A Phase 3, Open-Label, Multicenter Study of ALXN1210 in Children and Adolescents With Atypical Hemolytic Uremic Syndrome (aHUS)
Phase: PHASE3
Conditions: Atypical Hemolytic Uremic Syndrome (aHUS)
Sponsor: Alexion Pharmaceuticals, Inc.

A PHASE 3, OPEN-LABEL, MULTICENTER STUDY OF 
ALXN1210 IN CHILDREN AND ADOLESCENTS WITH 
ATYPICAL HEMOLYTIC UREMIC SYNDROME (aHUS)  
 
 
Unique Protocol ID: 
ALXN1210-aHUS-312 
NCT Number: 
NCT03131219 
EudraCT Number:  
2016‐002499‐ 29  
Date of Protocol: 
16 July 2019 
 

Protocol ALXN1210-aHUS-312 
 
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1. 
TITLE PAGE 
PROTOCOL ALXN1210-aHUS-312 
A PHASE 3, OPEN-LABEL, MULTICENTER STUDY OF ALXN1210 IN 
CHILDREN AND ADOLESCENTS WITH ATYPICAL HEMOLYTIC 
UREMIC SYNDROME (aHUS) 
 
Sponsor: 
Alexion Pharmaceuticals, Inc. (Alexion) 
100 College Street 
New Haven, CT 06510 USA 
 
Sponsor Contact: 
 
 
Alexion Pharma GmbH  
Giesshübelstrasse 30 
8045 Zürich  
Telephone: 
 
Email: 
 
 
Medical Monitor: 
  
 
Alexion Pharmaceuticals, Inc. 
100 College Street 
New Haven, CT 06510 USA 
Telephone: 
 
Email: 
 
IND Number: 
128367 
EudraCT Number: 
2016‐002499‐29 
Date of Initial Protocol: 
23 Jan 2017 
Amendment 1 (Japan): 
16 Mar 2017 
Amendment 2 (Germany): 21 Mar 2017 
Amendment 3 (Japan): 
19 Oct 2017 (finalized but not distributed) 
Amendment 4 (Japan): 
02 Feb 2018 
Amendment 5 (Global): 
23 Aug 2018 
Amendment 6 (Global): 
16 Jul 2019 
 
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Protocol ALXN1210-aHUS-312 
 
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This protocol contains confidential information and is provided for exclusive use of 
Investigators. This information may only be disclosed to those persons involved in this study 
who have a need to know with the obligation not to further disseminate this information. This 
information may not be disclosed to other individuals unless such disclosure is required by 
country, federal, or state law or regulations subject to the foregoing. These restrictions on 
disclosure will apply equally to all future oral or written information supplied to you by Alexion 
which is designated as “privileged” or “confidential.” 

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Protocol ALXN1210-aHUS-312 
 
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INVESTIGATOR’S AGREEMENT 
 
I have received and read the Investigator’s Brochure for ALXN1210. I have read the 
ALXN1210-aHUS-312 study protocol and agree to conduct the study in accordance with this 
protocol, all applicable government regulations, the principles of the ICH E6 Guidelines for 
Good Clinical Practice, and the principles of the World Medical Association Declaration of 
Helsinki. I also agree to maintain the confidentiality of all information received or developed in 
connection with this protocol.  
 
 
 
 
 
____________________________________ 
Printed Name of Investigator 
 
_____________________________________ 
Signature of Investigator 
 
_______________ 
Date 
 

Protocol ALXN1210-aHUS-312 
 
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STUDY CONTACT INFORMATION 
 
Emergency Contact Information 
Study Role 
Name 
Address and Telephone Number 
Clinical Project Leader 
   
Alexion Pharma GmbH  
Giesshübelstrasse 30 
8045 Zürich  
Telephone: 
 
Email: 
 
Medical Monitor 
 
Alexion Pharmaceuticals, Inc. 
100 College Street 
New Haven, CT 06510 USA 
Telephone: 
 
Email: 
 
24-Hour Emergency Contact 
Phone Number 
 
 
 
 
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2. 
SYNOPSIS 
Name of Sponsor/Company: Alexion Pharmaceuticals, Inc. 
Name of Investigational Product: ALXN1210 
Name of Active Ingredient: ALXN1210 
Title of Study: A Phase 3, Open-Label, Multicenter Study of ALXN1210 in Children and Adolescents with 
Atypical Hemolytic Uremic Syndrome (aHUS)  
Protocol Number: ALXN1210-aHUS-312 
EudraCT Number: 2016-002499-29 
Study Centers: Approximately 70 investigative sites globally. 
Length of Study:  
Date first patient treated: September 2017 
Estimated date last patient completed (last patient last visit): 
TBD 
Phase of Development: 3 
 
Primary Objective:  
The primary objective of the study is to assess the efficacy of ALXN1210 in complement inhibitor treatment-naïve 
pediatric patients (ie, Cohort 1) with aHUS to inhibit complement-mediated thrombotic microangiopathy (TMA) as 
characterized by thrombocytopenia, hemolysis, and renal impairment.  
Secondary Objectives:  
The secondary objectives for complement inhibitor treatment-naïve patients (ie, Cohort 1) are to assess the 
following: 
1. To characterize the safety and tolerability of ALXN1210 
2. To evaluate the efficacy of ALXN1210 by the following additional measures: 
a. 
Dialysis requirement status 
b. Time to Complete TMA Response 
c. 
Complete TMA Response status over time 
d. Observed value and change from baseline in estimated glomerular filtration rate (eGFR) 
e. 
Chronic kidney disease (CKD) stage, as evaluated by eGFR at select target days and classified as 
improved, stable (no change), or worsened compared to baseline 
f. 
Observed value and change from baseline in hematologic parameters (platelets, lactate 
dehydrogenase [LDH], hemoglobin) 
g. Increase in hemoglobin of ≥ 20 g/L from baseline, observed at 2 separate assessments obtained at 
least 4 weeks (28 days) apart, and any measurement in between 
h. Change from baseline in quality of life (QoL), as measured by Pediatric Functional Assessment of 
Chronic Therapy (FACIT) Fatigue questionnaire 
i. 
TMA parameters in patients who discontinue treatment in the Extension Period, but remain in the 
study  
3. To characterize the pharmacokinetics (PK)/pharmacodynamics (PD) of ALXN1210: 
a. 
Changes in serum ALXN1210 concentration over time  
b. Changes in serum free complement component 5 (C5) concentrations over time 
c. 
Changes in serum free C5 and serum ALXN1210 concentration in patients who discontinue treatment 
in the Extension Period, but remain in the study 
4. To evaluate the long-term safety and efficacy of ALXN1210 
The secondary objectives for eculizumab-experienced patients (ie, Cohort 2) are to assess the following: 
1. To characterize the safety and tolerability of ALXN1210 
2. To evaluate the efficacy of ALXN1210 by the following measures: 
a. 
Dialysis requirement status 
b. Observed value and change from baseline in eGFR 
c. 
CKD stage, as evaluated by eGFR at select target days and classified as improved, stable (no change), 
or worsened compared to baseline 

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d. Observed value and change from baseline in hematologic parameters (platelets, LDH, hemoglobin) 
e. 
Change from baseline in QoL, as measured by Pediatric FACIT Fatigue questionnaire 
f. 
TMA parameters in patients who discontinue treatment in the Extension Period, but remain in the 
study 
3. To characterize the PK/PD of ALXN1210: 
a. 
Changes in serum ALXN1210 concentration over time  
b. Changes in serum free C5 concentrations over time 
c. 
Changes in serum free C5 and serum ALXN1210 concentration in patients who discontinue treatment 
in the Extension Period, but remain in the study 
4. To evaluate the long-term safety and efficacy of ALXN1210 
Study Design and Methodology:  
This is a Phase 3, single-treatment arm, multicenter study to evaluate the safety, efficacy, PK, and PD of 
ALXN1210 administered by intravenous (IV) infusion in approximately 23 to 28 pediatric patients, from birth to 
< 18 years of age, with confirmed diagnosis of aHUS. The study has 2 cohorts. Cohort 1 includes complement 
inhibitor treatment-naïve patients; Cohort 2 includes eculizumab-experienced adolescent patients (12 to < 18 years 
of age). The study consists of a Screening Period (of up to 7 days for Cohort 1 or up to 28 days for Cohort 2), a 
26-week Initial Evaluation Period, and an Extension Period until the product is registered or approved (in 
accordance with country-specific regulations) or for up to 4.5 years, whichever occurs first. 
 
Abbreviations: q4w = once every 4 weeks; q8w = once every 8 weeks  
a The Screening Period is up to 7 days for complement inhibitor treatment-naïve patients (ie, Cohort 1) and up to 
28 days for eculizumab-experienced adolescent patients (ie, Cohort 2).  
 
Consenting patients in Cohort 1 will be screened for study eligibility up to 7 days prior to Day 1. Consenting 
patients in Cohort 2 will be screened for study eligibility up to 28 days prior to Day 1; first dose of study drug will 
be given 14 days from the eligible patient’s last dose of eculizumab. Patients who are eligible based on the 
Inclusion and Exclusion Criteria will be enrolled into the Initial Evaluation Period and receive a weight-based 
loading dose of ALXN1210 on Day 1, followed by weight-based maintenance treatment with ALXN1210 on Day 
15 and q8w thereafter for patients weighing ≥ 20 kg, or once every 4 weeks (q4w) for patients weighing < 20 kg, 
for a total of 26 weeks of treatment. Weight-based dosing is based on the patient’s body weight recorded on Dose 
Regimen Decision Days (if the Dose Regimen Day is a dosing day, body weight will be recorded predose), as 
shown in the table below:  
Body Weight 
Range (kg)a 
Loading Dose (mg) 
Maintenance Doses (mg) 
Maintenance Dosing Frequency  
≥ 5 to < 10 
600 
300 
q4w 
≥ 10 to < 20 
600 
600 
q4w 
≥ 20 to < 30 
900 
2100 
q8w 
≥ 30 to < 40 
1200 
2700 
q8w 

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≥ 40 to < 60 
2400 
3000 
q8w 
≥ 60 to < 100 
2700 
3300 
q8w 
≥ 100 
3000 
3600 
q8w 
Abbreviations: q4w = once every 4 weeks; q8w = once every 8 weeks  
a Body weight as recorded on Dose Regimen Decision Days. If the Dose Regimen Day is also dosing day, body 
weight will be recorded predose with dosing that day based on the previous Dose Regimen Day body weight. 
 
An initial analysis, including review of ALXN1210 PK and serum free C5 levels, will be conducted after 4 
complement inhibitor treatment-naïve (ie, Cohort 1) patients weighing ≥ 5 kg to < 40 kg have completed dosing 
through Day 71. In addition, safety data will be reviewed by an independent Data Monitoring Committee (DMC). 
Enrollment of patients will proceed without interruption while the analysis is ongoing. The primary purpose of this 
review is to assure patients are achieving adequate complement inhibition during this study with the goal of 
achieving complete terminal complement blockade. Based on this review, if dose adjustment is considered needed 
and tolerable, subsequent treatment for all patients will continue at the adjusted dose regimen. After the Initial 
Evaluation Period, patients will roll over into an Extension Period in which all patients continue their weight-based 
maintenance dose of ALXN1210 on Day 183 and q8w thereafter for patients weighing ≥ 20 kg, or q4w for patients 
weighing < 20 kg, until the product is registered or approved (in accordance with country-specific regulation) or 
for up to 4.5 years, whichever occurs first. Note, q4w visits during the Extension Period are not applicable for 
patients weighing ≥ 20 kg and receiving ALXN1210 q8w. The end of trial is defined as the last patient’s last visit 
or follow-up (whether on site or via phone call) of the 4.5-year Extension Period, whichever is later.  
Number of Patients (planned): Approximately 23 to 28 pediatric patients with documented aHUS are planned. 
The minimum number of patients for each age category is as follows: 
• 
Birth to < 2 years: 4 patients 
• 
2 to < 6 years: 4 patients 
• 
6 to < 12 years: 4 patients 
• 
12 to < 18 years: 8 patients 
Cohort 2 patients must be 12 to < 18 years of age. 
Diagnosis and Main Criteria for Inclusion and Exclusion:  
Patients must satisfy all inclusion and exclusion criteria, in order to have a confirmed diagnosis of aHUS and be 
eligible for the study. Patients who fail any of the eligibility criteria may be rescreened based on discussion and 
agreement between the Investigator and the Medical Monitor. Patients may be rescreened a maximum of 2 times.  
For Cohort 1, samples collected at Screening may be tested at either 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. All analyses in this study will 
be based on results from the central laboratory (unless the result is missing). If Cohort 1 patients are found not to 
satisfy the eligibility criteria for serum creatinine (Inclusion Criterion 2c) based on central laboratory results, they 
must not be enrolled into the study; if the subject has received the first dose of ALXN1210, the patient must be 
withdrawn from the study, and may be replaced. For Cohort 1 patients, laboratory results for Exclusion Criterion 
number 1 and/or Exclusion Criterion number 2 may not be available prior to first dose. Later results for Exclusion 
Criterion number 1 and/or Exclusion Criterion number 2 could lead to discontinuation and replacement of the 
patient. 
 
For Cohort 2, samples collected at Screening must be tested at a central laboratory; however, historical test results 
via chart review should be utilized for Inclusion Criterion 3 and Exclusion Criteria 1, 2, 3, and 24. 
 
The following entry criteria are applicable for patients in both cohorts unless otherwise noted as specific for Cohort 
1 or Cohort 2:   
 
Inclusion Criteria:  
1. Patients from birth up to < 18 years of age and weighing ≥ 5 kg at the time of consent who: 
a. 
For Cohort 1 patients, have not been previously treated with complement inhibitors  
b. For Cohort 2 patients, are between 12 and <18 years of age and have been treated with eculizumab 
according to the labelled dosing recommendation for aHUS for at least 90 days prior to Screening 
2. For Cohort 1 patients, evidence of TMA, including thrombocytopenia, evidence of hemolysis, and kidney 

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injury, based on the following laboratory findings: 
a. 
Platelet count < 150,000 per microliter (µL) during the Screening Period or within 28 days prior to 
the start of the Screening Period, and 
b. 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 within 28 days prior to the start of the Screening Period, and 
c. 
Serum creatinine level ≥ 97.5th percentile for age at Screening (patients who require dialysis for acute 
kidney injury are also eligible regardless of serum creatinine level). 
3. For Cohort 2 patients, documented diagnosis of aHUS including: 
a. 
Increase in LDH > ULN and creatinine > ULN, and decrease in platelets < LLN documented by local 
laboratories at the time of the TMA event 
4. For Cohort 2 patients, clinical evidence of response to eculizumab indicated by stable TMA parameters 
(via central laboratory results) at Screening, including: 
a. 
LDH < 1.5 X ULN, and 
b. Platelet count ≥ 150,000 /μL, and 
c. 
eGFR > 30 mL/min/1.73m2 using the Schwartz formula 
5. Among patients with a kidney transplant: 
a. 
Known history of aHUS prior to current kidney transplant, or 
b. No known history of aHUS, and 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). 
6. Among patients with onset of TMA postpartum, persistent evidence of TMA for > 3 days after the day of 
childbirth. 
7. To reduce the risk of meningococcal infection (Neisseria meningitidis), all patients must be vaccinated 
against meningococcal infections within 3 years prior to, or at the time of, initiating study drug. Patients 
who receive a meningococcal vaccine less than 2 weeks before initiating ALXN1210 treatment must 
receive treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination. Patients who 
have not been vaccinated prior to initiating ALXN1210 treatment should receive prophylactic antibiotics 
prior to and for at least 2 weeks after meningococcal vaccination. Patients who cannot be vaccinated must 
receive antibiotic prophylaxis for the entire treatment period and for 8 months following last dose. 
8. Patients must have been vaccinated against Haemophilus influenzae type b (Hib) and Streptococcus 
pneumoniae according to national and local vaccination schedule guidelines. 
9. Female patients of childbearing potential and male patients with female partners of childbearing potential 
must follow protocol-specified guidance for avoiding pregnancy while on treatment and for 8 months after 
last dose of study drug. 
10. Patient's legal guardian must be willing and able to give written informed consent and the patient must be 
willing to give written informed assent (if applicable as determined by the central or local Institutional 
Review Board [IRB]/Institutional (or Independent) Ethics Committee [IEC]) and comply with the study 
visit schedule. 
 
Exclusion Criteria: 
1. Known familial or acquired ‘a disintegrin and metalloproteinase with a thrombospondin type 1 motif, 
member 13’ (ADAMTS13) deficiency (activity < 5%). 
2. Known Shiga toxin-related hemolytic uremic syndrome (ST-HUS) as demonstrated by a positive test for 
Shiga toxin or culture of Shiga toxin producing bacteria. 
3. Positive direct Coombs test.  
4. Known Human Immunodeficiency Virus (HIV) infection. 
5. Unresolved meningococcal disease. 

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6. Patients with a 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 bacterial infection that, in the opinion of the 
Investigator, confounds an accurate diagnosis of aHUS or impedes the ability to manage the aHUS 
disease. 
8. Females who plan to become pregnant during the study or are currently pregnant or breastfeeding. 
9. Heart, lung, small bowel, pancreas, or liver transplant. 
10. Among patients with a kidney transplant, acute kidney dysfunction within 4 weeks of transplant consistent 
with the diagnosis of acute antibody-mediated rejection (AMR) according to Banff 2013 criteria.  
11. Among patients 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) 
12. Identified drug exposure-related HUS. 
13. For Cohort 1 patients, receiving plasma exchange/plasma infusion (PE/PI), for 28 days or longer, prior to 
the start of Screening for the current TMA.  
14. History of malignancy within 5 years of Screening with the exception of a non-melanoma skin cancer or 
carcinoma in situ of the cervix that has been treated with no evidence of recurrence. 
15. Bone marrow transplant (BMT)/hematopoietic stem cell transplant (HSCT) within the last 6 months prior 
to the start of Screening. 
16. HUS related known genetic defects of cobalamin C metabolism. 
17. Known systemic sclerosis (scleroderma), systemic lupus erythematosus (SLE), or antiphospholipid 
antibody positivity or syndrome. 
18. Chronic dialysis (defined as dialysis on a regular basis as renal replacement therapy for end-stage kidney 
disease [ESKD]). 
19. Patients 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. 
20. Patients receiving other immunosuppressive therapies such as steroids, mTORi (eg, sirolimus, 
everolimus), CNI (eg, cyclosporine or tacrolimus) are excluded unless:  
a. 
part of an established post-transplant antirejection regimen, or  
b. patient has confirmed anti-complement factor antibodies requiring immunosuppressive therapy, or  
c. 
steroids are being used for a condition other than aHUS (eg, asthma). 
21. Participation in another interventional treatment study or use of any experimental therapy within 30 days 
before initiation of study drug on Day 1 in this study or within 5 half-lives of that investigational product, 
whichever is greater. 
22. For Cohort 1 patients, prior use of any complement inhibitors 
23. For Cohort 2 patients, prior use of complement inhibitors other than eculizumab. 
24. For Cohort 2 patients, any known abnormal TMA parameters within 90 days prior to Screening (ie, LDH 
≥ 1.5 X ULN, or platelet count < 150,000/μL, or eGFR ≤ 30 mL/min/1.73m2 using the Schwartz formula). 
25. Hypersensitivity to any ingredient contained in the study drug, including hypersensitivity to murine 
proteins.  
26. Any medical or psychological condition that, in the opinion of the Investigator or Sponsor, could increase 
the risk to the patient by participating in the study or confound the outcome of the study. 
27. Known or suspected history of drug or alcohol abuse or dependence within 1 year prior to the start of 

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Screening. 
28. Use of tranexamic acid within 7 days prior to Screening is prohibited. 
Investigational Product, Dosage, and Mode of Administration:  
For Cohort 1 and Cohort 2, ALXN1210 loading doses on Day 1 and maintenance doses on Day 15 and q8w 
thereafter for patients weighing ≥ 20 kg, or q4w for patients weighing < 20 kg will be administered by IV infusion. 
Dosages are based on the patient’s body weight recorded on Dose Regimen Decision Days (if the Dose Regimen 
Day is a dosing day, body weight will be recorded predose), as shown in the table below: 
  
Body Weight 
Range (kg)a 
Loading Dose (mg) 
Maintenance Doses (mg) 
Maintenance Dosing Frequency  
≥ 5 to < 10 
600 
300 
q4w 
≥ 10 to < 20 
600 
600 
q4w 
≥ 20 to < 30 
900 
2100 
q8w 
≥ 30 to < 40 
1200 
2700 
q8w 
≥ 40 to < 60 
2400 
3000 
q8w 
≥ 60 to < 100 
2700 
3300 
q8w 
≥ 100 
3000 
3600 
q8w 
Abbreviations: q4w = once every 4 weeks; q8w = once every 8 weeks  
a Body weight as recorded on Dose Regimen Decision Days. If the Dose Regimen Day is also dosing day, body 
weight will be recorded predose with dosing that day based on the previous Dose Regimen Day body weight. 
 
During the Initial Evaluation Period, changes to dose regimen (dose level [ie, mg] or dose frequency [ie, q4w vs 
q8w]) will be based on the patient’s body weight on the “Dose Regimen Decision Day (patients on q4w or q8w 
schedules)” preceding the day of administration. Patients changing from q4w to q8w will be administered their first 
q8w dose on the ALXN1210 administration day (“ALXN1210 administration [patients weighing > 20 kg]”) 
following the “Dose Regimen Decision Day (patients on q4w or q8w schedules)”. Patients changing from q8w to 
q4w will be administered their first q4w dose on the ALXN1210 administration day (“ALXN1210 administration 
[patients weighing < 20 kg]”) following the “Dose Regimen Decision Day (patients on q4w or q8w schedules)”. 
 
During the Extension Period, the dose of ALXN1210 is based on the patient’s body weight on the preceding “Dose 
Regimen Decision Day (patients on q4w schedule)” or “Dose Regimen Decision Day (patients on q8w schedule)”. 
Patients changing from q4w to q8w will be administered their first q8w dose on the ALXN1210 administration day 
(“ALXN1210 administration [patients weighing > 20 kg]”) following the “Dose Regimen Decision Day (patients 
on q4w schedule)”. Patients changing from q8w to q4w will be administered their first q4w dose on the 
ALXN1210 administration day (“ALXN1210 administration [patients weighing < 20 kg]”) 8 weeks after the “Dose 
Regimen Decision Day (patients on q8w schedule)”.  
Planned Duration of Treatment: 26-week Initial Evaluation Period followed by an Extension Period until the 
product is registered or approved (in accordance with country-specific regulations) or for up to 4.5 years, 
whichever occurs first. 
Reference Therapy, Dosage, and Mode of Administration: Not applicable 
Endpoints:  
Efficacy Assessments  
As patients previously treated with eculizumab have stabilized TMA parameters at study entry, Cohort 2 patients 
will be excluded from the following efficacy assessments: Complete TMA Response, Time to Complete TMA 
Response, Complete TMA Response status over time, and increase in hemoglobin from baseline. 
Primary  
The primary efficacy endpoint for Cohort 1 is Complete TMA Response during the 26-week Initial 
Evaluation Period, as evidenced by normalization of hematological parameters (platelet count and LDH) 
and ≥ 25% improvement in serum creatinine from baseline. Patients must meet all Complete TMA 
Response criteria at two separate assessments obtained at least 4 weeks (28 days) apart, and any 
measurement in between.  
 

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Secondary 
The secondary efficacy endpoints for Cohort 1 are the following and will be measured through 26 weeks and over 
the entire study period: 
1. Dialysis requirement status 
2. Time to Complete TMA Response 
3. Complete TMA Response status over time 
4. Observed value and change from baseline in eGFR 
5. CKD stage, as evaluated by eGFR at select target days and classified as improved, stable (no change), or 
worsened compared to baseline 
6. Observed value and change from baseline in hematologic parameters (platelets, LDH, hemoglobin) 
7. Increase in hemoglobin of ≥ 20 g/L from baseline, observed at 2 separate assessments obtained at least 4 
weeks (28 days) apart, and any measurement in between 
8. Change from baseline in QoL, as measured by Pediatric FACIT Fatigue questionnaire (patients ≥ 5 years 
of age). 
9. TMA parameters in patients who discontinue treatment in the Extension Period, but remain in the study  
 
The secondary efficacy endpoints for Cohort 2 are the following and will be measured through 26 weeks and over 
the entire study period:  
1. Dialysis requirement status 
2. Observed value and change from baseline in eGFR 
3. CKD stage, as evaluated by eGFR at select target days and classified as improved, stable (no change), or 
worsened compared to baseline 
4. Observed value and change from baseline in hematologic parameters (platelets, LDH, hemoglobin) 
5. Change from baseline in QoL, as measured by Pediatric FACIT Fatigue questionnaire (patients ≥ 5 years 
of age) 
6. TMA parameters in patients who discontinue treatment in the Extension Period, but remain in the study 
 
Pharmacokinetics/Pharmacodynamics 
The following PK/PD endpoints are applicable for Cohort 1 and Cohort 2:  
1. Changes in serum ALXN1210 concentration over time  
2. Changes in serum free C5 concentrations over time 
3. Changes in serum free C5 and serum ALXN1210 concentration in patients who discontinue treatment in 
the Extension Period, but remain in the study 
 
Exploratory 
The following exploratory endpoints are applicable for Cohort 1 and Cohort 2: 
Biomarkers 
Exploratory biomarkers of PD effect may include, but are not limited to, change from baseline in levels of markers 
of complement dysregulation (eg, Factor Ba), vascular inflammation (eg, soluble tumor necrosis factor receptor 1 
[sTNFR1]), endothelial activation/damage (eg, soluble vascular adhesion molecule 1 [sVCAM-1], 
thrombomodulin), coagulation (eg, D-dimer), and renal injury (eg, cystatin C). Additional assessments may include 
measurements of ALXN1210 excretion in urine, chicken red blood cell (cRBC) hemolysis, total C5, autoantibodies 
to complement proteins (eg, anti-factor H). 
 
Genetics 
Exploratory genetics may be performed to investigate genetic variants in genes known to be associated with aHUS, 
as well as to identify novel genetic variants associated with aHUS, complement dysregulation, or metabolism or 
efficacy of ALXN1210. Patients (or legal guardian) may decline from providing a sample for exploratory genetics 
and still participate in the study. 
 

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Extra-renal Signs or Symptoms of aHUS 
The Investigator will evaluate extra-renal signs or symptoms of aHUS using clinical laboratory measurements, 
vital signs, and an organ system review. 
 
Safety  
For Cohort 1 and Cohort 2, the long-term safety and tolerability of ALXN1210 will be evaluated by physical 
examinations, vital signs, physical growth (height, weight, and head circumference [the latter only in patients ≤ 2 
years of age]), electrocardiograms (ECG), laboratory assessments, and incidence of adverse events (AEs) and 
serious adverse events (SAEs). The proportion of patients who develop antidrug antibodies (ADA) will also be 
assessed. 
Sample Size: 
The total planned sample size is approximately 23 to 28 patients. This sample size is deemed appropriate to get 
proper representation in each of the 4 planned age groups. 
Statistical methods:  
General: All data collected will be presented using summary tables, figures, and data listings. All analyses will be 
performed using SAS® release, version 9.4 or higher (SAS Institute Inc., Cary, NC, USA) or other validated 
statistical software. Continuous variables will be summarized using descriptive statistics, including number of 
observations and mean, standard deviation (SD), median, minimum, and maximum values. Categorical variables 
will be summarized by frequency counts and percentage of patients. The analyses for Cohort 1 and Cohort 2 will 
be conducted and reported separately. Analyses specific to Cohort 1 are indicated as such below; all other 
endpoints will be performed for both cohorts. Tabulated summaries will not include a direct comparison between 
Cohort 1 and Cohort 2.  
An interim clinical study report (CSR) will be prepared when 12 to 14 complement inhibitor treatment-naïve (ie, 
Cohort 1) patients have completed or withdrawn from the 26-week Initial Evaluation Period. An additional interim 
CSR will be prepared when all study patients have completed or withdrawn from the 26-week Initial Evaluation 
Period. Each interim CSR will include efficacy, safety, and PK/PD analyses. A final CSR to summarize long-term 
efficacy, safety, and PK/PD will be produced at study completion. Available exploratory data will be summarized 
after study completion but may not be included in the CSR. All data collected will be presented using summary 
tables, figures, and data listings. Planned summaries will be presented overall and by age groups when applicable. 
 
Efficacy: Efficacy analyses will be performed on the Full Analysis Set (FAS). The analysis of the FAS will be the 
primary analysis.  
The FAS for Cohort 1 will be based on a modified intent to treat (mITT) approach. With this approach, 
confirmation of eligibility in patients may occur after receiving study drug. This specifically applies to Inclusion 
Criterion number 2c (must be confirmed via a central laboratory), Exclusion Criterion number 1 (may be 
confirmed via a central or local laboratory), and Exclusion Criterion number 2 (may be confirmed via a central or 
local laboratory). Based on the above, the FAS will include all patients who receive at least 1 dose of ALXN1210, 
have at least 1 postbaseline efficacy assessment, and meet all of the following criteria (these are the same criteria 
that if not satisfied will result in discontinuation of the patient and potential replacement):  
• 
Patients who satisfy Inclusion Criterion number 2c  
• 
Patients who satisfy Exclusion Criterion number 1 
• 
Patients who satisfy Exclusion Criterion number 2 
 
The FAS for Cohort 2 will include all patients who receive at least 1 dose of ALXN1210 and have at least 1 
postbaseline efficacy assessment. 
 
The FAS will be determined prior to database lock and prior to the database snapshots for the analyses performed 
at the end of the 26-week Initial Evaluation Period. 
  
Primary efficacy: 
The primary efficacy endpoint is Complete TMA Response during the 26-week Initial Evaluation Period. The 
primary analysis will consist in estimating the proportion of complete TMA responders among ALXN1210 treated 
patients. This will be performed by calculating the point estimate and a 95% confidence interval (CI) for the 
proportion of complete TMA responders in ALXN1210 treated patients. The CI will be based on exact confidence 
limits using the Clopper-Pearson method. This analysis will only be performed for Cohort 1. 

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Secondary efficacy: 
For the secondary efficacy endpoint of time to Complete TMA Response, 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 (CDF) estimate, the number of patients at risk, the number of patients responding, 
and the number of patients censored at each postbaseline time point. The table will also present first quartile, 
median, and third quartile, along with corresponding 2-sided 95% CI, of time to complete response. This analysis 
will only be performed for Cohort 1. 
 
Complete TMA response will also be summarized over time by presenting the number and proportion of 
responders along with a 2-sided 95% CI for each postbaseline time point. A similar approach will be used to 
summarize the number and proportion of patients with an increase from baseline in hemoglobin ≥ 20 g/L, observed 
at 2 separate assessments obtained at least 4 weeks (28 days) apart, and any measurement in between. This analysis 
will only be performed for Cohort 1. 
 
Kidney function (dialysis requirement status, eGFR, CKD stage) as well as hematologic parameters (platelets, 
LDH, hemoglobin) will be summarized at baseline and each postbaseline time point. These analyses will be 
performed for both Cohort 1 and Cohort 2. Descriptive statistics for continuous variables (eGFR, platelets, LDH, 
hemoglobin) will be used to summarize the observed value as well as the change from baseline. A mixed model for 
repeated measures (MMRM) with the fixed, categorical effect of visit and fixed, continuous effect of the specific 
test’s baseline value as covariates may be fit to test whether changes differ from zero at each time point. Dialysis 
requirement status and CKD stage will be summarized over time. Dialysis requirement status will be summarized 
among patients receiving dialysis within 5 days prior to ALXN1210 treatment initiation by presenting the number 
and proportion of those patients receiving and not receiving dialysis at each time point. A 2-sided 95% CI for the 
proportion receiving dialysis will be provided. CKD stage will be summarized over time by presenting the number 
and proportion of patients that improved (excluding those with Stage 1 at baseline as they cannot improve), 
worsened (excluding those 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. 
A 2-sided 95% CI for the proportion will be provided for each category. 
 
Quality of life will be assessed in patients ≥ 5 years of age by the Pediatric FACIT Fatigue Questionnaire (patient-
reported for patients who were ≥ 8 years of age at the time of enrollment; caregiver-reported or caregiver assistance 
for patients who were 5 to < 8 years of age at the time of enrollment). This measure will be summarized at baseline 
and each postbaseline time point using descriptive statistics for continuous variables for the observed value as well 
as the change from baseline. A MMRM with the fixed, categorical effect of visit and fixed, continuous effect of the 
test’s baseline value as covariates may be fit to test whether changes differ from zero at each time point. These 
analyses will be performed for both Cohort 1 and Cohort 2. Analyses will be separate for patients who were 5 to 
< 8 years of age at the time of enrollment (ie, caregiver-reported or caregiver assistance) and patients who were ≥ 8 
years of age at the time of enrollment (ie, patient-reported). 
 
Safety: 
Safety analyses will be performed on the Safety Set defined as all patients who received at least 1 dose of 
ALXN1210 for both Cohort 1 and Cohort 2. The incidence of treatment emergent adverse events (TEAEs) and 
SAEs will be summarized by system organ class (SOC) and preferred term (PT) overall, by severity, and by 
relationship to treatment.  
 
Observed values and changes from baseline (last assessment prior to ALXN1210) in ECGs, vital signs, and 
laboratory assessments, as well as presence of ADA will be summarized. Shifts from baseline in laboratory 
assessments will be summarized for all study visits. These analyses will be performed for both Cohort 1 and 
Cohort 2. 
 
Pharmacokinetics/Pharmacodynamics:  
Sparse PK and PD (serum free C5) samples will be collected over the course of the study. Individual serum 
concentration data for all patients from the FAS and who have evaluable PK data will be used to derive the PK 
parameters for ALXN1210. These analyses will be performed for both Cohort 1 and Cohort 2. 
 

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Graphs of mean serum concentration-time profiles will be constructed. Graphs of serum concentration-time 
profiles for individual patients may also be provided. Actual dose administration and sampling times will be used 
for all calculations. Descriptive statistics will be calculated for serum concentration data at each sampling time, as 
appropriate. Assessment of population-PK may be considered using data from this study or in combination with 
data from other studies. 
 
Pharmacodynamic analyses will be performed for all patients from the Cohort 1 FAS and Cohort 2 FAS who have 
evaluable PD data. The PD effects of ALXN1210 will be evaluated by assessing the absolute values and changes 
and percentage changes from baseline in serum free C5 concentrations over time, as appropriate. Descriptive 
statistics will be calculated for the PD data at each sampling time, as appropriate.  Assessments of PK/PD 
relationships may be explored using data from this study or in combination with data from other studies. 
 
Exploratory 
Biomarkers: 
Exploratory analyses may be conducted for both Cohort 1 and Cohort 2 to evaluate changes from baseline in 
biomarkers which may include, but are not limited to, markers of complement dysregulation (eg, Factor Ba), 
vascular inflammation (eg, sTNFR1), endothelial activation/damage (eg, sVCAM-1, thrombomodulin) coagulation 
(eg, D-dimer), and renal injury (eg, cystatin C). Additional analysis may include evaluation of ALXN1210 
excretion in urine, cRBC hemolysis, total C5, autoantibodies to complement proteins (eg, anti-factor H). 
 
Genetics:  
Exploratory genetics may be performed for both Cohort 1 and Cohort 2 to investigate genetic variants in genes 
known to be associated with aHUS, as well as to identify novel genetic variants associated with aHUS, 
complement dysregulation, or metabolism or efficacy of ALXN1210. Patients (or legal guardian) may decline from 
providing a sample for exploratory genetics and still participate in the study. 
 
Extra-renal Signs or Symptoms of aHUS: 
Extra-renal signs or symptoms of aHUS will be summarized at baseline and each postbaseline assessment by 
presenting the number and proportion of patients with a specific symptom present. This analysis will be performed 
for both Cohort 1 and Cohort 2. 
 

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3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES  
TABLE OF CONTENTS 
1. 
TITLE PAGE ................................................................................................................1 
SPONSOR SIGNATURE PAGE ....................................................................................................3 
INVESTIGATOR’S AGREEMENT ...............................................................................................4 
STUDY CONTACT INFORMATION ...........................................................................................5 
2. 
SYNOPSIS ...................................................................................................................6 
3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............16 
TABLE OF CONTENTS ...............................................................................................................16 
LIST OF TABLES .........................................................................................................................21 
LIST OF FIGURES .......................................................................................................................21 
4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS .............................22 
5. 
INTRODUCTION ......................................................................................................24 
5.1. 
Benefits and Risks Assessment ..................................................................................25 
5.1.1. 
Potential Benefits ........................................................................................................25 
5.1.2. 
Identified and Potential Risks .....................................................................................25 
5.1.2.1. 
Meningococcal Infection ............................................................................................25 
5.1.2.2. 
Immunogenicity ..........................................................................................................25 
5.1.2.3. 
Pregnancy Exposure ...................................................................................................26 
6. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................27 
6.1. 
Study Objectives .........................................................................................................27 
6.1.1. 
Primary Objective .......................................................................................................27 
6.1.2. 
Secondary Objectives .................................................................................................27 
6.2. 
Endpoints ....................................................................................................................28 
6.2.1. 
Primary Efficacy Endpoint .........................................................................................28 
6.2.2. 
Secondary Efficacy Endpoints ....................................................................................28 
6.2.3. 
Pharmacokinetic and Pharmacodynamic Endpoints ...................................................29 
6.2.4. 
Safety Endpoints .........................................................................................................29 
6.2.5. 
Exploratory Endpoints ................................................................................................29 
6.2.5.1. 
Biomarkers ..................................................................................................................29 
6.2.5.2. 
Genetics Endpoints .....................................................................................................30 

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6.2.5.3. 
Extra-renal Signs or Symptoms of aHUS ...................................................................30 
7. 
INVESTIGATIONAL PLAN .....................................................................................31 
7.1. 
Summary of Study Design ..........................................................................................31 
7.2. 
Discussion of Design ..................................................................................................32 
7.3. 
Schedule of Assessments ............................................................................................32 
8. 
STUDY POPULATION .............................................................................................46 
8.1. 
Inclusion Criteria ........................................................................................................46 
8.2. 
Exclusion Criteria .......................................................................................................48 
8.3. 
Discontinuation ...........................................................................................................50 
8.3.1. 
Early Termination of Patients From the Study ...........................................................50 
8.3.2. 
Discontinuation of ALXN1210 Treatment in the Extension Period and 
Continuation in the Study ...........................................................................................51 
8.3.2.1. 
Retreatment of Patients Who Discontinue ALXN1210 Treatment in the 
Extension Period .........................................................................................................51 
8.3.3. 
Discontinuation of Study/Site Termination by Sponsor or Health Authority ............53 
8.3.4. 
Replacements ..............................................................................................................53 
8.3.5. 
End of Study Definition ..............................................................................................54 
9. 
STUDY TREATMENT ..............................................................................................55 
9.1. 
Materials and Supplies ................................................................................................55 
9.1.1. 
Description of Study Drugs ........................................................................................55 
9.1.2. 
Study Drug Packaging and Labeling ..........................................................................55 
9.1.3. 
Study Drug Storage .....................................................................................................55 
9.1.4. 
Study Drug Preparation and Infusion .........................................................................56 
9.1.5. 
Study Drug Handling and Disposal ............................................................................56 
9.2. 
Treatments Administered ............................................................................................57 
9.3. 
Method of Assignment to Treatment ..........................................................................58 
9.4. 
Rationale for Selection of Doses in the Study ............................................................59 
9.5. 
Special Treatment Considerations ..............................................................................59 
9.6. 
Prior and Concomitant Medications and Nonpharmacologic Procedures ..................59 
9.7. 
Prohibited Medications and Procedures .....................................................................60 
9.8. 
Vaccination .................................................................................................................60 
9.9. 
Treatment Compliance ................................................................................................61 
9.10. 
Contraception Guidance .............................................................................................61 

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10. 
EFFICACY ASSESSMENTS ....................................................................................63 
10.1. 
Primary Efficacy Assessment .....................................................................................63 
10.2. 
Secondary Efficacy Assessments ...............................................................................63 
11. 
SAFETY ASSESSMENTS ........................................................................................65 
11.1. 
Demographic/Medical History ...................................................................................65 
11.1.1. 
Demographics and Baseline Characteristics ...............................................................65 
11.1.2. 
Disease Characteristics ...............................................................................................65 
11.1.3. 
Medical History ..........................................................................................................65 
11.2. 
Physical Examinations ................................................................................................65 
11.3. 
Vital Signs ..................................................................................................................66 
11.4. 
Laboratory Assessments .............................................................................................66 
11.4.1. 
Pregnancy Screen ........................................................................................................67 
11.4.2. 
Hematology .................................................................................................................67 
11.4.3. 
Serum Chemistry ........................................................................................................67 
11.4.4. 
Coagulation .................................................................................................................67 
11.4.5. 
Urinalysis and Urine Chemistry .................................................................................67 
11.5. 
Electrocardiograms .....................................................................................................67 
11.6. 
Immunogenicity ..........................................................................................................67 
11.7. 
Adverse Event Management .......................................................................................68 
11.7.1. 
Targeted Adverse Events ............................................................................................68 
11.7.2. 
Severity Assessment ...................................................................................................68 
11.7.3. 
Causality Assessment .................................................................................................69 
11.7.4. 
Serious Adverse Events ..............................................................................................70 
11.7.5. 
Suspected Unexpected Serious Adverse Reactions ....................................................70 
11.7.6. 
Collection and Reporting of Adverse Events .............................................................70 
11.7.6.1. 
All Adverse Events .....................................................................................................70 
11.7.6.2. 
Serious Adverse Events ..............................................................................................71 
11.7.7. 
Sponsor Reporting Requirements ...............................................................................71 
11.7.8. 
Investigator Reporting Requirements .........................................................................72 
11.8. 
Exposure During Pregnancy and Breastfeeding .........................................................72 
11.9. 
Safety Monitoring .......................................................................................................72 
12. 
PHARMACOKINETICS AND PHARMACODYNAMICS 
ASSESSMENTS .........................................................................................................73 

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13. 
EXPLORATORY ASSESSMENTS ..........................................................................74 
13.1. 
Biomarker Assessments ..............................................................................................74 
13.2. 
Genetics ......................................................................................................................74 
13.3. 
Extra-renal Signs or Symptoms of aHUS ...................................................................74 
14. 
DATA QUALITY ASSURANCE ..............................................................................75 
14.1. 
Data Collection and Storage .......................................................................................75 
14.2. 
Records Retention .......................................................................................................76 
15. 
STATISTICAL METHODS AND PLANNED ANALYSES ...................................77 
15.1. 
General Considerations ...............................................................................................77 
15.2. 
Determination of Sample Size ....................................................................................78 
15.3. 
Analysis Sets ...............................................................................................................78 
15.4. 
Demographics and Baseline Characteristics ...............................................................78 
15.5. 
Patient Disposition ......................................................................................................79 
15.6. 
Prior and Concomitant Medications and Nonpharmacologic Therapies and 
Procedures ...................................................................................................................79 
15.7. 
Treatment Compliance ................................................................................................79 
15.8. 
Efficacy Analyses .......................................................................................................79 
15.8.1. 
Primary Efficacy Analysis ..........................................................................................79 
15.8.2. 
Key Secondary Efficacy Analyses ..............................................................................79 
15.8.2.1. 
Dialysis Requirement Status .......................................................................................79 
15.8.2.2. 
Time to Complete TMA Response .............................................................................80 
15.8.2.3. 
Complete TMA Response Status Over Time .............................................................80 
15.8.2.4. 
eGFR Value and Change from Baseline .....................................................................80 
15.8.2.5. 
CKD Stage ..................................................................................................................80 
15.8.2.6. 
Hematologic Parameters .............................................................................................80 
15.8.2.7. 
Hemoglobin Response ................................................................................................80 
15.8.2.8. 
Quality of Life ............................................................................................................81 
15.9. 
Safety Analyses ..........................................................................................................81 
15.9.1. 
Adverse Events ...........................................................................................................81 
15.9.2. 
Physical Examination and Vital Signs ........................................................................81 
15.9.3. 
Clinical Laboratory Tests ...........................................................................................82 
15.9.4. 
Electrocardiograms .....................................................................................................82 
15.9.5. 
Immunogenicity ..........................................................................................................82 

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15.10. 
Pharmacokinetic/ Pharmacodynamic Analyses ..........................................................82 
15.11. 
Exploratory Analyses ..................................................................................................83 
15.11.1. 
Biomarker Analyses ....................................................................................................83 
15.11.2. 
Genetics ......................................................................................................................83 
15.11.3. 
Extra-renal Signs or Symptoms of aHUS ...................................................................83 
15.12. 
Other Statistical Issues ................................................................................................83 
15.12.1. 
Missing or Invalid Data ..............................................................................................83 
15.13. 
Interim Analyses .........................................................................................................83 
16. 
INFORMED CONSENT, ETHICAL REVIEW, AND REGULATORY 
CONSIDERATIONS ..................................................................................................85 
16.1. 
Informed Consent and Assent .....................................................................................85 
16.2. 
Data Monitoring Committee .......................................................................................85 
16.3. 
Ethical Review ............................................................................................................86 
16.4. 
Regulatory Considerations ..........................................................................................86 
16.4.1. 
Changes/Deviations to Protocol .................................................................................86 
16.5. 
Publication Policy .......................................................................................................86 
17. 
LIST OF REFERENCES ............................................................................................87 
18. 
APPENDICES ............................................................................................................88 
APPENDIX A. BLOOD SAMPLING VOLUMES ....................................................................89 
APPENDIX B. COMMON CREATININE REFERENCE INTERVALS .................................90 
APPENDIX C. ANTIBODY MEDIATED REJECTION CRITERIA .......................................91 
APPENDIX D. MANAGEMENT OF POTENTIAL DRUG INFUSION REACTIONS ..........92 
APPENDIX E. PROTOCOL LABORATORY TESTS .............................................................94 
APPENDIX F. PEDIATRIC FACIT-FATIGUE ........................................................................95 
APPENDIX G. GLOMERULAR FILTRATION RATE CATEGORY/STAGE IN 
CHRONIC KIDNEY DISEASE .................................................................................96 
 

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LIST OF TABLES 
Table 1: 
Schedule of Study Visits and Assessments: Screening Period Through Initial 
Evaluation Period ........................................................................................................34 
Table 2: 
 Schedule of Study Visits and Assessments: Extension Period Day 183 to 
Day 911 .......................................................................................................................37 
Table 3: 
 Schedule of Study Visits and Assessments: Extension Period Day 939 to 
Day 1667 .....................................................................................................................40 
Table 4: 
 Schedule of Study Visits and Assessments: Extension Period Day 1695 to 
Day 1863 .....................................................................................................................43 
Table 5: 
Study Drug ..................................................................................................................55 
Table 6: 
Dosing Reference Chart for ALXN1210 Dose Preparation .......................................56 
Table 7: 
Loading and Maintenance Treatment Regimens ........................................................58 
Table 8: 
Adverse Event Severity Grading Scale .......................................................................69 
Table 9: 
Causality Assessment Descriptions ............................................................................69 
Table 10: Clinical Criteria for Diagnosing Anaphylaxis ............................................................93 
 
LIST OF FIGURES 
Figure 1: 
Study Design Schematic for Clinical Protocol ALXN1210-aHUS-312 .....................31 
 
 

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4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Definition 
ADA 
antidrug antibodies 
ADAMTS13 
a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13  
ADL 
activities of daily living 
AEs 
adverse events 
aHUS 
atypical hemolytic uremic syndrome 
AMR 
antibody-mediated rejection  
APC 
alternative pathway of complement 
BMT 
bone marrow transplant 
BP 
blood pressure 
C5 
complement component 5 
CDF 
cumulative distribution function 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CKD 
chronic kidney disease 
CNI 
calcineurin inhibitor  
cRBC 
chicken red blood cell 
CSR 
Clinical Study Report 
CTCAE 
Common Terminology Criteria for Adverse Events 
DMC 
Data Monitoring Committee 
ECG 
Electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
eGFR 
estimated glomerular filtration rate 
EOI 
end of infusion 
ESKD 
end-stage kidney disease  
ET 
early termination 
FACIT 
functional assessment of chronic illness therapy 
FAS 
full analysis set 
GCP 
good clinical practice 
GPV 
Global Pharmacovigilance 
Hib 
Haemophilus influenzae type b  
HIV 
human immunodeficiency virus 
HSCT 
hematopoietic stem cell transplant  
HUS 
hemolytic uremic syndrome 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
IEC 
Institutional (or Independent) Ethics Committee 
IRB 
Institutional Review Board 
IV 
Intravenous 
IVIg 
intravenous immunoglobulin  

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Abbreviation 
Definition 
LDH 
lactate dehydrogenase 
LLN 
lower limit of normal 
LLT 
lowest level term 
MedDRA® 
Medical Dictionary for Regulatory Activities 
mITT 
modified Intent to Treat 
MMRM 
mixed model for repeated measures 
mTORi 
mammalian target of rapamycin inhibitor  
PD 
pharmacodynamic 
PEF 
peak expiratory flow 
PE/PI 
plasma exchange/plasma infusion 
PK 
pharmacokinetic 
PNH 
paroxysmal nocturnal hemoglobinuria 
PO 
orally 
PT 
preferred term 
QoL 
quality of life 
q4w 
once every 4 weeks 
q8w 
once every 8 weeks 
SAEs 
serious adverse events 
SAP 
Statistical Analysis Plan 
SD 
standard deviation 
SLE 
systemic lupus erythematosus  
SOC 
system organ class 
SOPs 
standard operating procedures 
ST-HUS 
Shiga toxin-related hemolytic uremic syndrome 
sTNFR1 
soluble tumor necrosis factor receptor 1 
SUSAR 
suspected unexpected serious adverse reactions 
sVCAM-1 
soluble vascular adhesion molecule 1 
TEAEs 
treatment-emergent adverse events 
TMA 
thrombotic microangiopathy  
ULN 
upper limit of normal 
 

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5. 
INTRODUCTION 
Atypical hemolytic uremic syndrome (aHUS) is a complement-mediated thrombotic 
microangiopathy (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). Patients with aHUS are at risk for life-threatening manifestations of 
disease resulting from endothelial damage, including thrombocytopenia, intravascular hemolysis, 
acute renal failure, and extra-renal tissue damage. Importantly, approximately 20% of patients 
experience extra-renal manifestations of disease, including central nervous system, cardiac, 
gastrointestinal, distal extremity, and severe systemic organ involvement (Loirat, 2011; 
Brodsky, 2015). 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. 
Chronic, uncontrolled terminal complement activation, specifically, activation of complement 
component 5 (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 C5b-9, represents an important therapeutic 
mechanism of treatment.  
Eculizumab (Soliris®) is the standard of care for aHUS patients. Eculizumab is a humanized 
monoclonal antibody that specifically binds to the complement protein C5 with high affinity. 
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 IgG1 isotype to FcγR IIa. Upon binding to the complement protein C5, eculizumab blocks 
cleavage to C5a and C5b by C5 convertase; which prevents generation of the terminal 
complement complex C5b-9. These attributes underlie the established safety and therapeutic 
efficacy profile of eculizumab as demonstrated in the 3 pivotal Phase 2 clinical studies (C10-003, 
C10-004, and C08-002A/B) and supported by subsequent postmarketing experiences.  
ALXN1210 and eculizumab are both recombinant, humanized monoclonal antibodies against 
human complement protein C5 sharing over 99% amino acid sequence homology. The goal of 
treatment with these complement inhibitors is to achieve immediate, complete, and sustained 
blockade of terminal complement activity. ALXN1210 is produced in Chinese hamster cells and 
was designed through minimal targeted engineering to substitute 4 amino acids in the 
eculizumab heavy chain to extend antibody half-life. These changes are designed to increase the 
half-life of ALXN1210 relative to eculizumab, increasing the duration of complete terminal 
complement inhibition, while preserving both the high degree of specificity for binding to C5 
and the effectorless nature of the antibody. 
Two studies of ALXN1210 are ongoing in patients with paroxysmal nocturnal hemoglobinuria 
(PNH) who are naïve to treatment with complement inhibitors. Study ALXN1210-PNH-103 is a 
Phase 1b, open-label, multiple dose study, and Study ALXN1210-PNH-201 is a Phase 2, 
open-label, multiple dose study. ALXN1210-PNH-103 is designed to assess dose ranging over a 
2-fold range of trough exposure levels, while Study ALXN1210-PNH-201 is designed to assess 

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dose intervals of 4, 6, 8, and 12 weeks. Each study in patients with PNH also includes a 2-year 
extension phase. In addition, Study ALXN1210-HV-104 is being conducted to assess the 
pharmacokinetic (PK) profile of ALXN1210 in healthy Japanese subjects. 
Preliminary data from ALXN1210-PNH-103, indicate ALXN1210 treatment resulted in rapid 
reductions in lactate dehydrogenase (LDH) levels in 100% of patients, which were sustained 
through 2 to 4 monthly dosing intervals, consistent with the extended half-life (t½) of 
ALXN1210 (Lee, 2016). There was a notable decrease in the need for blood transfusions. These 
preliminary LDH data suggest that rapid, complete, and sustained complement inhibition with 
ALXN1210 results in highly effective blockade of intravascular hemolysis.  
More information about the PK, mechanism of action, known and expected benefits, risks, and 
reasonably anticipated adverse events (AEs) of ALXN1210 may be found in the current edition 
of the Investigator’s Brochure (IB). 
This amendment is designed to gain experience in adolescent patients switching from 
eculizumab to ALXN1210.  
5.1. 
Benefits and Risks Assessment 
5.1.1. 
Potential Benefits 
ALXN1210 and eculizumab are recombinant, humanized monoclonal antibodies that bind the 
same epitope on complement protein C5 and deliver rapid, sustained, and specific inhibition of 
C5 activation and the terminal complement cascade through identical mechanisms of action. Due 
to its close pharmacological relationship to eculizumab and specificity for C5, ALXN1210 is 
anticipated to allow longer dosing intervals while having a safety and efficacy profile similar to 
eculizumab. While eculizumab is an effective therapy for the treatment of aHUS, chronic 
administration of the eculizumab regimen may pose an important burden to patients, many of 
whom have to miss days of work or school to accommodate once-every-2-week treatment. In 
some cases, patients may refuse treatment or are not compliant due to the frequency of treatment. 
Practice survey research supports the assumption that less frequent once-every-8-week infusions 
associated with ALXN1210 will have a positive impact on daily life for patients and their 
caregivers. 
5.1.2. 
Identified and Potential Risks 
5.1.2.1. 
Meningococcal Infection 
Increased susceptibility to infection caused by Neisseria meningitidis, is a known risk associated 
with complement inhibition. Similar to eculizumab, the main risk associated with ALXN1210 is 
the risk of meningococcal infections. Specific risk mitigation measures are in place to address 
this risk, as described in Section 9.8. 
5.1.2.2. 
Immunogenicity 
As a humanized mAb, administration of ALXN1210 may be associated with immunogenicity 
reactions similarly to any therapeutic protein. Monitoring of immunogenicity is in place for this 
study as described in Section 7.3 and Section 11.6.  

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5.1.2.3. 
Pregnancy Exposure 
No studies of ALXN1210 have been conducted in pregnant women. Pregnant or nursing female 
patients are excluded from the clinical trial. Patients enrolled in the study, and their 
spouse/partner, will use a highly effective or acceptable method of contraception as required in 
Section 9.10. 
 

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6. 
STUDY OBJECTIVES AND ENDPOINTS 
6.1. 
Study Objectives 
6.1.1. 
Primary Objective 
The primary objective of the study is to assess the efficacy of ALXN1210 in complement 
inhibitor treatment naïve pediatric patients (ie, Cohort 1) with aHUS to inhibit 
complement-mediated TMA as characterized by thrombocytopenia, hemolysis, and renal 
impairment. 
6.1.2. 
Secondary Objectives 
The secondary objectives for complement inhibitor treatment-naïve patients (ie, Cohort 1) are to 
assess the following: 
1. To characterize the safety and tolerability of ALXN1210 
2. To evaluate the efficacy of ALXN1210 by the following additional measures: 
a. Dialysis requirement status 
b. Time to Complete TMA Response 
c. Complete TMA Response status over time 
d. Observed value and change from baseline in estimated glomerular filtration rate 
(eGFR) 
e. Chronic kidney disease (CKD) stage, as evaluated by eGFR at select target days and 
classified as improved, stable (no change), or worsened compared to baseline 
f. Observed value and change from baseline in hematologic parameters (platelets, LDH, 
hemoglobin) 
g. Increase in hemoglobin of ≥ 20 g/L from baseline, observed at 2 separate assessments 
obtained at least 4 weeks (28 days) apart, and any measurement in between 
h. Change from baseline in quality of life (QoL), as measured by Pediatric Functional 
Assessment of Chronic Therapy (FACIT) Fatigue questionnaire 
i. TMA parameters in patients who discontinue treatment in the Extension Period, but 
remain in the study 
3. To characterize the PK/pharmacodynamics (PD) of ALXN1210: 
a. Changes in serum ALXN1210 concentration over time  
b. Changes in serum free C5 concentration over time 
c. Changes in serum free C5 and serum ALXN1210 concentration in patients who 
discontinue treatment in the Extension Period, but remain in the study 
4. To evaluate the long-term safety and efficacy of ALXN1210 
 
The secondary objectives for eculizumab-experienced patients (ie, Cohort 2) are to assess the 
following: 
1. To characterize the safety and tolerability of ALXN1210 

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2. To evaluate the efficacy of ALXN1210 by the following measures: 
a. Dialysis requirement status 
b. Observed value and change from baseline in eGFR 
c. CKD stage, as evaluated by eGFR at select target days and classified as improved, 
stable (no change), or worsened compared to baseline 
d. Observed value and change from baseline in hematologic parameters (platelets, LDH, 
hemoglobin) 
e. Change from baseline in QoL, as measured by Pediatric FACIT Fatigue questionnaire 
f. TMA parameters in patients who discontinue treatment in the Extension Period, but 
remain in the study 
3. To characterize the PK/PD of ALXN1210: 
a. Changes in serum ALXN1210 concentration over time  
b. Changes in serum free C5 concentrations over time 
c. Changes in serum free C5 and serum ALXN1210 concentration in patients who 
discontinue treatment in the Extension Period, but remain in the study 
4. To evaluate the long-term safety and efficacy of ALXN1210 
6.2. 
Endpoints 
6.2.1. 
Primary Efficacy Endpoint 
The primary efficacy endpoint for Cohort 1 is Complete TMA Response during the 26-week 
Initial Evaluation Period, as evidenced by normalization of hematological parameters (platelet 
count and LDH) and ≥ 25% improvement in serum creatinine from baseline. Patients must meet 
all Complete TMA Response criteria at 2 separate assessments obtained at least 4 weeks 
(28 days) apart, and any measurement in between. 
6.2.2. 
Secondary Efficacy Endpoints 
The secondary efficacy endpoints for Cohort 1 are the following and will be measured through 
26 weeks and over the entire study period: 
1. Dialysis requirement status 
2. Time to Complete TMA Response 
3. Complete TMA Response status over time 
4. Observed value and change from baseline in eGFR 
5. CKD stage, as evaluated by eGFR at select target days and classified as improved, stable 
(no change), or worsened compared to baseline 
6. Observed value and change from baseline in hematologic parameters (platelets, LDH, 
hemoglobin) 
7. Increase in hemoglobin of ≥ 20 g/L from baseline, observed at 2 separate assessments 
obtained at least 4 weeks (28 days) apart, and any measurement in between 

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8. Change from baseline in QoL, as measured by Pediatric FACIT Fatigue questionnaire 
(patients ≥ 5 years of age) 
9. TMA parameters in patients who discontinue treatment in the Extension Period, but 
remain in the study 
The secondary efficacy endpoints for Cohort 2 are the following and will be measured through 
26 weeks and over the entire study period: 
1. Dialysis requirement status 
2. Observed value and change from baseline in eGFR 
3. CKD stage, as evaluated by eGFR at select target days and classified as improved, stable 
(no change), or worsened compared to baseline 
4. Observed value and change from baseline in hematologic parameters (platelets, LDH, 
hemoglobin) 
5. Change from baseline in QoL, as measured by Pediatric FACIT Fatigue questionnaire 
(patients ≥ 5 years of age) 
6. TMA parameters in patients who discontinue treatment in the Extension Period, but 
remain in the study 
6.2.3. 
Pharmacokinetic and Pharmacodynamic Endpoints 
The following PK/PD endpoints are applicable for Cohort 1 and Cohort 2: 
1. Changes in serum ALXN1210 concentration over time 
2. Changes in serum free C5 concentration over time 
3. Changes in serum free C5 and serum ALXN1210 concentration in patients who 
discontinue treatment in the Extension Period, but remain in the study 
6.2.4. 
Safety Endpoints 
For Cohort 1 and Cohort 2, the safety and tolerability of ALXN1210 will be evaluated by 
physical examinations, vital signs, physical growth (height, weight, and head circumference [the 
latter only in patients ≤ 2 years of age]) electrocardiograms (ECGs), laboratory assessments, and 
incidence of AEs and serious adverse events (SAEs). The proportion of patients who develop 
antidrug antibodies (ADA) will also be assessed. 
6.2.5. 
Exploratory Endpoints 
The following exploratory endpoints are applicable for Cohort 1 and Cohort 2: 
6.2.5.1. 
Biomarkers 
Exploratory biomarkers of PD effect may include, but are not limited to, change from baseline in 
levels of markers of complement dysregulation (eg, Factor Ba), vascular inflammation (eg, 
soluble tumor necrosis factor receptor 1 [sTNFR1]), endothelial activation/damage (eg, soluble 
vascular adhesion molecule 1 [sVCAM-1], thrombomodulin), coagulation (eg, D-dimer), and 
renal injury (eg, cystatin C). Additional assessments may include measurements of ALXN1210 

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excretion in urine, chicken red blood cell (cRBC) hemolysis, total C5, autoantibodies to 
complement proteins (eg, anti-factor H). 
6.2.5.2. 
Genetics Endpoints 
Exploratory genetics may be performed to investigate genetic variants in genes known to be 
associated with aHUS, as well as to identify novel genetic variants associated with aHUS, 
complement dysregulation or metabolism or efficacy of ALXN1210. Patients (or legal guardian) 
may decline from providing a sample for exploratory genetics and still participate in the study. 
6.2.5.3. 
Extra-renal Signs or Symptoms of aHUS 
The Investigator will evaluate extra-renal signs or symptoms of aHUS using clinical laboratory 
measurements, vital signs, and an organ system review. 
 

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7. 
INVESTIGATIONAL PLAN 
7.1. 
Summary of Study Design 
Study ALXN1210-aHUS-312 is a Phase 3, open-label, single-treatment arm, multicenter study to 
evaluate the safety, efficacy, PK, and PD of ALXN1210 administered by intravenous (IV) 
infusion to approximately 23 to 28 pediatric patients, from birth to < 18 years of age, with 
confirmed diagnosis of aHUS. The study has 2 cohorts. Cohort 1 includes complement inhibitor 
treatment-naïve patients; Cohort 2 includes eculizumab-experienced adolescent patients (12 to 
< 18 years of age). The study consists of 3 periods: a Screening Period (of up to 7 days for 
Cohort 1 patients or up to 28 days for Cohort 2 patients), a 26-week Initial Evaluation Period, 
and an Extension Period until the product is registered or approved (in accordance with 
country-specific regulations) or for up to 4.5 years, whichever occurs first. 
Figure 1 illustrates the study design. 
Figure 1: 
Study Design Schematic for Clinical Protocol ALXN1210-aHUS-312 
 
Abbreviations: q4w = once every 4 weeks; q8w = once every 8 weeks  
a  The Screening Period is up to 7 days for complement inhibitor treatment-naïve patients (ie, Cohort 1) and up to 
28 days for eculizumab-experienced adolescent patients (ie, Cohort 2). 
 
Consenting patients in Cohort 1 will be screened for study eligibility up to 7 days prior to Day 1.  
Consenting patients in Cohort 2 will be screened for study eligibility up to 28 days prior to 
Day 1; first dose of study drug will be given 14 days from the eligible patient’s last dose of 
eculizumab. Patients who are eligible based on the Inclusion and Exclusion Criteria will be 
enrolled into the Initial Evaluation Period and receive a loading dose of ALXN1210 on Day 1, 
followed by maintenance treatment with ALXN1210 on Day 15 and q8w thereafter for patients 
weighing ≥ 20 kg, or once every 4 weeks (q4w) for patients weighing < 20 kg. The loading dose 
and maintenance dose will be based on the patient’s body weight recorded on Dose Regimen 
Decision Days (Table 7). If the Dose Regimen Day is also dosing day, body weight will be 
recorded predose with dosing that day based on the previous Dose Regimen Day body weight. 

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An initial analysis, including review of ALXN1210 PK and serum free C5 levels, will be 
conducted after 4 complement inhibitor treatment-naïve (ie, Cohort 1) patients weighing ≥ 5 kg 
to < 40 kg have completed dosing through Day 71.  In addition, safety data will be reviewed by 
an independent Data Monitoring Committee (DMC). Enrollment of patients will proceed without 
interruption while the analysis is ongoing. The primary purpose of this review is to assure 
patients are achieving adequate complement inhibition during this study with goal of achieving 
complete terminal complement blockade. Based on this review, if dose adjustment is considered 
needed and tolerable, subsequent treatment for all patients will continue at the adjusted dose 
regimen. After the Initial Evaluation Period, patients will roll over into an Extension Period in 
which all patients continue their weight-based maintenance dose of ALXN1210 on Day 183 and 
q8w thereafter for patients weighing ≥ 20 kg, or q4w for patients weighing < 20 kg, until the 
product is registered or approved (in accordance with country-specific regulation) or for up to 
4.5 years, whichever occurs first. Note, q4w visits during the Extension Period are not applicable 
for patients weighing ≥ 20 kg and receiving ALXN1210 q8w. The end of trial is defined as the 
last patient’s last visit or follow-up (whether on site or via phone call) of the 4.5-year Extension 
Period, whichever is later.  
7.2. 
Discussion of Design  
This Phase 3, open-label, study will evaluate the PK/PD, efficacy, safety and tolerability of 
ALXN1210 in the treatment of pediatric patients with aHUS. This amendment is designed to 
gain experience in adolescent patients switching from eculizumab to ALXN1210. The study has 
2 cohorts. Cohort 1 includes complement inhibitor treatment-naïve patients; Cohort 2 includes 
eculizumab-experienced adolescent patients (12 to < 18 years of age). As the prevalence of 
newly diagnosed aHUS is lower in adolescents than in adults and younger ages, evaluation of 
ALXN1210 in an adolescent switch patient cohort (Cohort 2) will provide sufficient safety and 
PK data in this group to understand the safety and PK profile of ALXN1210 across the range of 
age groups. 
Four pediatric age groups were selected to test potential dose regimens across a series of body 
weight categories for the predicted Cmax and trough serum concentrations of ALXN1210. The 
doses and regimen are expected to result in a complete terminal complement blockade after the 
first dose for all aHUS patients within each body weight group and to maintain ALXN1210 
concentrations below the maximum ALXN1210 concentrations achieved in Phase 2. At least 
4 patients are planned for the birth to < 2 year, 2 to < 6 year, and 6 to < 12 year age groups. At 
least 8 patients are planned for the 12 to < 18 year age group. 
7.3. 
Schedule of Assessments 
The Schedule of Assessments for Screening and the Initial Evaluation Period is shown in 
Table 1. The Schedule of Assessments for the Extension Period is shown in Table 2, Table 3, and 
Table 4. 
Refer to the Laboratory Manual for details on the number of samples and volumes for all 
sampling and tests during the study. An alternative blood sampling schedule for infants, for 
whom less blood volume should be collected, must be used as detailed in the Study Operations 
Manual. 

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Additional (unscheduled) visits outside the specified visits are permitted at the discretion of the 
Investigator. Procedures, tests, and assessments will be performed at the discretion of the 
Investigator. Any tests, procedures, or assessments performed at the Unscheduled Visits must be 
recorded on the electronic Case Report Forms (eCRFs). Local laboratory or central laboratory 
analysis may be used for Unscheduled Visit tests. However, if local laboratory tests are to be 
used, duplicate samples will be collected at the Unscheduled Visit for central laboratory testing.  
In the event that a supplemental dose is administered or the loading dose for patients 
≥ 5 to < 10 kg is administered as 2 separate infusions no more than approximately 24 hours apart 
(as described in Section 9.2), an abbreviated physical examination will be conducted, vital signs 
will be collected, and the safety card will be reviewed with the patient. If a supplemental dose is 
administered, PK/PD samples will be collected predose and at end of infusion (EOI); a negative 
pregnancy test result is required prior to administering study drug to female patients of 
childbearing potential. If a loading dose is administered as 2 separate infusions < 24 hours apart, 
PK/PD samples will be collected before the first infusion (ie, the predose sample) and after the 
second infusion (ie, the EOI sample).

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Table 1: 
Schedule of Study Visits and Assessments: Screening Period Through Initial Evaluation Period  
Period 
Screening 
Initial Evaluation Period 
Study Day 
–7 or -28a to –1 
1 
8 
15 
22 
29 
43 
57 
71 
85 
99 
113 
127 
141 
155 
169 
183b/ET 
Window (day) 
N/A 
 
±2 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±5 
±5 
±5 
±5 
±5 
±5 
±2 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confirmation or administration of meningococcal 
vaccinationc 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history and demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ADAMTS13d 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ST-HUS screend, e 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Direct Coombs testd 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Head circumference (patients up to 2 years of age) 
X 
X 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Height and weightf 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy testg 
X 
X 
 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
Pediatric FACIT-Fatigue questionnaireh 
 
X 
X 
 
 
X 
 
 
X 
 
 
 
X 
 
 
 
X 
Physical examination 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Abbreviated physical examinationi 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Assessment of extra-renal signs or symptoms of aHUS 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signsj 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Safety 12-Lead ECGk 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
Chemistryl,f 
Xm 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology including free hemoglobin and coagulationn,f 
Xm 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis and urine chemistry 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
X 
PK/PD samplingo 
 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Exploratory serum and plasma biomarkersp 
X 
 
 
 
 
X 
 
 
X 
 
 
 
X 
 
 
 
X 
Exploratory urine biomarkersq 
 
X 
 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
Exploratory urine ALXN1210r 
 
X 
 
X 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
Exploratory autoantibodys 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Exploratory genetic samplet 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Immunogenicity (ADA)u 
 
X 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
Review safety cardv 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medicationsw 
 
←Monitor continuously→ 
Adverse events 
 
←Monitor continuously→ 
ALXN1210 administration (patients weighing < 20 kg)x 
 
X 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
ALXN1210 administration (patients weighing ≥ 20 kg)x 
 
X 
 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
Dose Regimen Decision Day (patients on q4w or q8w 
schedules)y 
X 
 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 

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Table 1: 
Schedule of Study Visits and Assessments: Screening Period Through Initial Evaluation Period (Continued) 
Abbreviations: ADA = antidrug antibody; ADAMTS13 = a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; aHUS = atypical hemolytic uremic 
syndrome; ECG = electrocardiogram; eCRF = electronic Case Report Form; EOI = end of infusion; ET = early termination; FACIT = functional assessment of chronic illness 
therapy; N/A = not applicable; LDH = lactate dehydrogenase; PD = pharmacodynamics; PK = pharmacokinetics; q4w = once every 4 weeks; q8w = once every 8 weeks; 
ST-HUS = Shiga toxin-related hemolytic uremic syndrome 
Note: If a patient discontinues from the study, an ET visit will be performed, and the Sponsor and site monitor should be notified as soon as possible. In addition, a Follow-up 
Phone Call will be performed 8 weeks (56 days) ± 5 days following the patient’s last ALXN1210 dose to collect concomitant medications, procedures, and adverse events. 
a  The Screening Period is up to 7 days for complement inhibitor treatment-naïve patients (ie, Cohort 1) and up to 28 days for eculizumab-experienced adolescent patients (ie, 
Cohort 2). For Cohort 1 patients, Screening and Day 1 visits can be performed on the same day. For Cohort 2 patients, Day 1 of study treatment will occur 14 days from the 
patient’s last dose of eculizumab.  
b The primary efficacy endpoint assessment is before dosing on Day 183. Dosing on Day 183 is the start of the Extension Period. Please refer to additional Day 183 postdose 
assessments in Table 2. 
c All patients must be vaccinated against meningococcal infections within 3 years prior to, or at the time of, initiating study drug. Patients who initiate study drug treatment less 
than 2 weeks after receiving a meningococcal vaccine must receive treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination. Patients who have not 
been vaccinated prior to initiating ALXN1210 treatment should receive prophylactic antibiotics prior to and for at least 2 weeks after meningococcal vaccination. Patients who 
cannot be vaccinated must receive antibiotic prophylaxis for the entire treatment period and for 8 months following last dose.  
d For Cohort 2 patients, historical test results via chart review should be utilized, and if not available, this assessment should be omitted. 
e Stool sample. 
f Predose on dosing days.   
g Female patients of childbearing potential only. Serum pregnancy test at Screening and Day 183/ET; urine (or serum if required per site policy) pregnancy test at all other required 
time points. A negative pregnancy test result is required prior to administering study drug to female patients of childbearing potential at the indicated study visits. 
h On dosing days, assessment will be performed prior to dosing. Pediatric FACIT-Fatigue only in patients ≥ 5 years of age (patient-reported for patients who were ≥ 8 years of age 
at the time of enrollment; caregiver-reported or caregiver assistance for patients who were 5 to < 8 years of age at the time of enrollment). 
i Abbreviated physical examination consists of a body system relevant examination based upon Investigator (or qualified designee) judgment and patient symptoms. At least 1 
body system must be checked for an abbreviated examination. 
j Vital sign measurements will be taken after the patient has been resting for at least 5 minutes and will include systolic and diastolic blood pressure (BP) (millimeters of mercury 
[mmHg]), pulse oximetry, heart rate (beats/minute), respiratory rate (breaths/minute), and temperature (degrees Celsius [°C] or degrees Fahrenheit [°F]). On dosing days, vital 
signs will be taken predose. 
k Single 12-lead ECG will be collected at Screening, Day 57, predose on Day 183, and at any time at ET. Patients must be supine for approximately 5 to 10 minutes before ECG 
collection and remain supine but awake during ECG collection. 
l Clinical safety laboratory measurements will be collected predose on dosing days. LDH for eligibility will be determined from the chemistry assessment. 
m For Cohort 1 patients, local laboratory or central laboratory analysis may be used to determine eligibility at Screening. However, if local laboratory tests are to be used, duplicate 
samples for LDH, platelet count, hemoglobin, and serum creatinine will be collected at this visit for central laboratory testing. For Cohort 2 patients, LDH, platelet count, 
hemoglobin, and serum creatinine samples collected at Screening must be tested at a central laboratory. 
n Assessment for safety as well as the primary and secondary endpoints. 
o Serum samples for PK/PD analyses will be collected at the indicated visits. For indicated visits falling on dosing days, samples will be collected predose (within 0.5 hour prior to 
the start of infusion) and at EOI (within 0.5 hour after the EOI from the patient’s opposite, noninfused arm). In order to minimize needle sticks to the patient, the predose sample 
may be drawn through the venous access created for the dose infusion, prior to administration of the dose.  As noted, the postdose sample must be drawn from the opposite, 
noninfused arm. For indicated visits not falling on dosing days, samples may be collected at any time that visit day. If a supplemental dose is administered, PK/PD samples will 
be collected predose and at EOI. If a loading dose is administered as 2 separate infusions < 24 hours apart, PK/PD samples will be collected before the first infusion (ie, the 
predose sample) and after the second infusion (ie, the EOI sample). All collection times will be recorded in the eCRF. 
 

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Table 1: 
Schedule of Study Visits and Assessments: Screening Period Through Initial Evaluation Period (Continued) 
p Baseline samples may be obtained during the Screening period or on Day 1 in accordance with daily blood volume restrictions.  Collection will be predose on dosing days. For 
indicated visits not falling on dosing days, samples may be collected at any time that visit day. All collection times will be recorded in the eCRF. An alternative blood sampling 
schedule for infants, for whom less blood volume should be collected, must be used as detailed in the Study Operations Manual. 
q Collection will be predose and combined with urine stabilizing buffer. All collection times will be recorded in the eCRF. 
r Urine sample for drug measurement will be collected at EOI (within 0.5 hour after the EOI) on Days 1, 15, and 71; and at any time on Day 29. 
s Collection can be at anytime during the study.  
t A single whole blood collection from those patients who consent to genetic testing can be collected anytime during the study. 
u ADA serum samples will be collected predose on Days 1, 71, and 127. Day 183 collection will occur prior to first dose in the Extension Period. ET collection will occur at any 
time on the visit day. All collection times will be recorded in the eCRF.   
v Review the Clinical Trial Participant Safety Information Card with the patient/caregiver and discuss the importance of carrying the safety card at all times, and the risks 
ALXN1210 treatment, including the risk of meningococcal infection.   
w Concomitant medications must be collected at all study visits and checked against the prohibited medication listed in Section 9.7. 
x The dose of ALXN1210 is based on the patient’s body weight on the preceding “Dose Regimen Decision Day (patients on q4w or q8w schedules)”.  
y Dose Regimen Decision Day for patients currently on a q4w or q8w schedule: Changes to dose regimen (dose level [ie, mg] or dose frequency [ie, q4w vs q8w]) will be based on 
the patient’s body weight on the “Dose Regimen Decision Day (patients on q4w or q8w schedules)” preceding the day of administration. Patients changing from q4w to q8w will 
be administered their first q8w dose on the ALXN1210 administration day (“ALXN1210 administration [patients weighing > 20 kg]”) following the “Dose Regimen Decision 
Day (patients on q4w or q8w schedules)”. Patients changing from q8w to q4w will be administered their first q4w dose on the ALXN1210 administration day (“ALXN1210 
administration [patients weighing < 20 kg]”) following the “Dose Regimen Decision Day (patients on q4w or q8w schedules)”. 
 

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Table 2:  
Schedule of Study Visits and Assessments: Extension Period Day 183 to Day 911 
Period 
Extension Period 
Study Day 
183a 
211 
239 
267 
295 
323 
351 
379 
407 
435 
463 
491 
519 
547 
575 
603 
631 
659 
687 
715 
743 
771 
799 
827 
855 
883 
911 
Window (day) 
±2 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
 
Head 
circumference 
(patients up to 2 
years of age) 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Height and weightb 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy testc 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Pediatric FACIT-
Fatigue 
questionnaired 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
Abbreviated 
physical 
examinatione 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Assessment of 
extra-renal signs or 
symptoms of aHUS 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Vital signsf 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Chemistryb 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Hematology and 
coagulationg, b 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Urinalysis and 
urine chemistry 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
PK/PD samplingh 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
Exploratory serum 
and plasma 
biomarkersi 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Exploratory urine 
biomarkersj 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Immunogenicity 
(ADA)k 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
Review safety cardl 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 

Protocol ALXN1210-aHUS-312 
 
Alexion Pharmaceuticals, Inc. 
Amendment 6 (Global) 16 Jul 2019 
Page 38 of 96 
CONFIDENTIAL 
Table 2: 
Schedule of Study Visits and Assessments: Extension Period Day 183 to Day 911 (Continued) 
Period 
Extension Period 
Study Day 
183a 
211 
239 
267 
295 
323 
351 
379 
407 
435 
463 
491 
519 
547 
575 
603 
631 
659 
687 
715 
743 
771 
799 
827 
855 
883 
911 
Window (day) 
±2 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
 
Concomitant 
medicationsm 
←Monitor continuously→ 
Adverse events 
←Monitor continuously→ 
ALXN1210 
administration 
(patients weighing 
< 20 kg)n 
Xa 
Xo 
X 
Xo 
X 
Xo 
X 
Xo 
X 
Xo 
X 
Xo 
X 
Xo 
X 
Xo 
X 
Xo 
X 
Xo 
X 
Xo 
X 
Xo 
X 
Xo 
X 
ALXN1210 
administration 
(patients weighing 
≥ 20 kg)n 
Xa 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Dose Regimen 
Decision Day 
(patients on q4w 
schedule)p 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Dose Regimen 
Decision Day 
(patients on q8w 
schedule)q 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Abbreviations: ADA = antidrug antibody; aHUS = atypical hemolytic uremic syndrome; ECG = electrocardiogram; eCRF = electronic Case Report Form; EOI = end of infusion; 
ET = early termination; FACIT = functional assessment of chronic illness therapy; PD = pharmacodynamics; PK = pharmacokinetics; q4w = once every 4 weeks; q8w = once 
every 8 weeks 
Note: For patients who terminate the study early, information on the assessments to be conducted on the ET visit day and further follow-up is provided in Table 4.  
Patients who discontinue ALXN1210 treatment in the Extension Period, but remain in the study without treatment, should continue attending their scheduled protocol visits until 
Day 1863 (Section 8.3.2). 
For patients who discontinue ALXN1210 treatment in the Extension Period, remain in the study, and further receive retreatment should undergo assessments as described in 
Section 8.3.2.1. 
a Extension Period begins at the start of Day 183 dosing. 
b Predose on dosing days.   
c Female patients of childbearing potential only. Urine (or serum if required per site policy) pregnancy test at all required time points. A negative pregnancy test result is required 
prior to administering ALXN1210 at the indicated study visits. 
d On dosing days, assessment will be performed prior to dosing. Pediatric FACIT-Fatigue only in patients ≥ 5 years of age (patient-reported for patients who were ≥ 8 years of age 
at the time of enrollment; caregiver-reported or caregiver assistance for patients who were 5 to < 8 years of age at the time of enrollment). 
e Abbreviated physical examination consists of a body system relevant examination based upon Investigator (or qualified designee) judgment and patient symptoms. At least 1 
body system must be checked for an abbreviated examination. 

Protocol ALXN1210-aHUS-312 
 
Alexion Pharmaceuticals, Inc. 
Amendment 6 (Global) 16 Jul 2019 
Page 39 of 96 
CONFIDENTIAL 
Table 2: 
Schedule of Study Visits and Assessments: Extension Period Day 183 to Day 911 (Continued) 
f Vital sign measurements will be taken after the patient has been resting for at least 5 minutes and will include systolic and diastolic BP (millimeters of mercury [mmHg]), pulse 
oximetry, heart rate (beats/minute), respiratory rate (breaths/minute), and temperature (degrees Celsius [°C] or degrees Fahrenheit [°F]). On dosing days, vital signs will be taken 
predose. 
g Assessment for safety as well as the primary and secondary endpoints.  
h Serum samples for PK/PD analysis will be collected predose (within 0.5 hour prior to the start of infusion) and EOI (within 0.5 hour after the EOI) on Days 351, 575, 743, and 
911; postdose on Day 183. End of infusion samples will be drawn from the patient’s opposite, noninfused arm. In order to minimize needle sticks to the patient, the predose 
sample may be drawn through the venous access created for the dose infusion, prior to administration of the dose. For patients who discontinue treatment in the Extension 
Period, but remain in the study, 1 PK/PD sample at any time will be collected as per protocol schedule until approximately 39 weeks after the last dose of ALXN1210. If a 
supplemental dose is administered, PK/PD samples will be collected predose and at EOI. All collection times will be recorded in the eCRF. 
i Collection will be predose on days of dosing and for days without dosing, at any time that visit day. All collection times will be recorded in the eCRF.  
j Collection will be predose on days of dosing and for days without dosing, at any time that visit day. Sample will be combined with urine stabilizing buffer. All collection times 
will be recorded in the eCRF. 
k A predose serum sample will be collected on Days 351, 575, 743, and 911. For patients who discontinue treatment in the Extension Period, but remain in the study, ADA sample 
will be collected at any time during the visits as per protocol schedule until approximately 39 weeks after the last dose of ALXN1210. All collection times will be recorded in the 
eCRF.  
l Review the Clinical Trial Participant Safety Information Card with the patient and discuss the importance of carrying the safety card at all times, and the risks ALXN1210 
treatment, including the risk of meningococcal infection.   
m Concomitant medications must be collected at all study visits (and at the Follow-up Phone Call 8 weeks [56days] ± 5 days after the last dose of ALXN1210 for patients who 
terminate the study early) and checked against the prohibited medication listed in Section 9.7. 
n The dose of ALXN1210 is based on the patient’s body weight on the preceding “Dose Regimen Decision Day (patients on q4w schedule) or Dose Regimen Decision Day 
(patients on q8w schedule)”. For patients who discontinue ALXN1210 treatment in the Extension Period, remain in the study, and further receive retreatment, the dosing and 
assessment details are provided in Section 8.3.2.1. 
o These visits are not applicable for patients on a q8w dosing schedule during the Extension Period. 
p Dose Regimen Decision Day for patients currently on a q4w schedule: Predose body weight will be measured before dosing on the “Dose Regimen Decision Day (patients on 
q4w schedule)”. Should this weight change the dose regimen (dose level [ie, mg] or dose frequency [ie, q4w vs q8w]), the change will occur on the visit 4 weeks later. Patients 
changing from q4w to q8w will be administered their first q8w dose on the ALXN1210 administration day (“ALXN1210 administration [patients weighing > 20 kg]”) following 
the “Dose Regimen Decision Day (patients on q4w schedule)”. 
q Dose Regimen Decision Day for patients currently on a q8w schedule: Predose body weight will be measured before dosing on the “Dose Regimen Decision Day (patients on 
q8w schedule)”. Should this weight change the dose regimen (dose level [ie, mg] or dose frequency [ie, q4w vs q8w]), the change will occur on the visit 8 weeks later. Patients 
changing from q8w to q4w will be administered their first q4w dose on the ALXN1210 administration day (“ALXN1210 administration [patients weighing < 20 kg]”) 8 weeks 
after the “Dose Regimen Decision Day (patients on q8w schedule)”. 
 
 

Protocol ALXN1210-aHUS-312 
 
Alexion Pharmaceuticals, Inc. 
Amendment 6 (Global) 16 Jul 2019 
Page 40 of 96 
CONFIDENTIAL 
 
Table 3:  
Schedule of Study Visits and Assessments: Extension Period Day 939 to Day 1667 
Period 
Extension Period 
Study Day 
939 
967 
995 
1023 
1051 
1079 
1107 
1135 
1163 
1191 
1219 
1247 
1275 
1303 
1331 
1359 
1387 
1415 
1443 
1471 
1499 
1527 
1555 
1583 
1611 
1639 
1667 
Window (day) 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
 
Head 
circumference 
(patients up to 2 
years of age) 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Height and weighta 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy testb 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Pediatric 
FACIT-Fatigue 
questionnairec 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
Abbreviated 
physical 
examinationd 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Assessment of 
extra-renal signs or 
symptoms of aHUS 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
Vital signse 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Chemistrya 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Hematology and 
coagulationf, a 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Urinalysis and 
urine chemistry 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
PK/PD samplingg 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
Exploratory serum 
and plasma 
biomarkersh 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Exploratory urine 
biomarkersi 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Immunogenicity 
(ADA)j 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
Review safety 
cardk 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
medicationsl 
←Monitor continuously→ 

Protocol ALXN1210-aHUS-312 
 
Alexion Pharmaceuticals, Inc. 
Amendment 6 (Global) 16 Jul 2019 
Page 41 of 96 
CONFIDENTIAL 
Table 3: 
Schedule of Study Visits and Assessments: Extension Period Day 939 to Day 1667 (Continued) 
Period 
Extension Period 
Study Day 
939 
967 
995 
1023 
1051 
1079 
1107 
1135 
1163 
1191 
1219 
1247 
1275 
1303 
1331 
1359 
1387 
1415 
1443 
1471 
1499 
1527 
1555 
1583 
1611 
1639 
1667 
Window (day) 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
Adverse events 
←Monitor continuously→ 
ALXN1210 
administration 
(patients weighing 
< 20 kg)m 
Xn 
X 
Xn 
X 
Xn 
X 
Xn 
X 
Xn 
X 
Xn 
X 
Xn 
X 
Xn 
X 
Xn 
X 
Xn 
X 
Xn 
X 
Xn 
X 
Xn 
X 
Xn 
ALXN1210 
administration 
(patients weighing 
≥ 20 kg)m 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Dose Regimen 
Decision Day 
(patients on q4w 
schedule)o 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Dose Regimen 
Decision Day 
(patients on q8w 
schedule)p 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Abbreviations: ADA = antidrug antibody; aHUS = atypical hemolytic uremic syndrome; eCRF = electronic Case Report Form; EOI = end of infusion; ET = early termination; 
FACIT = functional assessment of chronic illness therapy; PD = pharmacodynamics; PK = pharmacokinetics; q4w = once every 4 weeks; q8w = once every 8 weeks 
Note: For patients who terminate the study early, information on the assessments to be conducted on the ET visit day and further follow-up is provided in Table 4. 
Patients who discontinue ALXN1210 treatment in the Extension Period, but remain in the study without treatment, should continue attending their scheduled protocol visits until 
Day 1863 (Section 8.3.2). 
For patients who discontinue ALXN1210 treatment in the Extension Period, remain in the study, and further receive retreatment should undergo assessments as described in 
Section 8.3.2.1. 
a Predose on dosing days.   
b Female patients of childbearing potential only. Urine (or serum if required per site policy) pregnancy test at all required time points. A negative pregnancy test result is required 
prior to administering ALXN1210 at the indicated study visits. 
c On dosing days, assessment will be performed prior to dosing. Pediatric FACIT-Fatigue only in patients ≥ 5 years of age (patient-reported for patients who were ≥ 8 years of age 
at the time of enrollment; caregiver-reported or caregiver assistance for patients who were 5 to < 8 years of age at the time of enrollment). 
d Abbreviated physical examination consists of a body system relevant examination based upon Investigator (or qualified designee) judgment and patient symptoms. At least 
1 body system must be checked for an abbreviated examination.  
e Vital sign measurements will be taken after the patient has been resting for at least 5 minutes and will include systolic and diastolic BP (millimeters of mercury [mmHg]), pulse 
oximetry, heart rate (beats/minute), respiratory rate (breaths/minute), and temperature (degrees Celsius [°C] or degrees Fahrenheit [°F]). On dosing days, vital signs will be taken 
predose. 
f Assessment for safety as well as the primary and secondary endpoints.  

Protocol ALXN1210-aHUS-312 
 
Alexion Pharmaceuticals, Inc. 
Amendment 6 (Global) 16 Jul 2019 
Page 42 of 96 
CONFIDENTIAL 
Table 3: 
Schedule of Study Visits and Assessments: Extension Period Day 939 to Day 1667 (Continued) 
g Serum samples for PK/PD analysis will be collected predose (within 0.5 hour prior to the start of infusion) and EOI (within 0.5 hour after the EOI) on Days 1079, 1247, 1415, 
and 1639. End of infusion samples will be drawn from the patient’s opposite, noninfused arm. In order to minimize needle sticks to the patient, the predose sample may be drawn 
through the venous access created for the dose infusion, prior to administration of the dose. For patients who discontinue treatment in the Extension Period, but remain in the 
study, 1 PK/PD sample at any time will be collected as per protocol schedule until approximately 39 weeks after the last dose of ALXN1210. If a supplemental dose is 
administered, PK/PD samples will be collected predose and at EOI. All collection times will be recorded in the eCRF. 
h Collection will be predose on days of dosing and for days without dosing, at any time that visit day. All collection times will be recorded in the eCRF.  
i Collection will be predose on days of dosing and for days without dosing, at any time that visit day. Sample will be combined with urine stabilizing buffer. All collection times 
will be recorded in the eCRF. 
j A predose serum sample will be collected on Days 1079, 1247, 1415, and 1639. For patients who discontinue treatment in the Extension Period, but remain in the study, ADA 
sample will be collected at any time during the visits as per protocol schedule, until approximately 39 weeks after the last dose of ALXN1210. All collection times will be 
recorded in the eCRF.  
k Review the Clinical Trial Participant Safety Information Card with the patient and discuss the importance of carrying the safety card at all times, and the risks ALXN1210 
treatment, including the risk of meningococcal infection.   
l Concomitant medications must be collected at all study visits (and at the Follow-up Phone Call 8 weeks [56 days] ± 5 days after the last dose of ALXN1210 for patients who 
terminate the study early) and checked against the prohibited medication listed in Section 9.7. 
m The dose of ALXN1210 is based on the patient’s body weight on the preceding “Dose Regimen Decision Day (patients on q4w schedule) or Dose Regimen Decision Day 
(patients on q8w schedule)”. For patients who discontinue ALXN1210 treatment in the Extension Period, remain in the study, and further receive retreatment, the dosing and 
assessment details are provided in Section 8.3.2.1. 
n These visits are not applicable for patients on a q8w dosing schedule during the Extension Period. 
o Dose Regimen Decision Day for patients currently on a q4w schedule: Predose body weight will be measured before dosing on the “Dose Regimen Decision Day (patients on 
q4w schedule)”. Should this weight change the dose regimen (dose level [ie, mg] or dose frequency [ie, q4w vs q8w]), the change will occur on the visit 4 weeks later. Patients 
changing from q4w to q8w will be administered their first q8w dose on the ALXN1210 administration day (“ALXN1210 administration [patients weighing > 20 kg]”) following 
the “Dose Regimen Decision Day (patients on q4w schedule)”. 
p Dose Regimen Decision Day for patients currently on a q8w schedule: Predose body weight will be measured before dosing on the “Dose Regimen Decision Day (patients on 
q8w schedule)”. Should this weight change the dose regimen (dose level [ie, mg] or dose frequency [ie, q4w vs q8w]), the change will occur on the visit 8 weeks later. Patients 
changing from q8w to q4w will be administered their first q4w dose on the ALXN1210 administration day (“ALXN1210 administration [patients weighing < 20 kg]”) 8 weeks 
after the “Dose Regimen Decision Day (patients on q8w schedule)”. 
 
 

Protocol ALXN1210-aHUS-312 
 
Alexion Pharmaceuticals, Inc. 
Amendment 6 (Global) 16 Jul 2019 
Page 43 of 96 
CONFIDENTIAL 
 
Table 4:  
Schedule of Study Visits and Assessments: Extension Period Day 1695 to Day 1863 
Period 
Extension Period 
Study Day 
1695 
1723 
1751 
1779 
1807 
1835 
1863/ET/
EOS 
Window (day) 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
Head circumference (patients up to 2 years of age) 
X 
 
X 
 
X 
 
X 
Height and weighta 
X 
X 
X 
X 
X 
X 
X 
Pregnancy testb 
X 
 
X 
 
X 
 
X 
Pediatric FACIT-Fatigue questionnairec 
 
 
 
 
X 
 
X 
Physical examination 
 
 
 
 
 
 
X 
Abbreviated physical examinationd 
X 
 
X 
 
X 
 
 
Assessment of extra-renal signs or symptoms of aHUS 
 
 
 
 
X 
 
X 
Vital signse 
X 
 
X 
 
X 
 
X 
Safety 12 lead ECGf 
 
 
 
 
 
 
X 
Chemistrya 
X 
 
X 
 
X 
 
X 
Hematology and coagulationg, a 
X 
 
X 
 
X 
 
X 
Urinalysis and urine chemistry 
X 
 
X 
 
X 
 
X 
PK/PD samplingh 
 
 
 
 
X 
 
X 
Exploratory serum and plasma biomarkersi 
X 
 
X 
 
X 
 
X 
Exploratory urine biomarkersj 
X 
 
X 
 
X 
 
X 
Immunogenicity (ADA)k 
 
 
 
 
X 
 
X 
Review safety cardl 
X 
X 
X 
X 
X 
X 
X 
Concomitant medicationsm 
←Monitor continuously→ 
Adverse events 
←Monitor continuously→ 
ALXN1210 administration (patients weighing < 20 kg)n 
X 
Xo 
X 
Xo 
X 
Xo 
 
ALXN1210 administration (patients weighing ≥ 20 kg)n 
X 
 
X 
 
X 
 
 
Dose Regimen Decision Day (patients on q4w schedule)p 
 
X 
 
X 
 
X 
 
Dose Regimen Decision Day (patients on q8w schedule)q 
X 
 
X 
 
X 
 
 
Abbreviations: ADA = antidrug antibody; aHUS = atypical hemolytic uremic syndrome; ECG = electrocardiogram; eCRF = electronic Case Report Forms; EOI = end of infusion 
EOS = end of study; ET = early termination; FACIT = functional assessment of chronic illness therapy; PD = pharmacodynamics; PK = pharmacokinetics; q4w = once every 
4 weeks; q8w = once every 8 weeks 
Note:  For patients who complete the study on the q4w regimen and do not initiate commercially available aHUS treatment within 8 weeks of their last ALXN1210 dose, a 
Follow-up Phone Call will be performed 8 weeks (56 days) ± 5 days after their last dose of ALXN1210, to collect information on concomitant medications, nonpharmacological 
therapies and procedures, and adverse events. 
If a patient terminates from the study early, ET assessments will be conducted as soon as possible. A Follow-up Phone Call will be performed 8 weeks (56 days) ± 5 days 
following the patient’s last dose of ALXN1210 to collect information on concomitant medications, nonpharmacological therapies and procedures, and adverse events.  
 

Protocol ALXN1210-aHUS-312 
 
Alexion Pharmaceuticals, Inc. 
Amendment 6 (Global) 16 Jul 2019 
Page 44 of 96 
CONFIDENTIAL 
Table 4:  
Schedule of Study Visits and Assessments: Extension Period Day 1695 to Day 1863 (Continued) 
Patients who discontinue ALXN1210 treatment in the Extension Period, but remain in the study without treatment, should continue attending their scheduled protocol visits until 
Day 1863 (Section 8.3.2). 
For patients who discontinue ALXN1210 treatment in the Extension Period, remain in the study, and further receive retreatment should undergo assessments as described in 
Section 8.3.2.1. 
a Predose on dosing days. 
b Female patients of childbearing potential only. Serum pregnancy test at Day 1863/ET/EOS only; urine (or serum if required per site policy) pregnancy test at all other required 
time points. A negative pregnancy test result is required prior to administering ALXN1210 to female patients of childbearing potential at the indicated study visits. 
c On dosing days, assessment will be performed prior to dosing. Pediatric FACIT-Fatigue only in patients ≥ 5 years of age (patient-reported for patients who were ≥ 8 years of age 
at the time of enrollment; caregiver-reported or caregiver assistance for patients who were 5 to < 8 years of age at the time of enrollment). 
d Abbreviated physical examination consists of a body system relevant examination based upon Investigator (or qualified designee) judgment and patient symptoms. At least 
1 body system must be checked for an abbreviated examination. 
e Vital sign measurements will be taken after the patient has been resting for at least 5 minutes and will include systolic and diastolic BP (millimeters of mercury [mmHg]), pulse 
oximetry, heart rate (beats/minute), respiratory rate (breaths/minute), and temperature (degrees Celsius [°C] or degrees Fahrenheit [°F]). On dosing days, vital signs will be taken 
predose. 
f Single 12-lead ECG will be collected at Day 1863 or ET. Patients must be supine for approximately 5 to 10 minutes before ECG collection and remain supine but awake during 
ECG collection. 
g Assessment for safety as well as the primary and secondary endpoints.  
h Serum samples for PK/PD analysis will be collected predose (within 0.5 hour prior to the start of infusion) and EOI (within 0.5 hour after the EOI) on Day 1807 and at any time 
on Day 1863 or ET. End of infusion samples will be drawn from the patient’s opposite, noninfused arm. In order to minimize needle sticks to the patient, the predose sample may 
be drawn through the venous access created for the dose infusion, prior to administration of the dose. For patients who discontinue treatment in the Extension Period, but remain 
in the study, 1 PK/PD sample at any time will be collected as per protocol schedule until approximately 39 weeks after the last dose of ALXN1210. If a supplemental dose is 
administered, PK/PD samples will be collected predose and at EOI. All collection times will be recorded in the eCRF. 
i Collection will be predose on days of dosing and for days without dosing, at any time that visit day. All collection times will be recorded in the eCRF.  
j Collection will be predose on days of dosing and for days without dosing, at any time that visit day. Sample will be combined with urine stabilizing buffer. All collection times 
will be recorded in the eCRF. 
k A predose serum sample will be collected on Day 1807. A serum sample will also be collected at any time on Day 1863 or ET. For patients who discontinue treatment in the 
Extension Period, but remain in the study, ADA sample will be collected at any time during the visits as per protocol schedule, approximately 39 weeks after the last dose of 
ALXN1210. All collection times will be recorded in the eCRF.  
l Review the Clinical Trial Participant Safety Information Card with the patient and discuss the importance of carrying the safety card at all times, and the risks ALXN1210 
treatment, including the risk of meningococcal infection.   
m Concomitant medications must be collected at all study visits (and at the Follow-up Phone Call 8 weeks [56 days] ± 5 days after the last dose of ALXN1210 for patients who 
terminate the study early) and checked against the prohibited medication listed in Section 9.7. 
n The dose of ALXN1210 is based on the patient’s body weight on the preceding “Dose Regimen Decision Day (patients on q4w schedule) or Dose Regimen Decision Day 
(patients on q8w schedule)”. For patients who discontinue ALXN1210 treatment in the Extension Period, remain in the study, and further receive retreatment, the dosing and 
assessment details are provided in Section 8.3.2.1. 
o These visits are not applicable for patients on a q8w dosing schedule during the Extension Period. 
p Dose Regimen Decision Day for patients currently on a q4w schedule: Predose body weight will be measured before dosing on the “Dose Regimen Decision Day (patients on 
q4w schedule)”. Should this weight change the dose regimen (dose level [ie, mg] or dose frequency [ie, q4w vs q8w]), the change will occur on the visit 4 weeks later. Patients 
changing from q4w to q8w will be administered their first q8w dose on the ALXN1210 administration day (“ALXN1210 administration [patients weighing > 20 kg]”) following 
the “Dose Regimen Decision Day (patients on q4w schedule)”. 
 

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Table 4: 
 
Schedule of Study Visits and Assessments: Extension Period Day 1695 to Day 1863 (Continued) 
q Dose Regimen Decision Day for patients currently on a q8w schedule: Predose body weight will be measured before dosing on the “Dose Regimen Decision Day (patients on 
q8w schedule)”. Should this weight change the dose regimen (dose level [ie, mg] or dose frequency [ie, q4w vs q8w]), the change will occur on the visit 8 weeks later. Patients 
changing from q8w to q4w will be administered their first q4w dose on the ALXN1210 administration day (“ALXN1210 administration [patients weighing < 20 kg]”) 8 weeks 
after the “Dose Regimen Decision Day (patients on q8w schedule)”. 

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8. 
STUDY POPULATION 
Approximately 23 to 28 pediatric (< 18 years of age) patients with documented aHUS are 
planned for this study. The minimum number of patients for each age category is as follows:  
• Birth to < 2 years: 4 patients 
• 2 to < 6 years: 4 patients 
• 6 to < 12 years: 4 patients 
• 12 to < 18 years: 8 patients 
Cohort 2 patients must be 12 to < 18 years of age. 
Patients will be enrolled and assigned to treatment with ALXN1210 during the Initial Evaluation 
Period at approximately 70 investigative sites globally. All enrolled patients will also receive 
ALXN1210 during the 4.5-year Extension Period. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened based on discussion and agreement between the Investigator and the Medical 
Monitor. Patients may be rescreened a maximum of 2 times. 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
The following entry criteria are applicable for patients in both cohorts unless otherwise noted as 
specific for Cohort 1 or Cohort 2.   
8.1. 
Inclusion Criteria 
Patients are eligible for enrollment in the study only if they satisfy all of the following criteria: 
1. Patients from birth up to < 18 years of age and weighing ≥ 5 kg at the time of consent 
who: 
a. For Cohort 1 patients, have not been previously treated with complement inhibitors  
b. For Cohort 2 patients, are between 12 and <18 years of age and have been treated 
with eculizumab according to the labelled dosing recommendation for aHUS for at 
least 90 days prior to Screening 
2. For Cohort 1 patients, evidence of TMA, including thrombocytopenia, evidence of 
hemolysis, and kidney injury, based on the following laboratory findings: 
a. Platelet count < 150,000 per microliter (µL) during the Screening Period or within 28 
days prior to the start of the Screening Period, and 
b. 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 within 28 days prior 
to the start of the Screening Period, and 
c. Serum creatinine level ≥ 97.5th percentile for age (Appendix B) at Screening (patients 
who require dialysis for acute kidney injury are also eligible regardless of serum 
creatinine level). 

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3. For Cohort 2 patients, documented diagnosis of aHUS including: 
a. Increase in LDH > ULN and creatinine > ULN, and decrease in platelets < LLN 
documented by local laboratories at the time of the TMA event 
4. For Cohort 2 patients, clinical evidence of response to eculizumab indicated by stable 
TMA parameters (via central laboratory results) at Screening, including: 
a. LDH < 1.5 X ULN, and 
b. Platelet count ≥ 150,000 /μL, and 
c. eGFR > 30 mL/min/1.73m2 using the Schwartz formula 
5. Among patients with a kidney transplant: 
a. Known history of aHUS prior to current kidney transplant, or 
b. No known history of aHUS, and 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). 
6. Among patients with onset of TMA postpartum, persistent evidence of TMA for > 3 days 
after the day of childbirth. 
7. To reduce the risk of meningococcal infection (Neisseria meningitidis), all patients must 
be vaccinated against meningococcal infections within 3 years prior to, or at the time of, 
initiating study drug. Patients who receive a meningococcal vaccine less than 2 weeks 
before initiating ALXN1210 treatment must receive treatment with appropriate 
prophylactic antibiotics until 2 weeks after vaccination. Patients who have not been 
vaccinated prior to initiating ALXN1210 treatment should receive prophylactic 
antibiotics prior to and for at least 2 weeks after meningococcal vaccination. Patients who 
cannot be vaccinated must receive antibiotic prophylaxis for the entire treatment period 
and for 8 months following last dose. 
8. Patients must have been vaccinated against Haemophilus influenzae type b (Hib) and 
Streptococcus pneumoniae according to national and local vaccination schedule 
guidelines. 
9. Female patients of childbearing potential and male patients with female partners of 
childbearing potential must follow protocol-specified guidance (Section 9.10) for 
avoiding pregnancy while on treatment and for 8 months after last dose of study drug. 
10. Patient’s legal guardian must be willing and able to give written informed consent and the 
patient must be willing to give written informed assent (if applicable as determined by the 
central or local Institutional Review Board [IRB]/ Institutional (or Independent) Ethics 
Committee [IEC]) and comply with the study visit schedule. 
For Cohort 1, samples collected at Screening may be tested at either 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. All analyses in this study will be based on results from the central laboratory 
(unless the result is missing [see Section 15.12.1]). If Cohort 1 patients are found to not satisfy 
the eligibility criteria for serum creatinine (Inclusion Criterion 2c) based on central laboratory 

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results, they must not be enrolled into the study; if the subject has received the first dose of 
ALXN1210 the patient must be withdrawn from the study, and may be replaced (please refer to 
Section 8.3 for potential discontinuation and replacement details).  
For Cohort 2, samples collected at Screening must be tested at a central laboratory; however, 
historical test results via chart review should be utilized for Inclusion Criterion 3 and Exclusion 
Criteria 1, 2, 3, and 24.  
8.2. 
Exclusion Criteria 
Patients will be excluded from study enrollment if they meet any of the following criteria: 
1. Known familial or acquired ‘a disintegrin and metalloproteinase with a thrombospondin 
type 1 motif, member 13’ (ADAMTS13) deficiency (activity < 5%). 
2. Known Shiga toxin-related hemolytic uremic syndrome (ST-HUS) as demonstrated by a 
positive test for Shiga toxin or culture of Shiga toxin producing bacteria. 
3. Positive direct Coombs test.  
4. Known Human Immunodeficiency Virus (HIV) infection. 
5. Unresolved meningococcal disease. 
6. Patients with a 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 bacterial infection that, in the 
opinion of the Investigator, confounds an accurate diagnosis of aHUS or impedes the 
ability to manage the aHUS disease. 
8. Females who plan to become pregnant during the study or are currently pregnant or 
breastfeeding. 
9. Heart, lung, small bowel, pancreas, or liver transplant. 
10. Among patients with a kidney transplant, acute kidney dysfunction within 4 weeks of 
transplant consistent with the diagnosis of acute antibody-mediated rejection (AMR) 
according to Banff 2013 criteria (Appendix C). 
11. Among patients 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) 
12. Identified drug exposure-related HUS. 
13. For Cohort 1 patients, receiving plasma exchange/plasma infusion (PE/PI), for 28 days or 
longer, prior to the start of Screening for the current TMA. 

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14. History of malignancy within 5 years of Screening with the exception of a non-melanoma 
skin cancer or carcinoma in situ of the cervix that has been treated with no evidence of 
recurrence. 
15. Bone marrow transplant (BMT)/hematopoietic stem cell transplant (HSCT) within the 
last 6 months prior to the start of Screening. 
16. HUS related to known genetic defects of cobalamin C metabolism. 
17. Known systemic sclerosis (scleroderma), systemic lupus erythematosus (SLE), or 
antiphospholipid antibody positivity or syndrome. 
18. Chronic dialysis (defined as dialysis on a regular basis as renal replacement therapy for 
ESKD). 
19. Patients 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. 
20. Patients receiving other immunosuppressive therapies such as steroids, mTORi (eg, 
sirolimus, everolimus), CNI (eg, cyclosporine or tacrolimus) are excluded unless:  
a. part of an established post-transplant antirejection regimen, or  
b. patient has confirmed anti-complement factor antibodies requiring 
immunosuppressive therapy, or  
c. steroids are being used for a condition other than aHUS (eg, asthma). 
21. Participation in another interventional treatment study or use of any experimental therapy 
within 30 days before initiation of study drug on Day 1 in this study or within 5 half-lives 
of that investigational product, whichever is greater. 
22. For Cohort 1 patients, prior use of any complement inhibitors. 
23. For Cohort 2 patients, prior use of complement inhibitors other than eculizumab. 
24. For Cohort 2 patients, any known abnormal TMA parameters within 90 days prior to 
Screening (ie, LDH ≥ 1.5 X ULN, or platelet count < 150,000/μL, or eGFR ≤ 30 
mL/min/1.73m2 using the Schwartz formula). 
25. Hypersensitivity to any ingredient contained in the study drug, including hypersensitivity 
to murine proteins. 
26. Any medical or psychological condition that, in the opinion of the Investigator or 
Sponsor, could increase the risk to the patient by participating in the study or confound 
the outcome of the study.  
27. Known or suspected history of drug or alcohol abuse or dependence within 1 year prior to 
the start of Screening. 
28. Use of tranexamic acid within 7 days prior to Screening is prohibited. 
For Cohort 1 patients, laboratory results for Exclusion Criterion number 1 and/or Exclusion 
Criterion number 2 may not be available prior to first dose. Later results for Exclusion Criterion 

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number 1 and/or Exclusion Criterion number 2 could lead to discontinuation and replacement of 
the patient (please refer to Section 8.3 for potential discontinuation and replacement details). 
8.3. 
Discontinuation 
8.3.1. 
Early Termination of Patients From the Study 
The criteria for early termination of patients from the study include: 
• Withdrawal of consent: A patient has the right to withdraw from the study at any 
time.  
• Patient with prior kidney transplant developing AMR (C4d positive renal biopsy) and 
for whom rituximab is deemed the appropriate therapy: patient must be terminated 
from the study and receive standard of care therapy. 
• Intake of certain prohibited medications as described in Section 9.7. 
• Patient who is receiving ALXN1210 as a part of retreatment (Section 8.3.2.1) chooses 
to discontinue ALXN1210. 
• The Sponsor Medical Monitor or the Investigator deems it is in the best interest of the 
patient. 
During the Initial Evaluation Period, if any of the following occur, patient should be permanently 
discontinued from ALXN1210 treatment and terminated from the study: 
• Serious infusion reaction (such as bronchospasm with wheezing or requiring 
ventilator support, or symptomatic hypotension, refer to Appendix D) or serum 
sickness-like reactions manifesting 1 to 14 days after drug administration 
• Pregnancy or planned pregnancy 
If a patient terminates from the study early, the Sponsor and site monitor should be notified and 
an Early Termination (ET) visit (as shown in the Schedule of Assessments, Section 7.3) will be 
performed as soon as possible. In addition, a Follow-up Phone Call will be performed 8 weeks 
(56 days) ± 5 days following the patient’s last ALXN1210 dose to collect concomitant 
medications, nonpharmacological therapies and procedures, and AEs.  
At the time of the termination, if there is an ongoing AE or an unresolved laboratory result that 
in the opinion of the Investigator, is significantly outside of the reference range and clinically 
significant (Section 11.4), the Investigator will attempt to provide follow-up until a satisfactory 
clinical resolution of the laboratory result or AE is achieved. 
The reason for early termination will be recorded on the eCRF. 
Patients who terminate early from the study will not be replaced. 

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8.3.2. 
Discontinuation of ALXN1210 Treatment in the Extension Period and 
Continuation in the Study  
In the Extension Period, patients who discontinue ALXN1210 treatment will be allowed to 
continue in the study for the remainder of the visits without receiving ALXN1210 dosing. 
Note: In the Initial Evaluation Period, patients who discontinue ALXN1210 treatment will not be 
allowed to continue in the study. 
Patients should be permanently discontinued from ALXN1210 treatment if any of the following 
occur during the study: 
• Receiving other complement inhibitors (including eculizumab) or undergoing PE/PI 
after the first dose of study drug (refer to Section 9.7) 
• Serious infusion reaction (such as bronchospasm with wheezing or requiring 
ventilator support, or symptomatic hypotension, refer to Appendix D) or serum 
sickness-like reactions manifesting 1 to 14 days after drug administration; 
• Pregnancy or planned pregnancy; or 
• The Sponsor Medical Monitor or the Investigator deems it is in the best interest of the 
patient. 
The Investigator should notify the Medical Monitor as soon as possible prior to discontinuing a 
patient’s study treatment and provide the rationale for discontinuing.  
If a patient is discontinued from ALXN1210 treatment in the Extension Period, but remains in 
the study, patient should continue attending his or her scheduled protocol visits per body weight, 
until Day 1863. During these visits, all assessments except for ALXN1210 administration as 
described in the Schedule of Assessments, Section 7.3, should be performed. The PK/PD (1 
sample at any time) and ADA samples will be collected as per protocol schedule until about 
39 weeks after the last dose of ALXN1210.  
Any patient who discontinues the ALXN1210 treatment in the Extension Period, but remains in 
the study and develops abnormal TMA parameter (as specified in Section 8.3.2.1) before 
Day 1863, will have the opportunity for retreatment (Section 8.3.2.1). If the study drug is 
discontinued again (after retreatment), then the patient will be terminated from the study and ET 
procedures and follow-up will be performed as described in Section 8.3.1.  
The reason for the treatment or study discontinuation will be recorded on the eCRF.  
If a female patient is permanently discontinued from ALXN1210 treatment due to pregnancy, the 
Investigator will attempt to follow-up until the outcome of the pregnancy (Section 11.8). 
8.3.2.1. 
Retreatment of Patients Who Discontinue ALXN1210 Treatment in the 
Extension Period 
A patient who discontinues ALXN1210 treatment in the Extension Period, but remains in the 
study, and develops abnormal TMA parameter (as indicated by criteria No. 1 below) before 
Day 1863, may be restarted on ALXN1210, if all 3 conditions below are fulfilled: 
1. Evidence of TMA, including thrombocytopenia, evidence of hemolysis, or kidney injury 
based on any 1 of the following laboratory findings: 

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• Platelet count < 150,000/μL, or 
• LDH > 1.5 × ULN with hemoglobin ≤ LLN for age and gender, or 
• Serum creatinine ≥ 97.5th percentile for age (Appendix B). 
Note: The TMA laboratory parameter must be confirmed on at least 1 repeated measure. 
The above laboratory results can be obtained at either the central laboratory (preferable) 
or the site’s local laboratory. 
2. The Investigator believes that the patient will potentially benefit from retreatment, 
initiates a discussion with the Sponsor Medical Monitor, and provides a medically 
justified rationale. The Investigator and Medical Monitor mutually agree on retreatment, 
and the decision is documented. 
3. The patient agrees to the consent addendum for retreatment. 
If the decision to re-treat with ALXN1210 occurs on a scheduled study visit, then dosing may 
begin on that day. Note: A negative pregnancy test result is required prior to administering any 
study drug to female patients of childbearing potential. 
• The patient will receive a loading dose of ALXN1210 IV based on the body weight 
(Table 7). All assessments will be performed per the protocol schedule (Section 7.3). 
If start of the retreatment occurs on a visit which does not include PK/PD, ADA, 
exploratory serum and plasma biomarker, exploratory urine biomarker, hematology, 
coagulation, or chemistry sample collection, PK/PD samples will be collected predose 
and at EOI, and ADA, exploratory serum and plasma biomarker, exploratory urine 
biomarker, hematology, coagulation, and chemistry samples will be collected 
predose.  
• Two weeks after the loading dose, the patient will receive a supplemental 
maintenance dose of ALXN1210 IV at an unscheduled visit, based on the body 
weight (Table 7). An abbreviated physical examination will be conducted, vital signs 
will be collected, predose hematology, coagulation, and chemistry samples will be 
collected, and the safety card will be reviewed with the patient. Pharmacokinetic/PD 
samples will be collected predose and at EOI along with a predose ADA sample.  
• The patient will return to the site for the next 2 maintenance doses of ALXN1210 IV 
at 3-week (if on q4w regimen) or 7-week (if on q8w regimen) intervals. These visits 
will correspond to the next 2 scheduled dosing visits per the protocol schedule and 
will not be considered deviations to the visit windows. At these 2 visits, the patient 
will receive maintenance doses of ALXN1210 IV and undergo all assessments per the 
protocol schedule (Section 7.3), including hematology, coagulation, and chemistry, if 
not included as a part of this visit, and then continue to attend the visits per the 
protocol schedule. 
If the decision to re-treat with ALXN1210 occurs between scheduled study visits, then the below 
apply. Note: A negative pregnancy test result is required prior to administering any study drug to 
female patients of childbearing potential. 
• At an unscheduled visit, a supplemental loading dose of ALXN1210 IV may be 
administered based on the body weight (Table 7). An abbreviated physical 

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examination will be conducted, vital signs will be collected, predose exploratory 
serum and plasma biomarker, exploratory urine biomarker, hematology, coagulation, 
and chemistry samples will be collected, and the safety card will be reviewed with the 
patient. Pharmacokinetic/PD samples will be collected predose and at EOI along with 
a predose ADA sample. 
• The Medical Monitor and the Investigator will determine administration of 
maintenance dose of ALXN1210 IV further to facilitate alignment with the Schedule 
of Assessments (Section 7.3), as appropriate. The timing of subsequent visits may be 
modified to accommodate realignment to the Schedule of Assessments, these will not 
be considered deviations to visit windows. 
8.3.3. 
Discontinuation of Study/Site Termination by Sponsor or Health Authority 
The Sponsor or Health Authority may terminate the study for reasonable cause. Conditions that 
may warrant termination of the study include, but are not limited to:  
• Discovery of an unexpected, serious, or unacceptable risk to patients enrolled in the 
study  
• Sponsor decision to suspend or discontinue testing, evaluation, or development of the 
study drug  
• Failure of the Investigator to comply with the approved protocol, pertinent guidelines, 
and/or regulations  
• Submission of knowingly false information from the Investigator to the Sponsor 
and/or regulatory authorities 
Should the study be terminated early, the Sponsor will notify the national competent authority 
and the IRB/IEC according to local requirements. 
8.3.4. 
Replacements 
For Cohort 1, if it is determined at any point that a patient’s Screening data does not satisfy 
Inclusion Criterion number 2c, Exclusion Criterion number 1, and/or Exclusion Criterion number 
2, after receiving at least 1 dose of investigational product (eg, patient local laboratory data used 
to confirm eligibility criteria are subsequently determined by a central laboratory to no longer 
meet eligibility criteria), the patient will be discontinued from the study and may be replaced. 
Early termination procedures will be performed on patients who are terminated early 
(Section 8.3.1) and all AEs will be collected until 8 weeks (56 days) after the patient’s last dose 
of study drug (Section 11.7.6.1). 
As described in Section 15.3, the Full Analysis Set (FAS) for Cohort 1 and Cohort 2 will be 
based on a modified intent to treat (mITT) approach, and the patients discontinued from the 
study for the reasons described above will be excluded from the FAS. The aim of the 
replacement process is to yield a FAS that includes the planned number of patients all satisfying 
key inclusion and exclusion criteria. 

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8.3.5. 
End of Study Definition 
The end of the study is defined as the date of the last patient’s last visit or follow-up (whether on 
site or via phone call) in the Extension Period, whichever is later. 

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9. 
STUDY TREATMENT 
9.1. 
Materials and Supplies 
9.1.1. 
Description of Study Drugs 
ALXN1210, a recombinant, humanized anti-C5 monoclonal antibody composed of two 448 
amino acid heavy chains and two 214 amino acid light chains, is an IgG2/4 kappa 
immunoglobulin consisting of human constant regions, and murine complementarity-
determining regions grafted onto human framework light- and heavy-chain variable regions. 
ALXN1210 is produced in Chinese hamster cells and was designed through minimal targeted 
engineering of eculizumab by introducing 4 unique amino acid substitutions to its heavy chain to 
extend antibody half-life. ALXN1210 and eculizumab share over 99% primary amino acid 
sequence identity and have very similar pharmacology. 
ALXN1210 drug product 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. 
Refer to Table 5 and the current IB for additional information. 
Table 5: 
Study Drug 
Product Name 
ALXN1210 
Dosage Form 
Concentrated solution (10 mg/mL) for infusion 
Route of Administration 
Intravenous infusion 
Physical Description 
Clear to translucent, slight whitish color, practically free from particles 
Manufacturer 
Alexion Pharmaceuticals, Inc. or Contracted Manufacturing Organization 
9.1.2. 
Study Drug Packaging and Labeling 
ALXN1210 is packaged in United States Pharmacopeia (USP)/European Union Pharmacopeia 
(EP) Type 1 borosilicate glass vials and stoppered with a butyl rubber stopper with an aluminum 
overseal and a flip-off cap. Study drug will be supplied in kits. Please refer to the ALXN1210 
Pharmacy Manual for details. 
ALXN1210 orders will be released to each site upon receipt of all required documents based 
upon applicable regulations and once the site is activated in IXRS®. 
9.1.3. 
Study Drug Storage 
Upon arrival of the study drug kits at the study site, the pharmacist (or trained designee) should 
promptly remove the study drug kits from the shipping cooler and store them in their original 
cartons under refrigerated conditions at 2°C to 8°C (35°F to 47°F) and protected from light. 
ALXN1210 should not be frozen. Study drug must be stored in a secure, limited-access storage 
area, and the temperature must be monitored daily.  
The admixed drug product should be at room temperature prior to administration. The material 
must not be heated (eg, by using a microwave or other heat source) other than by ambient air 
temperature. 

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Please consult the Pharmacy Manual for further information regarding the storage conditions of 
reconstituted ALXN1210. 
9.1.4. 
Study Drug Preparation and Infusion 
ALXN1210 must NOT be administered as an IV push or bolus injection. Infusions of study 
drug should be prepared using aseptic technique. The patient’s required dose of ALXN1210 will 
be further diluted into commercially available saline (0.9% sodium chloride; country-specific 
pharmacopeia) at the volume specified in Table 6. ALXN1210 admixture will be administered to 
the patient using an IV tubing administration set via an infusion pump. Use of a 0.2 micron filter 
is required during infusion. 
Table 6: 
Dosing Reference Chart for ALXN1210 Dose Preparation 
Dose Type 
Body Weight 
(kg)a 
Dose 
(mg) 
ALXN1210 
Volume (mL) 
Saline 
Volume 
(mL) 
Total 
Volume 
(mL) 
Minimum 
Infusion 
Duration 
minutes 
(hours) 
Maximum 
Infusion 
Rate 
(mL/hour) 
Loading 
≥ 5 to < 10 
600 
60 
60 
120 
228 (3.8) 
31.5 
≥ 10 to < 20 
600 
60 
60 
120 
113 (1.9) 
63.1 
≥ 20 to < 30 
900 
90 
90 
180 
86 (1.5) 
120.0 
≥ 30 to < 40 
1200 
120 
120 
240 
77 (1.3) 
184.6 
≥ 40 to < 60 
2400 
240 
240 
480 
114 (1.9) 
253 
≥ 60 to < 100 
2700 
270 
270 
540 
102 (1.7) 
318 
≥ 100 
3000 
300 
300 
600 
108 (1.8) 
333 
Maintenance 
≥ 5 to < 10 
300 
30 
30 
60 
113 (1.9) 
31.5 
≥ 10 to < 20 
600 
60 
60 
120 
113 (1.9) 
63.1 
≥ 20 to < 30 
2100 
210 
210 
420 
194 (3.3) 
127.2 
≥ 30 to < 40 
2700 
270 
270 
540 
167 (2.8) 
192.8 
≥ 40 to < 60 
3000 
300 
300 
600 
140 (2.4) 
250 
≥ 60 to < 100 
3300 
330 
330 
660 
120 (2.0) 
330 
≥ 100 
3600 
360 
360 
720 
132 (2.2) 
328 
Please refer to the Pharmacy Manual for additional dose preparation instructions.  
a Body weight as recorded on Dose Regimen Decision Days. If the Dose Regimen Day is also dosing day, body 
weight will be recorded predose with dosing that day based on the previous Dose Regimen Day body weight. 
Doses of study drug must only be prepared and dispensed by qualified study personnel. Study 
drug is to be dispensed only to enrolled patients who are confirmed eligible for participation in 
this study. Once study drug is prepared for a patient, it can only be administered to that patient. 
Vials of study drug are for one-time use only and any drug product remaining in the vial should 
not be used for another patient. Any drug remaining in the infusion tubing or infusion bag should 
not be used for another patient. 
Further details on preparation and dose administration of ALXN1210, as well as disposal of 
study drug, can be found in the Pharmacy Manual.  
9.1.5. 
Study Drug Handling and Disposal 
All clinical study material provided to the Investigator will be stored in a secure place, and 
allocated and dispensed by appropriately trained persons. Detailed records of the amounts of the 
investigational product received, dispensed, and destroyed will be maintained. 

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Unless otherwise notified, empty vials and vials with residual materials should be kept for 
inspection and accountability by the study monitor prior to their destruction or handled per local 
pharmacy standard operating procedures (SOPs) for clinical study drugs. To satisfy regulatory 
requirements regarding drug accountability, at the end of the study all remaining ALXN1210 
inventory will be reconciled and destroyed or returned to Alexion or designee according to 
applicable regulations. 
Please refer to the ALXN1210-aHUS-312 Pharmacy Manual for further information. 
9.2. 
Treatments Administered 
Patients will receive ALXN1210 for 26 weeks during the Initial Evaluation Period. ALXN1210 
will be administered as an IV infusion. ALXN1210 must NOT be administered as an IV push 
or bolus injection. 
The dose regimen for ALXN1210 during the Initial Evaluation Period is based on the patient’s 
body weight recorded on Dose Regimen Decision Days (Table 7). If the Dose Regimen Day is 
also dosing day, body weight will be recorded predose with dosing that day based on the 
previous Dose Regimen Day body weight. Patients will receive a loading dose of ALXN1210 on 
Day 1, followed by maintenance dosing of ALXN1210 on Day 15 and q8w thereafter for patients 
weighing ≥ 20 kg, or q4w for patients weighing < 20 kg. For Cohort 2 patients, Day 1 of study 
treatment will occur 14 days from the patient’s last dose of eculizumab. Changes in dose regimen 
(dose level [ie, mg] or dose frequency [ie, q4w vs q8w]) will be based on the patient’s body 
weight on the “Dose Regimen Decision Day” (Table 1, Table 2, Table 3, and Table 4) as 
follows:  
• During the Initial Evaluation Period, changes to dose regimen (dose level [ie, mg] or 
dose frequency [ie, q4w vs q8w]) will be based on the patient’s body weight on the 
“Dose Regimen Decision Day (patients on q4w or q8w schedules)” preceding the day 
of administration.  
− Patients changing from q4w to q8w will be administered their first q8w dose on 
the ALXN1210 administration day (“ALXN1210 administration [patients 
weighing > 20 kg]”) following the “Dose Regimen Decision Day (patients on 
q4w or q8w schedules)”.  
− Patients changing from q8w to q4w will be administered their first q4w dose on 
the ALXN1210 administration day (“ALXN1210 administration [patients 
weighing < 20 kg]”) following the “Dose Regimen Decision Day (patients on 
q4w or q8w schedules)”. 
• During the Extension Period, the dose of ALXN1210 is based on the patient’s body 
weight on the preceding “Dose Regimen Decision Day (patients on q4w schedule)” or 
“Dose Regimen Decision Day (patients on q8w schedule)”. 
− For patients on a q4w schedule: Predose body weight will be measured before 
dosing on the Dose Regimen Decision Day (patients on q4w schedule). Should 
this weight change the dose regimen (dose level [ie, mg] or dose frequency [ie, 
q4w vs q8w]), the change will occur on the visit 4 weeks later. Patients changing 
from q4w to q8w will be administered their first q8w dose on the ALXN1210 

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administration day (“ALXN1210 administration [patients weighing > 20 kg]”) 
following the “Dose Regimen Decision Day (patients on q4w schedule)”. 
− For patients on a q8w schedule: Predose body weight will be measured before 
dosing on the Dose Regimen Decision Day (patients on q8w schedule). Should 
this weight change the dose regimen (dose level [ie, mg] or dose frequency [ie, 
q4w vs q8w]), the change will occur on the visit 8 weeks later. Patients changing 
from q8w to q4w will be administered their first q4w dose on the ALXN1210 
administration day (“ALXN1210 administration [patients weighing < 20 kg]”) 
8 weeks after the “Dose Regimen Decision Day (patients on q8w schedule)”. 
• If the Investigator and Alexion Medical Monitor mutually agree that a patient will 
potentially benefit from a supplemental dose of ALXN1210, it may be administered 
and the decision will be documented.  
• Should the Investigator and Alexion Medical Monitor mutually agree the infusion 
volume (120 mL) of the loading dose for patients ≥ 5 to < 10 kg (600 mg) is too high 
for an individual patient, this dose may be administered as 2 separate infusions no 
more than approximately 24 hours apart and the decision will be documented. 
Table 7: 
Loading and Maintenance Treatment Regimens 
Body Weight 
Range (kg)a 
Loading Dose (mg) 
Maintenance Doses (mg) 
Maintenance Dosing Frequency  
≥ 5 to < 10 
600 
300 
q4w 
≥ 10 to < 20 
600 
600 
q4w 
≥ 20 to < 30 
900 
2100 
q8w 
≥ 30 to < 40 
1200 
2700 
q8w 
≥ 40 to < 60 
2400 
3000 
q8w 
≥ 60 to < 100 
2700 
3300 
q8w 
≥ 100 
3000 
3600 
q8w 
Abbreviations: q4w = once every 4 weeks; q8w = once every 8 weeks  
a Body weight as recorded on Dose Regimen Decision Days. If the Dose Regimen Day is also dosing day, body 
weight will be recorded predose with dosing that day based on the previous Dose Regimen Day body weight. 
After the Initial Evaluation Period, all patients will roll over into an Extension Period in which 
all patients continue their weight-based maintenance dose of ALXN1210 on Day 183 and q8w 
thereafter for patients weighing ≥ 20 kg, or q4w for patients weighing < 20 kg, until the product 
is registered or approved (in accordance with country-specific regulation) or for up to 4.5 years, 
whichever occurs first. 
The actual time of all dose administrations, including any supplemental dose or dose 
administered as 2 separate infusions as noted above, will be recorded in the patient’s eCRF. 
9.3. 
Method of Assignment to Treatment 
This is an open-label study. Patients who meet all criteria for enrollment will be assigned to 
study treatment with ALXN1210 at the Baseline Visit (Day 1). The interactive voice- or web-
response system (IxRS) will be used to assign vials containing ALXN1210 to each patient. 

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9.4. 
Rationale for Selection of Doses in the Study 
The weight-based dosages of ALXN1210 in this study (Table 7) are premised on PK/PD data 
from early development studies in healthy adult volunteers as well as the available data from 
patients with PNH in an ongoing Phase 1b dose-finding study (ALXN1210-PNH-103) and an 
ongoing Phase 2 proof-of-concept study (ALXN1210-PNH-201). The selection of ALXN1210 
dose regimen for patients with aHUS is based on targeting immediate, complete and sustained 
inhibition of terminal complement in patients with PNH, which is expected to correspond to 
immediate, complete and sustained inhibition of terminal complement in patients with aHUS. As 
stated in Section 7.1, a planned initial analysis of ALXN1210 PK and serum free C5 levels was 
conducted after 4 complement inhibitor treatment-naïve (ie, Cohort 1) patients weighing ≥ 5 kg 
to < 40 kg completed dosing through Day 71. Based on the results of this analysis, the loading 
dose for patients ≥ 5 to < 10 kg has changed by way of this amendment from 300 mg to 600 mg.   
9.5. 
Special Treatment Considerations 
Infusion of other monoclonal antibodies has been associated with infusion reactions, with onset 
typically during or shortly after completion of the infusion. Please refer to Appendix D for 
guidance on identifying and managing potential drug infusion reactions. 
9.6. 
Prior and Concomitant Medications and Nonpharmacologic 
Procedures 
Prior medications (including vitamins and herbal preparations)—including those discussed in the 
exclusion criteria (Section 8.2) and procedures (any therapeutic intervention, such as 
surgery/biopsy or physical therapy) the patient takes or undergoes within 28 days prior to the 
start of Screening until the first dose of ALXN1210—will be recorded on the patient’s eCRF. In 
addition, history of meningococcal vaccination must be collected for the 3 years prior to first 
dose of study drug, and for patients < 18 years of age at the time of enrollment, vaccination 
history for Hib and Streptococcus pneumoniae must be collected from birth.  
All medication use and procedures undertaken during the study will be recorded in the patient’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. 
Concomitant medications and procedures will be recorded from the first infusion of study drug 
through 56 days after the patient’s last dose of study drug. Any changes in concomitant 
medications also will be recorded in the patient’s source document/medical chart and eCRF. Any 
concomitant medication deemed necessary for the patient’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 patient’s source 
document/medical chart and eCRF. 
A Follow-up Phone Call to collect concomitant medications, procedures, and adverse events is 
required 8 weeks (56 days) ± 5 days after the patient’s last dose of ALXN1210 in the following 
circumstances: 
1. Patient terminates from the study early. 

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2. Patient completes the study on the q4w regimen and does not initiate commercially 
available aHUS treatment within 8 weeks of their last ALXN1210 dose.  
9.7. 
Prohibited Medications and Procedures 
Patients are prohibited from receiving any of the following medications and procedures at any 
time after the first dose of study drug for all patients in the study (even those who discontinue 
ALXN1210 treatment in the Extension Period, but remain in the study) until completion of the 
study or early termination of the patient from the study: 
• Eculizumab or other complement inhibitors 
• Use of any other investigational drug or device as part of a clinical trial 
• IVIg (unless for an unrelated medical need e.g. hypogammaglobinemia)  
• Rituximab 
• PE/PI 
• New dialysis within the first 48-hour period following the first dose of ALXN1210 
unless there is a compelling medical need as assessed by (1) hypervolemia 
unresponsive to diuretics, (2) refractory electrolyte imbalance, or (3) new-onset 
uremic encephalopathy. Exceptions must be approved prior to administration of 
dialysis on a case-by-case basis by the Sponsor.  
The following concomitant medications and procedures are allowed under certain circumstances 
and with the following restrictions: 
• Use of other immunosuppressive therapies (such as steroids, mTORi [eg, sirolimus, 
everolimus], CNI [eg, cyclosporine or tacrolimus]) during the study are not allowed 
unless: a) part of an established post-transplant antirejection regime, or b) patient has 
confirmed anti-complement factor antibodies requiring immunosuppressive therapy, 
or c) steroids are being used for a condition other than aHUS (eg, asthma), or 
d) steroids initiated empirically prior to enrollment and are being tapered as standard 
of care.  
Any patients receiving other complement inhibitors (including eculizumab) or undergoing PE/PI 
after the first dose of study drug will be withdrawn from the study.   
9.8. 
Vaccination  
Due to its mechanism of action, the use of ALXN1210 increases the patient’s susceptibility to 
infection. To reduce the risk of infection, all patients must be vaccinated against N. meningitidis, 
Hib, and Streptococcus pneumoniae.  
Patients must be vaccinated against N. meningitidis within 3 years prior to, or at the time of, 
receiving the first dose of ALXN1210. Patients who will be treated with drug less than 2 weeks 
after receiving a meningococcal vaccine must receive treatment with appropriate prophylactic 
antibiotics until 2 weeks after vaccination. Vaccines against serotypes A, C, Y, W135, and B, 
where available, are recommended to prevent common pathogenic meningococcal serotypes. 

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Patients must be vaccinated or revaccinated according to current national vaccination guidelines 
or local practice for vaccination use with complement inhibitors (eg, eculizumab). 
It is recognized that some patients who have not been vaccinated against N. meningitidis within 
3 years prior to receiving the first dose of ALXN1210 may not be able to receive a vaccination at 
the time of the first dose. Patients who have not been vaccinated prior to initiating ALXN1210 
treatment should receive prophylactic antibiotics prior to and for at least 2 weeks after 
meningococcal vaccination. Patients who cannot be vaccinated must receive antibiotic 
prophylaxis for the entire treatment period and for 8 months following last dose. 
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. All 
patients should be monitored for early signs of meningococcal infection, evaluated immediately 
if infection is suspected, and treated with appropriate antibiotics, if necessary. 
To increase risk awareness and promote quick disclosure of any potential signs or symptoms of 
infection experienced by the patients during the course of the study, patients will be provided a 
safety card to carry with them at all times and for 8 months after last dose of ALXN1210. 
Additional discussion and explanation of the potential risks, signs, and symptoms will occur at 
specific time points as part of the review of the patient safety card and throughout the study as 
described in the Schedule of Assessments (Table 1, Table 2, Table 3, and Table 4).  
Patients must be vaccinated against Hib and Streptococcus pneumoniae according to national and 
local vaccination schedule guidelines, prior to, or at the time of, receiving the first dose of 
ALXN1210. 
Vaccination status for N. meningitidis, Hib, and S. pneumoniae will be recorded on the patient’s 
eCRF. 
9.9. 
Treatment Compliance 
Patients will be administered study drug in a controlled setting under the supervision of the 
Investigator or designee, thereby ensuring compliance with study drug administration. The 
Investigator or designee will ensure that all patients are adequately informed on the specific 
dosing regimen required for compliance with the study protocol, ensure that the patient receives 
the appropriate dose at the designated time points during the study and that adequate safety 
monitoring occurs during the infusion (Section 9.5). 
9.10. 
Contraception Guidance 
Female patients of childbearing potential must use a highly effective or acceptable method of 
contraception (as defined below), starting at Screening and continuing for at least 8 months after 
the last dose of study drug. 
Highly effective contraceptive methods include: 
1. Hormonal contraception associated with inhibition of ovulation 
2. Intrauterine device 
3. Intrauterine hormone-releasing system 
4. Bilateral tubal occlusion 

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5. Vasectomized partner, provided that the partner is the patient’s sole sexual partner 
6. Sexual abstinence, defined as refraining from heterosexual intercourse during the entire 
period of risk associated with the study drug treatment; reliability of sexual abstinence 
needs to be evaluated in relation to the duration of the clinical study and the preferred and 
usual lifestyle of the patient 
Acceptable contraceptive methods include: 
1. A combination of male condom with either cap, diaphragm, or sponge with spermicide 
(double barrier methods) 
The above-listed method(s) of contraception chosen for an individual patient can be determined 
by the Investigator with consideration for the patient’s medical history and concomitant 
medications. 
Male patients with a female spouse/partner of childbearing potential or a pregnant or 
breastfeeding spouse or partner must agree to use double barrier contraception (male condom 
plus appropriate barrier method for the female partner) while on treatment and for at least 8 
months after the last dose of study drug. Double barrier contraception is required even with 
documented medical assessment of surgical success of a vasectomy.  
Male patients must not donate sperm while on treatment and for at least 8 months after the last 
dose of study drug. 

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10. 
EFFICACY ASSESSMENTS 
As patients previously treated with eculizumab have stabilized TMA parameters at study entry, 
Cohort 2 patients will be excluded from the following efficacy assessments: Complete TMA 
Response, Time to Complete TMA Response, Complete TMA Response status over time, and 
increase in hemoglobin from baseline. 
10.1. 
Primary Efficacy Assessment 
The primary efficacy assessment for Cohort 1 is Complete TMA Response during the 26-week 
Initial Evaluation Period. The criteria for Complete TMA Response are the following:  
1. Normalization of platelet count 
2. Normalization of LDH 
3. ≥ 25% improvement in serum creatinine from baseline  
Patients 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.  
10.2. 
Secondary Efficacy Assessments 
The following secondary efficacy assessments for Cohort 1 will be measured through 26 weeks 
and over the entire study period:  
1. Dialysis requirement status 
2. Time to Complete TMA Response 
3. Complete TMA Response status over time 
4. Observed value and change from baseline in eGFR 
5. CKD stage, as evaluated by eGFR at select target days and classified as improved, stable 
(no change), or worsened compared to baseline 
6. Observed value and change from baseline in hematologic parameters (platelets, LDH, 
hemoglobin) 
7. Increase in hemoglobin of ≥ 20 g/L from baseline, observed at 2 separate assessments 
obtained at least 4 weeks (28 days) apart, and any measurement in between 
8. Change from baseline in QoL, as measured by Pediatric FACIT Fatigue questionnaire 
(patients ≥ 5 years of age) 
9. TMA parameters in patients who discontinue treatment in the Extension Period, but 
remain in the study 
 
The following secondary efficacy assessments for Cohort 2 will be measured through 26 weeks 
and over the entire study period:  

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1. Dialysis requirement status 
2. Observed value and change from baseline in eGFR 
3. CKD stage, as evaluated by eGFR at select target days and classified as improved, stable 
(no change), or worsened compared to baseline 
4. Observed value and change from baseline in hematologic parameters (platelets, LDH, 
hemoglobin) 
5. Change from baseline in QoL, as measured by Pediatric FACIT Fatigue questionnaire 
(patients ≥ 5 years of age) 
6. TMA parameters in patients who discontinue treatment in the Extension Period, but 
remain in the study 

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11. 
SAFETY ASSESSMENTS 
The Investigator or his/her designee will meet with patients/caregivers to discuss the potential 
safety risks of ALXN1210 and to give the Investigator the opportunity to address any of the 
patient’s safety concerns regarding the study. 
The collection of AEs will be monitored from the time informed consent is obtained until study 
completion. Investigators are instructed to follow any AEs through to their conclusion 
(resolution or stabilization) as described in Section 11.7.6. In the event of patient withdrawal 
from the study, AE monitoring should continue through the last patient’s last study visit if 
possible.  
The timing of the clinical and laboratory assessments to be performed is specified in the 
Schedule of Assessments (Section 7.3). Any clinically significant abnormal results should be 
followed until resolution or stabilization. 
11.1. 
Demographic/Medical History 
11.1.1. 
Demographics and Baseline Characteristics  
A review of demographic parameters, including age, gender, race, and ethnicity will be 
performed. A complete medical history will be taken and documented. Weight and height will be 
recorded.  
11.1.2. 
Disease Characteristics 
The patient’s aHUS medical history, including onset of first aHUS symptom and date of 
diagnosis, will be documented at the Screening Visit.  
11.1.3. 
Medical History 
The patient’s medical history, including prior and concomitant conditions/disorders, will be 
recorded at the Screening Visit. Medication (prescription or over-the-counter, including vitamins 
and/or herbal supplements) use within 28 days prior to the start of Screening will also be 
recorded. Meningococcal vaccination within 3 years prior to the first dose of study drug, and 
vaccination history for Hib and Streptococcus pneumoniae from birth, will also be recorded, as 
described in Section 9.6. For Cohort 2 patients, medical history should be used to document 
ADAMTS13, Shiga toxin status, and direct Coombs at the previous TMA event, if available. 
11.2. 
Physical Examinations 
A physical examination will include the following assessments: general appearance; skin; head, 
ear, eye, nose, and throat; neck; lymph nodes; chest; heart; abdominal cavity; limb; central 
nervous system; and musculoskeletal system. An abbreviated physical examination consists of a 
body system relevant examination based upon Investigator (or qualified designee) judgment and 
patient symptoms. Physical growth (height, weight, and head circumference [the latter only in 
patients ≤ 2 years of age]) will be assessed. 

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11.3. 
Vital Signs 
Vital sign measurements will be taken after the patient has been resting for at least 5 minutes, 
and will include systolic and diastolic BP (millimeters of mercury [mmHg]), pulse oximetry, 
heart rate (beats/minute), respiratory rate (breaths/minute), and temperature (degrees Celsius [°C] 
or degrees Fahrenheit [°F]).  
11.4. 
Laboratory Assessments 
Samples for serum pregnancy, hematology, chemistry, coagulation, and urinalysis will be 
performed at the times specified in the Schedule of Assessments (Section 7.3). Specific 
laboratory assessments are provided in Appendix E. Samples for laboratory assessments will be 
collected before each study drug administration. An alternative blood sampling schedule for 
infants, for whom less blood volume should be collected, must be used as detailed in the Study 
Operations Manual. 
For Cohort 1, samples collected at Screening may be tested at either 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. All analyses in this study will be based on results from the central laboratory 
(unless the result is missing [see Section 15.12.1]). If Cohort 1 patients are found not to satisfy 
the eligibility criteria for serum creatinine (Inclusion Criterion 2c) based on central laboratory 
results, they must not be enrolled into the study; if the subject has received the first dose of 
ALXN1210, the patient must be withdrawn from the study, and may be replaced. For Cohort 1 
patients, laboratory results for Exclusion Criterion number 1 and/or Exclusion Criterion number 
2 may not be available prior to first dose. Later results for Exclusion Criterion number 1 and/or 
Exclusion Criterion number 2 could lead to discontinuation and replacement of the patient 
(please refer to Section 8.3 for potential discontinuation and replacement details). 
For Cohort 2, samples collected at Screening must be tested at a central laboratory; however, 
historical test results via chart review should be utilized for Inclusion Criterion 3 and Exclusion 
Criteria 1, 2, 3, and 24.  Please refer to the Laboratory Manual for time windows for collection 
and detailed instructions for collecting, processing, storing, and shipping blood samples for 
safety assessments. Laboratory reports will be made available to the Investigators in a timely 
manner for clinical management of patients.   
It is anticipated that some laboratory values may be outside the normal value range due to the 
underlying disease. The Investigators should use their medical judgment when assessing the 
clinical significance of these values. Clinical significance is defined as any variation in 
laboratory measurements that has medical relevance and which results in a change in medical 
care. If clinically significant laboratory changes from baseline value are noted, the changes will 
be documented as AEs on the AE eCRF. The Investigator will also assess the relationship to 
study treatment for all clinically significant out-of-range values (Section 15.9.3). The 
Investigator will continue to monitor the patient through additional laboratory assessments until 
(1) values have returned to the normal range or baseline level, or (2) in the judgment of the 
Investigator, values that are outside the normal range are not related to the administration of 
study drug or other protocol-specific procedures. 

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11.4.1. 
Pregnancy Screen 
For females of childbearing potential, a serum or urine pregnancy test (ie, beta-human chorionic 
gonadotropin [β-hCG]) will be performed according to the Schedule of Assessments 
(Section 7.3). 
11.4.2. 
Hematology 
Blood samples will be analyzed for the hematology parameters listed in Appendix E. 
11.4.3. 
Serum Chemistry 
Blood samples will be analyzed for the serum chemistry parameters listed in Appendix E. 
Indirect bilirubin is calculated from total and direct bilirubin values; therefore, indirect bilirubin 
results will not be available if direct bilirubin is below the limit of quantification. 
Chemistry assessments will be performed at the time points specified in the Schedule of 
Assessments (Section 7.3). The eGFR will be calculated for all visits at which serum chemistries 
are collected using the Schwartz formula. 
11.4.4. 
Coagulation 
Blood samples will be analyzed for the coagulation parameters listed in Appendix E. 
11.4.5. 
Urinalysis and Urine Chemistry 
Urine samples will be analyzed for the parameters listed in Appendix E. A microscopic 
examination of urine samples will be performed if the results of the macroscopic analysis are 
abnormal. 
Urine samples will also be analyzed to measure proteins and creatinine in order to calculate the 
urine total protein:creatinine ratio. 
11.5. 
Electrocardiograms 
For each patient, single 12-lead digital ECGs will be collected according to the Schedule of 
Assessments (Section 7.3). Patients must be supine for approximately 5 to 10 minutes before 
ECG collection and remain supine but awake during ECG collection. 
The Investigator or designee will be responsible for reviewing the ECG to assess whether the 
ECG is within normal limits and to determine the clinical significance of the results. These 
assessments will be indicated on the CRF. For any clinically significant abnormal ECG results, 
the Investigator must contact the Medical Monitor to discuss the patient’s continued eligibility to 
participate in this protocol. 
11.6. 
Immunogenicity 
Blood samples will be collected to test for presence and titer of ADAs to ALXN1210 in serum 
prior to study drug administration as indicated in the Schedule of Assessments (Section 7.3). 
Further characterization of antibody responses may be conducted as appropriate, including 
binding and neutralizing antibodies, to PK/PD, safety, and activity of ALXN1210.  

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Please refer to the Laboratory Manual for time windows for collection and detailed instructions 
for collecting, processing, storing, and shipping blood samples for immunogenicity analysis.  
11.7. 
Adverse Event Management 
An AE is any untoward medical occurrence in a patient administered a pharmaceutical product 
and which does not necessarily have a causal relationship with this treatment. An AE can 
therefore be any unfavorable or unintended sign (eg, an abnormal laboratory finding), symptom, 
or disease temporally associated with the use of a medicinal product, whether or not considered 
related to the medicinal product. 
Situations in which an untoward medical occurrence did not occur (eg, hospitalization for 
elective surgery if planned before the start of the study, admissions for social reasons or 
convenience), and anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen are not AEs. 
Lack of drug effect is not an AE in clinical studies, because the purpose of the clinical study is to 
establish drug effect. 
A medication error (including intentional misuse, abuse, and overdose of the product) or use 
other than what is defined in the protocol is not considered an AE unless there is an untoward 
medical occurrence as a result of a medication error.  
Cases of pregnancy that occur during maternal or paternal exposure to investigational product 
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. 
Adverse events should be recorded from the time of signed consent. An AE reported after 
informed consent but before study drug administration will be considered a pretreatment AE. 
Alexion has reporting standards for AEs that are to be followed as described in Section 11.7.6 
regardless of applicable regulatory requirements that may be less stringent.  
11.7.1. 
Targeted Adverse Events 
The following events are important identified risks in this study: 
• Meningococcal infections 
11.7.2. 
Severity Assessment 
The severity of AEs will be graded using Common Terminology Criteria for Adverse Events 
(CTCAE) version 4.03 or higher. A grading (severity) scale is provided for each AE term. Each 
CTCAE term is a Lowest Level Term (LLT) per the Medical Dictionary for Regulatory 
Activities (MedDRA®). Each LLT will be coded to a MedDRA preferred term (PT). 
Grade refers to the severity of the AE. The CTCAE assigns a grade of 1 through 5, with unique 
clinical descriptions of severity for each AE (Table 8). 

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Table 8: 
Adverse Event Severity Grading Scale 
Grade 
Description 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not 
indicated 
Grade 2 
Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental 
activities of daily living (ADL)a 
Grade 3 
Severe or medically significant, but not immediately life-threatening; hospitalization or prolongation 
of hospitalization indicated; disabling; limiting self-care ADLb 
Grade 4 
Life-threatening consequences; urgent intervention indicated. 
Grade 5 
Death related to AE. 
Abbreviations: ADL = activities of daily living; AE = adverse event 
a  Instrumental ADL refers to preparing meals, shopping for groceries or clothes, using the telephone, managing 
money, etc. 
b  Self-care ADL refers to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not 
bedridden. 
Any change in the severity of an AE should be documented based on specific guidelines in the 
eCRF Completion Guidelines. 
Severity and seriousness must be differentiated: severity describes the intensity of an AE, while 
the term seriousness refers to an AE that has met specific criteria for a SAE as described in 
Section 11.7.4. 
11.7.3. 
Causality Assessment 
An Investigator must provide a causality assessment (Unrelated, Unlikely, Possible, Probable, or 
Definite) for all AEs (both serious and nonserious) based upon the Investigator’s medical 
judgment and the observed symptoms associated with the event (Table 9). This assessment must 
be recorded on the eCRF and any additional forms as appropriate. 
Table 9: 
Causality Assessment Descriptions 
Assessment 
Description 
Not Related/Unrelated 
Suggests that there is no causal association between the investigational product 
and the reported event. 
Unlikely Related 
Suggests that the clinical picture is highly consistent with a cause other than the 
investigational product but attribution cannot be made with absolute certainty 
and a relationship between the investigational product and AE cannot be 
excluded with complete confidence. 
Possibly Related 
Suggests that treatment with the investigational product may have caused or 
contributed to the AE (ie, the event follows a reasonable temporal sequence 
from the time of drug administration and/or follows a known response pattern to 
the investigational product, but could also have been produced by other factors). 
Probably Related 
Suggests that a reasonable temporal sequence of the event with the 
investigational product administration exists and the likely causal association of 
the event with the investigational product. This will be based upon the known 
pharmacological action of the investigational product, known or previously 
reported adverse reactions to the investigational product or class of drugs, or 
judgment based on the Investigator’s clinical experience. 
Definitely Related 
Temporal relationship to the investigational product, other conditions 
(concurrent illness, concurrent medication reaction, or progression/expression 
of disease state) do not appear to explain event, corresponds with the known 
pharmaceutical profile, improvement on discontinuation, reappearance on 
rechallenge. 

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11.7.4. 
Serious Adverse Events 
An SAE is any untoward medical occurrence that: 
• Results in death 
• Is life-threatening (ie, patient was at risk of death at the time of the event) 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity 
• Is a congenital anomaly/birth defect 
Important medical events that may not result in death, be immediately life-threatening, or require 
hospitalization, may be considered a serious adverse event when, based upon appropriate 
medical judgment, they may jeopardize the patient or may require intervention to prevent one of 
the outcomes listed above. 
The expectedness of an SAE will be determined by Alexion, based on the current version of the 
IB. 
Information pertaining to the collection and reporting of SAEs is provided in Section 11.7.6.  
11.7.5. 
Suspected Unexpected Serious Adverse Reactions 
Suspected unexpected serious adverse reactions (SUSARs) are serious events that are not listed 
in the IB and that the Investigator identifies as related to investigational product or procedure. 
United States Title 21 Code of Federal Regulations (CFR) 312.32 and European Union Clinical 
Trial Directive 2001/20/EC and the associated detailed guidances or national regulatory 
requirements in participating countries require the reporting of SUSARs. Alexion has procedures 
that will be followed for the recording and expedited reporting of SUSARs that are consistent 
with global regulations and the associated detailed guidances. Suspected unexpected serious 
adverse reactions will be reported to the national competent authority and IRBs/IECs where 
applicable. 
11.7.6. 
Collection and Reporting of Adverse Events 
11.7.6.1. All Adverse Events 
All AEs (serious and nonserious) will be collected from the signing of the informed consent form 
(ICF) until 8 weeks (56 days) after the last dose of study drug. For patients who discontinue 
study drug, but remain in the study, AE data collection will continue at subsequent visits per the 
Schedule of Assessments, until the patient’s last visit. For patients who terminate early from the 
study, an ET visit will be conducted as soon as possible, and a Follow-up Phone Call will be 
performed 8 weeks (56 days) ± 5 days following the patient’s last dose of the study drug. All 
AEs must be recorded on the eCRF upon the Investigator or his/her staff becoming aware of their 
occurrence. 
Investigators will be instructed to report the SAE including their assessment (eg, severity, 
seriousness, and potential relatedness to study drug) to Alexion Global Pharmacovigilance 
(GPV) within 24 hours of first awareness of the event via the Safety Gateway. 

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If a patient’s treatment is discontinued as a result of an AE, study site personnel must clearly 
capture the circumstances and data leading to any such dose interruption or discontinuation of 
treatment in the AE and Exposure pages of the eCRF. 
11.7.6.2. Serious Adverse Events 
All SAEs will be recorded regardless of the Investigator’s assessment of causality. No time limit 
exists on reporting SAEs that are thought to be causally related to the study drug. Investigators 
are at liberty to report SAEs irrespective of causality at any time.  
For all SAEs, the Investigator must provide the following: 
• Appropriate and requested follow-up information in the time frame detailed below 
• Causality of the SAE(s) 
• Treatment of/intervention for the SAE(s) 
• Outcome of the SAE(s) 
• Supporting medical records and laboratory/diagnostic information 
All SAEs must be reported to Alexion GPV within 24 hours of the Investigator or site staff 
awareness. These timelines for reporting SAE information to the sponsor need to be followed for 
the initial SAE report and for all follow-up SAE information.  
The Investigator or designee must record the SAE data in the eCRF and verify the accuracy of 
the information with corresponding source documents. The SAE report should be submitted 
electronically via the Safety Gateway.  
In the event that either the electronic data capture (EDC) or the Safety Gateway is unavailable at 
the site(s), the SAE must be reported on paper. Facsimile transmission or email may be used in 
the event of electronic submission failure. 
Email: 
 
Facsimile: 
 (NOTE: A local facsimile number will be provided for non-US 
sites) 
When further information becomes available, the eCRF should be updated with the new 
information and an updated SAE report should be submitted to Alexion GPV via Safety 
Gateway.  
If applicable, additional information such as relevant medical records should be submitted to 
Alexion GPV via the email address or fax number noted above. 
All paper forms and follow-up information submitted to the sponsor outside of the Safety 
Gateway (eg, discharge summary) should be kept in the appropriate section of the study file.  
11.7.7. 
Sponsor Reporting Requirements 
Alexion GPV or its legal representative is responsible for notifying the relevant regulatory 
authorities of SAEs meeting the reporting criteria. This protocol will use the current IB as the 
Reference Safety Document. The expectedness and reporting criteria of an SAE will be 
determined by the sponsor from the Reference Safety Document. 
PPD
PPD

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11.7.8. 
Investigator Reporting Requirements 
The Investigator must fulfill all local regulatory obligations required for the study Investigators. 
It is the PI’s responsibility to notify the IRB/IEC of all SAEs that occur at his or her site, as 
required per IRB/IEC SOPs. Investigators will also be notified of all SUSAR events that occur 
during the clinical study. Each site is responsible for notifying its IRB/IEC of these additional 
SAEs as per IRB/IEC SOPs.  
11.8. 
Exposure During Pregnancy and Breastfeeding 
Pregnancy data will be collected during this study for all patients and female spouse/partner of 
male patients. Exposure during pregnancy (also referred to as exposure in utero) can be the result 
of either maternal exposure or transmission of drug product via semen following paternal 
exposure. 
For all Alexion products, both in development or postapproval, exposure during pregnancy must 
be recorded and the pregnancy followed until the outcome of the pregnancy is known (ie, 
spontaneous miscarriage, elective termination, normal birth, or congenital abnormality), even if 
the patient discontinues study drug or withdraws from the study. 
If a female patient or a patient’s female partner becomes pregnant during the conduct of this 
study, the Investigator must submit the “Pregnancy Reporting and Outcome/Breastfeeding” form 
to Alexion GPV via fax or email (Section 11.7.6.2). When the outcome of the pregnancy 
becomes known, the form should be updated and submitted to Alexion GPV. If additional 
follow-up is required, the Investigator will be requested to provide the information. 
Exposure of an infant to an Alexion product during breastfeeding must also be reported (via the 
“Pregnancy Reporting and Outcome Form/Breastfeeding”) and any AEs experienced by the 
infant must be reported to Alexion Global Pharmacovigilance or designee via email or facsimile 
(Section 11.7.6). 
Pregnancy in itself is not regarded as an AE unless there is a suspicion that the investigational 
product 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. 
11.9. 
Safety Monitoring 
The Alexion medical monitor, GPV physician, or both will monitor safety data throughout the 
course of the study. 
Alexion will review all information pertaining to the SAEs within the time frames mandated by 
company procedures. The Alexion medical monitor will, as appropriate, consult with the GPV 
safety physician, to review trends in safety data.  

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12. 
PHARMACOKINETICS AND PHARMACODYNAMICS 
ASSESSMENTS 
Blood samples for determination of serum drug concentrations and PD assessments will be 
collected before and after administration of study drug at the time points indicated in the 
Schedule of Assessments (Section 7.3). The actual date and time (24-hour clock time) of each 
sampling will be recorded. The number of PK samples obtained for any given patient will not 
exceed the currently planned number of time points. 
End of infusion blood samples for PK and PD assessment should be collected from the arm 
opposite to the arm used for infusing drug. Please refer to the Laboratory Study Manual for 
details on sample collection, including blood volume requirements.  
Assessments for PK/PD are as follows: 
1. Changes in serum ALXN1210 concentration over time  
2. Changes in serum free C5 concentrations 
3. Changes in serum free C5 and serum ALXN1210 concentration in patients who 
discontinue treatment in the Extension Period, but remain in the study 

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13. 
EXPLORATORY ASSESSMENTS 
13.1. 
Biomarker Assessments 
Exploratory biomarker analyses may be performed to evaluate changes from baseline in 
biomarkers which may include, but are not limited to, markers of complement dysregulation (eg, 
Factor Ba), vascular inflammation (eg, sTNFR1), endothelial activation/damage (eg, sVCAM-1, 
thrombomodulin), coagulation (eg, D-dimer), and renal injury (eg, cystatin C). Additional 
analysis may include evaluation of ALXN1210 excretion in urine, cRBC hemolysis, total C5, 
and autoantibodies to complement proteins (eg, anti-factor H). 
Please refer to the Laboratory Study Manual for details on sample collection, including blood 
volume requirements. Biomarker samples may be analyzed after study completion. 
13.2. 
Genetics 
For patients who sign an additional optional consent, a whole blood sample for exploratory 
genetics can be drawn anytime during the study. Exploratory genetics may be performed to 
investigate genetic variants in genes known to be associated with aHUS, as well as to identify 
novel variants associated with aHUS, complement dysregulation, or metabolism or efficacy of 
ALXN1210. A patient (or legal guardian) may decline from providing a sample for exploratory 
genetics and still participate in the study. 
Please refer to the Laboratory Study Manual for details on sample collection, including blood 
volume requirements. 
13.3. 
Extra-renal Signs or Symptoms of aHUS 
The Investigator will evaluate extra-renal signs or symptoms of aHUS using clinical laboratory 
measurements (eg, troponin I, amylase, and lipase), vital signs (eg, heart rate, respiratory rate, 
pulse oximetry), and an organ system review. 

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14. 
DATA QUALITY ASSURANCE 
To ensure accurate, complete, and reliable data, the sponsor or its representatives will do the 
following: 
• Provide instructional material to the study sites, as appropriate. 
• Perform start-up training to instruct the Investigators and study personnel. This 
training will give instruction on the protocol, the completion of the eCRFs, and study 
procedures. 
• Make periodic visits to the study site. 
• Be available for consultation and stay in contact with the study site personnel by 
email, telephone, or facsimile. 
• Review and evaluate eCRF data and use standard computer edits to detect errors in 
data collection. 
• Conduct a quality review of the database. 
Authorized representatives of the sponsor, a regulatory authority, or an IRB/IEC may visit the 
site to perform audits or inspections, including source data verification. The purpose of an 
Alexion audit or inspection is to systematically and independently examine all study-related 
activities and documents to determine whether these activities were conducted, and data were 
recorded, analyzed, and accurately reported according to the protocol, good clinical practice 
(GCP) guidelines of the International Conference on Harmonisation (ICH), and any applicable 
regulatory requirements. The Investigator should contact the sponsor immediately if contacted by 
a regulatory agency about an inspection. 
To ensure the safety of participants in the study, and to ensure accurate, complete, and reliable 
data, the Investigator will keep records of laboratory tests, clinical notes, and patient medical 
records in the patient files as original source documents for the study. If requested, the 
Investigator will provide the sponsor, applicable regulatory agencies, and applicable IRBs/IECs 
with direct access to original source documents. 
14.1. 
Data Collection and Storage 
All clinical data will be recorded promptly and accurately in the EDC system. When recorded 
electronically, CRFs will be electronically generated. All raw data will be preserved in order to 
maintain data integrity. The Investigator or designee will assume the responsibility of ensuring 
the completeness, accuracy, and timeliness of the clinical data. 
The EDC system is fully validated and compliant with CFR Title 21 Part 11. The EDC system 
will maintain a complete audit trail of all data changes. At each scheduled monitoring visit, the 
Investigator or designee will cooperate with the sponsor’s representative(s) for the periodic 
review of study documents to ensure the accuracy and completeness of the EDC system. 
Electronic consistency checks and manual review will be used to identify any errors or 
inconsistencies in the data. This information will be provided to the respective study sites by 
means of electronic or manual queries. 

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The Investigator or designee will prepare and maintain adequate and accurate source documents 
(medical records, ECGs, AE and concomitant medication reporting, raw data collection forms) 
designed to record all observations and other pertinent data for each patient receiving study drug. 
The Investigator will allow the sponsor’s representatives, contract designees, authorized 
regulatory authority inspectors, and the IRB/IEC to have direct access to all documents 
pertaining to the study. 
14.2. 
Records Retention 
The Investigator must maintain all documentation relating to the study for a period of 2 years 
after the last marketing application approval, or if not approved, 2 years following the 
discontinuance of the test article for investigation or longer if required per local regulations. If it 
becomes necessary for the sponsor or the sponsor’s designee or the Regulatory Authority to 
review any documentation relating to the study, the Investigator must permit access to such 
records. 

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15. 
STATISTICAL METHODS AND PLANNED ANALYSES 
The analyses for complement inhibitor treatment-naïve patients (ie, Cohort 1) and eculizumab-
experienced adolescent patients (ie, Cohort 2) will be conducted and reported separately. 
Analyses specific to Cohort 1 are indicated as such below; all other endpoints will be performed 
for both cohorts. Tabulated summaries will not include a direct comparison between Cohort 1 
and Cohort 2.  
15.1. 
General Considerations 
All data collected will be presented in summary tables and tabulations. 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. All analyses will be performed using SAS® release, 
version 9.4 or higher (SAS Institute Inc., Cary, NC, USA) or other validated statistical software. 
Continuous variables will be summarized using descriptive statistics, including number of 
observations and mean, standard deviation (SD), median, minimum, and maximum values. 
Categorical variables will be summarized by frequency counts and percentage of patients. Prior 
to finalizing and locking the database, all decisions concerning the inclusion or exclusion of data 
from the analysis for each patient will be determined by appropriate medical and statistical 
personnel. Any and all exclusions will be documented in patient listings.  
Planned summaries will be presented overall and by age groups when applicable. 
Details of the statistical analyses described below will be specified in a separate Statistical 
Analysis Plan (SAP) before database lock and analysis. Any change to the data analysis methods 
described in the protocol will require an amendment only if it changes the primary or key 
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. 
An interim CSR will be prepared when 12 to 14 complement inhibitor treatment-naïve (ie, 
Cohort 1) patients have completed or withdrawn from the end of the 26-week Initial Evaluation 
Period. An additional interim CSR will be prepared when all study patients have completed or 
withdrawn from the 26-week Initial Evaluation Period. Each interim CSR will include efficacy, 
safety, and PK/PD analyses. A final CSR to summarize long-term efficacy, safety, and PK/PD 
will be produced at study completion. Available exploratory data will be summarized after study 
completion but may not be included in the CSR. 
For patients who discontinue ALXN1210 treatment in the Extension Period, but remain in the 
study, their data will be summarized along with data from patients remaining on treatment for 
8 weeks (56 days) after their last dose of study drug. Data beyond this point will be presented in 
separate supplemental listings strictly limited to these patients. If such patients start retreatment 
with ALXN1210, their data from the time of study treatment restart will also be presented in 
separate supplemental listings limited to patients who will have the study treatment restarted. 
However, data on AE, concomitant medications, and nonpharmacologic therapies and 
procedures from the time of treatment restart will be considered treatment emergent or 

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concomitant, and will be summarized as such, combined with data from patients who remained 
on treatment throughout the study. 
Pharmacokinetic/PD and ADA data from patients who discontinue ALXN1210 treatment in the 
Extension Period, but remain in the study, will be summarized along with data from patients 
remaining on treatment, until 8 weeks (56 days) after their last dose of study drug. Data beyond 
this point will be presented in separate supplemental listings limited to these patients. If such 
patients start retreatment with ALXN1210, their PK/PD and ADA data from the time of study 
treatment restart will also be presented in separate supplemental listings limited to patients who 
will have the study treatment restarted. 
15.2. 
Determination of Sample Size 
The total planned sample size is approximately 23 to 28. This sample size is deemed appropriate 
to get proper representation in each of the 4 planned age groups and provide adequate safety 
information and precision level for the planned estimation. 
15.3. 
Analysis Sets 
Efficacy analyses will be performed on the FAS. The analysis of the FAS will be the primary 
analysis.  
The FAS for Cohort 1 will be based on a mITT approach. With this approach, confirmation of 
eligibility in patients may occur after receiving study drug. This specifically applies to Inclusion 
Criterion number 2c (must be confirmed via a central laboratory), Exclusion Criterion number 1 
(may be confirmed via a central or local laboratory), and Exclusion Criterion number 2 (may be 
confirmed via a central or local laboratory).  Based on the above, the FAS will include all 
patients who receive at least 1 dose of ALXN1210, have at least 1 postbaseline efficacy 
assessment, and meet all of the following criteria:  
• Patients who satisfy Inclusion Criterion number 2c  
• Patients who satisfy Exclusion Criterion number 1 
• Patients who satisfy Exclusion Criterion number 2 
The FAS for Cohort 2 will include all patients who receive at least 1 dose of ALXN1210 and 
have at least 1 postbaseline efficacy assessment. 
The FAS will be determined prior to database lock and prior to the database snapshot for the 
analysis performed at the end of the 26-week Initial Evaluation Period. 
Safety analyses will be performed on the Safety Set, defined as all patients who receive at least 
1 dose of study drug for both Cohort 1 and Cohort 2.  
Pharmacokinetic and PD analyses will be performed on all patients from the FAS who have 
evaluable PK and PD data. 
15.4. 
Demographics and Baseline Characteristics 
Patient demographic and baseline characteristics, including medical history and transplant 
history, will be summarized for the FAS and Safety Set for both Cohort 1 and Cohort 2.  

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15.5. 
Patient Disposition 
All patients will be included in the summaries of patient disposition, which will describe the 
frequency and percentage of patients enrolled and treated and who completed or withdrew from 
the study, along with reason for withdrawal from the study. 
The numbers of patients who are treated, discontinue treatment (along with reason for treatment 
discontinuation), complete or withdraw from the Initial Evaluation Period (along with reason for 
withdrawal), enter the Extension Period, and complete or withdraw from the Extension Period 
(along with reason for withdrawal) will be tabulated. 
These summaries will be presented for both Cohort 1 and Cohort 2. 
15.6. 
Prior and Concomitant Medications and Nonpharmacologic 
Therapies and Procedures  
Each patient’s prior and concomitant medication use will be coded using the World Health 
Organization Drug Dictionary, and the frequency and percentage of concomitant medications 
will be summarized. Medications will be summarized by Anatomic-Therapeutic-Chemical 
(ATC) class and preferred drug name using frequency counts and percentages of patients in the 
FAS and Safety Set for both Cohort 1 and Cohort 2. 
15.7. 
Treatment Compliance 
The number of infusions received per patient will be tabulated for the FAS and Safety Set for 
both Cohort 1 and Cohort 2. 
15.8. 
Efficacy Analyses 
All efficacy analyses will be conducted for the FAS. The FAS is the primary analysis set for all 
efficacy analyses.  
15.8.1. 
Primary Efficacy Analysis 
The primary efficacy endpoint is Complete TMA Response during the 26-week Initial 
Evaluation Period. The primary analysis will consist in estimating the proportion of complete 
TMA responders among ALXN1210 treated patients. This will be performed by calculating the 
point estimate and a 95% confidence interval (CI) for the proportion of complete TMA 
responders in ALXN1210 treated patients. The CI will be based on exact confidence limits using 
the Clopper-Pearson method. This analysis will only be performed for Cohort 1. 
15.8.2. 
Key Secondary Efficacy Analyses 
15.8.2.1. Dialysis Requirement Status 
For patients requiring dialysis within 5 days prior to ALXN1210 treatment initiation, the 
proportion of patients no longer requiring dialysis will be summarized over time. A 2-sided 95% 
CI for the proportion receiving dialysis will be provided for both Cohort 1 and Cohort 2. 

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15.8.2.2. Time to Complete TMA Response 
For the secondary efficacy endpoint of time to Complete TMA Response, Kaplan-Meier 
cumulative distribution curves will be generated along with 2-sided 95% CIs. The corresponding 
summary table will present the cumulative distribution function (CDF) estimate, the number of 
patients at risk, the number of patients responding, and the number of patients censored at each 
postbaseline time point. The table will also present first quartile, median, and third quartile, 
along with corresponding 2-sided 95% CI, of time to complete response. This analysis will only 
be performed for Cohort 1. 
15.8.2.3. Complete TMA Response Status Over Time 
Complete TMA Response will also be summarized over time by presenting the number and 
proportion of responders along with a 2-sided 95% CI for each postbaseline time point. This 
analysis will only be performed for Cohort 1. 
15.8.2.4. eGFR Value and Change from Baseline 
Kidney function evaluated by eGFR will be summarized at baseline and each postbaseline time 
point using descriptive statistics for continuous variables for the observed value as well as the 
change from baseline. A value for eGFR will be imputed for patients requiring dialysis for acute 
kidney injury. A mixed model for repeated measures (MMRM) with the fixed, categorical effect 
of visit and fixed, continuous effect of the baseline value as covariates may be fit to test whether 
changes differ from zero at each time point. This analysis will be performed for both Cohort 1 
and Cohort 2. 
15.8.2.5. CKD Stage 
CKD (Appendix G) stage will be summarized over time by presenting the number and 
proportion of patients that improved (excluding those with Stage 1 at baseline as they cannot 
improve), worsened (excluding those 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. A 2-sided 95% CI for the proportion will be 
provided for each category. This analysis will be performed for both Cohort 1 and Cohort 2. 
15.8.2.6. Hematologic Parameters 
Hematologic parameters (platelets, LDH, hemoglobin) will be summarized at baseline and each 
postbaseline time point using descriptive statistics for continuous variables for the observed 
value as well as the change from baseline. A MMRM with the fixed, categorical effect of visit 
and fixed, continuous effect of the specific test’s baseline value as covariates may be fit to test 
whether changes differ from zero at each time point. This analysis will be performed for both 
Cohort 1 and Cohort 2. 
15.8.2.7. Hemoglobin Response 
The number and proportion of patients with an increase from baseline in hemoglobin ≥ 20g/L, 
observed at 2 separate assessments obtained at least 4 weeks (28 days) apart, and any 
measurement in between, will be summarized over time by presenting the number and proportion 

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of responders along with a 2-sided 95% CI for each postbaseline time point. This analysis will 
only be performed for Cohort 1. 
15.8.2.8. Quality of Life 
Quality of life will be assessed in patients > 5 years of age by the Pediatric FACIT Fatigue 
Questionnaire (patient-reported for patients who were ≥ 8 years of age at the time of enrollment; 
caregiver-reported or caregiver assistance for patients who were 5 to < 8 years of age at the time 
of enrollment; Appendix F). FACIT Fatigue data will be summarized at baseline and each 
postbaseline time point using descriptive statistics for continuous variables for the observed 
value as well as the change from baseline. A MMRM with the fixed, categorical effect of visit 
and fixed, continuous effect of the test’s baseline value as covariates may be fit to test whether 
changes differ from zero at each time point. These analyses will be performed for both Cohort 1 
and Cohort 1. Analyses will be separate for patients who were 5 to < 8 years of age at the time of 
enrollment (ie, caregiver-reported or caregiver assistance) and patients who were ≥ 8 years of 
age at the time of enrollment (ie, patient-reported). 
15.9. 
Safety Analyses 
All safety analyses will be performed for the Safety Set, defined as all patients who receive at 
least 1 dose of ALXN1210.  
15.9.1. 
Adverse Events 
The following definitions will be used for AEs: 
• Pretreatment adverse events: Any AE that starts after providing informed consent, but 
before the first infusion of study drug 
• Treatment-emergent adverse event: Any AE that starts during or after the first infusion of 
study drug. Adverse events that start 56 days or later after the last dose of study drug will 
not be considered as treatment emergent. 
• Treatment-emergent SAE: A treatment-emergent AE (TEAE) that is serious 
(Section 11.7.4 for definitions). 
The incidence of TEAEs, TEAEs leading to withdrawal from the study, TEAEs leading to study 
treatment discontinuation, drug-related TEAEs, TEAEs during study drug administration, severe 
TEAEs, and SAEs will be summarized. All AEs will be coded using MedDRA version 18 or 
higher, and will be summarized by system organ class (SOC) and PT overall, by severity, and by 
relationship to treatment. Detailed by-patient listings of TEAEs, SAEs, related TEAEs, TEAEs 
during study drug administration, TEAEs leading to withdrawal from the study, and TEAEs 
leading to study treatment discontinuation will be provided. This analysis will be performed for 
both Cohort 1 and Cohort 2. 
15.9.2. 
Physical Examination and Vital Signs 
Adverse changes from baseline in physical examination findings will be classified as AEs and 
analyzed accordingly. 

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Vital signs will be summarized descriptively at baseline and postbaseline time points and for 
changes from baseline. 
By-patient listings will be provided. 
This analysis will be performed for both Cohort 1 and Cohort 2. 
15.9.3. 
Clinical Laboratory Tests 
Observed values and changes from baseline in clinical chemistry, hematology, and urinalysis 
will be summarized descriptively at baseline, and at each postbaseline time point. For laboratory 
results that can be classified as normal, low or high based on normal range values, shifts from 
baseline in classification will be summarized for all study visits. This analysis will be performed 
for both Cohort 1 and Cohort 2. 
15.9.4. 
Electrocardiograms 
By-patient data listings of ECG parameters will be provided. Electrocardiograms will be 
evaluated and summarized as normal, abnormal not clinically significant, or abnormal clinically 
significant. A shift from baseline to worst on-study ECG table will be presented for ECG results. 
Observed values and change from baseline in ECG intervals (PR, RR, QT, and QTc) will be 
summarized descriptively at baseline and each postbaseline time point. QT interval will be 
corrected for heart rate using Fridericia’s formula (QTcF). This analysis will be performed for 
both Cohort 1 and Cohort 2. 
15.9.5. 
Immunogenicity 
Abnormal immunogenicity findings, including the incidence and titers for ADAs to ALXN1210 
will be presented at each postbaseline time point in tabular format. The proportion of patients 
ever positive and the proportion of patients always negative may be explored. This analysis will 
be performed for both Cohort 1 and Cohort 2. 
15.10. 
Pharmacokinetic/ Pharmacodynamic Analyses 
Individual serum concentration data for all patients from the FAS and who have evaluable PK 
data will be used to derive PK parameters for ALXN1210. 
Graphs of mean serum ALXN1210 concentration-time profiles will be constructed. Graphs of 
serum concentration-time profiles for individual patients may also be provided. Actual dose 
administration and sampling times will be used for all calculations. Descriptive statistics will be 
calculated for serum concentration data at each sampling time, as appropriate. Assessment of 
population-PK may be considered using data from this study or in combination with data from 
other studies. 
Pharmacodynamic analyses will be performed for all patients from the FAS and who have 
evaluable PD data. The PD effects of ALXN1210 will be evaluated by assessing the absolute 
values and changes and percentage changes from baseline in serum free C5 concentrations over 
time, as appropriate. Descriptive statistics will be calculated for the PD data at each sampling 
time, as appropriate.  Assessments of PK/PD relationships may be explored using data from this 
study or in combination with data from other studies. 

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This analysis will be performed for both Cohort 1 and Cohort 2. 
15.11. 
Exploratory Analyses 
15.11.1. 
Biomarker Analyses 
For exploratory biomarker analyses, summary statistics may be presented for absolute, change 
and percentage change from baseline.  
The relationship between ALXN1210 concentration and exploratory biomarkers or the 
correlation between clinical benefit and key exploratory biomarkers may be assessed by 
graphical display. Exploratory analysis and potential relationships between clinical outcomes, 
PK/PD, genetic profile, and biomarker levels may also be performed. Autoantibody results will 
be summarized if evaluated.  
This analysis may be performed for both Cohort 1 and Cohort 2. 
15.11.2. 
Genetics 
Exploratory genetics may be performed to investigate genetic variants in genes known to be 
associated with aHUS, as well as to identify novel genetic variants associated with aHUS, 
complement dysregulation, or metabolism or efficacy of ALXN1210. This analysis may be 
performed for both Cohort 1 and Cohort 2. 
15.11.3. 
Extra-renal Signs or Symptoms of aHUS  
Extra-renal signs or symptoms of aHUS will be summarized at baseline and each postbaseline 
assessment by presenting the number and proportion of patients with a specific symptom present. 
This analysis will be performed for both Cohort 1 and Cohort 2. 
15.12. 
Other Statistical Issues 
15.12.1. 
Missing or Invalid Data 
If a Day 1 assessment is missing, the Screening assessment will be used as the baseline 
assessment. If the Day 1 and Screening assessments are missing, local laboratory data will be 
used as the baseline assessment. 
For evaluation of Complete TMA Response during the 26-week Initial Evaluation Period 
(primary endpoint), patients missing an efficacy assessment that is part of the definition of 
Complete TMA Response while still on-study, will have their last observation carried forward 
(LOCF). For patients who will have early termination from the study prior to Week 26, their data 
up to the time of discontinuation will be used to assess Complete TMA Response.  
Missing data for QoL instruments will be handled as specified in the instructions for each 
instrument. 
15.13. 
Interim Analyses 
An interim analysis is planned when 12 to 14 complement inhibitor treatment-naïve (ie, 
Cohort 1) patients have completed or withdrawn from the 26-week Initial Evaluation Period. A 
second interim analysis is planned after all study patients have completed or withdrawn from the 

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26-week Initial Evaluation Period. Additionally, a final analysis to summarize long-term 
efficacy, safety, and PK parameters will be performed at the end of the 4.5-year Extension 
Period. 

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16. 
INFORMED CONSENT, ETHICAL REVIEW, AND 
REGULATORY CONSIDERATIONS 
16.1. 
Informed Consent and Assent 
The Investigator or designee is responsible for ensuring that the patient/caregiver understands the 
potential risks and benefits of participating in the study, including answering any questions the 
patient may have throughout the study and sharing in a timely manner any new information that 
may be relevant to the patient’s willingness to continue his or her participation in the study. 
The ICF will be used to explain the potential risks and benefits of study participation to the 
patient in simple terms before the patient is entered into the study, and to document that the 
patient is satisfied with his or her understanding of the risks and benefits of participating in the 
study and desires to participate in the study. 
The Investigator or designee is responsible for ensuring that informed consent is given by each 
patient or the patient’s legal representative. This includes obtaining the appropriate signatures 
and dates on the ICF prior to the performance of any protocol procedures and prior to the 
administration of investigational product. The Investigator or designee must retain the original 
version of the signed ICF. If the ICF is amended, the original signed, amended version must also 
be retained. A copy of the signed ICF(s) must be given to the patient. 
As used in this protocol, the term “informed consent” includes all informed consent given by 
patients or, as applicable, informed consent by their legally authorized representatives if the 
patient is unable to provide informed consent. 
16.2. 
Data Monitoring Committee 
An independent DMC comprising experts in relevant biomedical fields who have no direct 
relationship with the study will be appointed by the sponsor. The DMC will review and evaluate 
the accumulated study data for patient safety and make recommendations on continuing study 
drug administration or termination of the study. The DMC will review study information on a 
regular basis as outlined in the DMC charter, which is maintained separately from the study 
protocol.  
Final decisions regarding the conduct of the study will be made by the sponsor after consultation 
with the DMC. All appropriate regulatory authorities and Ethics Committees will be notified of 
any significant action.  
Each member of the DMC will be required to sign a contract agreement, which includes a 
confidentiality and financial disclosure statement, assuring no conflicts of interest as a condition 
for membership on the committee.  
The specific responsibilities of the DMC are described in the DMC Charter, which is maintained 
as a separate document. 

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16.3. 
Ethical Review 
All ICFs must be compliant with the ICH guideline on GCPs.  
Documentation of IRB/IEC approval of the protocol and the ICF must be provided to the sponsor 
before the study may begin at the investigational sites. The IRB/IEC(s) will review the protocol 
as required. 
16.4. 
Regulatory Considerations 
This study will be conducted in accordance with: 
1. Consensus ethics principles derived from international ethics guidelines, including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
(CIOMS) International Ethical Guidelines 
2. The ICH GCP Guideline [E6] 
3. The ICH Clinical Trials of Medicinal Products in the Pediatric Population [E11] 
4. Applicable national and local laws and regulations 
The Investigator or designee will promptly submit the protocol to applicable IRB/IEC(s). 
Some of the obligations of the sponsor will be assigned to a third-party organization. 
An identification code assigned to each patient by the EDC system will be used in lieu of the 
patient’s name to protect the patient’s identity when reporting AEs and other study-related data. 
16.4.1. 
Changes/Deviations to Protocol 
The Investigator may need to deviate from the protocol to eliminate an immediate hazard to a 
trial subject without prior notification of the IRB/IEC. Any deviations from the protocol must be 
fully documented. The deviation and the reasons for it should be submitted to the IRB/IEC, 
Sponsor, and appropriate regulatory authority if required (ICH GCP E6 [R1] 4.5.4).  
After the commencement of the clinical trial, the Sponsor may make changes to the protocol. If 
those changes are significant, the regulatory authority and applicable IRB/IEC will be notified. 
16.5. 
Publication Policy 
The full terms regarding publication of the results of this study are outlined in the applicable 
Clinical Study Agreement. 

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17. 
LIST OF REFERENCES 
Brodsky RA. Complement in hemolytic anemia. Blood. 2015;126:2459-65. 
Ceriotti F, Boyd JC, Klein G, Henny J, Queralto J, Kairisto V, et al. Reference intervals for 
serum creatinine concentrations: assessment of available data for global application. Clin Chem. 
2008;54:559-66. 
Haas M. An updated Banff schema for diagnosis of antibody-mediated rejection in renal 
allografts. Curr Opin Organ Transplant. 2014a;19:315-22. 
Haas M, Sis B, Racusen LC, Solez K, Glotz D, Colvin R, et al. Banff 2013 meeting report: 
inclusion of c4d-negative antibody-mediated rejection and antibody-associated arterial lesions. 
Am J Transplant. 2014b; 14:272–83. 
KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney 
Disease. Kidney International Supplements. 2013; 3:19-62. 
Lee W, Bachman E, Aguzzi, R, Jang J-H, Kim J-S, Rottinghaus S, et al. ALXN1210, a long-
acting C5 inhibitor, results in rapid and sustained reduction of LDH with a monthly dosing 
interval in patients with PNH: preliminary data from a dose-escalation study. 2016; European 
Hematology Association Learning Center; 19 May 2016; cited 09 Jun 2016]. 
Loirat C, Frémeaux-Bacchi V. Atypical hemolytic uremic syndrome. Orphanet J Rare Dis. 
2011;6:60. 
Noris M, Caprioli J, Bresin E, Mossali C, Pianetti G, Gamba S, et al. Relative role of genetic 
complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. 
Clin J Am Soc Nephrol. 2010;5:1844–59. 
Panteghini M. Enzymatic assays for creatinine: time for action. Clin Chem Lab Med. 
2008;46:567–72. 
Sellier-Leclerc A-L, Frémeaux-Bacchi V, Dragon-Durey M-A, Macher MA, Niaudet P, Guest G, 
et al. et al. Differential impact of complement mutations on clinical characteristics in atypical 
hemolytic uremic syndrome. J Am Soc Nephrol. 2007;18:2392-2400. 
Sampson HA, Munoz-Furlong A, Campbell RL, Adkinson NF, Bock SA, Branum A, et al. 
Second symposium on the definition and management of anaphylaxis: summary report--second 
National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network 
symposium. Ann Emerg Med. 2006;47(4):373-80. 
Sis B, Jhangri GS, Bunnag S, Allanach K, Kaplan B, Halloran. Endothelial Gene Expression in 
Kidney Transplants with Alloantibody Indicates Antibody-Mediated Damage Despite Lack of 
C4d Staining. Am J Transplant. 2009;9:2312-23. 

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18. 
APPENDICES 
 

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APPENDIX A. BLOOD SAMPLING VOLUMES 
The following procedures for blood collection should be adhered to: 
1. Number of attempts: The number of attempts for sampling blood is limited to 3 times per 
day. This means that, after 3 punctures for collection of blood have been performed and 
no or insufficient blood could be collected, no other puncture will be done on the same 
day.  
2. Volume of blood samples: Per study patient, the study-related blood loss (including any 
losses in the collection procedure) should not exceed 3% of the total blood volume during 
a period of 4 weeks, and should not exceed 1% at any single time. The total volume of 
blood is estimated at 80 to 90 mL/kg body weight. Three percent (3%) is 2.4 mL blood 
per kg of body weight. If an investigator decides to deviate from these limits, the 
deviation must be fully documented, and the investigator should provide justification for 
the deviation. If the required blood volume cannot be obtained, due to the above 
mentioned safety limits, priority will be given to safety-relevant investigations. 
3. EMLA (eutectic mixture of local anesthetics) cream/plaster: To minimize the possible 
pain and discomfort due to collection of blood, the Investigator should apply an EMLA 
cream/plaster at the puncture site. 
 
Reference:  European Commission. European Commission Ethical Considerations for Clinical 
Trials on Medicinal Products Conducted with the Paediatric Population: Recommendations of 
the ad hoc group for the development of implementing guidelines for Directive 2001/20/EC 
relating to the good clinical practice in the conduct of clinical trials on medicinal products for 
human use.  2008.  

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APPENDIX B. COMMON CREATININE REFERENCE INTERVALS 
Age (Gender) Group 
97.5th Percentile Value (mg/dL) 
97.5th Percentile Value (μmol/L) 
Birth 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 age 
0.81 
72 
15 to Adult (males) 
1.18 
104 
15 to Adult (females) 
1.02 
90 
Source: Adapted from Panteghini, 2008; Ceriotti, 2008. 

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APPENDIX C. ANTIBODY MEDIATED REJECTION CRITERIA 
The revised (Banff 2013) classification of acute/active antibody-mediated rejection in renal 
allografts will be used to assess antibody mediated rejection. All 3 features must be present for 
diagnosis. 
Criteriaa,b,c 
Histologic evidence of acute tissue injury, including one or more of the following: 
Microvascular inflammation (g score > 0d and/or ptc score > 0) 
Intimal or transmural arteritis (v score > 0)e 
Acute thrombotic microangiopathy, in the absence of any other cause 
Acute tubular injury, in the absence of any other apparent cause 
Evidence of current/recent antibody interaction with vascular endothelium, including at least one of the following: 
Linear C4d staining in peritubular capillaries (involving at least 10% of ptc by immunofluorescence on frozen 
sections, or any ptc by IHC on paraffin sections) 
At least moderate microvascular inflammation (sum of g and ptc scores ≥ 2)f 
Increased expression of gene transcripts in the biopsy tissue indicative of endothelial injury, if thoroughly 
validatedg 
Serologic evidence of donor-specific antibodies (HLA or other antigens) 
Source: Haas, 2014a 
a For all antibody-mediated rejection (ABMR) diagnoses, it should be specified in the report whether the lesion is 
C4d-positive [involving ≥ 10% of ptc by immunofluorescence on frozen sections or any ptc by 
immunohistochemistry (IHC) on paraffin sections] or without evident C4d deposition (< 10% of ptc by 
immunofluorescence on frozen sections; completely negative by IHC on paraffin sections). 
b These lesions may be clinically acute, smoldering, or subclinical. Biopsies showing 2 of the 3 features, except 
those with donor-specific antibody (DSA) and C4d without histologic abnormalities potentially related to AMR or 
cell-mediated rejection (the latter seen mainly in ABO-incompatible renal allografts) may be designated as 
‘suspicious’ for acute/active ABMR. 
c Modified from Haas, 2014b. 
d Recurrent/de-novo glomerulonephritis should be excluded. 
e It should be noted that these arterial lesions may be indicative of ABMR, T-cell-mediated rejection (TCMR), or 
mixed ABMR/TCMR. Arterial lesions are only scored in arteries having a continuous media with 2 or more 
smooth muscle layers. 
f In the presence of acute TCMR, borderline infiltrates, or evidence of infection, ptc score at least 2 alone is not 
sufficient to define moderate microvascular inflammation, and glomerulitis must be present (g score ≥ 1). 
g At present, the only validated molecular marker meeting this criterion is ENDAT expression, and this has only 
been validated in a single center (University of Alberta). The use of ENDAT expression at other centers or other 
test(s) of gene expression within the biopsy as evidence of ABMR must first undergo independent validation as 
was done for ENDAT expression by Sis, 2009. 

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APPENDIX D. MANAGEMENT OF POTENTIAL DRUG INFUSION 
REACTIONS 
Infusion of other monoclonal antibodies has been associated with infusion reactions, with onset 
typically during or shortly after completion of the infusion. For this reason, patients will be 
carefully observed during each infusion.  
Patients who develop AEs of rash, hives, itching, or dysphagia of mild to moderate intensity 
during their infusion of ALXN1210 may continue to receive the infusion if deemed to be 
medically appropriate by the Investigator. Medical intervention may include, but is not limited 
to, slowing of the infusion rate (with or without treatment) or interrupting or stopping the 
infusion.  
Any acute reaction should be treated according to standard medical practice depending upon 
clinical signs and symptoms. If a patient requires medical intervention, the patient should remain 
at the investigational site until his or her condition stabilizes. The AE and any associated 
concomitant medications must be captured on the patient’s source document and eCRF.  
Some patients treated with IV infusions of monoclonal antibodies have experienced concurrent 
reactions with signs or symptoms that can be classified as acute allergic 
reactions/hypersensitivity reactions or cytokine release syndrome. Signs and symptoms include 
headache, fever, facial flushing, pruritus, myalgia, nausea, chest tightness, dyspnea, vomiting, 
erythema, abdominal discomfort, diaphoresis, shivers, hypertension, lightheadedness, 
hypotension, palpitations, and somnolence. Anaphylaxis might occur at any time during an 
infusion; therefore, patients will be monitored closely during the infusion. In addition, the re-
administration of some monoclonal antibodies has been associated with serum sickness-like 
reactions manifesting 1 to 14 days after drug administration. All AEs that may indicate an 
infusion-related response will be graded according to CTCAE Version 4.03 or higher. 
Before any infusion is started, the treating physician and other appropriate personnel must make 
certain that medication (ie, adrenaline, inhaled beta agonists, antihistamines, corticosteroids) and 
other equipment to treat anaphylaxis are readily available. The infusion must be stopped 
immediately if Grade ≥ 2 allergic/hypersensitivity reactions (including drug fever) or Grade ≥ 3 
cytokine release syndrome/acute infusion reaction occurs. The sponsor must be notified within 
24 hours of any infusion reaction requiring interruption or discontinuation of study drug.  
Patients who experience a reaction during the administration of study drug should be treated 
according to institutional guidelines. For a Grade 1 or Grade 2 infusion reaction, the infusion 
should be temporarily stopped and treatment with an antihistamine (eg, diphenhydramine 25 to 
50 mg orally [PO] or equivalent) and acetaminophen (650 mg orally or equivalent) may be 
considered. If the patient’s signs and symptoms have resolved (with or without administration of 
the above medication), the infusion may be restarted. However, the patients should be infused at 
a slower rate and be monitored closely for any signs and symptoms of infusion reactions during 
the remainder of the infusion. Patients experiencing an infusion reaction should be observed in 
the clinic until resolution of the reaction, or until the Investigator determines the patient is no 
longer at risk. Patients who experience a severe reaction during administration of study drug 
resulting in discontinuation of study drug should undergo all scheduled safety, PK, and PD 
evaluations required by the protocol. 

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If anaphylaxis occurs according to the criteria listed below, then administration of subcutaneous 
epinephrine (1/1000, 0.3 to 0.5 mL, or equivalent) should be considered. In the case of 
bronchospasm, treatment with an inhaled beta agonist also should be considered. Patients 
administered an antihistamine for the treatment or prevention of an infusion reaction should be 
given appropriate warnings about drowsiness and impairment of driving ability before being 
discharged from the center.  
Table 10: 
Clinical Criteria for Diagnosing Anaphylaxis 
Anaphylaxis is highly likely when any 1 of the following 3 criteria is fulfilled: 
1. Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both 
(eg, generalized hives, pruritus or flushing, swollen lips-tongue-uvula), and at least 1 of the following: 
a. 
Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced peak expiratory flow 
(PEF), hypoxemia) 
b. Reduced blood pressure (BP) or associated symptoms of end-organ dysfunction (eg, hypotonia 
[collapse], syncope, incontinence) 
2. Two or more of the following that occur rapidly after exposure to a likely allergen for that patient (minutes 
to several hours): 
a. 
Involvement of the skin-mucosal tissue (eg, generalized hives, itch-flush, swollen lips/tongue/uvula) 
b. Respiratory compromise (eg, dyspnea, wheeze/bronchospasm, stridor, reduced PEF, hypoxemia) 
c. 
Reduced BP or associated symptoms (eg, hypotonia [collapse], syncope, incontinence) 
d. Persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting) 
3. Reduced BP after exposure to known allergen for that patient (minutes to several hours): 
a. 
Systolic BP of less than 90 mm Hg or greater than 30% decrease from that person’s baseline 
Source: Sampson, 2006 
Abbreviations: BP= blood pressure; PEF = peak expiratory flow 

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APPENDIX E. PROTOCOL LABORATORY TESTS 
Hematology: 
Clinical Chemistry: 
Free hemoglobin 
Haptoglobin 
Hematocrit 
Hemoglobin 
Mean corpuscular hemoglobin 
Platelet count  
RBC distribution width 
RBC mean corpuscular volume 
RBC count  
Reticulocyte count 
White blood cell count  
White blood cell differential 
 
Coagulation Panel: 
International normalized ratio 
Prothrombin time 
Partial thromboplastin time 
D-dimera 
 
Urine Chemistry: 
Microalbumin 
Creatinine 
Total protein 
 
Urinalysis: 
Albumin 
Appearance 
Bilirubin 
Blood 
Color 
Creatinine 
Glucose 
Ketone 
Nitrite 
pH 
Protein 
Specific gravity 
Urobilinogen 
 
Alanine aminotransferase 
Albumin 
Alkaline phosphatase 
Amylase 
Aspartate aminotransferase 
Bicarbonate 
Blood urea nitrogen 
C-reactive protein 
Calcium 
Chloride 
Creatinine 
Gamma-glutamyltransferase 
Glucose 
Lactate dehydrogenase 
Lipase 
Magnesium 
Phosphorus 
Potassium 
Sodium 
Total bilirubin (direct and indirect) 
Total protein 
Troponin I 
Uric acid 
 
Pregnancy Test
 
(females only) 
Beta human chorionic gonadotropin 
 
Other: 
ADAMTS13 activity 
ADA 
Coombs, direct 
Serum free C5 
PK 
Shiga toxin-related HUS screen (eg, Shiga toxin 
enzyme immunoassay/PCR in stool/stool culture) 
Note: This table excludes exploratory tests (except D-dimer).  
Abbreviations: ADA = antidrug antibodies; ADAMTS13 = a disintegrin and metalloproteinase with a 
thrombospondin type 1 motif, member 13; C5 = complement component 5; HUS = hemolytic uremic syndrome; 
PCR = polymerase chain reaction; PK = pharmacokinetic; RBC = red blood cell 
a Included with coagulation panel but will be reported as exploratory rather than safety. 
 

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APPENDIX F. PEDIATRIC FACIT-FATIGUE 
 
 

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APPENDIX G. GLOMERULAR FILTRATION RATE 
CATEGORY/STAGE IN CHRONIC KIDNEY DISEASE 
GFR Category/Stage 
GFR (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 
a Relative to young adult level 
Note: In the absence of evidence of kidney damage, neither GFR category/stage G1 nor G2 fulfill the criteria for 
CKD 
Source: KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. 
2013. 3:19-62.