A Phase 3, Randomized, Open-Label, Active-Controlled Study of ALXN1210 Versus Eculizumab in Complement Inhibitor-Naïve Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Phase: PHASE3
Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)
Sponsor: Alexion Pharmaceuticals, Inc.

Protocol ALXN1210-PNH-301 
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1.
TITLE PAGE
PROTOCOL ALXN1210-PNH-301 
A PHASE 3, RANDOMIZED, OPEN-LABEL, ACTIVE-CONTROLLED 
STUDY OF ALXN1210 VERSUS ECULIZUMAB IN COMPLEMENT 
INHIBITOR-NAÏVE ADULT PATIENTS WITH PAROXYSMAL 
NOCTURNAL HEMOGLOBINURIA (PNH) 
Sponsor: 
Alexion Pharmaceuticals, Inc. (Alexion) 
100 College Street 
New Haven, CT 06510 USA 
Sponsor Contact: 
 
Alexion Pharma GmbH 
Giesshübelstrasse 30 
8045 Zürich, Switzerland 
Telephone: 
  
Email:
 
Medical Monitor: 
  
 
Alexion Pharmaceuticals, Inc. 
121, Seaport, Boston USA 
Telephone: 
 
Email: 
 
IND Number: 
128367 
EudraCT Number: 
2016-002025-11 
Date of Initial Protocol: 
09 August 2016 
Amendment 1 (Japan): 
23 September 2016 
Amendment 2 (Global): 
28 September 2016 
Amendment 3 (Global) 
25 January 2017 
Amendment 4 (Global): 
23 October 2017 
Amendment 5 (Global): 
01 March 2019 
Amendment 6 (Global): 
12 April 2021 
NCT #: NCT02946463

Protocol ALXN1210-PNH-301 
 
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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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INVESTIGATOR’S AGREEMENT 
 
I have received and read the Investigator’s Brochure for ALXN1210. I have read the 
ALXN1210-PNH-301 study protocol and agree to conduct the study in accordance with this 
protocol, all applicable government regulations, the principles of the ICH E6 Guidelines for 
Good Clinical Practice, and the principles of the World Medical Association Declaration of 
Helsinki. I also agree to maintain the confidentiality of all information received or developed in 
connection with this protocol.  
 
 
 
 
 
____________________________________ 
Printed Name of Investigator 
 
_____________________________________ 
Signature of Investigator 
 
_______________ 
Date 
 

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STUDY CONTACT INFORMATION 
 
Emergency Contact Information 
Study Role 
Name 
Address and Telephone Number 
Clinical Project Leader 
 
 
Alexion Pharma GmbH 
Giesshübelstrasse 30 
8045 Zürich, Switzerland 
Telephone: 
  
Email: 
 
Medical Monitor 
 
Alexion Pharmaceuticals, Inc. 
121, Seaport, Boston USA 
Telephone: 
 
Email: 
 
24-Hour Emergency 
Contact Phone Number 
 
+ 1.855.585.8266 
 

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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, Randomized, Open-Label, Active-Controlled Study of ALXN1210 Versus 
Eculizumab in Complement Inhibitor-Naïve Adult Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) 
Protocol No: ALXN1210-PNH-301 
EudraCT Number: 2016-002025-11 
Study Center(s): Approximately 300 investigative sites globally. 
Length of Study:  
Estimated date first patient treated:  Dec 2016 
Estimated date last patient completed:   Jan 2023 
Phase of Development: 3 
 
Objective:   
The primary objective of this study is to assess the noninferiority of ALXN1210 compared to eculizumab in 
adult patients with PNH who have never been treated with a complement inhibitor.  
 
Noninferiority will be claimed if after 26 weeks of treatment: 1) the lower bound of the 95% confidence interval 
(CI) for the difference (ALXN1210-eculizumab) in transfusion avoidance (TA) rate is greater than -20%, and 2) 
the lower bound of the 95% CI for the odds ratio of ALXN1210 compared to eculizumab for lactate 
dehydrogenase normalization (LDH-N) is greater than 0.39. 
Study Design and Methodology: This is a Phase 3, open-label, randomized, active-controlled, multicenter 
study to evaluate the safety and efficacy of ALXN1210 versus eculizumab administered by intravenous (IV) 
infusion to adult patients with PNH who are naïve to complement inhibitor treatment. In addition, patients may 
be rolled over from other ongoing studies of ALXN1210 IV in patients with PNH into the Extension Period of 
Study ALXN1210-PNH-301 to receive ALXN1210 (hereafter referred to as Roll-over Cohort). Patients are 
allowed to roll over into Study ALXN1210-PNH-301 to receive continued ALXN1210 IV q8w maintenance 
treatment. 
 
For patients enrolled directly into Study ALXN1210-PNH-301, the study consists of a 4-week screening period, 
a 26-week randomized treatment period, and an extension period of up to 5 years. Patients will be stratified into 
1 of 6 groups based on their transfusion history (0, 1 to 14, or > 14 units of packed red blood cells [pRBCs] in 
the 1 year prior to first dose of study drug) and screening lactate dehydrogenase (LDH) levels (1.5 to  
< 3 × upper limit of normal [ULN] or ≥ 3 × ULN). The patients within each of the 6 groups will then be 
randomly assigned in a 1:1 ratio to receive ALXN1210 or eculizumab. Enrollment of patients without a history 
of transfusion in the past year will be capped at 20%.  
 
Prior to randomization and within 5 days prior to study drug administration on Day 1, each patient’s 
hemoglobin must be evaluated by either local or central laboratory. If at that time the patient’s hemoglobin 
value meets protocol-specified transfusion guidelines, the patient must be transfused with pRBCs to a 
hemoglobin level above the protocol-specified transfusion threshold in order to be eligible for randomization. 
The patient’s post-transfusion hemoglobin value should be confirmed by local or central laboratory to be above 
the protocol-specified transfusion threshold.  
 
Patients randomly assigned to the ALXN1210 group will receive a loading dose of ALXN1210 (2400 mg for 
patients weighing ≥ 40 to < 60 kg, 2700 mg for patients weighing ≥ 60 to < 100 kg, 3000 mg for patients 
weighing ≥ 100 kg) on Day 1, followed by maintenance doses of ALXN1210 (3000 mg for patients weighing ≥ 
40 to < 60 kg, 3300 mg for patients weighing ≥ 60 to < 100 kg, 3600 mg for patients weighing ≥ 100 kg) on 
Day 15 and every 8 weeks (q8w) thereafter for a total of 26 weeks of treatment. Patients randomly assigned to 
the eculizumab group will receive induction treatment with 600 mg of eculizumab IV on Days 1, 8, 15, and 22, 
followed by maintenance treatment with eculizumab 900 mg on Day 29 and every 2 weeks (q2w) thereafter for 
a total of 26 weeks of treatment. After completion of all assessments on Day 183, all patients will enter an 
extension period and receive ALXN1210 until the product is registered or approved (in accordance with 
country-specific regulations) or for up to 5 years, whichever occurs first. (In Norway and Denmark, patients will 
participate for a total of 2.5 years.) Beginning on Day 183, patients who had been randomized to the 

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ALXN1210 treatment group will receive a maintenance dose (as described above) of ALXN1210 q8w, and 
patients who had been randomized to the eculizumab group will receive a loading dose (as described above) of 
ALXN1210 followed 2 weeks later and q8w thereafter by a weight-based maintenance dose of ALXN1210. 
 
For the Roll-over Cohort, patients will receive ALXN1210 weight-based q8w maintenance dosing. 
 
 
Abbreviations: IV = intravenous;PNH = paroxysmal nocturnal hemoglobinuria; R = roll-over 
 
A pRBC transfusion will be administered when a patient has a hemoglobin value of 9 g/dL or lower with signs 
or symptoms of sufficient severity to warrant a transfusion, or a hemoglobin value of 7 g/dL or lower regardless 
of presence of clinical signs or symptoms. 
Number of Patients (planned) in the original Study ALXN1210-PNH-301 Cohort: Based on the coprimary 
endpoint of TA, approximately 214 patients will be randomly assigned in a 1:1 ratio to receive ALXN1210 (N = 
107) or eculizumab (N = 107) to ensure at least 193 evaluable patients (assumes no more than 10% drop-out 
rate).  
A maximum number of approximately 56 patients may roll over from other ongoing studies of ALXN1210 IV 
in patients with PNH into the Extension Period of Study ALXN1210-PNH-301. 
Diagnosis and Main Criteria for Inclusion and Exclusion:  
Patients must meet all inclusion and no exclusion criteria. Patients who fail any of the eligibility criteria may be 
rescreened once for participation, based on discussion and agreement between the Investigator and the Medical 
Monitor.  
 
Eligibility Criteria for Patient Cohort Originally Enrolled in Study ALXN1210-PNH-301 
Inclusion Criteria:  
1. Male or female, 18 years of age or older at the time of consent. 
2. Documented diagnosis of PNH, confirmed by high-sensitivity flow cytometry evaluation of red blood 
cells (RBCs) and white blood cells (WBCs), with granulocyte or monocyte clone size of ≥ 5%. 
3. Presence of 1 or more of the following PNH-related signs or symptoms within 3 months of Screening: 
fatigue, hemoglobinuria, abdominal pain, shortness of breath (dyspnea), anemia (hemoglobin < 10 

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g/dL), history of a major adverse vascular event (including thrombosis), dysphagia, or erectile 
dysfunction; or history of pRBC transfusion due to PNH. 
4. LDH level ≥ 1.5 × ULN at screening. 
5. 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 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. 
6. 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. 
7. Patients must be willing and able to give written informed consent and to comply with all study visits 
and procedures, including the use of any data collection device(s) to directly record patient data. 
Exclusion Criteria: 
1. Current or previous treatment with a complement inhibitor. 
2. Platelet count < 30,000/mm3 (30 × 109/L) at Screening. 
3. Absolute neutrophil count < 500/µL (0.5 × 109/L) at Screening. 
4. History of bone marrow transplantation. 
5. Body weight < 40 kg at Screening. 
6. History of N. meningitidis infection. 
7. History of unexplained, recurrent infection. 
8. Active systemic bacterial, viral, or fungal infection within 14 days prior to study drug administration 
on Day 1. 
9. Presence of fever ≥ 38°C (100.4°F) within 7 days prior to study drug administration on Day 1. 
10. Human immunodeficiency virus (HIV) infection (evidenced by HIV-1 or HIV-2 antibody titer). 
11. Immunized with a live-attenuated vaccine 1 month prior to study drug administration on Day 1. 
12. History of malignancy within 5 years of Screening with the exception of nonmelanoma skin cancer or 
carcinoma in situ of the cervix that has been treated with no evidence of recurrence. 
13. History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease (eg, active 
hepatitis) that, in the opinion of the Investigator or Sponsor, precludes the patient’s participation in an 
investigational clinical trial. 
14. Unstable medical conditions (eg, myocardial ischemia, active gastrointestinal bleed, severe congestive 
heart failure, anticipated need for major surgery within 6 months of randomization, coexisting chronic 
anemia unrelated to PNH) that would make them unlikely to tolerate the requirements of the protocol 
(eg, transfusion guidelines). 
15. Concomitant use of anticoagulants is prohibited if not on a stable regimen for at least 2 weeks prior to 
Day 1.  
16. History of hypersensitivity to any ingredient contained in the study drug, including hypersensitivity to 
murine proteins. 
17. Females who plan to become pregnant or are currently pregnant or breastfeeding. 
18. Females who have a positive pregnancy test result at Screening or on Day 1. 
19. 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. 
20. Known or suspected history of drug or alcohol abuse or dependence within 1 year prior to the start of 
Screening. 
21. Known medical or psychological condition(s) or risk factor that, in the opinion of the Investigator, 
might interfere with the patient’s full participation in the study, pose any additional risk for the patient, 
or confound the assessment of the patient or outcome of the study. 
Eligibility Criteria for Roll-over Cohort  
1. All patients regardless of age, who are currently receiving ALXN1210 IV in an ongoing ALXN1210 
study in patients with PNH 
2. Patients must be willing and able to give written informed consent and to comply with all Extension 
study visits and procedures, including the use of any data collection device(s) to directly record patient 
data 

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3. 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 
 
Investigational Product, Dosage, and Mode of Administration:  
ALXN1210 loading dose on Day 1 and maintenance doses on Day 15 and q8w thereafter, administered by IV 
infusion. For Roll-over Cohort, Day 1 will be the start of q8w weight-based maintenance dose. Dosages are 
based on the patient’s body weight, as shown in the table below: 
 
 
Body Weighta 
Loading Dose  
 
Maintenance Dose  
 
≥ 30 to < 40 kgb 
1200 mg 
2700 mg 
≥ 40 to < 60 kg 
2400 mg 
3000 mg 
≥ 60 to < 100 kg 
2700 mg 
3300 mg 
≥ 100 kg 
3000 mg 
3600 mg 
a  Dose regimen will be based on the last recorded study visit body weight. If the study drug is prepared the 
night before a visit, the weight from the most recent study visit should be used. 
b In the event that a patient drops below 30 kg during the course of the study, the approved ravulizumab atypical hemolytic 
uremic syndrome (aHUS) dosing for patients weighing ≥20 and < 30 kg will be used: a loading dose of 900 mg and 
maintenance dose of 2100 mg. 
Reference Therapy, Dosage, and Mode of Administration:  
Original Study ALXN1210-PNH-301 Cohort: Eculizumab 600 mg induction doses on Days 1, 8, 15, and 22; 
900 mg maintenance dose on Day 29 and q2w to Day 183, administered by IV infusion. 
For the Roll-over Cohort, there is no reference therapy. 
Planned Duration of Treatment:  
Original Study ALXN1210-PNH-301 Cohort: 26-week randomized treatment period followed by an 
extension period in which all patients will receive ALXN1210 until the product is registered or approved (in 
accordance with country-specific regulations) or for up to 5 years, whichever occurs first.  
Roll-over Cohort: patients will receive ALXN1210 until the product is registered or approved (in accordance 
with country-specific regulations) or for the duration of the current study (end of study [EOS] estimated 
January 2023), whichever occurs first.  

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Endpoints:  
Original Study ALXN1210-PNH-301 Cohort 
Efficacy 
Coprimary  
• 
Transfusion avoidance (TA), defined as the proportion of patients who remain transfusion-free and 
do not require a transfusion as per protocol-specified guidelines through Day 183 (Week 26)  
• 
Hemolysis as directly measured by the normalization of LDH levels (LDH-N) from Day 29 (first 
scheduled evaluation status post initiation of maintenance dosing) through Day 183 (Week 26)  
Key Secondary (to be tested in a hierarchical manner) 
1. Percentage change in LDH from Baseline to Day 183 (Week 26) 
2. Change in quality of life (QoL) assessed via the Functional Assessment of Chronic Illness Therapy 
(FACIT)-Fatigue Scale, Version 4, from Baseline to Day 183 (Week 26) 
3. Proportion of patients with breakthrough hemolysis, defined as at least one new or worsening 
symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness 
of breath [dyspnea], anemia [hemoglobin < 10 g/dL], major adverse vascular event [MAVE, 
including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥ 2 × 
ULN, after prior LDH reduction to < 1.5 × ULN on therapy 
4. Proportion of patients with stabilized hemoglobin, defined as avoidance of a ≥ 2 g/dL decrease in 
hemoglobin level from baseline in the absence of transfusion through Day 183 (Week 26) 
Other Secondary 
• 
Change in the European Organisation for Research and Treatment of Cancer (EORTC) Quality of 
Life Questionnaire-Core 30 Scale (QLQ-C30), Version 3.0, from Baseline to Day 183 (Week 26) 
• 
Time to first occurrence of LDH-N 
• 
Total number of units of pRBCs transfused through Day 183 (Week 26) 
• 
Change in clinical manifestations of PNH (fatigue, hemoglobinuria, abdominal pain, shortness of 
breath, chest pain, dysphagia, and erectile dysfunction) from Baseline to Day 183 (Week 26) 
• 
Proportion of patients experiencing MAVEs through Day 183 (Week 26) 
 
Pharmacokinetic/Pharmacodynamic (PK/PD) 
• 
Change in serum ALXN1210 and eculizumab concentrations over time 
• 
Change in chicken red blood cell (cRBC) hemolytic activity over time (exploratory) 
• 
Change in free complement component 5 (C5) concentrations over time 
Safety  
The safety and tolerability of ALXN1210 compared with eculizumab will be evaluated by physical 
examinations, vital signs, electrocardiograms (ECGs), laboratory assessments, and incidence of adverse events 
(AEs) and serious adverse events (SAEs). The proportion of patients who develop antidrug antibodies (ADAs) 
will also be assessed. 
Roll-over Cohort 
The long-term safety of Roll-over patients on ALXN1210 after their roll over into the Extension Period of 
Study ALXN1210-PNH-301 will be evaluated by the incidence of AEs and SAEs, laboratory assessments, and 
the proportion of patients who develop ADA. 
 
Statistical methods:  
Original Study ALXN1210-PNH-301 Cohort: 
General: A clinical study report (CSR) will be produced based on efficacy, safety, PK, and PD data collected 
through the end of the 26-week randomized treatment period (Day 183). A final CSR to summarize long-term 
efficacy, safety, PK, and PD parameters will be produced at study completion. 
 
Efficacy: Efficacy analyses will be performed on the Full Analysis Set (FAS). The coprimary efficacy endpoint 
analyses, as well as key secondary endpoint analyses will also be performed on the Per Protocol (PP) set. The 
FAS is the primary population for all efficacy analyses. The FAS will include all patients who receive at least 1 
dose of ALXN1210 or eculizumab and have at least 1 efficacy assessment post first infusion.  
The PP set, which will be finalized prior to database lock, will consist of FAS patients who meet all of the 
following criteria: 

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• 
Missed no doses of ALXN1210 or no more than 1 dose of eculizumab during the 26-week randomized 
treatment period. 
• 
Met inclusion criteria #2, 3, and 4 
• 
Did not meet exclusion criteria #1, 2, 3, or 4 
• 
Never received the wrong randomized treatment 
• 
Followed the protocol-specified transfusion guidelines 
 
Primary Efficacy Analyses 
The coprimary efficacy endpoints are 1) the difference between treatment groups in the proportion of patients 
who achieve TA through Day 183, and 2) the relative effect of treatment in LDH-N from Day 29 through Day 
183 expressed as an odds ratio.  
 
The percentage of patients who achieve TA with 95% CIs will be computed at Day 183 for both the ALXN1210 
and eculizumab treatment groups and the randomization strata. A difference in the percentage of patients 
achieving TA in the 2 treatment groups will be calculated between ALXN1210 and eculizumab treatment 
groups, along with a 95% CI for the difference. The difference between ALXN1210 and eculizumab treatment 
groups will be computed as a weighted combination of the differences between the ALXN1210 and eculizumab 
treatment groups within stratification groups (using Mantel-Haenszel). The 95% CI for the difference between 
ALXN1210 and eculizumab treatment groups will be calculated using the stratified Newcombe confidence 
interval method.  
 
LDH-N will be analyzed using a generalized estimating equation (GEE) approach which accounts for the 
repeated measures of LDH-N at each visit. The GEE approach provides odds ratios and CIs of treatment effect 
while controlling for the correlation between visits for a given patient and other baseline factors. LDH-N from 
Day 29 through Day 183 will be used as the dependent variable and an indicator variable for treatment, history 
of transfusion (as a categorical variable based on the stratification factor levels), and baseline LDH level (as a 
continuous variable) will be included in the model as explanatory variables. The within-patient correlation will 
assume a first-order autoregressive structure which assumes the highest correlation is between visits that are 
closest in time. Day 29 is the first scheduled assessment after initiation of maintenance dosing, and experience 
with eculizumab and Phase 1b/2 ALXN1210 data demonstrate near maximal suppression of LDH by 4 weeks of 
treatment. Results from the model will be presented as odds ratios with 95% CIs.   
 
In order to conclude ALXN1210 is noninferior to eculizumab, both coprimary endpoints individually need to 
demonstrate noninferiority. If the lower-bound of the 95% CI for the difference (ALXN1210-eculizumab) is 
greater than the noninferiority margin (NIM) of -20% for TA and the lower bound of the 95% CI for the odds 
ratio of ALXN1210 compared to eculizumab is greater than the NIM of 0.39 for LDH-N, then ALXN1210 
treatment will be concluded to be noninferior to eculizumab.  
 
Key Secondary Efficacy Analyses 
The 4 key secondary efficacy endpoints will be summarized by randomization strata and by treatment group at 
baseline and at the study visits where these assessments are collected during the 26-week randomized treatment 
period. Change in FACIT-Fatigue (and percent change in LDH) from baseline to Week 26 will be analyzed 
using a mixed model for repeated measures (MMRM) with the fixed, categorical effects of treatment, the 
stratification randomization indicators of transfusion history (0, 1 to 14, or > 14 units of pRBCs in the 1 year 
prior to first dose of study drug) and screening LDH levels (1.5 to < 3 × ULN or ≥ 3 × ULN), study visit and 
study visit by treatment group interaction as well as the continuous, fixed covariates of baseline FACIT-Fatigue 
(or LDH) and baseline FACIT-Fatigue (or LDH)-by-visit interaction as covariates. For percent change in LDH, 
the baseline LDH level as a continuous variable will be included. The Kenward-Roger approximation will be 
used to estimate denominator degrees of freedom. A difference between the ALXN1210 and eculizumab 
treatment groups along with a 2-sided 95% CI will be calculated.  
 
For breakthrough hemolysis and stabilized hemoglobin, the same approach used for TA will be employed. 
These key secondary efficacy endpoints will be tested in a hierarchical manner provided that noninferiority was 
declared for the coprimary endpoints.  

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When performing the analyses for the key secondary efficacy endpoints, a closed-testing procedure will be used 
so that the lack of significance of a test precludes assessment of subsequent tests. Estimates and CIs will be 
computed for all these key secondary efficacy endpoints irrespective of whether a lack of significance in a test 
precludes assessment of subsequent tests. 
1. If the upper bound of the 95% CI for the difference between the ALXN1210 and eculizumab 
treatment groups in the percentage change from Baseline to Week 26 in LDH is less than the NIM 
of 20%, then ALXN1210 will be declared noninferior for this parameter and the next parameter 
will be tested.  
2. If the lower bound of the 95% CI for the difference between the ALXN1210 and eculizumab 
treatment groups in change from baseline in FACIT-Fatigue is greater than the NIM of -5, then 
ALXN1210 will be declared noninferior for this parameter and the next parameter will be tested. 
3. If the upper bound of the 95% CI for the difference between the ALXN1210 and eculizumab 
treatment groups in the proportion of patients with breakthrough hemolysis is less than the NIM of 
20%, then ALXN1210 will be declared noninferior for this parameter and the next parameter will 
be tested. 
4. If the lower bound of the 95% CI for the difference between the ALXN1210 and eculizumab 
treatment groups in the proportion of patients with stabilized hemoglobin is greater than the NIM 
of -20%, then ALXN1210 will be declared noninferior for this parameter. 
 
If noninferiority is established for all key secondary endpoints then superiority will be assessed using a 
closed-testing procedure with the following order and using a 2-sided 0.05 test for each parameter: 
 
5. Proportion of patients with breakthrough hemolysis through Day 183 (Week 26) 
6. Percentage change from baseline to Day 183 (Week 26) in LDH 
7. Hemolysis as directly measured by LDH-N from Day 29 through Day183 (Week 26) 
8. Change from baseline to Day 183 (Week 26) in FACIT-Fatigue 
9. Proportion of patients with stabilized hemoglobin through Day 183 (Week 26) 
10. Transfusion avoidance 
 
Due to the hierarchical testing order being prespecified, no adjustment for type I error is required. 
 
Other Secondary Endpoints 
Changes from baseline in EORTC-QLQ-C30 will be summarized by treatment group at baseline and at the 
study visits where these assessments are collected. Shifts from baseline in clinical manifestations of PNH will 
be summarized by treatment group and at the study visits where these assessments are collected. The number of 
any treatment-emergent MAVEs (n) and number of patients with events (n, %) will be displayed by treatment 
group. Total number of units of pRBCs transfused during treatment will be summarized by treatment group. 
Kaplan-Meier curves for both treatment groups and estimates of time to first occurrence of LDH-N since first 
study drug will be produced. No statistical inference of these parameters is planned. 
  
Safety: All safety analyses will be conducted for the Safety set, defined as all patients who receive at least 1 
dose of ALXN1210 or eculizumab. Safety results will be reported by treatment group. The incidence of 
treatment-emergent adverse events will be summarized by system organ class and preferred term overall, by 
severity, and by relationship to treatment overall and by treatment group. The incidence of serious adverse 
events will also be summarized. Changes from baseline (last assessment prior to ALXN1210 or eculizumab) in 
ECGs, vital signs, and laboratory assessments will be summarized by treatment group. Shifts from baseline in 
laboratory assessments will be summarized for all study visits by treatment group. 
  
Pharmacokinetics/Pharmacodynamics: PK and PD samples will be collected over the course of the study. 
Individual serum concentration data for all patients who receive at least 1 dose of study drug (ie, ALXN1210 or 
eculizumab) and who have evaluable PK data will be used to derive PK parameters for ALXN1210 and 
eculizumab. Graphs of mean serum concentration-time profiles will be constructed. Graphs of serum 
concentration-time profiles for individual patients may also be generated. Actual dose administration and 
sampling times will be used for all calculations. Descriptive statistics will be calculated for serum concentration 

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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. 
 
PK and PD analyses will be performed for all patients who receive at least 1 dose of ALXN1210 or eculizumab 
and who have evaluable PK and PD data. Descriptive statistics will be presented for all ALXN1210 and 
eculizumab PD endpoints at each sampling time. The PD effects of ALXN1210 and eculizumab administered 
IV will be evaluated by assessing the absolute values and changes and percentage changes from baseline in total 
and free C5 serum concentrations and cRBC hemolysis over time, as appropriate. Assessments of ALXN1210 
PK/PD relationships may be explored using data from this study or in combination with data from other studies. 
 
Analysis of Roll-over Cohort:  
Analysis of data from patients who are rolled over from other ongoing ALXN1210 PNH studies will be 
performed as a separate cohort. The analysis will focus on the long-term safety after their roll over. The 
long-term safety will be evaluated by incidence of treatment-emergent adverse events and SAEs, laboratory 
assessments, and proportion of patients who develop ADAs.  
The analyses will be performed on the Roll-over Safety Set defined as all patients who receive at least 
1 ALXN1210 dose after roll over. A summary of long-term safety in the Roll-over Cohort will be included in 
the final CSR. 

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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 ...............14 
TABLE OF CONTENTS ...............................................................................................................14 
LIST OF TABLES .........................................................................................................................18 
LIST OF FIGURES .......................................................................................................................19 
4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS .............................20 
5. 
INTRODUCTION ......................................................................................................22 
5.1. 
Benefits and Risks Assessment ..................................................................................23 
5.1.1. 
Potential Benefits ........................................................................................................23 
5.1.2. 
Identified and Potential Risks .....................................................................................24 
5.1.2.1. 
Infections (N. Meningitidis and Other Encapsulated Organisms) ..............................24 
5.1.2.2. 
Immunogenicity ..........................................................................................................24 
5.1.2.3. 
Pregnancy Exposure ...................................................................................................25 
6. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................26 
6.1. 
Study Objectives .........................................................................................................26 
6.1.1. 
Original Study ALXN1210-PNH-301 Cohort ............................................................26 
6.1.1.1. 
Primary Objective .......................................................................................................26 
6.1.1.2. 
Secondary Objectives .................................................................................................26 
6.1.2. 
Rolled-over PNH Patients From Other Ongoing Studies of ALXN1210 IV .............26 
6.2. 
Endpoints ....................................................................................................................26 
6.2.1. 
Coprimary Efficacy Endpoints ...................................................................................27 
6.2.2. 
Key Secondary Efficacy Endpoints ............................................................................27 
6.2.3. 
Other Secondary Efficacy Endpoints ..........................................................................27 
6.2.4. 
Pharmacokinetic and Pharmacodynamic Endpoints ...................................................27 

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6.2.5. 
Safety Endpoints .........................................................................................................28 
7. 
INVESTIGATIONAL PLAN .....................................................................................29 
7.1. 
Summary of Study Design ..........................................................................................29 
7.2. 
Discussion of Design and Control ..............................................................................30 
7.3. 
Schedule of Assessments ............................................................................................31 
8. 
STUDY POPULATION .............................................................................................44 
8.1. 
Eligibility Criteria for Original Study ALXN1210-PNH-301 Cohort ........................44 
8.1.1. 
Inclusion Criteria ........................................................................................................44 
8.1.2. 
Exclusion Criteria .......................................................................................................45 
8.2. 
Eligibility Criteria for Roll-over Cohort .....................................................................46 
8.3. 
Discontinuation ...........................................................................................................46 
8.3.1. 
Withdrawal of Patients ...............................................................................................46 
8.3.2. 
Discontinuation of Study/Site Termination by Sponsor or Health Authority ............47 
8.4. 
End of Study Definition ..............................................................................................47 
9. 
STUDY TREATMENT ..............................................................................................48 
9.1. 
Materials and Supplies ................................................................................................48 
9.1.1. 
Description of Study Drugs ........................................................................................48 
9.1.2. 
Study Drug Packaging and Labeling ..........................................................................48 
9.1.3. 
Study Drug Storage .....................................................................................................49 
9.1.4. 
Study Drug Preparation and Infusion .........................................................................49 
9.1.5. 
Study Drug Handling and Disposal ............................................................................50 
9.2. 
Treatments Administered ............................................................................................50 
9.3. 
Method of Assignment to Treatment ..........................................................................52 
9.4. 
Rationale for Selection of Doses in the Study ............................................................52 
9.5. 
Special Treatment Considerations ..............................................................................53 
9.6. 
Blinding ......................................................................................................................53 
9.7. 
Prior and Concomitant Medications and Nonpharmacologic Procedures ..................53 
9.8. 
Vaccination .................................................................................................................53 
9.9. 
Treatment Compliance ................................................................................................54 
9.10. 
Home Visits During the Extension Period ..................................................................54 
9.11. 
COVID-19 Risk Assessment ......................................................................................55 
9.12. 
COVID-19 Vaccine Risk Assessment ........................................................................56 
9.13. 
Contraception Guidance .............................................................................................57 

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10. 
EFFICACY ASSESSMENTS ....................................................................................59 
10.1. 
Transfusions ................................................................................................................59 
10.2. 
LDH and Other Disease-Related Laboratory Parameters ...........................................59 
10.3. 
PNH Symptomatology ................................................................................................60 
10.4. 
Patient-Reported Outcome Measures .........................................................................60 
10.5. 
Major Adverse Vascular Events .................................................................................60 
11. 
SAFETY ASSESSMENTS ........................................................................................62 
11.1. 
Demographic/Medical History ...................................................................................62 
11.1.1. 
Demographics and Baseline Characteristics ...............................................................62 
11.1.2. 
Disease Characteristics ...............................................................................................62 
11.1.3. 
Medical History ..........................................................................................................62 
11.2. 
Physical Examinations ................................................................................................62 
11.3. 
Vital Signs ..................................................................................................................62 
11.4. 
Laboratory Assessments .............................................................................................63 
11.4.1. 
Pregnancy Testing ......................................................................................................63 
11.4.2. 
Hematology .................................................................................................................63 
11.4.3. 
Serum Chemistry ........................................................................................................63 
11.4.4. 
Coagulation .................................................................................................................64 
11.4.5. 
Urinalysis and Urine Chemistry .................................................................................64 
11.4.6. 
Virus Serology ............................................................................................................64 
11.5. 
Electrocardiograms .....................................................................................................64 
11.6. 
Immunogenicity ..........................................................................................................64 
11.7. 
Adverse Event Management .......................................................................................64 
11.7.1. 
Targeted Adverse Events ............................................................................................65 
11.7.2. 
Severity Assessment ...................................................................................................65 
11.7.3. 
Causality Assessment .................................................................................................66 
11.7.4. 
Serious Adverse Events ..............................................................................................67 
11.7.5. 
Suspected Unexpected Serious Adverse Reactions ....................................................67 
11.7.6. 
Collection and Reporting of Adverse Events .............................................................68 
11.7.6.1. 
All Adverse Events .....................................................................................................68 
11.7.6.2. 
Serious Adverse Events ..............................................................................................68 
11.7.7. 
Sponsor Reporting Requirements ...............................................................................69 
11.7.8. 
Investigator Reporting Requirements .........................................................................69 

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11.8. 
Exposure During Pregnancy and Lactation ................................................................69 
11.9. 
Safety Monitoring .......................................................................................................70 
12. 
PHARMACOKINETICS AND PHARMACODYNAMICS .....................................71 
13. 
DATA QUALITY ASSURANCE ..............................................................................72 
13.1. 
Data Collection and Storage .......................................................................................72 
13.2. 
Records Retention .......................................................................................................73 
14. 
STATISTICAL METHODS AND PLANNED ANALYSES ...................................74 
14.1. 
General Considerations ...............................................................................................74 
14.2. 
Determination of Sample Size ....................................................................................74 
14.3. 
Analysis Sets ...............................................................................................................76 
14.4. 
Demographics and Baseline Characteristics ...............................................................76 
14.5. 
Patient Disposition ......................................................................................................77 
14.6. 
Prior and Concomitant Medications and Nonpharmacologic Procedures ..................77 
14.7. 
Treatment Compliance ................................................................................................77 
14.8. 
Efficacy Analyses .......................................................................................................77 
14.8.1. 
Coprimary Efficacy Analysis .....................................................................................77 
14.8.2. 
Key Secondary Efficacy Analyses ..............................................................................78 
14.8.3. 
Other Secondary Efficacy Analyses ...........................................................................79 
14.9. 
Safety Analyses ..........................................................................................................79 
14.9.1. 
Adverse Events ...........................................................................................................80 
14.9.2. 
Physical Examination and Vital Signs ........................................................................80 
14.9.3. 
Clinical Laboratory Tests ...........................................................................................80 
14.9.4. 
Electrocardiograms .....................................................................................................80 
14.9.5. 
Immunogenicity ..........................................................................................................80 
14.10. 
Pharmacokinetic/Pharmacodynamic Analyses ...........................................................81 
14.11. 
Analysis of Data in the Roll-Over Cohort ..................................................................81 
14.12. 
Other Statistical Issues ................................................................................................82 
14.12.1. 
Missing or Invalid Data ..............................................................................................82 
15. 
INFORMED CONSENT, ETHICAL REVIEW, AND REGULATORY 
CONSIDERATIONS ..................................................................................................83 
15.1. 
Informed Consent .......................................................................................................83 
15.2. 
Safety Review .............................................................................................................83 
15.3. 
Ethical Review ............................................................................................................83 

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15.4. 
Regulatory Considerations ..........................................................................................83 
15.4.1. 
Changes/Deviations to Protocol .................................................................................84 
15.5. 
Publication Policy .......................................................................................................84 
16. 
LIST OF REFERENCES ............................................................................................85 
17. 
APPENDICES ............................................................................................................87 
APPENDIX A. MANAGEMENT OF POTENTIAL DRUG INFUSION REACTIONS ..........88 
APPENDIX B. FACIT-FATIGUE SUBSCALE VERSION 4 ...................................................90 
APPENDIX C. EORTC QUALITY OF LIFE QUESTIONNAIRE (EORTC QLQ-C30) .........91 
APPENDIX D. PROTOCOL LABORATORY TESTS .............................................................93 
 
LIST OF TABLES 
Table 1: 
Schedule of Study Visits and Assessments: Screening Through End of 
Randomized Treatment Period ...................................................................................32 
Table 2: 
Schedule of Study Visits and Assessments: Extension Period Day 183 to 
Day 1023 – Patients Entering from ALXN1210 Group .............................................34 
Table 3: 
Schedule of Study Visits and Assessments: Extension Period Day 1079 to 
Day 2031 – Patients Entering from ALXN1210 Group .............................................36 
Table 4: 
Schedule of Study Visits and Assessments: Extension Period Day 183 to 
Day 1037– Patients Entering from Eculizumab Group ..............................................38 
Table 5: 
Schedule of Study Visits and Assessments: Extension Period Day 1093 to 
Day 2045 – Patients Entering from Eculizumab Group .............................................40 
Table 6: 
Schedule of Study Visits and Assessments: Patients who Roll-over from 
Ongoing ALXN1210 IV PNH Studies .......................................................................42 
Table 7: 
Study Drug ..................................................................................................................48 
Table 8: 
Dosing Reference Chart for ALXN1210 Dose Preparation .......................................49 
Table 9: 
Dosing Reference Chart for Eculizumab Dose Preparation .......................................50 
Table 10: ALXN1210 Weight-Based Dosages ...........................................................................51 
Table 11: Eculizumab Dosages ...................................................................................................51 
Table 12: Potential Risks and Mitigation Measures due to COVID-19 .....................................56 
Table 13: Potential Risks and Mitigation Measures due to COVID19 Vaccine .........................57 
Table 14: Adverse Event Severity Grading Scale .......................................................................66 
Table 15: Causality Assessment Descriptions ............................................................................67 

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Table 16: Summary of Parameters Used in Estimating Sample Size with Coprimary 
Endpoints ....................................................................................................................76 
 
LIST OF FIGURES 
Figure 1: 
Study Design Schematic for Clinical Protocol ALXN1210-PNH-301 ......................30 
Figure 2: 
Dosing Schematic .......................................................................................................52 
 

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4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
 
Abbreviation 
Definition 
ADA 
antidrug antibody 
ADL 
activities of daily living 
AE 
adverse event 
BP 
blood pressure 
C5 
complement component 5 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CIOMS 
Council for International Organizations of Medical Sciences 
COVID-19 
coronavirus disease 2019 
cRBC 
chicken red blood cell 
CSR 
Clinical Study Report 
CTCAE 
Common Terminology Criteria for Adverse Events 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EORTC 
European Organisation for Research and Treatment of Cancer 
EOS 
end of study 
ET 
early termination 
FACIT-Fatigue 
Functional Assessment of Chronic Illness Therapy-Fatigue Scale 
FAS 
Full Analysis Set 
FSH 
follicle-stimulating hormone 
GCP 
good clinical practice 
GDS 
Global Drug Safety 
HIV 
human immunodeficiency virus 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
INR 
international normalized ratio 
IRB 
Institutional Review Board 
IV 
intravenous 
IxRS 
interactive voice- or web-response system 
LDH 
lactate dehydrogenase 
LDH-N 
lactate dehydrogenase normalization 
LLT 
lowest level term 
MAVE 
major adverse vascular event 
MedDRA 
Medical Dictionary for Regulatory Activities 
NIM 
noninferiority margin 
NO 
nitric oxide 
PD 
pharmacodynamic(s) 
PEF 
peak expiratory flow 
PK 
pharmacokinetic(s) 

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Abbreviation 
Definition 
PNH 
paroxysmal nocturnal hemoglobinuria 
PP 
per protocol 
pRBC 
packed red blood cell 
PT 
preferred term 
q2w 
once every 2 weeks 
q8w 
once every 8 weeks 
QLQ-C30 
Quality of Life Questionnaire-Core 30 Scale 
QoL 
quality of life 
RBC 
red blood cell 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SMT 
Safety Management Team 
SOC 
system organ class 
SRB 
Safety Review Board 
SUSAR 
suspected unexpected serious adverse reactions 
TA  
transfusion avoidance 
TEAE 
treatment-emergent adverse event 
ULN 
upper limit of normal 
 

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5. 
INTRODUCTION 
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic disorder that occurs most 
frequently in adults (Brodsky, 2015). The disease begins with the clonal expansion of a 
hematopoietic stem cell that has acquired a somatic mutation in the PIGA gene (Brodsky, 2014). 
Consequently, PNH blood cells lack the glycophosphatidylinositol anchor protein and are 
deficient in the membrane-bound complement inhibitory proteins CD55 and CD59. In the 
absence of CD55, there is increased deposition of complement protein C3 cleavage products on 
blood cell membrane surfaces, in turn leading to cleavage of component 5 (C5) into C5a and 
C5b. The pathology and clinical presentations in patients with PNH are driven by uncontrolled 
terminal complement activation on red blood cells (RBCs). 
C5a is a potent anaphylatoxin, chemotactic factor, and cell-activating molecule that mediates 
multiple pro-inflammatory and pro-thrombotic activities (Matis, 1995; Prodinger, 1999). C5b 
recruits the terminal complement components C6, C7, C8, and C9 to form the pro-inflammatory, 
pro-thrombotic cytolytic pore molecule C5b-9, a process that under normal circumstances would 
be blocked on the RBC membrane by CD59. In patients with PNH, however, these final steps 
proceed unchecked, culminating in hemolysis and the release of free hemoglobin, as well as 
platelet activation (Hill, 2013). The signs and symptoms of PNH can be attributed to chronic, 
uncontrolled complement C5 cleavage and release of C5a and C5b-9 leading to RBC hemolysis, 
which results in the release of intracellular free hemoglobin and lactate dehydrogenase (LDH) 
into circulation; irreversible binding to and inactivation of nitric oxide (NO) by hemoglobin, and 
inhibition of NO synthesis; vasoconstriction and tissue-bed ischemia due to absence of 
vasodilatory NO as well as possible microthrombi manifesting as abdominal pain, dysphagia, 
and erectile dysfunction; platelet activation; and a pro-inflammatory and prothrombotic state 
(Hill, 2013; Brodsky, 2014). A substantial proportion of patients with PNH experience renal 
dysfunction and pulmonary hypertension (Hillmen, 2010; Hill, 2012b; Hill, 2013). Patients also 
experience venous or arterial thrombosis in diverse sites, including the abdomen or central 
nervous system (Brodsky, 2014). 
Eculizumab (Soliris®) is a humanized monoclonal antibody approved for treating PNH. 
Eculizumab 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. These attributes underlie the established safety and therapeutic efficacy profile of 
eculizumab demonstrated in the 3 pivotal Phase 3 clinical studies and supported by subsequent 
postmarketing experience.  
ALXN1210 was engineered from eculizumab to preserve immediate and complete C5 inhibition 
while providing sustained complement inhibition throughout a prolonged dosing interval 
(1 month or longer). ALXN1210 and eculizumab share > 99% amino-acid sequence homology. 
ALXN1210 is a recombinant, humanized protein produced in Chinese hamster cells and was 
designed through minimal targeted engineering to substitute 4 amino acids in the eculizumab 
heavy chain. Two of these substitutions are in the complementarity determining regions, 
lowering the affinity of ALXN1210 for C5; the other two are in the Fc binding region which 
improves recycling of ALXN1210 into the vascular space instead of degrading. These changes 
were specifically designed (and have subsequently been proven) to increase the half-life of 

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ALXN1210 relative to eculizumab, increasing the duration of terminal complement inhibition, 
while preserving both the high degree of specificity for binding to C5 and the effectorless nature 
of the antibody. 
The main objective of effective PNH treatment with targeted therapy is to provide immediate, 
complete, and sustained inhibition of terminal complement activity to block hemolysis and 
prevent thrombosis. More specifically, incomplete C5 blockade may increase risk of potentially 
life-threatening breakthrough hemolysis (Hill, 2012a; Lee, 2013). Any loss of efficacy at the end 
of a dosing interval or missed doses due to inconvenience of dosing intervals may put patients at 
substantial medical risk. Patients treated with eculizumab are required to receive maintenance 
infusions every 2 weeks. Given that PNH is a chronic disease, this regimen may have a 
significant impact on patients in terms of individual patient concerns associated with missed 
work and more importantly may impact treatment compliance.  
ALXN1210 has been designed to have the same rapid onset of action and effective blockade of 
complement, with an increased serum half-life to yield an increased duration of pharmacologic 
activity relative to eculizumab. The substantially longer half-life of ALXN1210 is expected to 
produce sustained terminal complement inhibition during a longer dosing interval and thus 
reduce the potential risk of breakthrough complement-mediated hemolysis during the treatment 
period, thus improving the overall health of patients. 
Two studies of ALXN1210 are ongoing in patients with 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, proof-of-concept 
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 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. 
In this Phase 3, open-label, randomized study, the efficacy and safety of ALXN1210 will be 
assessed compared to eculizumab in patients with PNH who are naïve to treatment with 
complement inhibitor, including eculizumab. In addition, long-term safety of patients who rolled 
over from other ongoing studies of ALXN1210 intravenous (IV) in patients with PNH into the 
Extension Period of Study ALXN1210-PNH-301 will be evaluated. The study design rationale is 
further discussed in Section 7.2.  
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). 
5.1. 
Benefits and Risks Assessment 
5.1.1. 
Potential Benefits 
PNH is an ultra-rare, progressive, debilitating, and life-threatening disease, driven by chronic 
uncontrolled complement activation. The resulting inflammation and cellular damage lead to 
systemic complications, principally through intravascular hemolysis and thrombophilia  
(Brodsky, 2014; Socie, 1996). Chronic intravascular hemolysis due to continuous activation of 

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the complement pathway leads to the release of free hemoglobin, nitric oxide consumption and 
persistent smooth muscle cell contraction, chronic anemia, and an increased risk of severe 
thromboembolism. Patients with PNH are at risk of substantial morbidity and mortality and 
altered quality of life. The current standard of care for the treatment of PNH is eculizumab 
(Soliris®), a recombinant humanized mAb that binds to the human C5 complement protein and 
inhibits the activation of terminal complement. The efficacy and safety of eculizumab for the 
treatment of PNH are well established. The approved dosage regimen for eculizumab for PNH 
involves 4 weekly induction doses, followed by maintenance doses administered every 2 weeks 
starting at Week 5.  
Given that PNH is a chronic disease, the current eculizumab regimen may significantly affect 
patients, many of whom have to miss days of work or school to accommodate treatment. In some 
cases, patients may refuse treatment or be may be unable to comply with the treatment frequency 
of eculizumab. Practice survey research supports the assumption that the less frequent infusions 
associated with ALXN1210 will have a positive impact on daily life for patients and their 
caregivers. 
ALXN1210 is a recombinant, humanized mAb derived through minimal targeted engineering of 
eculizumab by introducing 4 unique amino acid substitutions. ALXN1210 has been designed to 
have the same rapid onset of action and effective blockade of complement, with an increased 
serum half-life to yield an increased duration of pharmacologic activity relative to eculizumab. 
By providing patients and physicians with an option for less frequent dosing, ALXN1210 will 
allow greater access to care for those patients who may not initiate treatment or may discontinue 
eculizumab due to frequency of dosing, or patients who are currently on therapy receiving 
eculizumab every 2 weeks. Additionally, the substantially longer half-life of ALXN1210 is 
expected to produce sustained terminal complement inhibition during a longer dosing interval. In 
PNH this may reduce the potential risk of breakthrough, complement-mediated hemolysis, as 
suggested by preliminary clinical data from the ongoing PNH studies, which demonstrate rapid 
and sustained reduction in lactate dehydrogenase (LDH) levels, a direct measure of hemolytic 
activity that is of comparable magnitude to that seen in studies of eculizumab. 
5.1.2. 
Identified and Potential Risks 
5.1.2.1. 
Infections (N. Meningitidis and Other Encapsulated Organisms) 
Increased susceptibility to infection, especially with encapsulated bacteria, 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. No immunogenicity reactions have been 
observed to date in clinical studies with ALXN1210. 

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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 
spouses/partners, will use a highly effective or acceptable method of contraception as required in 
Section 9.13. 
 

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6. 
STUDY OBJECTIVES AND ENDPOINTS 
6.1. 
Study Objectives 
6.1.1. 
Original Study ALXN1210-PNH-301 Cohort 
6.1.1.1. 
Primary Objective 
The primary objective of this study is to assess the noninferiority of ALXN1210 compared to 
eculizumab in adult patients with PNH who have never been treated with a complement 
inhibitor.  
Noninferiority will be claimed if after 26 weeks of treatment: 1) the lower bound of the 95% 
confidence interval (CI) for the difference (ALXN1210-eculizumab) in transfusion avoidance 
(TA) rate is greater than -20%, and 2) the lower bound of the 95% CI for the odds ratio of 
ALXN1210 compared to eculizumab for lactate dehydrogenase normalization (LDH-N) is 
greater than 0.39. 
6.1.1.2. 
Secondary Objectives 
The secondary objectives of the study are to assess the following: 
• To characterize the safety and tolerability of ALXN1210 in this patient population 
• To evaluate the efficacy of ALXN1210 by additional efficacy measures 
• To characterize the pharmacokinetics/pharmacodynamics (PK/PD) and 
immunogenicity of ALXN1210 
• To evaluate the long-term safety and efficacy of ALXN1210 
• To evaluate the safety and efficacy in patients who switch from eculizumab to 
ALXN1210 in the Extension Period 
• To quantify identified specific safety concerns during treatment with ALXN1210, 
including meningococcal infections, serious hemolysis after drug discontinuation in 
PNH, immunogenicity, serious infections, malignancies and hematologic 
abnormalities, and during pregnancy and breastfeeding 
6.1.2. 
Rolled-over PNH Patients From Other Ongoing Studies of ALXN1210 IV 
• Long-term safety of patients receiving ALXN1210 after roll over into 
Study ALXN1210-PNH-301 
6.2. 
Endpoints 
Section 6.2.1 through Section 6.2.4 describe the endpoints for the Original 
Study ALXN1210-PNH-301 Cohort. Section 6.2.5 describes the safety endpoints for both 
Original Study ALXN1210-PNH-301 Cohort and the Roll-over Cohort. 
 

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6.2.1. 
Coprimary Efficacy Endpoints 
The coprimary efficacy endpoints of the study are: 
• Transfusion avoidance, defined as the proportion of patients who remain transfusion-
free and do not require a transfusion per protocol-specified guidelines through 
Day 183 (Week 26) 
• Hemolysis as directly measured by LDH-N levels from Day 29 (first scheduled 
evaluation status post initiation of maintenance dosing) through Day 183 (Week 26) 
6.2.2. 
Key Secondary Efficacy Endpoints 
The key secondary efficacy endpoints of the study (to be tested in a hierarchical manner) are: 
1. Percentage change in LDH from Baseline to Day 183 (Week 26) 
2. Change in quality of life (QoL) assessed via the Functional Assessment of Chronic 
Illness Therapy (FACIT)-Fatigue Scale, Version 4, from Baseline to Day 183 (Week 26)  
3. Proportion of patients with breakthrough hemolysis, defined as at least one new or 
worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, 
abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin < 10 g/dL], major 
adverse vascular event [MAVE, including thrombosis], dysphagia, or erectile 
dysfunction) in the presence of elevated LDH ≥ 2 × upper limit of normal [ULN], after 
prior LDH reduction to < 1.5 × ULN on therapy 
4. Proportion of patients with stabilized hemoglobin, defined as avoidance of a ≥ 2 g/dL 
decrease in hemoglobin level from baseline in the absence of transfusion through 
Day 183 (Week 26) 
6.2.3. 
Other Secondary Efficacy Endpoints 
Other secondary efficacy endpoints of the study are: 
• Change in the European Organisation for Research and Treatment of Cancer 
(EORTC) Quality of Life Questionnaire-Core 30 Scale (QLQ-C30), Version 3.0, 
from Baseline to Day 183 (Week 26) 
• Time to first occurrence of LDH-N  
• Total number of units of packed red blood cells (pRBCs) transfused through Day 183 
(Week 26) 
• Change in clinical manifestations of PNH (fatigue, hemoglobinuria, abdominal pain, 
shortness of breath, chest pain, dysphagia, and erectile dysfunction) from Baseline to 
Day 183 (Week 26) 
• Proportion of patients experiencing MAVEs through Day 183 (Week 26) 
6.2.4. 
Pharmacokinetic and Pharmacodynamic Endpoints 
• Change in serum ALXN1210 and eculizumab concentration over time 
• Change in chicken red blood cell (cRBC) hemolytic activity over time (exploratory) 

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• Change in free complement component 5 (C5) concentrations over time 
6.2.5. 
Safety Endpoints 
For the original Study ALXN1210-PNH-301 Cohort, the safety and tolerability of ALXN1210 
compared with eculizumab will be evaluated by physical examinations, vital signs, 
electrocardiograms (ECGs), laboratory assessments, and incidence of adverse events (AEs) and 
serious adverse events (SAEs). The proportion of patients who develop antidrug antibodies 
(ADAs) will also be assessed. 
The long-term safety of patients on ALXN1210 after their roll over into the Extension Period of 
Study ALXN1210-PNH-301 will be evaluated by the incidence of AEs and SAEs, laboratory 
assessments, and the proportion of patients who develop ADA. 

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Amendment 6, 12 April 2021 
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7. 
INVESTIGATIONAL PLAN 
7.1. 
Summary of Study Design 
Study ALXN1210-PNH-301 is a Phase 3, open-label, randomized, active-controlled, multicenter 
study to evaluate the safety and efficacy of ALXN1210 versus eculizumab administered by 
intravenous (IV) infusion to adult patients with PNH who are naïve to complement inhibitor 
treatment. The study will enroll approximately 214 patients (107 patients per treatment group). 
In addition, patients may be rolled over from other ongoing studies of ALXN1210 IV in patients 
with PNH into the Extension Period of Study ALXN1210-PNH-301 to receive ALXN1210 
(hereafter referred to as Roll-over Cohort). 
For patients enrolled directly into Study ALXN1210-PNH-301, the study consists of a 4-week 
screening period, a 26-week randomized treatment period, and an extension period of up to 5 
years. Patients will be stratified into 1 of 6 groups based on their transfusion history (0, 1 to 14, 
or > 14 units of pRBCs in the 1 year prior to first dose of study drug) and screening LDH levels 
(1.5 to < 3 × ULN or ≥ 3 × ULN). The patients within each of the 6 groups will then be 
randomly assigned in a 1:1 ratio to receive ALXN1210 or eculizumab. Enrollment of patients 
without a history of transfusion in the past year will be capped at 20%. 
Prior to randomization and within 5 days prior to study drug administration on Day 1, each 
patient’s hemoglobin must be evaluated by either local or central laboratory. If at that time the 
patient’s hemoglobin value meets protocol-specified transfusion guidelines, the patient must be 
transfused with pRBCs to a hemoglobin level above the protocol-specified transfusion threshold 
in order to be eligible for randomization. The patient’s post-transfusion hemoglobin value should 
be confirmed by local or central laboratory to be above the protocol-specified transfusion 
threshold. 
Patients randomly assigned to the ALXN1210 group will receive a loading dose of ALXN1210 
(2400 mg for patients weighing ≥ 40 to < 60 kg, 2700 mg for patients weighing ≥ 60 to < 100 kg, 
3000 mg for patients weighing ≥ 100 kg) on Day 1, followed by maintenance doses of 
ALXN1210 (3000 mg for patients weighing ≥ 40 to < 60 kg, 3300 mg for patients weighing ≥ 60 
to < 100 kg, 3600 mg for patients weighing ≥ 100 kg) on Day 15 and every 8 weeks (q8w) 
thereafter for a total of 26 weeks of treatment. Patients randomly assigned to the eculizumab 
group will receive induction treatment with 600 mg of eculizumab IV on Days 1, 8, 15, and 22, 
followed by maintenance treatment with eculizumab 900 mg on Day 29 and every 2 weeks 
(q2w) thereafter for a total of 26 weeks of treatment. After completion of all assessments on 
Day 183, all patients will enter an extension period and receive ALXN1210 until the product is 
registered or approved (in accordance with country-specific regulations) or for up to 5 years, 
whichever occurs first. (In Norway and Denmark, patients will participate for a total of 
2.5 years.) Beginning on Day 183, patients who had been randomized to the ALXN1210 
treatment group will receive a maintenance dose (as described above) of ALXN1210 q8w, and 
patients who had been randomized to the eculizumab group will receive a loading dose (as 
described above) of ALXN1210 followed 2 weeks later and q8w thereafter by a weight-based 
maintenance dose of ALXN1210. For the Roll-over Cohort, patients will receive ALXN1210 
weight-based q8w maintenance dosing until the product is registered or approved (in accordance 

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Amendment 6, 12 April 2021 
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with country-specific regulations) or until the end of the current study (estimated end of study 
[EOS] January 2023), whichever occurs first. 
Figure 1 illustrates the study design. 
Figure 1: 
Study Design Schematic for Clinical Protocol ALXN1210-PNH-301 
 
 
Abbreviations: IV = intravenous; PNH = paroxysmal nocturnal hemoglobinuria; R = roll-over 
A pRBC transfusion will be administered when a patient has a hemoglobin value of 9 g/dL or 
lower with signs or symptoms of sufficient severity to warrant a transfusion, or a hemoglobin 
value of 7 g/dL or lower regardless of presence of clinical signs or symptoms. 
7.2. 
Discussion of Design and Control 
Published data support LDH as a reliable, objective, and direct measure of intravascular 
hemolysis in patients with PNH and is considered by experts to be the best measure of 
complement-mediated hemolysis, the hallmark of PNH disease activity (Dale, 1972;  
Parker, 2005; Canalejo, 2013). Results from the eculizumab clinical program showed that LDH 
concentrations remained markedly elevated and unchanged in untreated (placebo) patients, while 
eculizumab-treated patients had an immediate reduction in serum LDH to normal or near normal 
levels (Soliris® USPI and SmPC). This reduction mirrored a rapid reduction in symptoms and 
improvement in fatigue (Hillmen, 2006; Brodsky, 2008).  

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Amendment 6, 12 April 2021 
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Transfusion avoidance is chosen as the coprimary endpoint because it is informative regardless 
of the patient’s transfusion history. The incidence of transfusions was a coprimary endpoint in 
the pivotal TRIUMPH study (C04-001) for eculizumab, and TA was a key secondary endpoint. 
The safety parameters being evaluated are commonly used in clinical trials per International 
Conference on Harmonisation (ICH) and good clinical practice (GCP) guidances. 
Eculizumab was selected as the active control for ethical reasons. Eculizumab is currently the 
standard of care for patients with PNH. 
Patients with PNH receiving ALXN1210 IV in other ongoing ALXN1210 studies are allowed to 
roll over into Study ALXN1210-PNH-301 and receive continued ALXN1210 IV q8w 
maintenance treatment. 
7.3. 
Schedule of Assessments 
The Schedule of Assessments is provided in Table 1 for the Screening and Randomized 
Treatment Period and in Table 2 and Table 3 (patients entering from ALXN1210 group) and 
Table 4 and Table 5 (patients entering from eculizumab group) for the Extension Period. The 
Schedule of Assessments for patients who rolled over from ongoing ALXN1210 IV studies in 
patients with PNH is provided in Table 6. 
Refer to the Laboratory Manual for details on the number of samples and volumes for all 
sampling and tests during the study. 
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).  
Additionally, if a suspected event of breakthrough hemolysis occurs, LDH, PK, and PD 
parameters must be analyzed at the central laboratory. If the suspected event of breakthrough 
does not occur at a scheduled visit, an unscheduled visit should occur for evaluation of the 
patient and collection of the required LDH, PK, and PD parameters. For purposes of defining 
breakthrough hemolysis, assessment of LDH must be based on a central laboratory value.  

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Amendment 6, 12 April 2021 
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Table 1: 
Schedule of Study Visits and Assessments: Screening Through End of Randomized Treatment Period 
Period 
Screenin
g 
Randomized Treatment Period 
Study Day 
–28 to –1 
1 
8 
15 
22 
29 
43 
57 
71 
85 
99 
113 
127 
141 
155 
169 
183/
ET 
Window (day) 
N/A 
 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confirmation or administration of 
meningococcal vaccinationa 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history and demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV testing 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PNH clone sizeb 
X 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
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 
Record transfusions and 
transfusion parametersd 
Xe 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PNH symptomatologyf 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
FACIT-Fatigueg 
X 
X 
X 
 
 
X 
 
 
X 
 
 
 
X 
 
 
 
X 
EORTC QLQ-C30g 
X 
X 
X 
 
 
X 
 
 
X 
 
 
 
X 
 
 
 
X 
Physical examination 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviated physical examinationh 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
Vital signsi 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Safety 12-Lead ECGj 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
Chemistry including LDHk 
X 
X 
X  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology including free 
hemoglobin and coagulationk 
X 
X 
X  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis and urine chemistryk 
X 
X 
 
X 
 
X 
 
 
X 
 
 
 
X 
 
 
 
X 
PK/PD sampling 
 
Xl 
Xm 
Xl 
Xm 
Xm 
Xm 
Xm 
Xl 
Xm 
Xm 
Xm 
Xl 
Xm 
Xm 
Xm 
Xl 
Immunogenicity (ADA)n 
 
X 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
Review safety card 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Breakthrough hemolysiso 
 
←Monitor continuously→ 
Concomitant medications 
X 
←Monitor continuously→ 
Adverse events 
X 
←Monitor continuously→ 
Randomizationp 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ALXN1210 administrationq  
 
X 
 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
--r 
Eculizumab administration 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 

Protocol ALXN1210-PNH-301 
 
Alexion Pharmaceuticals, Inc. 
Amendment 6, 12 April 2021 
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Abbreviations: ADA = antidrug antibody; ECG = electrocardiogram; EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer, Quality of Life 
Questionnaire-Core 30 Scale; ET = early termination; FACIT-Fatigue = Functional Assessment of Chronic Illness Therapy-Fatigue Scale; LDH = lactate dehydrogenase; 
N/A = not applicable; PD = pharmacodynamics; PK = pharmacokinetics; PNH = paroxysmal nocturnal hemoglobinuria; RBC = red blood cell; WBC = white blood cell 
a 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. 
b WBC (granulocyte and monocyte) and RBC clone size measured by high-sensitivity flow cytometry at Screening and Day 1; RBC clone size only on Day 71 and Day 183. 
c Female patients of childbearing potential only. Serum pregnancy test at Screening and Day 183; urine pregnancy test at all other required time points. A negative urine test result 
is required prior to administering ALXN1210 or eculizumab to female patients of childbearing potential at the indicated visits. 
d Transfusions given during and between visits will be recorded.  
e Prior to randomization and within 5 days prior to study drug administration on Day 1, each patient’s hemoglobin must be evaluated by either local or central laboratory. If at that 
time the patient’s hemoglobin value meets protocol-specified transfusion guidelines (Section 10.1), the patient must be transfused with pRBCs to a hemoglobin level above the 
protocol-specified transfusion threshold in order to be eligible for randomization. The patient’s post-transfusion hemoglobin value should be confirmed by local or central 
laboratory to be above the protocol-specified transfusion threshold.  
f Investigator or designee assessment of the following events: fatigue, hemoglobinuria, abdominal pain, dyspnea, dysphagia, chest pain, and erectile dysfunction. 
g Physician- and patient-reported assessments will be performed prior to study drug administration. 
h Abbreviated physical examination consists of a body system relevant examination based upon Investigator (or designee) judgment and patient symptoms. At least 1 body system 
must be checked for an abbreviated physical examination.  
i 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]), 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 before study 
drug administration. 
 
j Single 12-lead ECG will be collected at Screening and predose on Day 57 and Day 183. Patients must be supine for approximately 5 to 10 minutes before ECG collection and 
remain supine but awake during ECG collection. 
k Clinical laboratory measurements will be collected predose on dosing days and not from a heparinized line. Follicle stimulating hormone levels will be measured during 
Screening only in order to confirm postmenopausal status.  
l Serum samples for PK/PD analyses will be collected predose (within 0.5 hours prior to the start of infusion) and at end-of-infusion (within 0.5 hours after the end of infusion). 
The predose PK/PD sample may be drawn through the venous access created for the dose infusion, prior to administration of the dose. End-of-infusion PK/PD samples will be 
drawn from the patient’s opposite, noninfused arm. Note that the Day 183 end-of-infusion sample is considered an Extension Period assessment (see Table 2 and Table 4). All 
collection times will be recorded in the eCRF. In the event of breakthrough hemolysis, a serum sample for PK/PD analysis will be collected. 
m Serum samples for PK/PD analyses will be collected predose (within 0.5 hours prior to the start of infusion) for eculizumab-treated patients and at any time for ALXN1210-
treated patients. All collection times will be recorded in the eCRF. In the event of breakthrough hemolysis, a serum sample for PK/PD analysis will be collected. 
n Samples for ADA will be collected predose. 
o If a suspected event of breakthrough hemolysis occurs, LDH, PK, and PD samples for analysis will be collected. If the suspected event of breakthrough does not occur at a 
scheduled visit, an unscheduled visit should occur for evaluation of the patient and collection of the required LDH, PK, and PD samples.  
p Patients will be randomly assigned to treatment based on screening LDH result and history of blood transfusions through an interactive voice or web response system (IxRS). 
q The dose of ALXN1210 is based on the patient’s last recorded study visit body weight. 
r 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 post dose 
procedures in Table 2 and Table 4. 
 
 

Protocol ALXN1210-PNH-301 
 
Alexion Pharmaceuticals, Inc. 
Amendment 6, 12 April 2021 
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Table 2: 
Schedule of Study Visits and Assessments: Extension Period Day 183 to Day 1023 – Patients Entering from 
ALXN1210 Group 
 
Abbreviations: ADA = antidrug antibody; ECG = electrocardiogram; EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer, Quality of Life 
Questionnaire-Core 30 Scale; EOS = end of study; ET = early termination; FACIT-Fatigue = Functional Assessment of Chronic Illness Therapy-Fatigue Scale; LDH = lactate 
dehydrogenase; PD = pharmacodynamics; PK = pharmacokinetics; PNH = paroxysmal nocturnal hemoglobinuria; RBC = red blood cell 
a All patients who roll over into the Extension Period will receive ALXN1210 on Day 183 after all assessments have been performed. 
b Granulocyte and RBC clone size measured by high-sensitivity flow cytometry on Days 351 and 743; RBC clone size only at other visits 
c Female patients of childbearing potential only. Serum pregnancy test at ET only; urine pregnancy test at all other time points. A negative urine test result is required prior to 
administering ALXN1210 to female patients of childbearing potential on dosing days. 
d Transfusions given during and between visits will be recorded. 
e Investigator or designee assessment of the following events: fatigue, hemoglobinuria, abdominal pain, dyspnea, dysphagia, chest pain, and erectile dysfunction. 
f Physician- and patient-reported assessments will be performed prior to study drug administration. 
g Abbreviated physical examination consists of a body system relevant examination based upon Investigator (or qualified designee) judgment and patient symptoms. At least one 
body system must be checked for an abbreviated physical examination. 
Period 
Extension Period 
Study Day 
183a 
239 
295 
351 
407 
463 
519 
575 
631 
687 
743 
799 
855 
911 
967 
1023 
Window (day) 
± 2 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
PNH clone sizeb 
 
X 
 X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Weight 
 
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 
X 
Record transfusions and transfusion 
parametersd 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PNH symptomatologye 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
FACIT-Fatiguef 
 
 
 
X 
 
 
 
X 
 
 
X 
 
 
 
X 
 
EORTC QLQ-C30f 
 
 
 
X 
 
 
 
X 
 
 
X 
 
 
 
X 
 
Abbreviated physical examinationg 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Vital signsh 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Chemistry including LDHi 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology including free hemoglobin 
and coagulationi 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis and urine chemistryi 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PK/PD samplingj 
X 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
Immunogenicity (ADA)k 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Review safety card 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Breakthrough hemolysisl 
←Monitor continuously→ 
Concomitant medications 
←Monitor continuously→ 
Adverse events 
←Monitor continuously→ 
ALXN1210 administrationm 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Alexion Pharmaceuticals, Inc. 
Amendment 6, 12 April 2021 
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h 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]), heart 
rate (beats/minute), respiratory rate (breaths/minute), and temperature (degrees Celsius [°C] or degrees Fahrenheit [°F]). Vital signs will be taken before each study drug 
administration. 
i Clinical laboratory measurements will be collected predose on dosing days and not from a heparinized line.  
j Serum samples for PK/PD analyses will be collected at end-of-infusion on Day 183; predose (within 0.5 hours prior to the start of infusion) and at end-of-infusion (within 0.5 
hours after the end of infusion) on Days 351, 575,  799 and 1023; and at any time at ET. The predose PK/PD sample may be drawn through the venous access created for the 
dose infusion, prior to administration of the dose. End-of-infusion PK/PD samples will be drawn from the patient’s opposite, noninfused arm. All collection times will be 
recorded in the eCRF. In the event of breakthrough hemolysis, a serum sample for PK/PD analysis will be collected. 
k Samples for ADA will be collected predose or at any time when a dose of study drug is not administered. 
l If a suspected event of breakthrough hemolysis occurs, LDH, PK, and PD samples for analysis will be collected. If the suspected event of breakthrough does not occur at a 
scheduled visit, an unscheduled visit should occur for evaluation of the patient and collection of the required LDH, PK, and PD samples. 
m The dose of ALXN1210 is based on the patient’s last recorded study visit body weight. 
 
 

Protocol ALXN1210-PNH-301 
 
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Amendment 6, 12 April 2021 
Page 36 of 93 
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Table 3: 
Schedule of Study Visits and Assessments: Extension Period Day 1079 to Day 2031 – Patients Entering from 
ALXN1210 Group 
Abbreviations: ADA = antidrug antibody; ECG = electrocardiogram; EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer, Quality of Life 
Questionnaire-Core 30 Scale; EOS = end of study; ET = early termination; FACIT-Fatigue = Functional Assessment of Chronic Illness Therapy-Fatigue Scale; LDH = lactate 
dehydrogenase; PD = pharmacodynamics; PK = pharmacokinetics; PNH = paroxysmal nocturnal hemoglobinuria; RBC = red blood cell 
a Granulocyte and RBC clone size measured by high-sensitivity flow cytometry on Days 1135, 1471, and 1863; RBC clone size only at other visits.  
b Female patients of childbearing potential only. Serum pregnancy test at ET only; urine pregnancy test at all other time points. A negative urine test result is required prior to 
administering ALXN1210 to female patients of childbearing potential on dosing days. 
Period 
Extension Period 
Study Day 
1079 
1135 
1191 
1247 
1303 
1359 
1415 
1471 
1527 
1583 
1639 
1695 
1751 
1807 
1863 
1919 
1975 
2031  
EOS/ 
ETn 
Window (day) 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
PNH clone sizea 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
 
 
X 
Weight 
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 
X 
X 
X 
X 
X 
Record transfusions and 
transfusion parametersc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PNH symptomatologyd 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
FACIT-Fatiguee 
 
 
X 
 
 
 
X 
 
 
 
 
X 
 
 
 X 
 
 
X 
EORTC QLQ-C30e 
 
 
X 
 
 
 
X 
 
 
 
 
X 
 
 
X 
 
 
X 
Abbreviated physical 
examinationf 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
X 
 
 
X 
Vital signsg 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
 
 
X 
Safety 12-Lead ECGh 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Chemistry including LDHi 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
 
 
X 
Hematology including free 
hemoglobin and coagulationi 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
 
 
X 
Urinalysis and urine chemistryi 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
 
 
X 
PK/PD samplingj 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
 
 
X 
Immunogenicity (ADA)k 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
X 
 
 
X 
Review safety card 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Breakthrough hemolysisl 
←Monitor continuously→ 
Concomitant medications 
←Monitor continuously→ 
Adverse events 
←Monitor continuously→ 
ALXN1210 administrationm 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X  
X 
X 
X 
X 
 

Protocol ALXN1210-PNH-301 
 
Alexion Pharmaceuticals, Inc. 
Amendment 6, 12 April 2021 
Page 37 of 93 
Alexion Confidential 
c Transfusions given during and between visits will be recorded. 
d Investigator or designee assessment of the following events: fatigue, hemoglobinuria, abdominal pain, dyspnea, dysphagia, chest pain, and erectile dysfunction. 
e Physician- and patient-reported assessments will be performed prior to study drug administration. 
f Abbreviated physical examination consists of a body system relevant examination based upon Investigator (or qualified designee) judgment and patient symptoms. At least one 
body system must be checked for an abbreviated physical examination. 
g 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]), heart 
rate (beats/minute), respiratory rate (breaths/minute), and temperature (degrees Celsius [°C] or degrees Fahrenheit [°F]). Vital signs will be taken before each study drug 
administration. 
h Single 12-lead ECG will be collected at Day 2031 or ET. Patients must be supine for approximately 5 to 10 minutes before ECG collection and remain supine but awake during 
ECG collection. 
i Clinical laboratory measurements will be collected predose on dosing days and not from a heparinized line.  
j Serum samples for PK/PD analyses will be collected predose (within 0.5 hours prior to the start of infusion) and at end-of-infusion (within 0.5 hours after the end of infusion) on 
Days 1247, 1471, 1695, and 1863; and at any time on Day 2031 or ET. The predose PK/PD sample may be drawn through the venous access created for the dose infusion, prior 
to administration of the dose. End-of-infusion PK/PD samples will be drawn from the patient’s opposite, noninfused arm. All collection times will be recorded in the eCRF. In 
the event of breakthrough hemolysis, a serum sample for PK/PD analysis will be collected. 
k Samples for ADA will be collected predose or at any time when a dose of study drug is not administered. 
l If a suspected event of breakthrough hemolysis occurs, LDH, PK, and PD samples for analysis will be collected. If the suspected event of breakthrough does not occur at a 
scheduled visit, an unscheduled visit should occur for evaluation of the patient and collection of the required LDH, PK, and PD samples. 
m The dose of ALXN1210 is based on the patient’s last recorded study visit body weight. 
n If a patient withdraws early from the study (eg, to begin treatment with marketed product), an ET visit will be performed. 
 
 
 

Protocol ALXN1210-PNH-301 
 
Alexion Pharmaceuticals, Inc. 
Amendment 6, 12 April 2021 
Page 38 of 93 
Alexion Confidential 
Table 4: 
Schedule of Study Visits and Assessments: Extension Period Day 183 to Day 1037– Patients Entering from 
Eculizumab Group 
 
 
Abbreviations: ADA = antidrug antibody; ECG = electrocardiogram; EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer, Quality of Life 
Questionnaire-Core 30 Scale; EOS = end of study; ET = early termination; FACIT-Fatigue = Functional Assessment of Chronic Illness Therapy-Fatigue Scale; LDH = lactate 
dehydrogenase; PD = pharmacodynamics; PK = pharmacokinetics; PNH = paroxysmal nocturnal hemoglobinuria; RBC = red blood cell 
a All patients who roll over into the Extension Period will receive ALXN1210 on Day 183 after all assessments have been performed. 
b Granulocyte and RBC clone size measured by high-sensitivity flow cytometry on Days 365 and 757; RBC clone size only at other visits. 
c Female patients of childbearing potential only. Serum pregnancy test at ET only; urine pregnancy test at all other time points. A negative urine test result is required prior to 
administering ALXN1210 to female patients of childbearing potential on dosing days. 
d Transfusions given during and between visits will be recorded. 
e Investigator or designee assessment of the following events: fatigue, chest pain, abdominal pain, dyspnea, dysphagia, erectile dysfunction, and red/dark urine or hemoglobinuria. 
f Physician- and patient-reported assessments will be performed prior to study drug administration. 
Period 
Extension Period 
 
 
Study Day 
183a 
197 
225 
253 
309 
365 
421 
477 
533 
589 
645 
701 
757 
813 
869 
925 
981 
1037 
Window (day) 
± 2 
± 3 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
PNH clone sizeb 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Weight 
 
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 
X 
X 
Record transfusions and transfusion 
parametersd 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PNH symptomatologye 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
FACIT-Fatiguef 
 
 
 
 
 
X 
 
 
 
X 
 
 
X 
 
 
 
X 
 
EORTC QLQ-C30f 
 
 
 
 
 
X 
 
 
 
X 
 
 
X 
 
 
 
X 
 
Abbreviated physical examinationg 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Vital signsh 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Chemistry including LDHi 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology including free hemoglobin and 
coagulationi 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis and urine chemistryi 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PK/PD samplingj 
X 
X 
X 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
Immunogenicity (ADA)k 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Review safety card 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Breakthrough hemolysisl 
 
←Monitor continuously→ 
Concomitant medications 
 
←Monitor continuously→ 
Adverse events 
 
←Monitor continuously→ 
ALXN1210 administrationm 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

Protocol ALXN1210-PNH-301 
 
Alexion Pharmaceuticals, Inc. 
Amendment 6, 12 April 2021 
Page 39 of 93 
Alexion Confidential 
g Abbreviated physical examination consists of a body system relevant examination based upon Investigator (or qualified designee) judgment and patient symptoms. At least one 
body system must be checked for an abbreviated physical examination. 
h 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]), heart 
rate (beats/minute), respiratory rate (breaths/minute), and temperature (degrees Celsius [°C] or degrees Fahrenheit [°F]). Vital signs will be taken before each study drug 
administration. 
i Clinical laboratory measurements will be collected predose on dosing days and not from a heparinized line.  
j Serum samples for PK/PD analyses will be collected predose (within 0.5 hours prior to the start of infusion) and at end-of-infusion (within 0.5 hours after the end of infusion) on 
Days 197, 365, 589,  813, and 1037; at end-of-infusion on Day 183; and at any time on Day 225 or ET. The predose PK/PD sample may be drawn through the venous access 
created for the dose infusion, prior to administration of the dose. End-of-infusion PK/PD samples will be drawn from the patient’s opposite, noninfused arm. All collection times 
will be recorded in the eCRF. In the event of breakthrough hemolysis, a serum sample for PK/PD analysis will be collected. 
k Samples for ADA will be collected predose or at any time when a dose of study drug is not administered. 
l If a suspected event of breakthrough hemolysis occurs, LDH, PK, and PD samples for analysis will be collected. If the suspected event of breakthrough does not occur at a 
scheduled visit, an unscheduled visit should occur for evaluation of the patient and collection of the required LDH, PK, and PD samples. 
m The dose of ALXN1210 is based on the patient’s last recorded study visit body weight. 
 
 

Protocol ALXN1210-PNH-301 
 
Alexion Pharmaceuticals, Inc. 
Amendment 6, 12 April 2021 
Page 40 of 93 
Alexion Confidential 
Table 5: 
Schedule of Study Visits and Assessments: Extension Period Day 1093 to Day 2045 – Patients Entering from 
Eculizumab Group 
Abbreviations: ADA = antidrug antibody; ECG = electrocardiogram; EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer, Quality of Life 
Questionnaire-Core 30 Scale; EOS = end of study; ET = early termination; FACIT-Fatigue = Functional Assessment of Chronic Illness Therapy-Fatigue Scale; LDH = lactate 
dehydrogenase; PD = pharmacodynamics; PK = pharmacokinetics; PNH = paroxysmal nocturnal hemoglobinuria; RBC = red blood cell 
a Granulocyte and RBC clone size measured by high-sensitivity flow cytometry on Days 1149, 1485, and 1877; RBC clone size only at other visits. 
b Female patients of childbearing potential only. Serum pregnancy test at ET only; urine pregnancy test at all other time points. A negative urine test result is required prior to 
administering ALXN1210 to female patients of childbearing potential on dosing days. 
c Transfusions given during and between visits will be recorded. 
Period 
Extension Period 
Study Day 
1093 
1149 
1205 
1261 
1317 
1373 
1429 
1485 
1541 
1597 
1653 
1709 
1765 
1821 
 
1877 
1933 
1989 
2045 
EOS/ 
ETn 
Window (day) 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
PNH clone sizea 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
 
 
X 
Weight 
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 
X 
 X 
 X 
X 
X 
Record transfusions and 
transfusion parametersc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 X 
 X 
X 
X 
PNH symptomatologyd 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 X 
 X 
 X 
X 
FACIT-Fatiguee 
 
 
X 
 
 
 
X 
 
 
 
 
X 
 
 
X 
 
 
X 
EORTC QLQ-C30e 
 
 
X 
 
 
 
X 
 
 
 
 
X 
 
 
X 
  
 
X 
Abbreviated physical 
examinationf 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
X 
  
 
X 
Vital signsg 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
 X 
 
 
X 
Safety 12-Lead ECGh 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Chemistry including LDHi 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
 
 
X 
Hematology including free 
hemoglobin and coagulationi 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
 
 
X 
Urinalysis and urine chemistryi 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
 
 
X 
PK/PD samplingj 
 
 
 
 X 
 
 
 
X 
 
 
 
X 
 
 
X 
  
 
X 
Immunogenicity (ADA)k 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
X 
  
 
X 
Review safety card 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 X 
 X 
 X 
X 
Breakthrough hemolysisl 
←Monitor continuously→ 
Concomitant medications 
←Monitor continuously→ 
Adverse events 
←Monitor continuously→ 
ALXN1210 administrationm 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X  
X 
X 
X 
 X 
  

Protocol ALXN1210-PNH-301 
 
Alexion Pharmaceuticals, Inc. 
Amendment 6, 12 April 2021 
Page 41 of 93 
Alexion Confidential 
d Investigator or designee assessment of the following events: fatigue, chest pain, abdominal pain, dyspnea, dysphagia, erectile dysfunction, and red/dark urine or hemoglobinuria. 
e Physician- and patient-reported assessments will be performed prior to study drug administration. 
f Abbreviated physical examination consists of a body system relevant examination based upon Investigator (or qualified designee) judgment and patient symptoms. At least one 
body system must be checked for an abbreviated physical examination. 
g 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]), heart 
rate (beats/minute), respiratory rate (breaths/minute), and temperature (degrees Celsius [°C] or degrees Fahrenheit [°F]). Vital signs will be taken before each study drug 
administration. 
h Single 12-lead ECG will be collected at Day 2045 or ET. Patients must be supine for approximately 5 to 10 minutes before ECG collection and remain supine but awake during 
ECG collection. 
i Clinical laboratory measurements will be collected predose on dosing days and not from a heparinized line.  
j Serum samples for PK/PD analyses will be collected predose (within 0.5 hours prior to the start of infusion) and at end-of-infusion (within 0.5 hours after the end of infusion) on 
Days 1261, 1485, 1709, and 1877; and at any time on Day 2045 or ET. The predose PK/PD sample may be drawn through the venous access created for the dose infusion, prior 
to administration of the dose. End-of-infusion PK/PD samples will be drawn from the patient’s opposite, noninfused arm. All collection times will be recorded in the eCRF. In 
the event of breakthrough hemolysis, a serum sample for PK/PD analysis will be collected. 
k Samples for ADA will be collected predose or at any time when a dose of study drug is not administered. 
l If a suspected event of breakthrough hemolysis occurs, LDH, PK, and PD samples for analysis will be collected. If the suspected event of breakthrough does not occur at a 
scheduled visit, an unscheduled visit should occur for evaluation of the patient and collection of the required LDH, PK, and PD samples. 
m The dose of ALXN1210 is based on the patient’s last recorded study visit body weight. 
n If a patient withdraws early from the study (eg, to begin treatment with marketed product), an ET visit will be performed. 
. 
 

Protocol ALXN1210-PNH-301 
 
Alexion Pharmaceuticals, Inc. 
Amendment 6, 12 April 2021 
Page 42 of 93 
Alexion Confidential 
Table 6: 
Schedule of Study Visits and Assessments: Patients who Roll-over from Ongoing ALXN1210 IV PNH Studies 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: ADA = antidrug antibody; BP = blood pressure; ECG = electrocardiogram; eCRF = electronic case report form; EORTC QLQ-C30 = European Organisation for 
Research and Treatment of Cancer, Quality of Life Questionnaire-Core 30 Scale; EOS = end of study; ET = early termination; FACIT-Fatigue = Functional Assessment of 
Chronic Illness Therapy-Fatigue Scale; IV = intravenous; LDH = lactate dehydrogenase; PD = pharmacodynamics; PK = pharmacokinetics; PNH = paroxysmal nocturnal 
hemoglobinuria; R = roll over; RBC = red blood cell; WBC = white blood cell 
a 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. 
b WBC (granulocyte and monocyte) and RBC clone size measured by high-sensitivity flow cytometry at Day 1 R; RBC clone size only on Day 168 and Day 336.  
c Female patients of childbearing potential only. Serum pregnancy test at ET only; urine pregnancy test at all other time points. A negative urine test result is required prior to 
administering ALXN1210 to female patients of childbearing potential on dosing days. 
Study Day  
1 R 
56R 
112R  
168R  
224R  
280R  
336R 
392 R 
 
448 R 
504 R 
EOS/ 
ETo,p 
Window (day) 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
Confirmation or administration of meningococcal 
vaccinationa 
X 
 
 
 
 
 
 
 
 
 
Medical History and Demographics 
X 
 
 
 
 
 
 
 
 
 
PNH clone sizeb 
X 
 
 
X 
 
 
X 
 
 
X 
Weight 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy testc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Record transfusions and transfusion parametersd 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PNH symptomatologye 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
FACIT-Fatiguef 
X 
 
 
 
 
 
 
 
 
X 
EORTC QLQ-C30f 
X 
 
 
 
 
 
 
 
 
X 
Abbreviated physical examinationg 
X 
 
 
X 
 
 
X 
 
 
X 
Vital signsh 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Safety 12-Lead ECGi 
 
 
 
 
 
 
 
 
 
X 
Chemistry including LDHj 
X 
 
 
X 
 
 
X 
 
 
X 
Hematology including free hemoglobin and 
coagulationj 
X 
 
 
X 
 
 
X 
 
 
X 
Urinalysis and urine chemistryj 
X 
 
 
X 
 
 
X 
 
 
X 
PK/PD samplingk 
X 
 
 
X 
 
 
X 
 
 
X 
Immunogenicity (ADA)l 
X 
 
 
X 
 
 
X 
 
 
X 
Review safety card 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Breakthrough hemolysism 
 
←Monitor continuously→ 
Concomitant medications 
 
←Monitor continuously→ 
Adverse events 
 
←Monitor continuously→ 
ALXN1210 administrationn 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 

Protocol ALXN1210-PNH-301 
 
Alexion Pharmaceuticals, Inc. 
Amendment 6, 12 April 2021 
Page 43 of 93 
Alexion Confidential 
d Transfusions given during and between visits will be recorded. 
e Investigator or designee assessment of the following events: fatigue, hemoglobinuria, abdominal pain, dyspnea, dysphagia, chest pain, and erectile dysfunction. 
f Physician- and patient-reported assessments will be performed prior to study drug administration. 
g Abbreviated physical examination consists of a body system relevant examination based upon Investigator (or qualified designee) judgment and patient symptoms. At least one 
body system must be checked for an abbreviated physical examination. 
h 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]), heart 
rate (beats/minute), respiratory rate (breaths/minute), and temperature (degrees Celsius [°C] or degrees Fahrenheit [°F]). Vital signs will be taken before each study drug 
administration. 
i Single 12-lead ECG will be collected at Day 504 or ET. Patients must be supine for approximately 5 to 10 minutes before ECG collection and remain supine but awake during 
ECG collection. 
j Clinical laboratory measurements will be collected predose on dosing days and not from a heparinized line.  
k Serum samples for PK/PD analyses will be collected predose (within 0.5 hours prior to the start of infusion) and at end-of-infusion (within 0.5 hours after the end of infusion) on 
Days 1, 168, 336, and at any time on Day 504 or ET. The predose PK/PD sample may be drawn through the venous access created for the dose infusion, prior to administration 
of the dose. End-of-infusion PK/PD samples will be drawn from the patient’s opposite, noninfused arm. All collection times will be recorded in the eCRF. In the event of 
breakthrough hemolysis, a serum sample for PK/PD analysis will be collected. 
l Samples for ADA will be collected predose . 
m If a suspected event of breakthrough hemolysis occurs, LDH, PK, and PD samples for analysis will be collected. If the suspected event of breakthrough does not occur at a 
scheduled visit, an unscheduled visit should occur for evaluation of the patient and collection of the required LDH, PK, and PD samples. 
n The dose of ALXN1210 is based on the patient’s last recorded study visit body weight. 
o If a patient withdraws early from the study (eg, to begin treatment with marketed product), an ET visit will be performed. 
p Depending on when patients roll over, the EOS will be adjusted such that it coincides with the planned EOS for the current protocol (estimated January 2023). 
 

Protocol ALXN1210-PNH-301 
 
Alexion Pharmaceuticals, Inc. 
Amendment 6, 12 April 2021  
 
Page 44 of 93 
Alexion Confidential 
8. 
STUDY POPULATION 
Original Study ALXN1210-PNH-301 Cohort: A total of approximately 214 patients with 
documented PNH will be enrolled and randomly assigned to treatment with either ALXN1210 or 
eculizumab at approximately 300 investigative sites globally. 
Roll-Over Cohort: A maximum number of approximately 56 patients may roll over from other 
ongoing studies of ALXN1210 IV in patients with PNH into the Extension Period of 
Study ALXN1210-PNH-301. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened once based on discussion and agreement between the Investigator and the Medical 
Monitor. 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
8.1. 
Eligibility Criteria for Original Study ALXN1210-PNH-301 Cohort 
8.1.1. 
Inclusion Criteria 
Patients are eligible for enrollment in the study only if they meet all of the following criteria and 
none of the exclusion criteria: 
1. Male or female, 18 years of age or older at the time of consent. 
2. Documented diagnosis of PNH, confirmed by high-sensitivity flow cytometry evaluation 
(Borowitz, 2010) of RBCs and white blood cells (WBCs), with granulocyte or monocyte 
clone size of ≥ 5%. 
3. Presence of 1 or more of the following PNH-related signs or symptoms within 3 months 
of Screening: fatigue, hemoglobinuria, abdominal pain, shortness of breath (dyspnea), 
anemia (hemoglobin < 10 g/dL), history of a major adverse vascular event (including 
thrombosis), dysphagia, or erectile dysfunction; or history of pRBC transfusion due to 
PNH. 
4. LDH level ≥ 1.5 × ULN at Screening. 
5. 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 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. 
6. Female patients of childbearing potential and male patients with female partners of 
childbearing potential must follow protocol-specified guidance (Section 9.13) for 
avoiding pregnancy while on treatment and for 8 months after last dose of study drug. 
7. Patients must be willing and able to give written informed consent and to comply with all 
study visits and procedures, including the use of any data collection device(s) to directly 
record patient data. 

Protocol ALXN1210-PNH-301 
 
Alexion Pharmaceuticals, Inc. 
Amendment 6, 12 April 2021  
 
Page 45 of 93 
Alexion Confidential 
8.1.2. 
Exclusion Criteria 
Patients will be excluded from study enrollment if they meet any of the following criteria: 
1. 
Current or previous treatment with a complement inhibitor. 
2. 
Platelet count < 30,000/mm3 (30 × 109/L) at Screening. 
3. 
Absolute neutrophil count < 500/µL (0.5 × 109/L) at Screening. 
4. 
History of bone marrow transplantation. 
5. 
Body weight < 40 kg at Screening. 
6. 
History of N. meningitidis infection. 
7. 
History of unexplained, recurrent infection. 
8. 
Active systemic bacterial, viral, or fungal infection within 14 days prior to study drug 
administration on Day 1. 
9. 
Presence of fever ≥ 38°C (100.4°F) within 7 days prior to study drug administration on 
Day 1. 
10. Human immunodeficiency virus (HIV) infection (evidenced by HIV-1 or HIV-2 
antibody titer). 
11. Immunized with a live-attenuated vaccine 1 month prior to study drug administration 
on Day 1. 
12. History of malignancy within 5 years of Screening with the exception of nonmelanoma 
skin cancer or carcinoma in situ of the cervix that has been treated with no evidence of 
recurrence. 
13. History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease 
(eg, active hepatitis) that, in the opinion of the Investigator or Sponsor, precludes the 
patient’s participation in an investigational clinical trial. 
14. Unstable medical conditions (eg, myocardial ischemia, active gastrointestinal bleed, 
severe congestive heart failure, anticipated need for major surgery within 6 months of 
randomization, coexisting chronic anemia unrelated to PNH) that would make them 
unlikely to tolerate the requirements of the protocol (eg, transfusion guidelines). 
15. Concomitant use of anticoagulants is prohibited if not on a stable regimen for at least 
2 weeks prior to Day 1.  
16. History of hypersensitivity to any ingredient contained in the study drug, including 
hypersensitivity to murine proteins. 
17. Females who plan to become pregnant or are currently pregnant or breastfeeding. 
18. Females who have a positive pregnancy test result at Screening or on Day 1. 
19. 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. 

Protocol ALXN1210-PNH-301 
 
Alexion Pharmaceuticals, Inc. 
Amendment 6, 12 April 2021  
 
Page 46 of 93 
Alexion Confidential 
20. Known or suspected history of drug or alcohol abuse or dependence within 1 year prior 
to the start of Screening. 
21. Known medical or psychological condition(s) or risk factor that, in the opinion of the 
Investigator, might interfere with the patient’s full participation in the study, pose any 
additional risk for the patient, or confound the assessment of the patient or outcome of 
the study. 
8.2. 
Eligibility Criteria for Roll-over Cohort  
1. All patients regardless of age, who are currently receiving ALXN1210 IV in an 
ongoing ALXN1210 study in patients with PNH 
2. Patients must be willing and able to give written informed consent and to comply with 
all Extension study visits and procedures, including the use of any data collection 
device(s) to directly record patient data 
3. 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 
8.3. 
Discontinuation 
8.3.1. 
Withdrawal of Patients 
A patient has the right to withdraw from the study at any time. If a patient withdraws consent, the 
assessments specified for the Early Termination (ET) visit (as shown in the Schedule of 
Assessments, Section 7.3) will be performed and the Sponsor and site monitor notified as soon as 
possible. Patients who withdraw from the study will not be replaced.  
Patients should be permanently discontinued from ALXN1210 treatment if any of the following 
occur during the study: 
• Serious infusion reaction (such as bronchospasm with wheezing or requiring 
ventilator support or symptomatic hypotension, refer to Appendix A) or serum 
sickness-like reactions manifesting 1 to 14 days after drug administration; 
• Severe uncontrolled infection; 
• Pregnancy or planned pregnancy; or 
• If the Alexion Medical Monitor or the Investigator deems it to be in the best interest 
of the patient. 
The Investigator should speak with the Medical Monitor prior to discontinuing a patient’s study 
treatment. If a patient is discontinued from study drug, the patient should be encouraged to return 
for the remainder of his or her scheduled protocol visits until starting a different complement-
targeted therapy. 
The reason for the treatment or study discontinuation will be recorded on the eCRF. 
If a patient is discontinued from the study with an ongoing adverse event or an unresolved 
laboratory result that, in the opinion of the Investigator, is significantly outside of the reference 

Protocol ALXN1210-PNH-301 
 
Alexion Pharmaceuticals, Inc. 
Amendment 6, 12 April 2021  
 
Page 47 of 93 
Alexion Confidential 
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 adverse event is achieved. 
As it is essential to obtain follow-up data on any patient withdrawn due to an AE or SAE, 
follow-up due diligence documentation will consist of 3 phone calls followed by 1 registered 
letter to the patient’s last known address. In any case, every effort must be made to undertake 
protocol specified safety follow-up procedures.  
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 (see Section 11.8). 
8.3.2. 
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 health authorities  
Should the study be terminated early, the Sponsor will notify the health authority and 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) according to local 
requirements. 
8.4. 
End of Study Definition 
The end of the study is defined as the date of the last patient’s last visit in the Extension Period. 

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9. 
STUDY TREATMENT 
9.1. 
Materials and Supplies 
9.1.1. 
Description of Study Drugs 
The study drugs in this study are ALXN1210 and eculizumab (active control). Both ALXN1210 
and eculizumab are humanized, anti-C5 monoclonal antibodies.  
Eculizumab 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. Eculizumab is composed of two 448 amino acid heavy chains and two 
214 amino acid light chains.  
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 and eculizumab drug products are supplied for clinical studies as sterile, 
preservative-free 10-mg/mL solutions 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 7, the current ALXN1210 IB, and the approved eculizumab local labeling or 
current eculizumab IB for additional information.  
Table 7: 
Study Drug 
 
Study Drug 
Product Name 
ALXN1210 
Eculizumab 
Dosage Form 
Concentrated solution (10 mg/mL) for 
infusion 
Concentrated solution (10 mg/mL) for 
infusion 
Route of Administration 
Intravenous infusion 
Intravenous infusion 
Physical Description 
Clear to translucent, slight whitish 
color, practically free from particles 
Clear, colorless solution practically 
free from particles  
Manufacturer 
Alexion Pharmaceuticals, Inc. or 
Contracted Manufacturing 
Organization 
Alexion Pharmaceuticals, Inc. or 
Contracted Manufacturing 
Organization 
9.1.2. 
Study Drug Packaging and Labeling 
ALXN1210 and eculizumab are packaged in US Pharmacopeia/European Pharmacopeia 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 Pharmacy Manual for 
details. 
Study drug orders will be released to each site upon receipt of all required documents based upon 
applicable regulations. 

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9.1.3. 
Study Drug Storage 
Upon arrival of the study drug kits at the study site, the pharmacist or 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 (36°F to 46°F) and protected from light. ALXN1210 
and eculizumab 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. 
Please consult the Pharmacy Manual for further information regarding the storage conditions of 
reconstituted ALXN1210 or eculizumab. 
9.1.4. 
Study Drug Preparation and Infusion 
Eculizumab or 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 or eculizumab will be further diluted into commercially available saline (0.9% 
sodium chloride; country-specific pharmacopeia) at the volume specified in Table 8 for 
ALXN1210 or Table 9 for eculizumab (see also approved local labeling or current IB for 
eculizumab). ALXN1210 or eculizumab 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 of ALXN1210. The permitted duration of an eculizumab infusion (excluding IV flush) 
ranges from a minimum of 25 minutes to a maximum of 45 minutes for both the 600 mg and 
900 mg doses, except in the management of an AE, when the duration may be extended to a 
maximum of 120 minutes. If an IV flush is included (expected to last no more than 15 minutes), 
the total infusion duration for eculizumab plus IV flush must not exceed 60 minutes (no more 
than 135 minutes if slowed or stopped due to AE). The total infusion duration, including an IV 
flush, will be recorded on the eCRF.  
Table 8: 
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 
 
 
≥ 30 to < 40 
1200 
120 
120 
240 
78 (1.3) 
184 
≥ 40 to < 60 
2400 
240 
240 
480 
114 (1.9) 
252 
≥ 60 to < 100 
2700 
270 
270 
540 
102 (1.7) 
317 
≥ 100 
3000 
300 
300 
600 
108 (1.8) 
333 
Maintenance 
 
 
≥ 30 to < 40 
2700 
270 
270 
540 
168 (2.8) 
192 
≥ 40 to < 60 
3000 
300 
300 
600 
 140 (2.4) 
257 
≥ 60 to < 100 
3300 
330 
330 
660 
120 (2.0) 
330 
≥ 100 
3600 
360 
360 
720 
132 (2.2) 
327 
Note: Please refer to the Pharmacy Manual for additional dose preparation instructions. 
a  Dose regimen will be based on the last recorded study visit body weight. If the study drug is prepared the night 
before a visit, the weight from the most recent study visit should be used. 

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Table 9: 
Dosing Reference Chart for Eculizumab Dose Preparation 
Dose Type 
Dose (mg) 
Eculizuma
b Volume 
(mL) 
Saline 
Volume 
(mL) 
Total 
Volume 
(mL) 
Approxima
te Infusion 
Durationa 
(minutes) 
Approxima
te 
Infusion 
Rate 
(mL/hour) 
Induction 
600 
60 
60 
120 
35 
200 
Maintenance 
900 
90 
90 
180 
35 
300 
a Acceptable range is 25-60 minutes, which includes a flush of up to 15 minutes. If an adverse event occurs during 
the administration of eculizumab, the infusion may be slowed or stopped at the discretion of the physician. If the 
infusion is slowed, the total infusion time may not exceed 135 minutes. 
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 study drug, 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. 
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 for clinical study drugs. 
To satisfy regulatory requirements regarding drug accountability, at the end of the study all 
remaining ALXN1210 and eculizumab inventory will be reconciled and destroyed or returned to 
Alexion or designee according to applicable regulations.  
Please refer to the Pharmacy Manual for further information. 
9.2. 
Treatments Administered 
Original Study ALXN1210-PNH-301 Cohort: This study involves a direct comparison of 
ALXN1210 versus the active control, eculizumab.  
Patients will be randomly assigned in a 1:1 ratio to receive either ALXN1210 or eculizumab for 
26 weeks. Study drug will be administered as a slow IV infusion (see Table 8 and Table 9).  
The dose regimen for ALXN1210 is a loading dose on Day 1 followed by maintenance doses on 
Day 15 and q8w thereafter. The dosage of ALXN1210 is based on the patient’s last recorded 
study visit body weight, as indicated in Table 10.  

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Table 10: 
ALXN1210 Weight-Based Dosages 
ALXN1210 Treatment Group 
 
Body Weight 
 
Loading Dose 
 
Maintenance Dose  
≥ 30 to < 40 kgb 
1200 mg 
2700 mg 
 
≥ 40 to < 60 kg 
2400 mg 
3000 mg 
 
≥ 60 to < 100 kg 
2700 mg 
3300 mg 
 
≥ 100 kg 
3000 mg 
3600 mg 
a Dose regimen will be based on the last recorded study visit body weight. If the study drug is prepared the night 
before a visit, the weight from the most recent study visit should be used. 
b In the event that a patient drops below 30 kg during the course of the study, the approved ravulizumab aHUS 
dosing for patients weighing ≥ 20 to < 30 kg will be used: a loading dose of 900 mg and maintenance dose of 
2100 mg. 
Patients randomly assigned to the eculizumab group will receive eculizumab according to the 
approved dosing regimen for the PNH indication, which is 4 weekly induction doses, followed 
by maintenance doses q2w starting at Week 5 (Table 11). 
Table 11: 
Eculizumab Dosages 
Eculizumab Treatment Group 
Induction Dose  
Maintenance Dose  
 
All patients 
600 mg 
900 mg 
After the randomized treatment period all patients will enter the Extension Period and receive 
ALXN1210 until the product is registered or approved (in accordance with country-specific 
regulations) or for up to 5 years, whichever occurs first. Beginning on Day 183, patients who had 
been randomized to the ALXN1210 treatment group will receive their weight-based maintenance 
dose of ALXN1210 q8w, and patients who had been randomized to the eculizumab group will 
receive a weight-based loading dose of ALXN1210 followed 2 weeks later and q8w thereafter by 
a weight-based maintenance dose of ALXN1210 (Table 10; Figure 2). 
In the Roll-over Cohort, patients will receive weight-based maintenance dosing of ALXN1210 
q8w from Day 1 of roll over (Table 10, Figure 2). 
The actual time of all dose administrations will be recorded on the patient’s eCRF. 

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Figure 2: 
Dosing Schematic  
Screening
Up to 4 weeks
Treatment Period 
26 weeks 
Extension Period
Up to 5 years
ALXN1210
15
1
Eculizumab
183
71
127
ALXN1210 infusion
Eculizumab infusion
1 8 15 22 29
43
71
85
57
113 127
99
155 169
141
183
239
295
351 407
463
519
575
631
1975
197
253
309 365 421
477
533
589
645
1989
Study Day:
Study Day:
q8w
q8w
 
 
Abbreviations: PNH = paroxysmal nocturnal hemoglobinuria; q8w = once every 8 weeks; R = roll over 
9.3. 
Method of Assignment to Treatment 
Original Study ALXN1210-PNH-301 Cohort: Patients who meet all criteria for enrollment will 
be randomly assigned to study treatment with ALXN1210 or eculizumab at the Baseline Visit 
(Day 1). Treatment group assignment will be determined by a computer-generated random 
sequence using an interactive voice- or web-response system (IxRS). The randomization will be 
a stratified randomization. Patients will be stratified into 1 of 6 groups based on their transfusion 
history (0, 1 to 14, or > 14 units of pRBCs in the 1 year prior to first dose of study drug) and 
screening lactate dehydrogenase (LDH) levels (1.5 to < 3 × ULN or ≥ 3 × ULN). The patients 
within each of the 6 groups will then be randomly assigned in a 1:1 ratio to receive ALXN1210 
or eculizumab during the 26-week randomized treatment period. 
All patients in the Roll-over Cohort will receive ALXN1210. 
9.4. 
Rationale for Selection of Doses in the Study 
The weight-based dosages of ALXN1210 in this study (Table 10) 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 is based on targeting immediate, complete and sustained inhibition of terminal 
complement in patients with PNH. 

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The eculizumab dosage is the labelled dose for the treatment of patients with PNH (Soliris® USPI 
and SmPC). 
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 A for 
guidance on identifying and managing potential drug infusion reactions. 
9.6. 
Blinding 
This is an open-label study. 
9.7. 
Prior and Concomitant Medications and Nonpharmacologic 
Procedures 
For the Original Study ALXN1210-PNH-301 Cohort, prior medications (including vitamins and 
herbal preparations)—including those discussed in the exclusion criteria (Section 8.1.2) 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 study 
drug—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. 
Transfusions of pRBCs received within 1 year prior to first study drug administration will be 
recorded on the patient’s eCRF. 
For both cohorts, 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 for PNH. Concomitant medications 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. 
Concomitant use of anticoagulants is prohibited if not on a stable dose regimen for at least 
2 weeks prior to Day 1. 
Use of complement inhibitors other than the patient’s assigned study treatment is prohibited. 
9.8. 
Vaccination 
Due to their mechanism of action, the use of eculizumab or ALXN1210 increases the patient’s 
susceptibility to meningococcal infection (N. meningitidis). To reduce the risk of meningococcal 
infection, 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 

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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. Patients must be vaccinated or revaccinated according to current national vaccination 
guidelines or local practice for vaccination use with complement inhibitors (eg, eculizumab). The 
vaccinations must be reconfirmed after 3 years or according to the current national vaccination 
guidelines. 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 and vaccination. 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. Additional discussion and explanation of the potential 
risks, signs, and symptoms will occur at each visit as part of the review of the patient safety card 
as described in the Schedule of Assessments (Section 7.3). Vaccination status for N. meningitidis 
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. 
Home Visits During the Extension Period 
During the Extension Period, and only for visits not requiring an abbreviated physical exam, 
patients may have the opportunity to have ALXN1210 administered at a medical facility that is 
located near the patient’s home if allowed by national legislation. This will also ensure patient 
safety and treatment continuity during the coronavirus disease 2019 (COVID-19) pandemic. 
Alternatively, ALXN1210 may be administered at the patient’s home under the orders of the 
Investigator and in accordance with all national, state, and local laws or regulations of the 
pertinent regulatory authorities. These visits will be conducted by a trained qualified staff 
member from the medical facility near the patient’s home or by qualified home health care 
professionals. The study drug will be prepared at the Investigator’s pharmacy and transported 
under controlled conditions to the patient’s home or the medical facility for administration by a 
dedicated courier. The use of a courier, specialized in medicinal product shipments, is needed to 
ensure traceability and temperature controlled delivery for the transfer of drug from 
Investigator’s pharmacy to patient’s home or the medical facility for administration, as specified 
in the home health care manual. During a remote dosing visit, all assessments will be performed 
according to the schedule of assessments, including recording of AEs and concomitant 
medications, collection of blood and urine samples, assessment of PNH symptomatology, vital 
signs, QoL assessments, and review of safety card. Patients must return to the study site for any 
visit at which an abbreviated physical examination is required, as specified in the Schedule of 

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Assessments (Section 7.3). Information about AEs concomitant medications, and samples for 
protocol-defined laboratory parameters must be sent to the Investigator’s site for evaluation on 
the day of the remote visit. In countries where local legislation does not allow infusions outside 
authorized study sites, the Investigators will be notified in writing that this provision is 
prohibited. 
9.11. 
COVID-19 Risk Assessment 
Paroxysmal nocturnal hemoglobinuria can cause irreversible morbidity and even mortality, if 
untreated. As such, and due to the limited number of available treatment options, the benefit a 
participant may receive from joining an investigational study with a therapeutic treatment is 
potentially significant. The fact that Study ALXN1210-PNH-301 is open-label and every 
participant is treated with the study intervention also contributes to the potential benefit a 
participant may derive from partaking in the study. Given that treatment for PNH does involve 
immunosuppression, there is a theoretical concern that the risk for infection may be higher than 
in participants not receiving immunosuppressants. However, there is no specific data to further 
inform this risk. The Investigator will therefore balance the risk/benefit considerations for the 
study participant, taking these factors into account.  
The potential risks identified and mitigation measures put in place in light of the COVID-19 
pandemic are provided in Table 12. 

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Table 12: 
Potential Risks and Mitigation Measures due to COVID-19 
Risks category 
Summary of Data/ 
Rationale for Risk 
Mitigation Strategy 
Healthcare institution 
availability for 
non-COVID-19 
related activities  
COVID-19 pandemic may impact the workload of 
healthcare institutions globally and may reduce staff 
availability to perform non-urgent activities and 
non-COVID-19 related activities. 
 
During the time that the 
COVID-19 pandemic is active, 
Alexion will not open study 
sites or enroll new participants 
at sites unless the sites have the 
resourcing and capabilities to 
implement the study per 
protocol. 
Data quality and 
integrity 
Lack of availability of site personnel to perform 
study assessments and capture study-specific data in 
a timely manner and to maintain adequate quality 
standards. 
Lack of availability of site personnel to ensure 
adequate and continuous chain of custody, storage 
conditions, and monitoring for investigational 
product and biological samples. 
Inability of study monitors and quality personnel to 
conduct in-person visits to exercise adequate 
oversight of study execution at investigational sites. 
Missing data (COVID-19 pandemic may impact 
study visit schedules and increase missed visits 
and/or participant study discontinuations, 
inadvertently resulting in missing data [eg, for 
protocol-specified procedures]). 
During the time that the 
COVID-19 pandemic is active, 
Alexion will only open study 
sites that report enough 
personnel capacity to 
sufficiently conduct clinical 
study-related activities.  
During this timeframe, 
participants eligibility as well as 
site capacity will be reviewed 
by the site Investigator and the 
study Medical Monitor prior to 
Screening. Each site will also be 
evaluated for the capacity to 
perform remote monitoring 
visits and remote source data 
verification. 
During the time that the 
COVID-19 pandemic is active, 
it will be important to capture 
specific information in the 
eCRF that explains the reason 
the data is missing (eg, missed 
study visits or participant study 
discontinuations due to 
COVID-19). 
Abbreviation: COVID-19 = coronavirus disease 2019; eCRF = electronic case report form 
9.12. 
COVID-19 Vaccine Risk Assessment 
Following a review of the available COVID-19 vaccine data (eg, Pfizer/BioNTech, Moderna, 
AstraZeneca, Johnson & Johnson), it is unlikely that the immune response to a COVID-19 
vaccine (and therefore the efficacy of the vaccination) would be diminished with concomitant 
ALXN1210 administration, based on ALXN1210’s mechanism of action. There is currently no 
information available evaluating the safety and efficacy of COVID-19 vaccines in participants 
treated with ALXN1210. The same precautions should be taken as described in Section 9.8. 
Vaccination may further activate complement. As a result, patients with complement-mediated 

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diseases may experience increased signs and symptoms of their underlying disease. Therefore, 
patients should be closely monitored for disease symptoms after recommended vaccination 
Because vaccines may activate complement, if possible, consider vaccination when the 
underlying complement mediated disease is clinically controlled and when systemic C5 inhibitor 
concentration (and subsequent complement blockade) is relatively high, shortly after 
administration. 
Local and national guidelines should be consulted for recommendations related to COVID-19 
vaccination. The potential risks identified and mitigation measures put in place in light of the 
COVID-19 vaccination rollout are provided in Table 13. 
Table 13: Potential Risks and Mitigation Measures due to COVID19 Vaccine 
Risks category 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Potential risks 
Data quality and 
integrity 
Missing data due to appointments for COVID-19 
vaccination or side effects of COVID-19 vaccine 
may impact study visit schedules, and increase 
missed visits and/or participant study 
discontinuations, inadvertently resulting in 
missing data (eg, for protocol-specified 
procedures). 
 Capture specific information in 
the eCRF that explains the reason 
the data is missing (eg, missed 
study visits due to appointments 
for COVID-19 vaccination or side 
effects of COVID-19 vaccine)  
Abbreviation: COVID-19 = coronavirus disease 2019. 
9.13. 
Contraception Guidance 
Before receiving study drug, female patients who consider themselves to be postmenopausal 
must provide evidence of menopause based on a combination of amenorrhea for at least 1 year 
and increased serum follicle-stimulating hormone (FSH) level (> 30 IU/L). 
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 
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:  

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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 
10.1. 
Transfusions 
A pRBC transfusion will be administered when a patient has a 
• hemoglobin value of 9 g/dL or lower with signs or symptoms of sufficient severity to 
warrant a transfusion 
• hemoglobin value of 7 g/dL or lower regardless of presence of clinical signs or 
symptoms  
Signs or symptoms typically associated with or that precipitate the patient’s need for transfusion 
will also be documented on the eCRF for each individual patient. Typical anemia-related 
symptoms warranting transfusions include angina, change in mental status (eg, syncope, light 
headedness, confusion, stroke, transient ischemic attack), severe or worsening shortness of 
breath, and severe or worsening fatigue. Other symptoms precipitating a potential need for 
transfusion should be discussed with the Medical Monitor before the transfusion is given. 
If a patient meets either transfusion criterion during the study, the Investigator will determine the 
appropriate number of units of pRBCs to be transfused. It is recommended that the transfusion be 
performed within 48 hours of the hemoglobin determination responsible for the transfusion. 
Administration of a transfusion, including the hemoglobin result and symptoms that triggered the 
transfusion, and the number of units transfused, will be documented in the eCRF.  
If there is a compelling medical need to deviate from these transfusion guidelines, the Alexion 
Medical Monitor must be consulted. 
For the original Study ALXN1210-PNH-301 Cohort, prior to randomization and within 5 days 
prior to study drug administration on Day 1, each patient’s hemoglobin must be evaluated by 
either local or central laboratory. If at that time the patient’s hemoglobin value meets these 
transfusion guidelines, the patient must be transfused with pRBCs to a hemoglobin level above 
the transfusion threshold in order to be eligible for randomization. The patient’s post-transfusion 
hemoglobin value should be confirmed by local or central laboratory to be above the transfusion 
threshold. 
10.2. 
LDH and Other Disease-Related Laboratory Parameters 
Blood and urine samples will be collected at the times indicated in the Schedule of Assessments 
(Section 7.3) and as indicated in Section 11.4.  
The following disease-related laboratory parameters will be measured during the study (refer to 
Section 12 for PK/PD assessments): 
• LDH 
• free hemoglobin 
• occult blood, urine 
• total C5 
• haptoglobin 

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• reticulocyte count 
• PNH RBC clone size evaluated by high-sensitivity flow cytometry (Borowitz, 2010) 
• D-dimer concentration 
• estimated glomerular filtration rate (calculated using the Modification of Diet in 
Renal Disease formula) 
• spot urine albumin:creatinine ratio 
• C-reactive protein 
10.3. 
PNH Symptomatology 
The Investigator or designee will record for each patient the presence or absence of the following 
signs and symptoms of PNH: fatigue, chest pain, abdominal pain, dyspnea, dysphagia, erectile 
dysfunction, and red/dark urine or hemoglobinuria.  
10.4. 
Patient-Reported Outcome Measures 
Two validated QoL scales will be administered to patients before study drug administration at 
the time points specified in the Schedule of Assessments (Section 7.3).  
• The FACIT-Fatigue scale, Version 4.0, is a collection of QoL questionnaires 
pertaining to the management of fatigue symptoms due to a chronic illness. The 
FACIT-Fatigue is a 13-item questionnaire that assesses self-reported fatigue and its 
impact upon daily activities and function over the preceding 7 days. Patients will 
score each item on a 5-point scale: 0 (Not at all) to 4 (Very much). Total scores range 
from 0 to 52, with higher score indicating better QoL. 
• The European Organization for Research and Treatment of Cancer (EORTC) Quality 
of Life Questionnaire-Core 30 Scale (QLQ-C30), Version 3.0, is a questionnaire 
developed to assess the QoL of cancer patients. The questionnaire includes the 
following subscales: global health status, functional scales (physical functioning, role 
functioning, emotional functioning, cognitive functioning, and social activity), 
symptom scales (fatigue, nausea and vomiting, and pain), and single items (dyspnea, 
insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Thirty 
questions related to QoL, with the first 28 questions scored on a 4-point scale (1 = not 
at all to 4 = very much) and the final 2 questions that probe the patient’s overall 
health and QoL scored on a scale of 1 (very poor) to 7 (excellent). Each subscale has 
a range of 0 to 100%, with a high score representing a higher response level. Thus, a 
high score for a functional scale represents a high level of functioning but a high 
score for a symptom scale represents a high level of symptomatology/problem. 
The FACIT-Fatigue and EORTC QLQ-C30 scales are provided in Appendix B and Appendix C, 
respectively.  
10.5. 
Major Adverse Vascular Events 
Major adverse vascular events (MAVEs) will be assessed as part of the planned evaluation for 
AEs as described in Section 11.7. 

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The description of the MAVE including the method of diagnosis (eg, magnetic resonance 
imaging, ultrasound, angiogram), date of diagnosis, and date resolved (or ongoing) will be 
collected on the eCRF as part of the patient’s medical history (prior to baseline). 
A MAVE is defined as follows: 
• Thrombophlebitis/deep vein thrombosis 
• Pulmonary embolus 
• Myocardial infarction 
• Transient ischemic attack 
• Unstable angina 
• Renal vein thrombosis 
• Acute peripheral vascular occlusion 
• Mesenteric/visceral vein thrombosis or infarction 
• Mesenteric/visceral arterial thrombosis or infarction 
• Hepatic/portal vein thrombosis (Budd-Chiari syndrome) 
• Cerebral arterial occlusion/cerebrovascular accident 
• Cerebral venous occlusion 
• Renal arterial thrombosis 
• Gangrene (nontraumatic; nondiabetic) 
• Amputation (nontraumatic; nondiabetic) 
• Dermal thrombosis 
• Other, specify 

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11. 
SAFETY ASSESSMENTS 
The Investigator or his/her designee will meet with patients to discuss the potential safety risks 
of ALXN1210 and eculizumab and to give the Investigator the opportunity to address any of the 
patient’s safety concerns regarding the study. 
Investigators are instructed to follow any AEs through to their conclusion (resolution or 
stabilization), as described in Section 11.7.6.  
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. For the Roll-over Cohort, select data referenced in the 
following sections may be obtained from the prior studies from which the patients rolled over. 
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. Height will be measured at Screening only. 
11.1.2. 
Disease Characteristics 
The patient’s PNH medical history, including PNH symptoms, date of diagnosis, PNH clone 
size, pRBC transfusions, and history of any MAVEs, will be documented at the Screening visit.  
11.1.3. 
Medical History 
The patient’s medical history, including prior and concomitant conditions/disorders and 
transfusion history, 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 and meningococcal vaccination within 3 years prior to the first dose of study drug will 
also be recorded, as described in Section 9.7. 
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 judgment and patient symptoms. 
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 blood pressure (BP; millimeters of mercury [mmHg]), 
heart rate (beats/minute), respiratory rate (breaths/minute), and temperature (degrees Celsius [°C] 
or degrees Fahrenheit [°F]).  

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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 D. Samples for laboratory assessments will be 
collected before each study drug administration. If a suspected event of breakthrough hemolysis 
occurs, an unscheduled visit must take place at which a sample is collected for analysis of LDH 
and PK/PD by the central laboratory.  
Laboratory assessments will be tested at a central laboratory facility. 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 14.9.3). 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. 
11.4.1. 
Pregnancy Testing 
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 D. 
11.4.3. 
Serum Chemistry 
Blood samples will be analyzed for the serum chemistry parameters listed in Appendix D. 
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. 
Serum FSH levels will be measured during Screening for postmenopausal female patients to 
confirm their postmenopausal status. 
Chemistry assessments will be performed at the time points specified in the Schedule of 
Assessments (Section 7.3). Estimated glomerular filtration rate will be calculated using the 
Modification of Diet in Renal Disease formula for all visits at which serum chemistries are 
collected. 

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11.4.4. 
Coagulation 
Blood samples will be analyzed for the coagulation parameters listed in Appendix D. 
11.4.5. 
Urinalysis and Urine Chemistry 
Urine samples will be analyzed for the parameters listed in Appendix D. 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 protein:creatinine ratio. 
11.4.6. 
Virus Serology 
HIV testing for human immunodeficiency virus type 1 (HIV-1) and human immunodeficiency 
virus type 2 (HIV-2) is required for all patients prior to enrollment. Known HIV positive patients 
will not be enrolled.  
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 or 
eculizumab 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, PK/PD, safety, and activity of 
ALXN1210 or eculizumab.  
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 for 
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. 

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Transfusions are treated as efficacy endpoints (see Section 6.2). Transfusions administered in the 
inpatient or outpatient setting should not be captured as AEs or SAEs unless identified as such by 
the Investigator. 
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 
As noted in Section 9.8, C5 inhibition is known to increase susceptibility to infections caused by 
encapsulated bacteria, particularly N. meningitidis. The following events are important identified 
risks in this study: 
• Meningococcal infections 
• Sepsis 
• Serious infections 
• Aspergillus infection 
• Infusion reactions 
Additional events of interest in this study include the following: 
• Serious cutaneous adverse reactions 
• Cardiac disorders (including ventricular fibrillation) 
• Angioedema 
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 14). 

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Table 14: 
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 an 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 15). This assessment 
must be recorded on the eCRF and any additional forms as appropriate. 

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Table 15: 
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. 
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 SAE 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 

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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 ICF for the original 
Study ALXN1210-PNH-301 Cohort and from Day 1 of roll over for the Roll-over Cohort, until 
56 days after the last dose of study drug for patients with ET or until 56 days after the last dose 
of study drug for patients who complete the study. 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 Drug Safety (GDS) 
within 24 hours of first awareness of the event via the Safety Gateway. 
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.  
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 GDS 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 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: 
clinicalsae@alexion.com 

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Facsimile: 
+ 1.203.439.9347 (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 GDS via Safety 
Gateway.  
If applicable, additional information such as relevant medical records should be submitted to 
Alexion GDS 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 GDS 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. 
11.7.8. 
Investigator Reporting Requirements 
The Investigator must fulfill all local regulatory obligations required for the study Investigators. 
It is the Investigator’s responsibility to notify the IRB/IEC of all SAEs that occur at his or her 
site, as required per IRB/IEC standard operating procedures (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 Lactation 
Pregnancy data will be collected during this study for all patients and a 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 GDS 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 GDS. 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 GDS or designee via email or facsimile (Section 11.7.6.2). 
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, 

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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, GDS 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 GDS 
physician, to review trends in safety data. 

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12. 
PHARMACOKINETICS AND PHARMACODYNAMICS 
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 sampling time points for any given patient will not 
exceed the currently planned number of time points; in the event of breakthrough hemolysis, an 
additional PK/PD sample will be required. 
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 Manual for details on 
sample collection, including blood volume requirements. 
Assessments for PK/PD are as follows: 
• Serum ALXN1210 and eculizumab concentration over time 
• cRBC hemolytic activity over time (exploratory) 
• Free and total C5 concentrations over time 
 

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13. 
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 site 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, GCP guidelines of the 
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. 
13.1. 
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. 
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. 

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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. 
13.2. 
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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14. 
STATISTICAL METHODS AND PLANNED ANALYSES 
Section 14.2 through Section 14.10 describe the statistical methods and planned analysis for the 
Original Study ALXN1210-PNH-301 Cohort. 
The statistical method for the Roll-over Cohort is described in Section 14.11. 
Section 14.1 applies to both cohorts. 
14.1. 
General Considerations 
All data collected will be presented in summary 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, median, minimum, and maximum values. Categorical variables will be 
summarized by frequency counts and percentage of patients. All statistical tests performed will 
be based on a 2-sided 5% level of significance unless otherwise specified. Any and all exclusions 
will be documented in patient listings.  
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. 
A CSR will be produced based on efficacy, safety, PK, PD, and immunogenicity data collected 
through the end of the 26-week randomized treatment period (Day 183). A final CSR to 
summarize long-term efficacy, safety, PK, PD, and immunogenicity parameters will be produced 
at study completion. 
14.2. 
Determination of Sample Size 
Approximately 214 patients will be randomly assigned in a 1:1 ratio to receive ALXN1210 
(N = 107) or eculizumab (N = 107) to ensure at least 193 evaluable patients (assumes no more 
than a 10% drop-out rate). The sample size estimation is based on a noninferiority design 
comparing patients treated with ALXN1210 to those treated with eculizumab. Coprimary 
endpoints of hemolysis as directly measured by the normalization of LDH (LDH-N) from 
Day 29 through Day 183 and the proportion of patients who achieve transfusion avoidance (TA) 
through Day 183 will be used to assess noninferiority. The sample size is based on the endpoint 
that requires the larger number of patients.  
For the coprimary endpoint of LDH-N, using a noninferiority margin (NIM) based on the 
relative benefit of eculizumab with respect to placebo of 0.39 and a type I error of 1-sided 2.5%, 
a minimum of 142 patients will provide 80% power to demonstrate noninferiority of ALXN1210 
to eculizumab. The NIM was determined based on a randomized placebo-controlled study 
(Hillmen, 2006) which showed a relative benefit of eculizumab over placebo with an odds ratio 

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of 6.5. This was based on several factors. As baseline LDH is a predictor of the rate of 
normalization, in order to preserve the constancy assumption, the rate of LDH-N was calculated 
adjusted to the observed baseline LDH of the current ALXN1210 Phase 1b and 2 data. The 
estimate of LDH-N for eculizumab was then calculated to be a weighted average of the 
proportions of LDH-N from Day 29 to Day 183 to be consistent with the proposed analysis plan 
for this study. As the proportion of LDH-N for placebo treated patients was 0% at all visits, the 
upper bound of the 95% CI was used in order to be able to calculate an odds ratio. The final 
estimate of benefit was based on a LDH-N proportion of 42% for eculizumab-treated patients 
and 10% for placebo. A traditional choice of NIM is one with ≤ 50% loss of benefit resulting in a 
NIM of an odds ratio of 0.39. The calculation of NIM follows (Ng, 2008) in which the NIM is 
given by 1/{OR0.5} where OR represents the odds ratio of eculizumab compared to placebo and 
is given by [0.42/(1-0.42)]/[0.1/(1-0.1)], and 0.5 is the fraction of benefit to be preserved. This 
approach chooses the NIM on the log odds scale, as described in Section IV of the 2010 Food 
and Drug Administration (FDA) Guidance for Industry: Non-Inferiority Clinical Trials. While 
more conservative approaches for constructing NIMs could be used, such as using the lower 
bound of the 95% CI for eculizumab, the resulting estimated sample size would make this study 
operationally infeasible in light of the rarity of PNH and the paucity of eculizumab-naïve 
patients. 
For the other coprimary endpoint of proportion of patients not receiving any transfusions through 
Day 183, using a NIM of -20% and a type I error of 1-sided 2.5%, a minimum of 193 patients 
will provide 80% power to demonstrate noninferiority between the treatment arms. The NIM was 
determined based on the global PNH Registry for eculizumab-treated patients enrolling into the 
registry in 2012 or later (Soliris Type II Variation Procedure No. EMEA/H/C/000791/II/66). 
History of transfusion is a predictor of on-treatment transfusion so to preserve the constancy 
assumption, the NIM was assessed based on available data from treated and untreated patients in 
proportion to enrollment expectations in the current study. Patients treated with eculizumab (TA 
rate of 57.1%) showed a benefit over untreated patients (TA rate of 18.6%) with a difference of 
approximately 40% (38.5%) after adjustment for history of transfusions 12 months prior to 
enrollment. The adjustment comes from an expected proportion of patients without a history of 
transfusions to be no more than 20%. Enrolled patients for this study will be capped at 20% for 
patients without a history of transfusions to ensure constancy is satisfied.   
A traditional choice of NIM is one with ≤ 50% loss of benefit which gives a NIM of 
approximately -20%. A more conservative NIM could be used using the lower bound of the 
95% CI for the difference in rates, but the resulting estimated sample size would make the study 
operationally infeasible in light of the rarity of PNH and the paucity of eculizumab-naïve patients 
with and without a history of transfusions. Further, given the proportion of patients with TA 
observed in preliminary results from the Phase 1b/2 program, it is expected that noninferiority 
can be demonstrated with more conservative NIMs for the given sample size with limited loss of 
power. 
Because the sample size estimate based on LDH-N is smaller than that based on TA (Table 16), 
the final sample size estimate selected for this study is based on the TA endpoint. Adjusting for a 
possible 10% dropout rate, approximately 214 patients will be enrolled in this study. 

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Table 16: 
Summary of Parameters Used in Estimating Sample Size with Coprimary 
Endpoints 
Parameters 
LDH Normalization 
(LDH-N) 
Transfusion Avoidance 
(TA) 
Power 
80% 
80% 
Type I error 
1-sided 0.025 
1-sided 0.025 
Noninferiority margin 
0.39 
-0.20 
Allocation ratio 
1:1 
1:1 
Mean eculizumab response 
0.42a 
0.57b 
Standard deviation of eculizumab response 
NA 
NA 
Assumed treatment difference 
1 
0 
 
 
 
Estimated sample size (SS) 
142 
193 
Adjusted SS for 10% dropouts 
158 
214 
Note: Software package: Hintze, J. (2011). PASS 11. NCSS, LLC. Kaysville, Utah, US. www.ncss.com. 
a. Response rate from TRIUMPH study adjusted for baseline LDH.  
b. Response rate from Global PNH Registry adjusted for history of transfusion.  
14.3. 
Analysis Sets 
Efficacy analyses will be performed on the Full Analysis Set (FAS). The coprimary efficacy 
endpoint analyses, as well as key secondary endpoint analyses, will also be performed on the Per 
Protocol (PP) set. The FAS is the primary population for all efficacy analyses. The FAS will 
include all patients who received at least 1 dose of ALXN1210 or eculizumab and have at least 
1 efficacy assessment post first infusion.  
The PP set, which will be finalized prior to database lock, will consist of FAS patients who meet 
all of the following criteria: 
• Missed no doses of ALXN1210 or no more than 1 dose of eculizumab during the 
26-week randomized treatment period 
• Met inclusion criteria #2, 3, and 4 
• Did not meet exclusion criteria #1, 2, 3, or 4 
• Never received the wrong randomized treatment 
• Followed the protocol-specified transfusion guidelines 
Safety analyses will be performed on the Safety Set, defined as all patients who receive at least 
1 dose of study drug.  
Pharmacokinetic and PD analyses will be performed on all patients who receive at least 1 dose of 
study drug and who have evaluable PK and PD data. 
14.4. 
Demographics and Baseline Characteristics 
Patient demographic and baseline characteristics, including medical history and transfusion 
history, will be summarized by treatment group and overall for the FAS, and Safety sets. No 
formal statistical comparisons will be made. 

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14.5. 
Patient Disposition 
All patients will be included in the summaries of patient disposition, which will describe the 
frequency and percentage of patients screened and treated and who completed or withdrew from 
the study, along with reason for withdrawal from the study, by treatment group.  
The numbers of patients who are treated, discontinue treatment (along with reason for treatment 
discontinuation), complete or withdraw from the Randomized Treatment 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 by treatment group and 
overall. 
14.6. 
Prior and Concomitant Medications and Nonpharmacologic 
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 
Safety set. 
14.7. 
Treatment Compliance 
The number of infusions received per patient will be tabulated by treatment group for the FAS 
and Safety sets. 
14.8. 
Efficacy Analyses 
14.8.1. 
Coprimary Efficacy Analysis 
The coprimary efficacy endpoints are 1) the difference between treatment groups in the 
proportion of patients who achieve TA through Day 183, and 2) the relative effect between 
treatments in LDH-N from Day 29 through Day 183 expressed as an odds ratio.   
Transfusion avoidance will be achieved only by those patients who did not receive a transfusion 
and did not meet the protocol-specified guidelines for transfusion. The percentage of patients 
who achieve TA with 95% CIs will be computed at Day 183 for both the ALXN1210 and 
eculizumab treatment groups and the randomization strata. A difference in the percentage of 
patients achieving TA in the 2 treatment groups will be calculated between ALXN1210 and 
eculizumab treatment groups, along with a 95% CI for the difference. The difference between the 
ALXN1210 and eculizumab treatment groups will be computed as a weighted combination of 
the differences between the ALXN1210 and eculizumab treatment groups within stratification 
groups (using Mantel-Haenszel). The 95% CI for the difference between ALXN1210 and 
eculizumab treatment groups will be calculated using the stratified Newcombe confidence 
interval method. 
LDH-N will be analyzed using a generalized estimating equation (GEE) approach which 
accounts for the repeated measures of LDH-N at each visit (Liang, 1986). The GEE approach 
provides odds ratios and CIs of treatment effect while controlling for the correlation between 
visits for a given patient and other baseline factors. LDH-N from Day 29 through Day 183 will 

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be used as the dependent variable and an indicator variable for treatment, history of transfusion 
(as a categorical variable based on the stratification factor levels), and baseline LDH level (as a 
continuous variable) will be included in the model as explanatory variables. The within-patient 
correlation will assume a first-order autoregressive structure which assumes the highest 
correlation is between visits that are closest in time. Day 29 is the first scheduled assessment 
after initiation of maintenance dosing, and experience with eculizumab and Phase 1b/2 
ALXN1210 data demonstrate near maximal suppression of LDH by 4 weeks of treatment. 
Results from the model will be presented as odds ratios with 95% confidence intervals.     
In order to conclude ALXN1210 is noninferior to eculizumab, both coprimary endpoints 
individually need to demonstrate noninferiority. If the lower-bound of the 95% CI for the 
difference (ALXN1210-eculizumab) is greater than the NIM of -20% for TA and the lower-
bound of the 95% CI for the odds ratio of ALXN1210 compared to eculizumab is greater than 
the NIM of 0.39 for LDH-N, then ALXN1210 treatment will be concluded to be noninferior to 
eculizumab.  
14.8.2. 
Key Secondary Efficacy Analyses 
The 4 key secondary efficacy endpoints will be summarized by randomization strata and by 
treatment group at baseline and at the study visits where these assessments are collected during 
the 26-week randomized treatment period. Change in FACIT-Fatigue (and percent change in 
LDH) from baseline to Week 26 will be analyzed using a mixed model for repeated measures 
(MMRM; Mallinckrodt, 2001, Mallinckrodt, 2004) with the fixed, categorical effects of 
treatment, the stratification randomization indicators of transfusion history (0, 1 to 14, or > 14 
units of pRBCs in the 1 year prior to first dose of study drug) and screening LDH levels (1.5 to 
< 3 × ULN or ≥ 3 × ULN), study visit and study visit by treatment group interaction as well as 
the continuous, fixed covariate of baseline FACIT-Fatigue (or LDH). For percent change in 
LDH, the baseline LDH level as a continuous variable will be included. The Kenward-Roger 
approximation will be used to estimate denominator degrees of freedom. A difference between 
the ALXN1210 and eculizumab treatment groups along with a 2-sided 95% CI will be 
calculated. 
For breakthrough hemolysis and stabilized hemoglobin, the same approach used for TA will be 
employed. These key secondary endpoints will be tested in a hierarchical manner provided that 
noninferiority was declared for the coprimary endpoints.  
When performing the analyses for the key secondary efficacy endpoints, a closed-testing 
procedure will be used so that the lack of significance of a test precludes assessment of 
subsequent tests. Estimates and CIs will be computed for all these key secondary efficacy 
endpoints irrespective of whether a lack of significance of a test precludes assessment of 
subsequent tests. 
1. If the upper bound of the 95% CI for the difference between the ALXN1210 and 
eculizumab treatment groups in the percentage change from Baseline to Week 26 in 
LDH is less than the NIM of 20%, then ALXN1210 will be declared noninferior for 
this parameter and the next parameter will be tested. 
2. If the lower bound of the 95% CI for the difference between the ALXN1210 and 
eculizumab treatment groups in change from baseline in FACIT-Fatigue is greater 

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than the NIM of -5, then ALXN1210 will be declared noninferior for this parameter 
and the next parameter will be tested. 
3. If the upper bound of the 95% CI for the difference between the ALXN1210 and 
eculizumab treatment groups in the proportion of patients with breakthrough 
hemolysis is less than the NIM of 20%, then ALXN1210 will be declared noninferior 
for this parameter and the next parameter will be tested. 
4. If the lower bound of the 95% CI for the difference between the ALXN1210 and 
eculizumab treatment groups in the proportion of patients with stabilized hemoglobin 
is greater than the NIM of -20%, then ALXN1210 will be declared noninferior for 
this parameter. 
If noninferiority is established for all key secondary endpoints, then superiority will be assessed 
using a closed-testing procedure with the following order and using a 2-sided 0.05 test for each 
parameter: 
5. Proportion of patients with breakthrough hemolysis through Day 183 (Week 26) 
6. Percentage change from baseline to Day 183 (Week 26) in LDH 
7. Hemolysis as directly measured by LDH-N from Day 29 through Day183 (Week 26) 
8. Change from baseline to Day 183 (Week 26) in FACIT-Fatigue 
9. Proportion of patients with stabilized hemoglobin through Day 183 (Week 26) 
10. Transfusion avoidance 
Due to the hierarchical testing order being prespecified, no adjustment of the type I error is 
required. 
14.8.3. 
Other Secondary Efficacy Analyses 
Changes from baseline in EORTC-QLQ-C30 will be summarized by treatment group at baseline 
and at the study visits where these assessments are collected (Section 7.3). Shifts from baseline 
in clinical manifestations of PNH will be summarized by treatment group and at the study visits 
where these assessments are collected. The number of any treatment-emergent MAVEs (n) and 
number of patients with events (n, %) will be displayed by treatment group. Total number of 
units of pRBCs transfused during treatment will be summarized by treatment group. Kaplan-
Meier curves for both treatment groups and estimates of time to first occurrence of LDH-N since 
first study drug will be produced. 
No statistical inference of these parameters is planned. 
14.9. 
Safety Analyses 
All safety analyses will be performed for the Safety set, defined as all patients who receive at 
least 1 dose of ALXN1210 or eculizumab. Safety results will be reported by treatment group. 

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14.9.1. 
Adverse Events 
The following definitions will be used for AEs: 
• Pretreatment AEs: Any AE that starts after providing informed consent, but before 
the first infusion of study drug 
• Treatment-emergent adverse event (TEAE): Any AE that starts during or after the 
first infusion of study drug. 
• Treatment-emergent SAE: A TEAE that is serious (refer to 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. 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. 
14.9.2. 
Physical Examination and Vital Signs 
Adverse changes from Baseline in physical examination findings will be classified as AEs and 
analyzed accordingly.  
Vital signs will be summarized descriptively at Baseline and postbaseline time points and for 
changes from Baseline by treatment group. 
By-patient data listings will be provided. 
14.9.3. 
Clinical Laboratory Tests 
Changes in clinical chemistry, hematology, and urinalysis results from Baseline to postbaseline 
study time points will be summarized descriptively by treatment group. Shift tables over time 
will be presented for all central laboratory values, where applicable, using normal, low, or high 
based on normal range values. Listings of patients with abnormal results will be provided. 
14.9.4. 
Electrocardiograms 
By-patient data listings of ECG parameters will be provided. Changes from baseline in 
electrocardiogram intervals (PR, RR, QT, and QTcF) will be provided by treatment group. QT 
interval will be corrected for heart rate using Fridericia’s formula (QTcF).  
14.9.5. 
Immunogenicity 
Abnormal immunogenicity findings, including the incidence and titers for ADAs to ALXN1210 
or eculizumab, will be summarized in tabular format by treatment group. The proportion of 
patients ever positive and the proportion of patients always negative may be explored. 

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14.10. 
Pharmacokinetic/Pharmacodynamic Analyses 
Individual serum concentration data for all patients who receive at least 1 dose of study drug (ie, 
ALXN1210 or eculizumab) and who have evaluable PK data will be used to derive PK 
parameters for ALXN1210 and eculizumab. 
Graphs of mean serum concentration-time profiles will be constructed. Graphs of serum 
concentration-time profiles for individual patients may also be provided. Actual dose 
administration and sampling times will be used for all calculations. Descriptive statistics will be 
calculated for serum concentration data at each sampling time, as appropriate. Assessment of 
population-PK may be considered using data from this study or in combination with data from 
other studies. 
PD analyses will be performed for all patients who receive at least 1 dose of ALXN1210 or 
eculizumab and who have evaluable PD data.  
Descriptive statistics will be presented for all ALXN1210 and eculizumab PD endpoints at each 
sampling time (Section 7.3). The PD effects of ALXN1210 and eculizumab administered IV will 
be evaluated by assessing the absolute values and changes and percentage changes from baseline 
in total and free C5 serum concentrations and cRBC hemolysis over time, as appropriate. 
Assessments of ALXN1210 PK/PD relationships may be explored using data from this study or 
in combination with data from other studies.  
14.11. 
Analysis of Data in the Roll-Over Cohort 
A maximum number of approximately 56 patients may roll over from other ongoing studies of 
ALXN1210 IV in patients with PNH into the Extension Period of Study ALXN1210-PNH-301. 
Analysis of data from patients who are rolled over from other ongoing ALXN1210 IV PNH 
studies will be performed as a separate cohort. The long-term safety will be evaluated by 
incidence of TEAEs and SAEs, laboratory assessments, and proportion of patients who develop 
ADA. The analyses will be performed on the Roll-over Safety Set defined as all patients who 
receive at least 1 ALXN1210 dose after roll over. 
TEAEs are defined as AEs with start dates and start times on or after the date and time of the 
first ALXN1210 dose after the roll over to ALXN1210-PNH-301. 
Similar to the original Study ALXN1210-PNH-301 Cohort, 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 the latest version of MedDRA, and will be 
summarized by SOC and PT. 
Clinical laboratory values and their changes from baseline will be summarized over time by visit.  
Vital signs, ECGs, and proportion of ADA-positive patients will be summarized at each study 
visit. Other assessments, such as EORTC-QLQ-C30 and FACIT-Fatigue will be summarized at 
each study visit. All endpoints will be presented in listings. 
The baseline for the roll-over patients is defined as the last measurement prior to the 1st infusion 
of study drug after roll over. 

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Details of the statistical analyses described above will be included in the SAP before study 
completion. A summary of long-term safety in the Roll-over Cohort will be included in the final 
CSR. 
14.12. 
Other Statistical Issues 
14.12.1. 
Missing or Invalid Data 
If a Day 1 assessment is missing, the Screening assessment will be used as the Baseline 
assessment.  
Missing data for QoL instruments will be handled as specified in the instructions for each 
instrument. 

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15. 
INFORMED CONSENT, ETHICAL REVIEW, AND 
REGULATORY CONSIDERATIONS 
15.1. 
Informed Consent 
The Investigator or designee is responsible for ensuring that the patient 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 consent given by patients or 
their legal representatives. 
15.2. 
Safety Review  
This study will be monitored by an Alexion Safety Management Team (SMT). The SMT is a 
multidisciplinary team responsible for safety that meets monthly and, if needed, on an ad-hoc 
basis. The team is composed of Alexion subject matter experts involved in the studies (eg, 
Medical Monitors/Global Medical Leads, Global Safety Leads). The objective of SMT review 
meetings is to ensure that emergent potential important safety concerns across all ALXN1210 
clinical studies are reviewed and evaluated and to make recommendations on continuing study 
drug administration or termination of the studies.  
15.3. 
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. 
15.4. 
Regulatory Considerations 
This study will be conducted in accordance with: 
• 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 
• The ICH GCP Guideline [E6] 

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• 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. 
15.4.1. 
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. 
15.5. 
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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16. 
LIST OF REFERENCES 
Borowitz MJ, Craig FE, DiGiuseppe JA, et al. Guidelines for the diagnosis and monitoring of 
paroxysmal nocturnal hemoglobinuria and related disorders by flow cytometry. Cytometry 
Part B. 2010;78B:211-230. 
Brodsky RA. Complement in hemolytic anemia. Blood. 2015;126:2459-2465. 
Brodsky RA. Paroxysmal nocturnal hemoglobinuria. Blood. 2014;124(18):2804-2711. 
Brodsky RA, Young NS, Antonioli E, et al. Multicenter phase 3 study of the complement 
inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria. 
Blood. 2008;111(4):1840-1847. 
Canalejo K, Cervantes NR, Felippo M, Sarandria C, Aixala M. Paroxysmal nocturnal 
haemoglobinuria. Experience over a 10 years period. Int J Lab Hemat. 2013;36(2):1213-1221. 
Dale J, Myhre E. Lactate dehydrogenase and mechanical trauma of erythrocytes. Acta Med 
Scand. 1972;191(1-2):133-136. 
Hill A, Kelly RJ, Hillmen, P. Thrombosis in paroxysmal nocturnal hemoglobinuria. Blood. 
2013;121:4985-4996. 
Hill A, Kelly RJ, Kulasekararaj AG, et al. Eculizumab in paroxysmal nocturnal hemoglobinuria 
(PNH): a report of all 153 patients treated in the UK [abstract]. Poster presented at American 
Society of Hematology (ASH) Annual Meeting, December 7-10, 2012a. Atlanta, Georgia. 
Hill A, Sapsford RJ, Scally A, et al. Under-recognized complications in patients with paroxysmal 
nocturnal haemoglobinuria: raised pulmonary pressure and reduced right ventricular function. Br 
J Haematol. 2012b;158:409-414. 
Hillmen P, Elebute M, Kelly R, et al. Long-term effect of the complement inhibitor eculizumab 
on kidney function in patients with paroxysmal nocturnal hemoglobinuria. Am J Hematol. 
2010;85(8):553-559. Erratum in Am J Hematol. 2010;85(11):911. 
Hillmen P, Young NS, Schubert J, et al. The complement inhibitor eculizumab in paroxysmal 
nocturnal hemoglobinuria. N Engl J Med. 2006;355:1233-1243. 
Lee JW, Jang JH, Kim JS, et al. Clinical signs and symptoms associated with increased risk for 
thrombosis in patients with paroxysmal nocturnal hemoglobinuria from a Korean Registry. Int J 
Hematol. 2013;97:749-757. 
Liang K-Y, Zeger SL. Longitudinal data analysis using generalized linear methods. Biometrika. 
1986;73(1):13-22. 
Mallinckrodt CH, Clark WS, David SR. Accounting for dropout bias using mixed-effects 
models. J Biopharm Stat. 2001;11:9-21. 
Mallinckrodt CH, Kaiser CJ, Watkin JG, Molenberghs G, Carroll RJ. The effect of correlation 
structure on treatment contrasts estimated from incomplete clinical trial data with likelihood-
based repeated measures compared with last observation carried forward ANOVA. Clinical 
Trials. 2004;1:477–489. 
Matis LA, Rollins SA. Complement-specific antibodies: designing novel anti-inflammatories. 
Nat Med. 1995;1:839–842. 

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Ng T-H. Noninferiority hypotheses and choice of noninferiority margin. Statist Med. 
2008;27:5392-5406. 
Parker C, Omine M, Richards S, et al. Diagnosis and management of paroxysmal nocturnal 
hemoglobinuria. Blood. 2005;106(12):3699-3709. 
Prodinger WM, Wurzner R, Erdei A, Dierich MP. Complement. In: Paul WE, editor. 
Fundamental immunology (4th ed). Philadelphia: Lippincott-Raven Publishers; 1999. P967-995. 
Sampson HA, Munoz-Furlong A, Campbell RL, 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):373-380. 
Socie G, Mary J-Y, de Gramont A, et al. Paroxysmal nocturnal hemoglobinuria: long term 
follow-up and prognostic factors. Lancet. 1996;348:573-577. 

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17. 
APPENDICES 

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APPENDIX A. 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 or eculizumab 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 electronic case 
report form (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 the CTCAE v4.03 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 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 

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discontinuation of study drug should undergo all scheduled safety, PK, and PD evaluations 
required by the protocol. 
If anaphylaxis occurs according to the criteria listed below, then administration of subcutaneous 
epinephrine (1/1000, 0.3 mL 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.  
 
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 B. FACIT-FATIGUE SUBSCALE VERSION 4 
 

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APPENDIX C. EORTC QUALITY OF LIFE QUESTIONNAIRE (EORTC 
QLQ-C30) 
 
 
 

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APPENDIX D. PROTOCOL LABORATORY TESTS 
 
Hematology 
Free hemoglobin 
Haptoglobin 
Hematocrit 
Hemoglobin 
Mean corpuscular hemoglobin 
Platelet count  
RBC count  
RBC distribution width 
RBC mean corpuscular volume 
Reticulocyte count 
WBC count  
WBC differential 
 
Coagulation Panel 
D-dimer 
International normalized ratio 
Partial thromboplastin time 
Prothrombin time 
 
Urinalysis 
Albumin 
Appearance 
Bilirubin 
Blood 
Color 
Creatinine 
Glucose 
Ketone 
Nitrite 
pH 
Protein 
Specific gravity 
Urobilinogen 
Clinical Chemistry 
Alanine aminotransferase 
Albumin 
Alkaline phosphatase 
Aspartate aminotransferase 
Bicarbonate 
Blood urea nitrogen 
Calcium 
Chloride 
C-reactive protein 
Creatinine 
Gamma-glutamyltransferase 
Glucose 
Lactate dehydrogenase 
Magnesium 
Phosphorus 
Potassium 
Sodium 
Total bilirubin (direct and indirect) 
Total protein 
Uric acid 
 
Virus Serology 
HIV-1 
HIV-2 
 
Other 
Antidrug antibody 
Beta human chorionic gonadotropin (females of 
childbearing potential only) 
Chicken RBC assay 
Free and total C5 
Pharmacokinetic assay 
PNH clone size  
Serum follicle-stimulating hormone (postmenopausal 
females only) 
Abbreviations: HIV-1 = human immunodeficiency virus type 1; HIV-2 = human immunodeficiency virus type 2; 
PNH = paroxysmal nocturnal hemoglobinuria; RBC = red blood cell; WBC = white blood cell