consistent with the diagnosis of acute antibody-mediated rejection according to 
Banff 2013 criteria. 
10. Among participants without a kidney transplant, history of kidney disease other than 
aHUS, such as: 
a. Known kidney biopsy finding suggestive of underlying disease other than aHUS 
b. Known kidney ultrasound finding consistent with an alternative diagnosis to aHUS 
(eg, small kidneys for age) 
c. Known family history and/or genetic diagnosis of noncomplement-mediated genetic 
renal disease (eg, focal segmental glomerulosclerosis) 
11.  Identified drug exposure-related HUS. 
12. History of malignancy within 5 years of Screening with the exception of a nonmelanoma 
skin cancer or carcinoma in situ of the cervix that has been treated with no evidence of 
recurrence. 
13. Bone marrow transplant/hematopoietic stem cell transplant within 6 months prior to the 
start of Screening. 
14. HUS related to vitamin B12 deficiency. 
15. HUS related to known genetic defects of cobalamin C metabolism. 
16. Known systemic sclerosis (scleroderma), systemic lupus erythematosus, or 
antiphospholipid antibody positivity or syndrome. 
17. Chronic dialysis (defined as dialysis on a regular basis as renal replacement therapy for 
ESKD for >3 months). 
18. Prior use of eculizumab or other complement inhibitors. 
19. Use of tranexamic acid within 7 days prior to the start of Screening. 
Prior/Concomitant Therapy 
20. Other immunosuppressive therapies such as acute steroids (within 28 days prior to the 
start of Screening), chronic steroids, mTORi (eg, sirolimus, everolimus), CNI (eg, 
cyclosporine or tacrolimus) are excluded unless: 
a. Part of an established post-transplant antirejection regimen, or 
b. Participant has confirmed anticomplement factor antibodies requiring 
immunosuppressive therapy, or 
c. Steroids are being used for a condition other than aHUS (eg, asthma), or 

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d. Participant is experiencing an acute aHUS relapse immediately after transplant (see 
Section 6.5.1) 
21. Receiving chronic intravenous immunoglobulin (IVIg) within 8 weeks prior to the start of 
Screening, unless for unrelated medical condition (eg, hypogammaglobinemia); or 
chronic rituximab therapy within 12 weeks prior to the start of Screening; or single dose 
of rituximab within 7 days prior to the start of Screening. 
22. Received vasopressors or inotropes within 7 days prior to Screening. 
23. Previously or currently treated with a complement inhibitor. 
Prior/Concurrent Clinical Study Experience 
24. Has participated in another interventional treatment study or used any experimental 
therapy within 30 days before initiation of study intervention on Day 1 in this study or 
within 5 half-lives of that investigational product, whichever is greater. 
Diagnostic Assessments 
25. Female participants who have a positive pregnancy test at Screening or Day 1. 
Other Exclusions 
26. Hypersensitivity to any excipient in eculizumab, including hypersensitivity to murine 
proteins. 
27. Pregnant, breastfeeding, or intending to conceive during the course of the study. 
28. Any medical or psychological condition that, in the opinion of the Investigator, could 
increase the risk to the participant by participating in the study or confound the outcome 
of the study. 
Laboratory results for Exclusion Criterion 1 and/or Exclusion Criterion 2 may not be available 
prior to first dose. Later results for Exclusion Criterion 1 and/or Exclusion Criterion 2 could lead 
to discontinuation of study intervention and replacement of the participant (refer to Section 7.1 
for study intervention discontinuation and replacement details). 
5.3. 
Lifestyle Considerations 
No lifestyle restrictions are required for this study. 
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently entered in the study. A minimal set of screen failure information is required to 
ensure transparent reporting of screen failure participants to meet the Consolidated Standards of 
Reporting Trials 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 SAEs and any related concomitant medication, occurring during the 
Screening Period. 
Individuals who do not meet the criteria for participation in this study (eg, screen failure) due to 
a reason that is expected to resolve or has resolved may be rescreened once after the reason for 

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screen fail has resolved or is expected to resolve prior to rescreening and after discussion and 
agreement between the Investigator and the Medical Monitor. Any abnormal laboratory 
parameter results outside of the reference range at Screening may be retested once within the 
Screening window at the Investigator’s discretion and after discussing with Alexion’s Medical 
Monitor for the purpose of determining eligibility. 

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6. 
STUDY INTERVENTION 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to the 
study protocol. 
6.1. 
Study Intervention Administered 
In this study, participants will receive open-label eculizumab during the Treatment Period. 
Specific details of the study intervention are provided in Table 9. 
Table 9: 
Study Intervention 
Study Intervention 
Name 
Eculizumab 
Type 
Monoclonal antibody 
Dose Formulation 
Sterile liquid 
Unit Dose Strength(s) 
300 mg/30 mL (10 mg/mL) as a clear, colorless solution in a single-dose vial 
Dosage Level(s) 
Dosing is based on body weight as follows: 
Body weight 
Induction 
Maintenance 
≥ 40 kg 
900 mg weekly × 4 doses 
1200 mg at Day 29; then 1200 mg every 
2 weeks 
30 to < 40 kg 
600 mg weekly × 2 doses 
900 mg at Day 15; then 900 mg every 
2 weeks 
20 to < 30 kg 
600 mg weekly × 2 doses 
600 mg at Day 15; then 600 mg every 
2 weeks 
10 to < 20 kg 
600 mg weekly × 1 dose 
300 mg at Day 8; then 300 mg every 
2 weeks 
5 to < 10 kg 
300 mg weekly × 1 dose 
300 mg at Day 8; then 300 mg every 
3 weeks 
Route of 
Administration 
Intravenous infusion 
Use 
Experimental 
IMP and NIMP 
IMP 
Sourcing 
Provided centrally by Alexion or contracted manufacturing organization 
Packaging and 
Labeling 
Eculizumab will be provided in glass vials and stoppered with a butyl rubber stopper 
with an aluminum overseal and a flip-off cap. Eculizumab will be supplied in kits and 
labeled as required per country requirement. 
Abbreviations: IMP = investigational medicinal product; NIMP = non-investigational medicinal product 
6.1.1. 
Study Intervention(s) Packaging and Labeling 
Study intervention will be labeled according to the country’s regulatory requirements. At a 
minimum, the container will be labeled with: 
x The protocol number 
x Lot number/expiry date 
x Alexion name and address 
x Instructions for use and storage 

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6.2. 
Preparation/Handling/Storage/Accountability 
Upon arrival of the study intervention at the study site, the study intervention kits should be 
removed from the shipping container and immediately stored in their original cartons under 
refrigerated conditions at 2°C to 8°C (35°F to 47°F) and protected from light. The study 
intervention should not be frozen. 
Prior to administration, the study intervention solution should be visually inspected for 
particulate matter and discoloration. The study intervention solution should be clear and 
colorless. 
Infusions of study intervention should be prepared using aseptic technique. 
1. The Investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received and that any discrepancies 
are reported and resolved before use of the study intervention. 
2. Only participants enrolled in the study may receive the study intervention and only 
authorized site staff may supply or administer the study intervention. All study 
intervention 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 intervention accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records). 
a. This responsibility includes the reporting of any temperature excursions and product 
complaints to AlexionIMPTE@alexion.com and productcomplaints@alexion.com 
within 1 business day of awareness. 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 performance of a 
product or clinical study 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 regarding preparation, handling, storage, and accountability and 
information for the final disposition of unused study intervention is provided in the 
Pharmacy Manual. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
This is an open-label study. All participants, site personnel, and Alexion staff will be unblinded 
to participant treatment. 
6.4. 
Study Intervention Compliance 
When participants are dosed at the investigational site, they will receive study intervention 
directly from the Investigator or designee, under medical supervision. The date and time of each 
dose administered in the clinic will be recorded in the source documents and recorded in the 
electronic case report form (eCRF). 

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6.5. 
Concomitant Therapy 
Any medication (including over-the-counter or prescription medicines, vitamins, and/or herbal 
supplements) or vaccine that the participant is receiving at the time of enrollment or receives 
during the study must be recorded along with: 
x Reason for use 
x Dates of administration, including start and end dates 
x Dosage information including dose and frequency 
The Medical Monitor should be contacted with any questions regarding concomitant or prior 
therapy. 
Prior medications (including vitamins and herbal preparations), including those discussed in the 
exclusion criteria (Section 5.2) and procedures (any therapeutic intervention, such as 
surgery/biopsy or physical therapy) the participant takes or undergoes within 28 days prior to the 
start of Screening until the first dose of study intervention, will be recorded in the participant’s 
eCRF. In addition, history of meningococcal vaccination must be collected prior to first dose of 
study intervention. 
All medications and therapies or procedures undertaken during the study will be recorded in the 
participant’s source document/medical chart and eCRF. This record will include all prescription 
drugs, herbal products, vitamins, minerals, over-the-counter medications, and current 
medications for aHUS. Concomitant medications will be recorded from the first infusion of study 
intervention through 8 weeks after the participant’s last dose of study intervention. Any changes 
in concomitant medications also will be recorded in the participant’s source document/medical 
chart and eCRF. Any concomitant medication deemed necessary for the participant’s standard of 
care during the study, or for the treatment of any AE, along with the allowed medications 
described below may be given at the discretion of the Investigator. However, it is the 
responsibility of the Investigator to ensure that details regarding all medications are recorded in 
full in the participant’s source document/medical chart and eCRF. 
6.5.1. 
Allowed Medicine and Therapy 
The following concomitant medications are allowed if the following conditions apply, and dose 
adjustments are not expected during the Treatment Period: 
x Erythropoietin, if the participant has been receiving a stable dose for at least 8 weeks 
before Screening. 
x Immunosuppressants, if the participant has been receiving a stable dose for at least 
8 weeks before Screening. 
x Corticosteroids, if the participant has been receiving a stable dose for at least 4 weeks 
before Screening. 
x Vitamin K antagonists (eg, warfarin), if the participant has had a stable international 
normalized ratio (INR) level (per Investigator’s discretion) for at least 4 weeks before 
Screening. 

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x Iron supplements or folic acid, if the participant has been receiving a stable dose for 
at least 4 weeks before Screening. 
Adjustments in the frequency or dose level in any of the above medications can be made if the 
Medical Monitor or Investigator deems it is in the best interest of the participant. 
The following concomitant medications and therapy during the study are allowed under certain 
circumstances and restrictions: 
x Other immunosuppressive therapies such as steroids, mTOR inhibitors, or tacrolimus 
are allowed under the following circumstances ONLY IF: 
 Part of an established post-transplant antirejection regime and dose of such 
medications must have been unchanged for at least 4 weeks prior to screening, or 
 Participant has confirmed anticomplement factor antibodies requiring 
immunosuppressive therapy and dose of such medications must have been 
unchanged for at least 4 weeks prior to Screening 
 Steroids are being used for a condition other than aHUS (eg, asthma) 
 Participant is experiencing an acute aHUS relapse immediately after transplant. In 
addition, a stable dose of these medications must be maintained during the 
Treatment Period unless there is a discussion and agreement between the 
Investigator and Alexion. 
The Medical Monitor should be contacted with any questions regarding concomitant or prior 
therapy. 
6.5.2. 
Disallowed Medicine and Therapy 
Participants must abstain from taking prescription or nonprescription drugs (including vitamins 
and dietary or herbal supplements) within 7 days (or 14 days if the drug is a potential enzyme 
inducer) or 5 terminal half-lives (whichever is longer) before the start of study intervention until 
completion of the Safety Follow-up Phone Call, unless, in the opinion of the Investigator and 
Alexion, the medication will not interfere with the study. 
Other concomitant medication may be considered on a case-by-case basis by the Investigator in 
consultation with the Medical Monitor, if required. 
Participants are prohibited from receiving any of the following medications and procedures at 
any time after the first dose of study intervention (including participants who discontinue 
eculizumab treatment but remain in study) until completion of the study or early termination of 
the participant from the study: 
x Use of any other investigational drug or device as part of a clinical study 
x Use of any other complement inhibitor 
x IVIg (unless for an unrelated medical need, eg, hypogammaglobinemia) 
x Rituximab 
x Plasma exchange/plasma infusion 

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x Traditional Chinese herbal preparations that in the opinion of the Investigator or 
Alexion might confound the assessment of the participant 
A participant who receives the above prohibited medications and/or procedures after the first 
dose of study intervention will be withdrawn from the study. 
6.5.3. 
Vaccination 
As with any terminal complement antagonist, the use of eculizumab increases a participant’s 
susceptibility to meningococcal infection (N meningitidis). To reduce the risk of meningococcal 
infection, all participants must be vaccinated against meningococcal infection if not already 
vaccinated within the period of active coverage specified by the vaccine manufacturer. 
x Participants who initiate study intervention less than 2 weeks after receiving a 
meningococcal vaccine must receive treatment with appropriate prophylactic antibiotics 
until 2 weeks after vaccination. 
x Participants must be administrated prophylactic antibiotics for prevention of 
meningococcal infection, if study intervention administration occurs before the 
vaccination administration. 
x Participants who permanently discontinue study intervention before vaccination against 
meningococcal infection must be administered prophylactic antibiotics for at least 
8 weeks or be vaccinated against meningococcal infection. 
x Participants must be vaccinated or revaccinated according to current national vaccination 
guidelines or local practice for vaccination use with complement inhibitors (eg, 
eculizumab). 
x Vaccines against serotypes A, C, Y, W135 are required, plus B where available, to 
prevent common pathogenic meningococcal serotypes. 
x Vaccination may not be sufficient to prevent meningococcal infection. Consideration 
should be given per official guidance and local practice on the appropriate use of 
antibacterial agents. 
x All participants should be monitored for early signs of meningococcal infection, 
evaluated immediately if infection is suspected, and treated with appropriate antibiotics, 
if necessary. 
Pediatric participants (< 18 years of age) are required to be vaccinated against Hib and 
S pneumoniae according to local vaccination schedule guidelines. 
To increase risk awareness and promote quick disclosure of any potential signs or symptoms of 
infection experienced by the participants during the course of the study, participants will be 
provided a safety card to carry with them at all times. Additional discussion and explanation of 
the potential risks, signs, and symptoms will occur at specific timepoints as part of the review of 
the safety card and throughout the study as described in the SoA (Section 1.3). 
6.6. 
Dose Modification 
Dose modification is not permitted. 

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6.7. 
Intervention After the End of the Study 
Participants who complete the study and show clinical benefit will be offered continued access to 
eculizumab as permitted by regulations until eculizumab is commercially available. 

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7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of Study Intervention 
In rare instances, it may be necessary for a participant to permanently discontinue (definitive 
discontinuation) the study intervention. If the study intervention is permanently discontinued, the 
participant should, if at all possible, remain in the study to be evaluated for all assessments at the 
scheduled visits described in the SoA (Section 1.3). 
If study intervention is permanently discontinued and the participant remains in the study, the 
participant should have the Safety Follow-up Phone Call 8 weeks after the last dose of study 
intervention. 
Participants must be considered for discontinuation from study intervention if any of the 
following occur during the study: 
x Serious hypersensitivity reaction 
x Pregnancy or planned pregnancy (Section 10.4.3) 
x Severe uncontrolled infection 
x Use of disallowed medication (defined in Section 6.5.2) 
x Alexion or Investigator deems it necessary for the participant 
7.1.1. 
Temporary Discontinuation 
In the event of a need for temporary discontinuation, the Investigator is encouraged to discuss the 
circumstances with the Medical Monitor in all cases. Temporary or permanent discontinuation of 
study intervention should be considered in the case of moderate to severe infections. For 
permanent discontinuation, refer to Section 7.1. 
7.2. 
Participant Discontinuation/Withdrawal from the Study 
x All efforts should be made to ensure participants are willing to comply with study 
participation prior to conducting the screening procedures. 
x The study staff should notify Alexion and their site monitor of all study withdrawals 
as soon as possible. The reason for participant discontinuation must be recorded in the 
source documents and eCRF. 
x A participant 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 activity is expected to be uncommon. 
x At the time of discontinuing from the study, if possible, an ED Visit should be 
conducted, as shown in the SoA (Section 1.3). Additionally, participants should have 
the 8-week Safety Follow-up Phone Call. Refer to the SoA for data to be collected at 
the time of study discontinuation and follow-up and for any further evaluations that 
need to be completed. 

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 The participant will be permanently discontinued both from the study intervention 
and from the study at that time. 
 If it is determined at any point that a participant’s Screening data do not satisfy 
ADAMTS13 negative testing (< 5% activity, Exclusion Criterion 1) or Shiga 
toxin negative testing (Exclusion Criterion 2) after receiving at least 1 dose of 
study intervention, the participant will be discontinued from the study and may be 
replaced. ED procedures described in the SoA (Section 1.3) will be performed, if 
possible, on participants who are terminated early from the study, and AEs will be 
collected through the 8-week Safety Follow-up Phone Call (Section 1.3). 
x The 8-week Safety Follow-up Phone Call will not be required if a participant 
withdraws consent. 
x If the participant withdraws consent for disclosure of future information, Alexion may 
retain and continue to use any data collected before such a withdrawal of consent. 
x If a participant withdraws from the study, the participant 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 
A participant will be considered lost to follow-up if the participant 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 participant fails to return to the clinic for a required 
study visit: 
x The site must attempt to contact the participant to reschedule the missed visit as soon 
as possible, counsel the participant on the importance of maintaining the assigned 
visit schedule and ascertain whether or not the participant wishes to and/or should 
continue in the study. 
x Before a participant is deemed lost to follow-up, the Investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record. 
x Should the participant continue to be unreachable, he/she will be considered lost to 
follow-up. 
Discontinuation of specific sites or of the study as a whole are handled as part of Section 10.1.8. 

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8. 
STUDY ASSESSMENTS AND PROCEDURES 
x Study procedures and their timing are summarized in the SoA (Section 1.3). Protocol 
waivers or exemptions are not allowed. 
x Immediate safety concerns should be discussed with Alexion immediately upon 
occurrence or awareness to determine if the participant should continue or 
discontinue study intervention. 
x Adherence to the study design requirements, including those specified in the SoA 
(Section 1.3), is essential and required for study conduct. 
x All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The Investigator will maintain a screening log 
to record details of all participants screened and to confirm eligibility or record 
reasons for screening failure, as applicable. 
x Procedures conducted as part of the participant’s routine clinical management (eg, 
blood count) and obtained before signing of the informed consent/assent form 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 (Section 1.3). 
x See Section 10.2 for the list of clinical laboratory tests. 
x Repeat or unscheduled samples may be obtained for safety reasons or for technical 
issues with the samples. 
8.1. 
Efficacy Assessments 
8.1.1. 
Laboratory Assessments for Efficacy Estimands/Endpoints 
Laboratory assessments (platelets, LDH, and estimated glomerular filtration rate [eGFR]) to 
determine Complete TMA Response, hematologic response, and renal response will be 
performed according to the SoA (Section 1.3) and will be assessed based on the predetermined 
criteria for Complete TMA Response as defined below. 
The primary efficacy endpoint is Complete TMA Response during the 26-week Treatment 
Period. The criteria for Complete TMA Response are the following: 
1. Normalization of platelet count (defined as platelet count ≥ 150000/μL) 
2. Normalization of LDH (defined as LDH ≤ ULN) 
3. ≥ 25% improvement in serum creatinine from baseline 
Participants must meet all Complete TMA Response criteria at 2 separate assessments obtained 
at least 4 weeks (28 days) apart, and any measurement in between, to be classified as having met 
the primary efficacy endpoint. 
8.1.2. 
Kidney Function Parameters 
eGFR will be calculated from serum creatinine. The eGFR calculation will be based on the 
Modification of Diet in Renal Disease (MDRD) formula according to demographics. 

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Proteinuria will be determined from the urine protein to creatinine ratio on a spot urine test at 
select target days as specified in the SoA (Section 1.3). 
Dialysis requirement status will be collected prior to Screening, during Screening, and during the 
Treatment Period as specified in the SoA (Section 1.3). 
8.1.3. 
Other Disease-related Laboratory Parameters 
Blood and urine samples will be collected at the times indicated in the SoA (Section 1.3). 
The response of increase in hemoglobin of ≥ 20 g/L from baseline through Week 26 is defined as 
follows: 
Participants must meet the criteria of increase in hemoglobin of ≥ 20 g/L from baseline at 
2 separate assessments obtained at least 4 weeks (28 days) apart, and any measurement in 
between, to be classified as having achieved the response. 
Chronic kidney disease (CKD) stage classification (Table 10) will include improved (excluding 
participants with Stage 1 at baseline as they cannot improve), worsened (excluding participants 
with Stage 5 at baseline as they cannot worsen), and stayed the same compared to CKD stage at 
baseline. Stage 5 will be considered the worst category, while Stage 1 will be considered the best 
category. 
Table 10: 
Estimated Glomerular Filtration Rate Category/Stage in Chronic Kidney 
Disease 
eGFR Category/Stage 
eGFR (mL/min/1.73 m2) 
Terms 
G1 
≥ 90 
Normal or high 
G2 
60 - 89 
Mildly decreaseda 
G3a 
45 - 59 
Mildly to moderately decreased 
G3b 
30 – 44 
Moderately to severely decreased 
G4 
15 – 29 
Severely decreased 
G5 
< 15 
Kidney failure 
Note: In the absence of evidence of kidney damage, neither eGFR category/stage G1 nor G2 fulfill the criteria for 
CKD. 
a Relative to the adult level. 
Abbreviations: CKD = chronic kidney disease; eGFR = estimated glomerular filtration rate 
Source: Levin, 2013 
8.2. 
Safety Assessments 
Planned timepoints for all safety assessments are provided in the SoA (Section 1.3). 
8.2.1. 
Physical Examinations 
x A complete physical examination will include, at a minimum, assessments of general 
appearance; skin; head, ear, eye, nose, and throat; neck; lymph nodes; chest; heart; 
abdominal cavity; limb; central nervous system; and musculoskeletal system. Height 
and weight will also be measured and recorded. 
x An abbreviated physical examination will include a body-system relevant 
examination based on Investigator judgment and participant symptoms. 

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x Height will be measured recorded at Screening for all participants. Weight will be 
measured and recorded at every visit for all participants. Weight must be recorded 
prior to dosing at every study visit. Weight will not need to be measured at each study 
visit if eculizumab is permanently discontinued. 
x Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 
8.2.2. 
Vital Signs 
x Body temperature (°C or °F), pulse rate, respiratory rate, and systolic and diastolic 
blood pressure (mm Hg) will be assessed. 
x Blood pressure and pulse measurements will be assessed seated with a completely 
automated device. Manual techniques will be used only if an automated device is not 
available. 
x Blood pressure and pulse measurements should be preceded by at least 5 minutes of 
rest for the participant in a quiet setting without distractions (eg, television, cell 
phones). Ideally, the same arm for each participant should be used for measurements. 
x On dosing days, vital sign measurements will be taken before study intervention 
administration. 
8.2.3. 
Electrocardiograms 
x Single 12-lead electrocardiogram (ECG) will be conducted as outlined in the SoA 
(Section 1.3) to obtain heart rate, PR, QRS, QT, and QTc intervals. 
x Participants must be supine for approximately 5 to 10 minutes before ECG collection 
and remain supine but awake during ECG collection. 
x The Investigator or designee will be responsible for reviewing the ECG to assess 
whether the ECG is within normal limits and to determine the clinical significance of 
the results. These assessments will be indicated on the eCRF. For any clinically 
significant abnormal ECG results, the Investigator must contact the Medical Monitor 
to discuss the participant’s continued eligibility to participate in this study. 
8.2.4. 
Clinical Safety Laboratory Assessments 
x 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 participant’s condition. 
x All laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within 8 weeks after the final dose of study intervention 
should be repeated until the values return to normal or baseline or are no longer 
considered clinically significant by the Investigator or Medical Monitor. 

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 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 
collected in accordance with the Laboratory Manual and the SoA (Section 1.3). 
 Laboratory assessments performed at the institution’s local laboratory that require 
a change in participant management or are considered clinically significant by the 
Investigator must be recorded in the AE or SAE eCRF. When possible, parameter 
value outside of the reference range should be entered in a free-text field. 
8.2.5. 
Pregnancy 
x Pregnancy data from female participants of childbearing potential and female 
spouses/partners of male participants will be collected from the first dose of study 
intervention through 5 months after the final dose of study intervention. Any female 
participant who becomes pregnant during the study should be considered for 
discontinuation from the study intervention and withdrawn from the study. If a pregnancy 
is reported, the Investigator must immediately inform Alexion within 24 hours of 
awareness of the pregnancy and follow the procedures outlined in Section 10.4.3. 
8.2.6. 
Participant Safety Card 
Before the first dose of study intervention, a Participant Safety Card will be provided to 
participants to carry with them at all times until 3 months after the final dose of study 
intervention. The card is provided to increase participant awareness of the risk of meningococcal 
infection and promote quick recognition and disclosure of any potential signs or symptoms of 
infection experienced during the course of the study and to inform participants on what actions 
must be taken if they are experiencing signs or symptoms of infection. 
At each visit throughout the study, the study staff will ensure that the participant has the 
Participant Safety Card. 
8.3. 
Adverse Events and Serious Adverse Events 
The definitions of AEs and SAEs can be found in Section 10.3. 
All AEs will be reported to the Investigator or qualified designee by the participant (or, when 
appropriate, by a caregiver, surrogate, or the participant’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 intervention or study procedures, or that 
caused the participant to discontinue the study intervention (see Section 7). 
Procedures for recording, evaluating, follow-up, and reporting AEs and SAEs are outlined in 
Section 10.3. 

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8.3.1. 
Time Period and Frequency for Collecting AE and SAE Information 
All AEs and SAEs will be collected from the signing of the informed consent form (ICF) at the 
timepoints specified in the SoA (Section 1.3). 
All SAEs will be recorded and reported to Alexion 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 the date the investigational site became aware of 
the event. 
Investigators are not obligated to actively seek AE or SAE data after conclusion of the study 
participation. However, if the Investigator learns of any SAE, including a death, at any time after 
a participant has been discharged from the study, and he/she considers the event to be reasonably 
related to the study intervention or study participation, the Investigator must promptly notify 
Alexion. 
8.3.2. 
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 
nonleading verbal questioning of the participant is the preferred method to inquire about AE 
occurrences. 
8.3.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow-up on each 
participant at subsequent visits/contacts. All SAEs will be followed up until resolution, 
stabilization, the event is otherwise explained, or the participant is lost to follow-up (as defined 
in Section 7.3). Further information on follow-up procedures is provided in Section 10.3. 
8.3.4. 
Regulatory Reporting Requirements for SAEs 
x Prompt notification of an SAE by the Investigator to Alexion is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety 
of a study intervention under clinical investigation are met. 
x Alexion has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study intervention under clinical 
investigation. Alexion will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, Institutional Review Boards 
(IRBs)/Independent Ethics Committees (IECs), and Investigators. 
x Alexion is required to submit individual suspected unexpected serious adverse 
reaction (SUSAR) reports (defined in Section 10.3.2) in the format of 
MedWatch 3500 or Council for International Organizations of Medical Sciences 
(CIOMS) I Form to health authorities and Investigators as required. 
x 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 

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review and then file it along with the Investigator’s Brochure (IB) and will notify the 
IRB/IEC, if appropriate according to local requirements. 
8.3.5. 
Adverse Events of Special Interest (AESI) 
Meningococcal infections are considered to be AESIs. 
8.4. 
Treatment of Overdose 
For this study, any dose of study intervention 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. 
In the event of an overdose or suspected overdose, the Investigator/Treating Physician should: 
1. Contact the Medical Monitor immediately. 
2. Closely monitor the participant 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 participant. 
8.5. 
Pharmacokinetics 
x Serum samples will be collected for measurement of concentrations of eculizumab as 
specified in the SoA (Section 1.3). 
x 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. In the event of breakthrough hemolysis, a serum sample for PK/PD analysis 
will be collected at any time that day. 
x Samples will be used to evaluate the PK of eculizumab. PK samples may also be used 
to evaluate safety or efficacy aspects related to concerns arising during or after the 
study. 
Full details of the analytical method used will be described in a separate bioanalytical report. 
8.6. 
Pharmacodynamics 
x Serum samples will be collected for measurement of C5 as specified in the SoA 
(Section 1.3). 

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x 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. 
x Samples will be used to evaluate the PD of eculizumab. PD samples may also be used 
to evaluate safety or efficacy aspects related to concerns arising during or after the 
study. 
Full details of the analytical method used will be described in a separate bioanalytical report. 
8.7. 
Genetics 
Genetics are not evaluated in this study. 
8.8. 
Biomarkers 
Biomarkers are not evaluated in this study. 
8.9. 
Immunogenicity Assessments 
Serum samples for ADA and neutralizing antibody analysis will be collected at timepoints 
according to SoA (Section 1.3). All efforts will be made to obtain the immunogenicity samples at 
the exact nominal time relative to dosing. Out-of-window protocol deviation capture for 
immunogenicity samples follows that specified for PK sample collection (Section 8.5). 
8.9.1. 
ADA Variables 
ADA variables include ADA response category incidence and titer over the duration of the study 
as follows. ADA response category definitions and titer thresholds will be provided in the SAP. 
ADA response categories 
x ADA negative 
x ADA positive 
Participants that are ADA positive will be categorized as follows: 
x Pre-existing immunoreactivity 
x Treatment-emergent ADA responses 
 Persistent treatment-emergent responses 
 Transient treatment-emergent responses 
 Indeterminate treatment-emergent responses 
x Treatment-boosted ADA responses 
x Neutralizing antibody positive 
8.10. 
Health Economics Data and/or Medical Resource Utilization 
Medical resource utilization and/or health economics data will not be collected during this study. 

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8.11. 
Other Assessments and Procedures 
8.11.1. 
Informed Consent 
The Investigator or qualified designee must obtain signed and dated informed consent and assent, 
where applicable, from each participant or legally authorized representative prior to conducting 
any study procedures. All efforts should be made to ensure participants are willing to comply 
with study participation prior to conducting the screening procedures. 
8.11.2. 
Demographics 
A review of demographic parameters, including age, gender, race, and ethnicity will be 
performed. 
8.11.3. 
Inclusion and 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 participant qualifies for study participation. 
The 97.5th percentile serum creatinine reference intervals by age are presented in Table 11. 
Table 11: 
97.5th Percentile Serum Creatinine Reference Intervals 
Age (Gender) Group 
97.5th Percentile Value (mg/dL) 
97.5th Percentile Value (μmol/L) 
2 months to < 1 year of age 
0.39 
34 
1 to < 3 years of age 
0.35 
31 
3 to < 5 years of age 
0.42 
37 
5 to < 7 years of age 
0.48 
42 
7 to < 9 years of age 
0.55 
48 
9 to < 11 years of age 
0.64 
57 
11 to < 13 years of age 
0.71 
63 
13 to < 15 years of ag 
0.81 
72 
15 to adult (males) 
1.18 
104 
15 to adult (females) 
1.02 
90 
Source: Adapted from Ceriotti, 2008 
8.11.4. 
Medical History and aHUS History 
The participant’s aHUS medical history, including onset of first aHUS symptom, date of 
diagnosis, and emergency room visits, will be documented at the Screening Visit. The 
participant’s medical history, including prior and concomitant conditions/disorders, will be 
recorded at the Screening Visit. Medication use (prescription or over-the-counter, including 
vitamins and/or herbal supplements) within 28 days prior to the start of Screening will also be 
recorded. Participants must be complement inhibitor treatment naïve to enroll in the study. 

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8.11.5. 
Prior and Concomitant Medications Review 
8.11.5.1. Prior Medications 
Prior medications (including vitamins, herbal preparations, and those discussed in the exclusion 
criteria [Section 5.2]), vaccines, and procedures (any therapeutic intervention, such as 
surgery/biopsy or physical therapy) that the participant takes or undergoes within 28 days before 
the start of Screening or during the Screening Period before the first dose of eculizumab, as well 
as any meningococcal vaccine administered, will be recorded in the participant’s eCRF. 
Additionally, all medications or therapies ever used for treatment of aHUS before the first dose 
of eculizumab must be collected. 
8.11.5.2. Concomitant Medications 
Use of concomitant medications and nondrug therapies (Section 6.5) will be evaluated during the 
study. At each visit (specified in the SoA [Section 1.3]), participants should be questioned about 
any new medication or nondrug therapies or changes to concomitant medications and nondrug 
therapies since the last visit. Concomitant medications and nondrug therapies should be recorded 
in the source documents and the participant’s eCRF. 
8.11.6. 
Study Intervention Administration 
This section describes the dosage regimen of study intervention. At the scheduled dosing visits 
(Section 1.3), study intervention administration should be performed after all other tests and 
procedures have been completed, excluding the postdose blood sampling for PK and serum free 
C5. 
Based on the result of weight assessment prior to dosing, a participant may be attributed to a 
different weight cohort from previous visit due to weight gain or weight loss. The schedule of 
activities from this point on will follow the below criteria: 
1. If the current visit is a scheduled visit for both the updated and previous weight cohorts, 
then all the activities to be performed at this visit should follow the plan for the updated 
weight cohort (the criteria for hematology and clinical chemistry can be overruled by 
bullet #3 mentioned below). For all future visits, the schedule should be based on the 
updated weight cohort unless further change of weight cohort occurs. 
2. If the current visit is NOT a scheduled visit for the updated weight cohort (eg, a 
participant in the 5 to < 10 kg cohort has a scheduled visit at Day 71/Week 10 and is 
weighed above 10 kg at the visit, then under the new weight cohort of 10 to < 20 kg, 
Day 71/Week 10 is NOT a scheduled visit), then the activities to be performed at this 
visit should follow the plan of the most recent past scheduled visit under the updated 
weight cohort (eg, the participant mentioned above is now in the 10 to < 20 kg cohort, 
and at Day 71/Week 10, this participant will follow the scheduled activity of 
Day 64/Week 9), (the criteria for hematology and clinical chemistry can be overruled by 
bullet #3 mentioned below). For all future visits, the schedule should be based on the 
updated weight cohort unless further change of weight cohort occurs. 
3. Regardless of the schedule for the updated weight cohort (either current visit day/week is 
a scheduled visit or not), if under the previous weight cohort the participant is scheduled 

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to take any assessment related to efficacy (hematology and clinical chemistry) at the 
current visit, then these assessments will still be performed at the current visit (eg, a 
participant who is originally in the 5 to < 10 kg weight cohort comes for the 
Day 71/Week 10 visit and weighs 10 to < 20 kg, per the above criteria, this participant 
will follow the schedule of Day 64/Week 9, except that clinical chemistry and 
hematology will still be assessed). This criterion overrules the previous 2 criteria for 
efficacy assessments. 
If eculizumab is permanently discontinued and the participant remains in the study, for the rest of 
the scheduled visits, the SoA will not need to be adjusted based on weight. 
Refer to Section 6 for additional information about study intervention including preparation, 
handling, storage, and accountability. For detailed instructions, refer to the Pharmacy Manual. 
Eculizumab is supplied for clinical studies as a sterile, preservative-free 10 mg/mL solution in 
single-use vials and designed for infusion by diluting into commercially available saline (0.9% 
sodium chloride injection; country-specific pharmacopeia) for administration via IV infusion. 
Eculizumab must NOT be administered as an IV push or bolus injection. 
Eculizumab will be administered by IV infusion according to body weight as presented in 
Table 12. 
Table 12: 
Eculizumab Induction and Maintenance Dosing by Weight Cohorta 
Body Weight 
Induction 
Maintenance 
≥ 40 kg 
900 mg weekly × 4 doses 
1200 mg at Day 29; then 1200 mg every 2 weeks 
30 to < 40 kg 
600 mg weekly × 2 doses 
900 mg at Day 15; then 900 mg every 2 weeks 
20 to < 30 kg 
600 mg weekly × 2 doses 
600 mg at Day 15; then 600 mg every 2 weeks 
10 to < 20 kg 
600 mg weekly × 1 dose 
300 mg at Day 8; then 300 mg every 2 weeks 
5 to < 10 kg  
300 mg weekly × 1 dose 
300 mg at Day 8; then 300 mg every 3 weeks 
a Participants will be weighed at each study visit as eculizumab dosing will be based on the weight assessment. 
 

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9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical Hypotheses 
No formal statistical hypotheses will be tested. 
9.2. 
Sample Size Determination 
Approximately 25 eligible participants will be enrolled. Based on the adult (Study C10-004) and 
pediatric (Study C10-003) studies, 65% of participants are expected to achieve Complete TMA 
Response. Twenty-five participants would yield a 95% confidence interval (CI) for the 
proportion of response with a half-width of approximately 20%. 
9.3. 
Populations for Analyses 
Efficacy analyses will be performed on the Full Analysis Set (FAS). Safety analyses will be 
performed on the Safety Set. PK analyses will be performed on the PK Analysis Set. The 
populations are defined in Table 13. 
Table 13: 
Populations for Analyses 
Population 
Description 
Full Analysis Set 
All participants who receive at least 1 dose of study intervention and have at 
least 1 efficacy assessment post first dose. 
Safety Set 
All participants who receive at least 1 dose of study intervention.  
Pharmacokinetic Analysis Set 
All participants who receive at least 1 dose of study intervention and have 
evaluable pharmacokinetic data. 
Pharmacodynamic Analysis Set 
All participants who receive at least 1 dose of study intervention and have 
evaluable pharmacodynamic data. 
9.4. 
Statistical Analyses 
Statistical methods described in this section will be further elaborated in a separate SAP before 
database lock and analysis, including procedures for accounting for missing data. Any change to 
the data analysis methods described in the protocol will require an amendment only if it changes 
the primary or secondary objectives or the study conduct. Any other change to the data analysis 
methods described in the protocol or SAP, and the justification for making the change, will be 
described in the clinical study report (CSR). Additional exploratory analyses of the data may be 
conducted as deemed appropriate. 
All data collected will be presented using summary tables, figures, and data listings. All data, as 
well as any outcomes derived from the data, will be presented in detailed data listings. Graphical 
displays may also be provided, when appropriate. Continuous variables will be summarized 
using descriptive statistics, including the number of observations, and mean, standard deviation, 
median, minimum, and maximum values. Categorical variables will be summarized by frequency 
counts and the percentage of participants. All summaries and statistical analysis will be stratified 
by age group (< 18 years and ≥ 18 years), if appropriate, and overall. 
Analyses will be performed using the SAS® software version 9.4 or higher. 

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9.4.1. 
Efficacy Analyses 
9.4.1.1. 
Analyses of Primary Efficacy Estimand(s) and Endpoint 
The primary endpoint is Complete TMA Response during the 26-week Treatment Period. 
The estimand corresponding to the analysis for this endpoint will consist of estimating the 
proportion of complete TMA responders in the FAS. This will be performed by calculating the 
point estimate and a 95% CI for the proportion of complete TMA responders in 
eculizumab-treated participants. The CI will be based on exact confidence limits using the 
Clopper-Pearson method. Complete TMA Response will also be analyzed by subgroups based on 
age (< 18 years and ≥ 18 years), if appropriate. 
9.4.1.2. 
Analyses of Secondary Efficacy Estimand(s) and/or Endpoint(s) 
9.4.1.2.1. Time to Complete TMA Response 
For this endpoint, a Kaplan-Meier cumulative distribution curve will be generated along with a 
2-sided 95% CI. The corresponding summary table will present the cumulative distribution 
function estimate, the number of participants at risk, the number of participants responding, and 
the number of participants censored at each postbaseline timepoint. The table will also present 
first quartile, median, and third quartile, along with corresponding 2-sided 95% CI of time to 
Complete TMA Response. 
9.4.1.2.2. Increase in Hemoglobin 
The response of increase in hemoglobin of > 20 g/L from baseline through Week 26 will be 
analyzed in the same manner as the primary efficacy endpoint. 
9.4.1.2.3. Other Efficacy Endpoints 
eGFR will be measured at select target days as specified in the SoA (Section 1.3) and CKD stage 
assessed by eGFR (Table 10) will be classified as improved, stable (no change), or worsened 
compared to baseline. The eGFR will be calculated for all visits at which serum chemistry values 
are collected using the MDRD formula in participants ≥ 18 years of age and MDRD Schwartz 
formula in participants < 18 years of age. 
Observed values and changes from baseline in eGFR and hematologic parameters (platelets, 
LDH, hemoglobin), CKD classification, and dialysis requirement status will be summarized over 
time at all scheduled visits. 
For participants requiring dialysis within 5 days prior to Day 1, the proportion of participants no 
longer requiring dialysis will be summarized over time. A 2-sided 95% CI for the proportion of 
participants receiving dialysis will be provided. 
9.4.1.3. 
Multiplicity Adjustment 
This section is not applicable, as all analyses are descriptive, and p-values will not be provided. 
9.4.1.4. 
Analyses of Exploratory Estimand(s) and/or Endpoint(s) 
Not applicable. 

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9.4.2. 
Safety Analyses 
All safety analyses will be performed on the Safety Set. 
The following definitions will be used for AEs: 
x Pretreatment AEs: Any AE that starts after providing informed consent/assent but 
before the first infusion of study intervention. 
x TEAE: Any AE that starts during or after the first infusion of study intervention. 
The incidence of TEAEs, TEAEs leading to withdrawal from the study, TEAEs leading to study 
intervention discontinuation, study intervention-related TEAEs, TEAEs during study 
intervention administration, severe TEAEs, treatment-emergent serious adverse events 
(TESAEs), and AESI will be summarized. All AEs will be coded using Medical Dictionary for 
Regulatory Activities (MedDRA) version 24.0 or higher and will be summarized by System 
Organ Class and Preferred Term. 
Hematology, blood chemistry and urinalysis results will be summarized (actual values as well as 
change from baseline) by visit using summary statistics (n, mean, median, standard deviation, 
minimum and maximum) for continuous variables and shift tables for categorical variables. 
9.4.3. 
Other Analyses 
Other analyses will be described in the SAP. 
9.4.3.1. 
PK/PD 
PK and PD analyses will be described in the SAP (or PK analysis plan, as applicable), and 
finalized before database lock. Individual serum eculizumab (PK), free, and total C5 
concentration-time data will be listed, plotted, and summarized with descriptive statistics, with 
mean concentration-time data plotted. 
The PK data in this study might be pooled with other studies to conduct a population-PK 
modelling analyses. The potential impact of participant characteristics (covariates) on PK will be 
evaluated. The relationship between PK exposure and PD response may be explored. The 
population-PK analysis will be described in a separate SAP. The results of population-PK 
analysis will be presented in a separate report. 
9.4.3.2. 
Immunogenicity 
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. 
All ADA analyses will be performed on the Safety Set using the ADA variables included in 
Section 8.9.1. Additional details will be provided in the SAP. 
9.5. 
Interim Analyses 
An interim analysis will not be performed. 

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9.6. 
Data Monitoring Committee 
This study will not include a Data Monitoring Committee. 

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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Regulatory, Ethical, and Study Oversight Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
x This study will be conducted in accordance with the protocol and the following: 
 Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and CIOMS International Ethical Guidelines 
 Applicable ICH GCP Guidelines 
 Applicable laws and regulations 
x The protocol, substantial protocol amendments, ICF, IB, and other relevant 
documents (eg, advertisements) must be submitted to an IRB/IEC by the 
Investigator/Alexion and reviewed and approved by the IRB/IEC before the study is 
initiated. 
 If any of these documents require regulatory/health authority approval per local 
regulations, Alexion will also obtain such approval before the study is initiated. 
x Any substantial amendments to the protocol will require IRB/IEC and 
regulatory/health authority approval before implementation of changes made to the 
study design, except for changes necessary to eliminate an immediate hazard to study 
participants. 
x The Investigator will be responsible for the following: 
 Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC 
 Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
 Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 Code of Federal Regulations (CFR), ICH guidelines, the 
IRB/IEC, Directive 2001/20/EC, European regulation 536/2014 for clinical 
studies (if applicable), and all other applicable local regulations 
10.1.2. 
Financial Disclosure 
Investigators and Sub-Investigators will provide Alexion with sufficient, accurate financial 
information as requested to allow Alexion to submit complete and accurate financial certification 
or disclosure statements to the appropriate regulatory authorities. Investigators are responsible 
for providing information on financial interests during the course of the study and for 1 year after 
completion of the study. 

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10.1.3. 
Informed Consent Process 
x It is the responsibility of the Investigator or designee to obtain signed (written or 
electronic signature) informed consent and assent, where applicable, from all study 
participants, or the participant’s legally authorized representative, prior to performing 
any study-related procedures including screening assessments. 
x The Investigator or designee will explain the nature of the study (including but not 
limited to the objectives, potential benefits and risks, inconveniences, and the 
participant’s rights and responsibilities) to the participant 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. 
x Participants must be informed that their participation is voluntary. Participants or 
their legally authorized representative will be required to sign a statement of informed 
consent or assent or a certified translation, if applicable, that meets the requirements 
of 21 CFR 50, local regulations, EU General Data Protection Regulation (GDPR), 
ICH GCP guidelines, Health Insurance Portability and Accountability Act (HIPAA) 
requirements, where applicable, and the IRB/IEC or study center. 
x The participant’s medical record must include a statement that signed (written or 
electronic) informed consent or assent was obtained before any screening procedures 
were performed with a participant, and the date the written consent was obtained. The 
authorized person obtaining the informed consent or assent must also sign the 
informed consent or assent form(s). 
x Participants must be reconsented or reassented to the most current version of the 
informed consent or assent form(s) during their participation in the study, as 
applicable. 
x A copy of the signed (written or electronic) informed consent or assent 
documentation (ie, a complete set of participant information sheets and fully executed 
signature pages) must be provided to the participant or the participant’s legally 
authorized representative, as applicable. This document may require translation into 
the local language. Original signed (written or electronic) consent or assent forms 
must remain in each participant’s study file and must be available for verification at 
any time. 
Participants who are rescreened outside of the Screening window (Section 1.3) are required to 
sign a new ICF (Section 5.4).] 
10.1.4. 
Data Protection 
x Participants will be assigned a unique identifier by Alexion. Any participant records 
or datasets that are transferred to Alexion will contain the identifier only; participant 
names, initials, or any information which would make the participant identifiable will 
not be transferred. 
x Participants must be informed that their personal study-related data will be used in 
accordance with applicable data protection law, and participants must also be 
informed of any individual rights they may have with regard to their personal data. 

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Participants will be informed about how their personal study-related data will be 
disclosed and will be required to agree to the information contained in the informed 
consent and provide consent to the processing of their personal data, if required by 
applicable data protection law. 
x Participants must be informed that their medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by Alexion, 
appropriate IRB/IEC members, and inspectors from regulatory authorities. 
x Alexion as a data controller has implemented privacy and security controls designed 
to help protect participant personal data, including information security controls, 
firewalls, incident detection, and secure transfer measures. 
x In the event of any accidental or unlawful destruction, loss, alteration, unauthorized 
disclosure of, or access to, personal data (“breach”), the controller has implemented 
procedures and measures to promptly address and mitigate any risk to the data 
participant. In the event of a breach, the controller will notify the appropriate 
regulatory authorities and/or the data participant in accordance with applicable data 
protection law. 
10.1.5. 
Dissemination of Clinical Study Data 
Study-related information and study results may be posted on publicly accessible clinical study 
databases (eg, the US website www.clinicaltrials.gov or the EU website 
www.clinicaltrialsregister.eu), as appropriate, and in accordance with national, regional, and 
local regulations. 
10.1.6. 
Data Quality Assurance 
x All participant data relating to the study will be recorded on the 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 
electronically signing the eCRF. 
x The Investigator must maintain accurate documentation (source data) that supports 
the information entered in the eCRF. 
x The Investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents. 
x Alexion or designee is responsible for the data management of this study including 
quality checking of the data. 
x 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 participants 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. 

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 Remote source data verification may be employed where permitted by local 
regulations. 
 The scope of the source data verification will be described in detail in the Clinical 
Monitoring Plan. 
x Records and documents, including signed ICFs, pertaining to the conduct of this 
study must be retained by the Investigator after study completion per local regulations 
or institutional policies. No records may be destroyed without the written approval of 
Alexion. No records may be transferred to another location or party without written 
notification to Alexion. 
10.1.7. 
Source Documents 
Source documents provide evidence for the existence of the participant 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, raw data collection forms) designed to record all observations and other pertinent data 
for each participant. 
Data reported on the eCRF that are transcribed from source documents must be consistent with 
the source documents or the discrepancies must be explained. eCRFs must be completed by the 
Investigator or designee as indicated in the site delegation log. The Investigator may need to 
request previous medical records or transfer records, depending on the study. Also, current 
medical records must be available to Alexion, Alexion delegates, and health authorities, as 
requested. Source documents are filed at the investigational site. 
Per ICH E6 (R2) guidelines and good documentation practice requirements, source documents 
and study records in all media (eg, paper, electronic) must be Attributable, Legible, 
Contemporaneous, Original, Accurate, and Complete. 
10.1.8. 
Study and Site Start and Closure 
The study start date is the date of the first signed ICF. 
Alexion reserves the right to close the study site or terminate the study at any time for any reason 
at its sole discretion. 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 participants 
have completed the EOS or ED Visit and Safety Follow-up Phone Call if applicable, all data 
have been collected and entered into the electronic data capture (EDC) system, all required 
documents and study supplies have been collected and reconciled, 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: 
x Failure of the Investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, Alexion’s procedures, or ICH GCP guidelines 

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x Inadequate recruitment of participants by the Investigator 
x Discontinuation of further study intervention development 
Alexion or health authority may terminate the study for reasonable causes. Conditions that may 
warrant termination of the study include, but are not limited to: 
x Discovery of an unexpected, serious, or unacceptable risk of the study intervention to 
participants enrolled or continuing in the study. 
x Alexion decision to suspend or discontinue testing, evaluation, or development of the 
study intervention. 
If the study is prematurely terminated or suspended, Alexion shall promptly inform the 
Investigators, IRBs/IECs, 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 participant and should assure 
appropriate participant therapy and/or follow-up. 
10.1.9. 
Publication Policy 
x 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 EOS, whichever is earlier. 
x 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. 
x 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 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. 
x Primary publications, including congress and journal publications, containing the 
protocol-specified results of a study should occur prior to the 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. 
x Alexion will comply with the requirements for publication of study results as defined 
by the Pharmaceutical Research and Manufacturers of America and the International 
Committee of Medical Journal Editors and per the Alexion Publication Policy. In 

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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. 
x 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. 
x Alexion will publish Patient Lay Summaries and include participants and/or 
caregivers as reviewers for readability and understanding of lay person language. 
10.1.10. 
Good Clinical Practice Compliance 
Alexion and any third party to whom aspects of the study management or monitoring have been 
delegated will undertake their assigned roles for this study in compliance with all applicable 
industry regulations, ICH GCP Guideline E6 (R2), EU Directive 2001/20/EC, as well as all 
applicable national and local laws and regulations. 
Visits to sites are conducted by representatives of Alexion and/or the company 
organizing/managing the research on behalf of Alexion to inspect study data, participants’ 
medical records, and eCRFs in accordance with current GCP and respective local and national 
government regulations and guidelines. Records and data may additionally be reviewed by 
auditors or by regulatory authorities. 
Alexion ensures that local regulatory authority requirements are met before the start of the study. 
Alexion (or designee) is responsible for the preparation, submission, and confirmation of receipt 
of any regulatory authority approvals required prior to release of study intervention for shipment 
to the site. 

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10.2. 
Clinical Laboratory Tests 
x The tests detailed in Table 14 will be performed by the central laboratory. 
x Local laboratory results are only required in the event that the central laboratory 
results are not available in time for either study intervention administration and/or 
response evaluation. If a local sample is required, it is important that the sample for 
central analysis is obtained at the same time. Additionally, if the local laboratory 
results are used to make either a study intervention decision or response evaluation, 
the results must be entered into the CRF. 
x Protocol-specific requirements for inclusion or exclusion of participants are detailed 
in Section 5 of the protocol. 
x Additional tests may be performed at any time during the study as determined 
necessary by the Investigator or required by local regulations. 
x Women of childbearing potential (WOCBP) should only be enrolled after a negative 
serum pregnancy test. Additional pregnancy testing (urine or serum) should be 
performed per the timepoints specified in the SoA (Section 1.3). 
x Investigators must document their review of each laboratory safety report. 

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Table 14: 
Protocol-Required Safety Laboratory Assessments 
Hematology 
Free hemoglobin 
Haptoglobin 
Hematocrit 
Hemoglobin 
Mean corpuscular hemoglobin 
Platelet count 
RBC count 
RBC distribution width 
RBC mean corpuscular volume 
Reticulocyte count 
WBC count 
WBC differential 
 
Coagulation Panel 
International normalized ratio 
Partial thromboplastin time 
Prothrombin time 
 
Urine Chemistry 
Microalbumin 
Creatinine 
Total protein 
 
Urinalysis 
Albumin 
Appearance 
Bilirubin 
Blood 
Color 
Creatinine 
Glucose 
Ketone 
Nitrite 
pH 
Protein 
Specific gravity 
Urobilinogen 
Clinical Chemistry 
Alanine aminotransferase 
Albumin 
Alkaline phosphatase 
Amylase 
Aspartate aminotransferase 
Bicarbonate 
Blood urea nitrogen 
C-reactive protein 
Calcium 
Chloride 
Creatinine 
Gamma-glutamyltransferase 
Glucose 
Lactate dehydrogenase 
Magnesium 
Phosphorus 
Potassium 
Sodium 
Total bilirubin (direct and indirect) 
Total protein 
Uric acid 
Coombs 
 
Virus Serology 
HIV-1 
HIV-2 
 
Other 
ADA 
ADAMTS13 activity 
Beta human chorionic gonadotropin (females of 
childbearing potential only) 
Serum free and total C5 
Pharmacokinetic assay 
Shiga toxin-related HUS screen (eg, Shiga toxin enzyme 
immunoassay/PCR in stool/stool culture) 
Serum follicle-stimulating hormone (postmenopausal 
females only) 
Abbreviations: ADA = antidrug antibody; ADAMTS13 = a disintegrin and metalloproteinase with a 
thrombospondin type 1 motif, member 3; C5 = complement component 5; HIV = human immunodeficiency virus; 
HUS = hemolytic uremic syndrome; PCR = polymerase chain reaction; RBC = red blood cell; WBC = white blood 
cell 
Investigators must document their review of each laboratory safety report. 

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10.3. 
Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting 
10.3.1. 
Definition of AE 
AE Definition 
x 
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered 
a pharmaceutical product and which does not necessarily have to have a causal relationship with this 
treatment (ICH E2A). 
x 
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 the study 
intervention, whether or not considered related to the study intervention. 
 
Events Meeting the AE Definition 
x 
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). 
x 
Exacerbation of a chronic or intermittent pre-existing condition including either an increase in frequency 
and/or intensity of the condition. 
x 
New conditions detected or diagnosed after study intervention administration even though it may have been 
present before the start of the study. 
x 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
x 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study intervention 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. 
 
Events Not Meeting the AE Definition 
x 
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). 
x 
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. 
x 
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. 
x 
Cases of pregnancy that occur during maternal or paternal exposure to study intervention 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. 
x 
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 participant’s condition. 
x 
The disease/disorder being studied or expected progression, signs, or symptoms of the disease/disorder being 
studied, unless more severe than expected for the participant’s condition. 
x 
Situations in which an untoward medical occurrence did not occur (social and/or convenience admission to a 
hospital). 
x 
“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 fulfill the definition of 
an AE or SAE. 

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10.3.2. 
Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (eg, hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease). 
An SAE is defined as any untoward medical occurrence that, at any dose: 
1. Results in death 
2. Is life-threatening 
The term “life-threatening” in the definition of “serious” refers to an event in which the participant 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 participant 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 
x 
The term disability means a substantial disruption of a person’s ability to conduct normal life functions. 
x 
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: 
x 
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 participant 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. 
x 
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. 
 
A suspected unexpected serious adverse reaction (SUSAR) is defined as: 
An event that is assessed as serious by the Investigator and/or Alexion that is not listed in the appropriate 
Reference Safety Information (IB) and has been assessed that there is at least a reasonable possibility that the 
event is related to the investigational medicinal product by the Investigator and/or Alexion. 
Alexion has procedures that will be followed for the recording, medical assessment, and expedited reporting of 
SUSARs that are consistent with global regulations, legislation, and guidance documents. 
 
SUSARs will undergo expedited reporting to the national regulatory authorities, IRBs/IECs, and Investigators 
following local regulatory reporting requirements where applicable. 
10.3.3. 
Recording and Follow-Up of AE and/or SAE 
Recording of AE and/or SAE 
x 
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. 
x 
The Investigator will then record all relevant AE/SAE information in the eCRF. 
x 
It is not acceptable for the Investigator to send photocopies of the participant’s medical records to Alexion 
in lieu of completion of the Alexion AE/SAE eCRF page. 

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Recording of AE and/or SAE 
x 
There may be instances when copies of medical records for certain cases are requested by Alexion. In this 
case, all participant identifiers, with the exception of the participant number, will be redacted on the copies 
of the medical records before submission to Alexion. 
x 
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: 
x 
Grade 1: Mild (awareness of sign or symptom, but easily tolerated) 
x 
Grade 2: Moderate (discomfort sufficient to cause interference with normal activities) 
x 
Grade 3: Severe (incapacitating, with inability to perform normal activities) 
x 
Grade 4: Life-threatening 
x 
Grade 5: Fatal 
 
An event is defined as “serious” when it meets at least one of the predefined outcomes as described in the 
definition of an SAE, not when it is rated as severe. 
 
Assessment of Causality 
x 
The Investigator is obligated to assess the relationship between the study intervention 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 intervention 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 intervention. 
 
Related: There is a reasonable possibility the study intervention caused the AE. 
 
The AE has a temporal relationship to the administration of the study intervention. 
 
The event does not have a likely alternative etiology. 
 
The event corresponds with the known pharmaceutical profile of the study 
intervention. 
 
There is improvement on discontinuation and/or reappearance on rechallenge. 
x 
The Investigator will use clinical judgment to determine the relationship. 
x 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, as well as the 
temporal relationship of the event to study intervention administration will be considered and investigated. 
x 
The Investigator will also consult the IB and/or Product Information, for marketed products, in his/her 
assessment. 
x 
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. 
x 
There may be situations in which an SAE has occurred, and the Investigator has minimal information to 
include in the initial report to Alexion. 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. 
x 
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. 
x 
The causality assessment is one of the criteria used when determining regulatory reporting requirements. 
 

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Follow-up of AEs and SAEs 
x 
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 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. 
x 
If a participant dies during participation in the study or during a recognized follow-up period, the 
Investigator will provide Alexion with a copy of any postmortem findings including histopathology. 
x 
New or updated information will be recorded in the originally completed eCRF. 
x 
The Investigator will submit any updated SAE data to Alexion within 24 hours of receipt of the 
information. 
10.3.4. 
Reporting of SAEs 
SAE Reporting to Alexion via an Electronic Data Collection Tool 
x 
All SAEs will be recorded and reported to Alexion immediately and within 24 hours of awareness. 
x 
The primary mechanism for reporting an SAE to Alexion will be the EDC system. 
x 
If the electronic system is unavailable or site staff is unable to process the SAE via the EDC 
system 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 facsimile or email. Facsimile transmission or 
email may also be used in the event of electronic submission failure. 
 
Email: clinicalsae@alexion.com or Fax: + 1.203.439.9347 
x 
The site will enter the SAE data into the EDC system as soon as it becomes available. 
x 
When further information becomes available, the EDC should be updated immediately with the 
new information and an updated SAE report should be submitted to Alexion Global Drug Safety 
(GDS) within 24 hours of Investigator/site awareness. 
x 
After the participant has completed the study, no new data or changes to existing data are expected to be 
entered in the EDC system. 
o 
If a site receives a report of a new SAE from a study participant which the Investigator 
considers to be related to the study intervention, or the site receives updated data on a 
previously reported SAE after the EDC system has been taken offline, then the site can report 
this information on a paper Contingency Form for SAE Reporting via facsimile or email. 

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10.4. 
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 intervention, additional evaluation should be considered. 
Women in the Following Categories Are Not Considered WOCBP 
1. Premenarchal 
2. Premenopausal female with one of the following: 
x Documented hysterectomy 
x Documented bilateral tubal ligation or bilateral salpingectomy 
x Documented bilateral oophorectomy 
x 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. 
x Note: Documentation can come from the site personnel’s review of the participant’s 
medical records, medical examination, or medical history interview. 
3. Postmenopausal female 
x A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause prior to the Day 1 Visit. 
 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 one FSH measurement 
may be required. In the absence of 12 months of amenorrhea the reason for not 
obtaining FSH levels should be documented by the Investigator at the time of 
Screening. 
x 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. 
4. Permanent sterilization at least 6 weeks prior to the Day 1 Visit. 

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10.4.2. 
Contraception Guidance 
Contraceptive use by male or female participants should be consistent with local regulations 
regarding the methods of contraception utilized for those participating in clinical studies. If 
teratogenic effects are suspected to be transferred to a fetus/embryo from a female spouse/partner 
of a male participant, pregnancy follow-up information will be obtained for the partner who 
becomes pregnant (refer to Section 10.4.3.1). In these cases, follow-up will be conducted on the 
pregnant partner in the same manner as a female participant who becomes pregnant during the 
study. 
10.4.2.1. Guidance for Female Participants 
Female participants of childbearing potential must have a negative serum pregnancy test as 
required by local regulations before the first dose of study intervention. Additional requirements 
for pregnancy testing during and after dosing with study intervention are indicated in the SoA 
(Section 1.3). 
The Investigator is responsible for the review of medical history, menstrual history, and recent 
sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. 
The Investigator should evaluate the potential for contraceptive method in relationship to the first 
dose of study intervention. 
Female participants of childbearing potential must use a highly effective method of 
contraception, including at least 1 of the following until at least 5 months after the final dose of 
study intervention. 
1. Intrauterine device in place for at least 6 weeks prior to first dose of study intervention. 
2. Progestogen-only hormonal contraception associated with inhibition of ovulation (either 
oral, injectable, or implantable) for at least 6 weeks prior to first dose of study 
intervention. 
3. Intrauterine progestogen releasing system for at least 6 weeks prior to first dose of study 
intervention. 
4. Bilateral tubal occlusion for at least 6 weeks prior to first dose of study intervention. 
5. Combined (estrogen- and progestogen-containing) hormonal contraception (either oral, 
intravaginal, or transdermal) for at least 6 weeks prior to first dose of study intervention. 
6. Surgical sterilization of the male partner (medical assessment of azoospermia is required 
if vasectomy was performed within 6 months prior to first dose of study intervention). 
Male partner is still required to use condom during sexual intercourse. 
7. Sexual abstinence for female participants: 
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 participant’s preferred and usual lifestyle. Abstinent female 
participants must refrain from heterosexual intercourse for at least 5 months after the 
final dose of study intervention. 

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Other methods of contraception that are not considered as highly effective for female 
participants, but are acceptable birth control methods that result in a failure rate of more than 1% 
per year include: 
1. Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the 
primary mode of action 
2. Male or female condom with or without spermicide 
3. Cap, diaphragm, or sponge with spermicide 
4. A combination of male condom with cap, diaphragm, or sponge with spermicide 
(double-barrier methods) 
The following methods are considered unacceptable (ie, are not allowed) in this study: 
 Periodic abstinence (calendar, symptothermal or post ovulation methods) 
 Withdrawal (coitus interruptus) 
 Spermicides only 
 Lactational amenorrhea method 
 Female condom and male condom should not be used together 
10.4.2.2. Guidance for Male Participants 
Contraception is the responsibility of the heterosexually active male participants in the study, 
regardless of his female partner’s method of contraception. 
Male participants who have had a vasectomy > 6 months prior to the first dose of study 
intervention must use a condom during heterosexual intercourse. Male participants who have had 
a vasectomy < 6 months prior to the first dose study intervention and those who have not had a 
vasectomy must use a condom with or without spermicide during heterosexual intercourse for at 
least 5 months after their final dose of study intervention. 
10.4.2.2.1. Sexual Abstinence for Male Participants 
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 
participant’s preferred and usual lifestyle. Abstinent male participants who become 
heterosexually active must use a condom with or without 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 participants. 
Male participants must not donate sperm from the Day 1 Visit until 5 months (generally 
5.5 terminal half-lives) after their final dose of study intervention. 
10.4.3. 
Collection of Pregnancy Information 
Pregnancy data will be collected during this study for all female participants and female 
spouses/partners of male participants from the first dose of study intervention through 5 months 
after the final dose of study intervention. Any female participant who becomes pregnant during 

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the study should be considered for discontinuation from the study intervention and withdrawn 
from the study. Exposure during pregnancy (also referred to as exposure in utero) can be the 
result of either maternal exposure or transmission of study intervention via semen following 
paternal exposure. If a female participant or a male participant’s female spouse/partner becomes 
pregnant during the conduct of this study, the Investigator must submit the 
“Pregnancy/Breastfeeding Reporting and Outcome Form” to Alexion 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 intervention during breastfeeding must also be reported (via the 
“Pregnancy/Breastfeeding Reporting and Outcome Form”) and any AEs experienced by the 
infant must be reported to Alexion GDS via email or facsimile. 
Pregnancy is not regarded as an AE unless there is a suspicion that the study intervention 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. 
10.4.3.1. Male Participants with Partners Who Become Pregnant 
x The Investigator will attempt to collect pregnancy information on any male 
participant’s female partner who becomes pregnant while the male participant is in 
this study. This applies only to male participants who receive study intervention. 
x After obtaining the necessary signed informed consent from the pregnant female 
partner directly, the Investigator will record pregnancy information on the appropriate 
“Pregnancy/Breastfeeding Reporting and Outcome 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 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 Participants Who Become Pregnant 
x The Investigator will collect pregnancy information on any female participant who 
becomes pregnant while participating in this study. The information will be recorded 
on the “Pregnancy/Breastfeeding Reporting and Outcome Form” and submitted to 
Alexion within 24 hours of learning of a participant’s pregnancy. 
x 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 participant discontinues the study intervention 
or withdraws from the study. The Investigator will collect follow-up information on 
the participant and the neonate and the information will be forwarded to Alexion. 

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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. 
x 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 poststudy 
pregnancy-related SAE considered reasonably related to the study intervention by the 
Investigator will be reported to Alexion. While the Investigator is not obligated to 
actively seek this information in former study participants, he or she may learn of an 
SAE through spontaneous reporting. 
x Any female participant who becomes pregnant while participating in the study will 
discontinue study intervention and be withdrawn from the study. 
 

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10.5. 
COVID-19 Risk Assessment 
aHUS is a life-threatening disease if untreated. As such, and due to the limited number of 
available treatment options, the benefit a participant may receive from joining an investigational 
study with a therapeutic treatment is potentially significant. In this particular case, the fact that 
the study is open-label and every participant is treated with the study intervention also 
contributes to the potential benefit a participant may derive from participating in the study. 
Given that treatment for aHUS does involve immunosuppression, there is a theoretical concern 
that the risk for infection may be higher than in participants not receiving immunosuppressants. 
However, there is no specific data to further inform this risk. The site Investigator will therefore 
balance the risk/benefit considerations in the study participant taking these factors into account. 
The potential risks identified and mitigation measures put in place in light of the COVID-19 
pandemic are provided in Table 15. 
Table 15: 
Potential Risks and Mitigation Measures due to COVID-19 
Risks Category 
Summary of Data/ 
Rationale for Risk 
Mitigation Strategy 
Potential risks 
Healthcare institution 
availability for 
non-COVID-19-related 
activities  
COVID-19 pandemic may impact the workload of 
healthcare institutions globally and may reduce staff 
availability to perform nonurgent activities and 
non-COVID-19-related activities. 
During the time that the 
COVID-19 pandemic is active, 
Alexion will not open study 
sites or enroll new participants 
at sites unless the sites have the 
resourcing and capabilities to 
implement the study per 
protocol. 
Data quality and 
integrity 
Lack of availability of site personnel to perform 
study assessments and capture study specific data in 
a timely manner and to maintain adequate quality 
standards. 
Lack of availability of site personnel to ensure 
adequate and continuous chain of custody, storage 
conditions, and monitoring for investigational 
product and biological samples. 
Inability of study monitors and quality personnel to 
conduct in-person visits to exercise adequate 
oversight of study execution at investigational sites. 
Missing data (COVID-19 pandemic may impact 
study visit schedules and increase missed visits 
and/or participant study discontinuations 
inadvertently resulting in missing data [eg, for 
protocol-specified procedures]). 
During the time that the 
COVID-19 pandemic is active, 
Alexion will only open study 
sites that report enough 
personnel capacity to 
sufficiently conduct clinical 
study-related activities. 
During this timeframe, site 
capacity will be reviewed by the 
site Investigator and the study 
Medical Monitor prior to 
screening. Each site is also 
evaluated for the capacity to 
perform remote monitoring 
visits and remote source data 
verification. 
During the time that the 
COVID-19 pandemic is active, 
it will be important to capture 
specific information in the 
eCRF that explains the reason 

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Table 15: 
Potential Risks and Mitigation Measures due to COVID-19 
Risks Category 
Summary of Data/ 
Rationale for Risk 
Mitigation Strategy 
the data is missing (eg, missed 
study visits or participant study 
discontinuations due to 
COVID-19). 
Abbreviations: COVID-19 = coronavirus disease 2019; eCRF = electronic case report form 
 

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10.6. 
Protocol Amendment History 
The Protocol Amendment Summary of Changes table for the current amendment is located 
directly after the Table of Contents. 
DOCUMENT HISTORY 
Document 
Date 
Summary of Key Changes in the Amendment 
Protocol Amendment 1 
20 Jun 2022 
This amendment was initiated mainly to update exclusion criteria 
and pregnancy language 
Original Protocol 
30 Nov 2021 
Not applicable 
 

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10.7. 
Abbreviations 
The following abbreviations and terms are used in this study protocol. 
Table 16: 
Abbreviations and Specialist Terms 
Abbreviation or 
Term  
Explanation 
ADA 
antidrug antibody 
ADAMTS13 
a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 
AE 
adverse event 
AESI 
adverse event of special interest 
aHUS 
atypical hemolytic uremic syndrome 
APC 
alternative pathway of complement 
C5 
complement component 5 
C5b-9 
terminal complement complex 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CIOMS 
Council for International Organizations of Medical Sciences 
CKD 
chronic kidney disease 
CNI 
calcineurin inhibitor 
COVID-19 
coronavirus disease 2019 
CSR 
clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
ED 
early discontinuation from the study 
EDC 
electronic data capture 
eGFR 
estimated glomerular filtration rate  
ESKD 
end-stage kidney disease 
EOS 
end of study 
FAS 
Full Analysis Set 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 
GDS 
Global Drug Safety 
Hib 
Haemophilus influenzae type b 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
human immunodeficiency virus 
HRT 
hormonal replacement therapy 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements for Pharmaceuticals 
for Human Use 
IEC 
Independent Ethics Committee 
IgG1 
immunoglobulin G1 
INR 
international normalized ratio 

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Table 16: 
Abbreviations and Specialist Terms 
Abbreviation or 
Term  
Explanation 
IRB 
Institutional Review Board 
IV 
intravenous 
IVIg 
intravenous immunoglobulin 
LDH 
lactate dehydrogenase 
LLN 
lower limit of normal 
mAb 
monoclonal antibody 
MDRD 
Modification of Diet in Renal Disease 
MedDRA 
Medical Dictionary for Regulatory Activities 
mTORi 
mammalian target of rapamycin inhibitors 
PD 
pharmacodynamic(s) 
PK 
pharmacokinetic(s) 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SoA 
Schedule of Activities 
ST-HUS 
Shiga toxin-related hemolytic uremic syndrome 
SUSAR 
suspected unexpected serious adverse reactions 
TEAE 
treatment-emergent adverse event 
TESAE 
treatment-emergent serious adverse event 
TMA 
thrombotic microangiopathy 
ULN 
upper limit of normal 
WOCBP 
women of childbearing potential 
 

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11. 
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Ceriotti F, Boyd JC, Klein G, et al. Reference intervals for serum creatinine concentrations: 
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Constantinescu AR, Bitzan M, Weiss LS, et al. Non-enteropathic hemolytic uremic syndrome: 
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Fakhouri F, Fila M, Provot F, et al. Pathogenic Variants in Complement Genes and Risk of 
Atypical Hemolytic Uremic Syndrome Relapse after Eculizumab Discontinuation. Clin J Am 
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Levin A, Stevens P, Bilous R, et al. Kidney Disease Improving Global Outcomes (KDIGO). 
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Loirat C, Fremeaux-Bacchi V. Atypical hemolytic uremic syndrome. Orphanet J Rare Dis. 
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Noris M, Caprioli J, Bresin E, et al. Relative role of genetic complement abnormalities in 
sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol. 
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Salvadori M, Bertoni E. Update on hemolytic uremic syndrome: Diagnostic and therapeutic 
recommendations. World journal of nephrology. 2013;2(3):56-76. 
Schaefer F, Ardissino G, Ariceta G, et al. Clinical and genetic predictors of atypical hemolytic 
uremic syndrome phenotype and outcome. Kidney Int. 2018;94(2):408-418. 
Sellier-Leclerc AL, Fremeaux-Bacchi V, Dragon-Durey MA, et al. Differential impact of 
complement mutations on clinical characteristics in atypical hemolytic uremic syndrome. J Am 
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Socié G, Caby-Tosi MP, Marantz JL, et al. Eculizumab in paroxysmal nocturnal 
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