Phase 4, Single-Arm Study of Ravulizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Currently Treated With High-Dose Eculizumab
Phase: PHASE4
Conditions: Paroxysmal Nocturnal Hemoglobinuria
Sponsor: Alexion Pharmaceuticals, Inc.

NCT04320602

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 2 of 82 
Alexion Confidential 
INVESTIGATOR’S AGREEMENT 
 
I have read the study protocol and agree to conduct the study in accordance with this protocol, all 
applicable government regulations, the principles of the ICH E6 Guidelines for Good Clinical 
Practice, and the principles of the World Medical Association Declaration of Helsinki. I also 
agree to maintain the confidentiality of all information received or developed in connection with 
this protocol. 
 
 
 
 
 
____________________________________ 
Printed Name of Investigator 
 
_____________________________________ 
Signature of Investigator 
 
_______________ 
Date 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 3 of 82 
Alexion Confidential 
PROTOCOL AMENDMENT SUMMARY OF CHANGES  
This summary of changes document has been prepared to indicate the major changes made to 
Protocol ALXN1210-PNH-401, Amendment 3.0. 
Amendment 3 (07 May 2021) 
This amendment is considered to be non-substantial based on the criteria set forth in Article 
10(a) of Directive 2001/20/EC of the European Parliament and the Council of the European 
Union. 
Other changes implemented through this Amendment constitute minor editorial corrections and 
fixing of inconsistencies. 
Overall Rationale for the Amendment: 
The main rationale for this Amendment is to include COVID-19 vaccine risk assessment. 
Section # and Name 
Description of Change 
Brief Rationale 
Section 1.1 Synopsis  
Text regarding ravulizumab dosing 
language around home visits in 
Synopsis updated to match Section 4.1.  
To clarify and make information 
consistent within the protocol.  
Section 1.3 Schedule of 
Activities Table 1 
Note added to clarify that all study 
assessments for a given study day are 
to be completed on the same day. 
Additionally, note added to clarify that 
PD sampling is measurement of serum 
free C5 and total C5 concentration. 
Added for clarity.  
Section 9.4.5 Prior and 
Concomitant Medication 
Text updated to clarify use of 
medication 28 days prior to start of 
Screening.  
To clarify and make information 
consistent within the protocol. 
Section 10.3 Appendix 3 
Adverse Events: Definitions 
and Procedures for Recording, 
Evaluating, Follow-up, and 
Reporting 
Deleted text pertaining to reporting of 
serious adverse events 
Safety Reporting will not be done via 
the RAVE Electronic Safety 
Gateway in this study as RAVE 
Classic is being used, which does not 
have this feature. 
Section 10.7 COVID-19 
Vaccine Risk Assessment 
COVID-19 vaccines risk assessment 
language included.  
Section newly added to provide 
potential risks identified and 
mitigation measures put in place in 
light of the COVID-19 vaccination 
rollout. 
 
 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 4 of 82 
Alexion Confidential 
TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
INVESTIGATOR’S AGREEMENT ...............................................................................................2 
PROTOCOL AMENDMENT SUMMARY OF CHANGES ..........................................................3 
TABLE OF CONTENTS .................................................................................................................4 
LIST OF TABLES ...........................................................................................................................8 
1. 
PROTOCOL SUMMARY ............................................................................................9 
1.1. 
Synopsis ........................................................................................................................9 
1.2. 
Schema ........................................................................................................................11 
1.3. 
Schedules of Activities ...............................................................................................12 
2. 
INTRODUCTION ......................................................................................................19 
2.1. 
Study Rationale ...........................................................................................................19 
2.2. 
Background .................................................................................................................19 
2.3. 
Benefit/Risk Assessment ............................................................................................20 
2.3.1. 
Risk Assessment .........................................................................................................20 
2.3.2. 
Benefit Assessment .....................................................................................................22 
2.3.3. 
Overall Benefit/Risk Conclusion ................................................................................22 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................23 
4. 
STUDY DESIGN .......................................................................................................24 
4.1. 
Overall Design ............................................................................................................24 
4.2. 
Scientific Rationale for Study Design ........................................................................24 
4.3. 
Justification for Dose ..................................................................................................24 
4.4. 
End of Study Definition ..............................................................................................25 
5. 
STUDY POPULATION .............................................................................................26 
5.1. 
Inclusion Criteria ........................................................................................................26 
5.2. 
Exclusion Criteria .......................................................................................................27 
5.3. 
Lifestyle Considerations .............................................................................................28 
5.4. 
Screen Failures ............................................................................................................28 
6. 
STUDY TREATMENTS ............................................................................................30 
6.1. 
Study Drug(s) Administered .......................................................................................30 
6.1.1. 
Ravulizumab Dosing ..................................................................................................30 
6.2. 
Preparation/Handling/Storage/Accountability ............................................................31 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 5 of 82 
Alexion Confidential 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................................32 
6.4. 
Study Drug Compliance .............................................................................................32 
6.5. 
Concomitant Therapy .................................................................................................32 
6.5.1. 
Meningococcal Vaccination .......................................................................................33 
6.5.2. 
Rescue Medicine .........................................................................................................34 
6.6. 
Dose Modification ......................................................................................................34 
6.6.1. 
Supplemental Dosing ..................................................................................................34 
6.6.2. 
Permitted Change in Dosing Interval .........................................................................34 
6.7. 
Intervention after the End of the Study .......................................................................34 
7. 
DISCONTINUATION OF STUDY DRUG AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................36 
7.1. 
Discontinuation of Study Drug ...................................................................................36 
7.2. 
Participant Discontinuation/Withdrawal from the Study ...........................................36 
7.3. 
Lost to Follow up ........................................................................................................37 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................38 
8.1. 
Efficacy Assessments .................................................................................................38 
8.1.1. 
Transfusions ................................................................................................................38 
8.1.2. 
Lactate Dehydrogenase and Other Disease-Related Laboratory Parameters .............38 
8.1.3. 
Paroxysmal Nocturnal Hemoglobinuria Symptomatology .........................................39 
8.1.4. 
Major Adverse Vascular Events .................................................................................39 
8.2. 
Safety Assessments .....................................................................................................40 
8.2.1. 
Physical Examinations ................................................................................................40 
8.2.2. 
Vital Signs ..................................................................................................................40 
8.2.3. 
Electrocardiograms .....................................................................................................40 
8.2.4. 
Clinical Safety Laboratory Assessments ....................................................................40 
8.3. 
Adverse Events and Serious Adverse Events .............................................................41 
8.3.1. 
Time Period and Frequency for Collecting Adverse Event and Serious 
Adverse Event Information .........................................................................................41 
8.3.2. 
Method of Detecting AEs and SAEs ..........................................................................42 
8.3.3. 
Follow-up of AEs and SAEs .......................................................................................42 
8.3.4. 
Regulatory Reporting Requirements for SAEs ...........................................................42 
8.3.5. 
Pregnancy ...................................................................................................................42 
8.3.6. 
Adverse Events of Special Interest .............................................................................43 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 6 of 82 
Alexion Confidential 
8.4. 
Treatment of Overdose ...............................................................................................43 
8.5. 
Pharmacokinetics/Pharmacodynamics Sampling .......................................................44 
8.5.1. 
Sample Collection During the Screening Period ........................................................44 
8.5.2. 
Sample Collection during Confirmation Visit Through Follow-up ...........................44 
8.6. 
Pharmacodynamics .....................................................................................................44 
8.7. 
Genetics ......................................................................................................................44 
8.8. 
Biomarkers ..................................................................................................................44 
8.9. 
Immunogenicity Assessments ....................................................................................44 
8.10. 
Patient-Reported Symptoms and Health Resource Utilization questionnaires ...........45 
8.11. 
Visits during COVID-19 Pandemic ............................................................................45 
9. 
STATISTICAL CONSIDERATIONS .......................................................................46 
9.1. 
Statistical Hypotheses .................................................................................................46 
9.2. 
Sample Size Determination ........................................................................................46 
9.3. 
Populations for Analyses ............................................................................................46 
9.4. 
Statistical Analyses .....................................................................................................46 
9.4.1. 
Efficacy Analyses .......................................................................................................47 
9.4.2. 
Safety Analyses ..........................................................................................................47 
9.4.2.1. 
Analysis of Adverse Events ........................................................................................47 
9.4.2.2. 
Analysis of Clinical Laboratory Parameters, Vital Sign Measurements and 
Electrocardiogram Parameters ....................................................................................47 
9.4.3. 
Demographics and Baseline Characteristics ...............................................................47 
9.4.4. 
Participant Disposition ................................................................................................48 
9.4.5. 
Prior and Concomitant Medications ...........................................................................48 
9.4.6. 
Pharmacokinetics and Pharmacodynamics Analyses .................................................48 
9.5. 
Interim Analyses .........................................................................................................48 
9.6. 
Data Monitoring Committee .......................................................................................48 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................49 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations ....................49 
10.1.1. 
Regulatory and Ethical Considerations ......................................................................49 
10.1.2. 
Financial Disclosure ...................................................................................................49 
10.1.3. 
Informed Consent Process ..........................................................................................50 
10.1.4. 
Data Protection ...........................................................................................................50 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 7 of 82 
Alexion Confidential 
10.1.5. 
Dissemination of Clinical Study Data ........................................................................50 
10.1.6. 
Data Quality Assurance ..............................................................................................50 
10.1.7. 
Source Documents ......................................................................................................51 
10.1.8. 
Study and Site Start and Closure ................................................................................51 
10.1.9. 
Publication Policy .......................................................................................................52 
10.2. 
Appendix 2: Clinical Laboratory Tests .......................................................................53 
10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ........................................................................55 
10.4. 
Appendix 4: Pregnancy Information ..........................................................................58 
10.4.1. 
Definitions ..................................................................................................................58 
10.4.1.1. 
Woman of Childbearing Potential ..............................................................................58 
10.4.1.2. 
Women in the following categories are not considered WOCBP ..............................58 
10.4.2. 
Contraception Guidance .............................................................................................58 
10.4.3. 
Pregnancy Testing ......................................................................................................60 
10.4.4. 
Collection of Pregnancy Information .........................................................................60 
10.4.4.1. 
Male Participants with Partners who Become Pregnant .............................................60 
10.4.4.2. 
Female Participants who Become Pregnant ...............................................................60 
10.5. 
Appendix 5: Questionnaires PNH Symptoms and Health Resource 
Utilization ...................................................................................................................62 
10.5.1. 
PNH Patient-Reported Symptoms questionnaire ........................................................62 
10.5.2. 
Health Resource Utilization questionnaire .................................................................74 
10.6. 
Appendix 6: COVID-19 Risk Assessment .................................................................75 
10.7. 
Appendix 7: COVID-19 Vaccine Risk Assessment ...................................................77 
10.8. 
Appendix 8: Abbreviations .........................................................................................78 
10.9. 
Appendix 9: Protocol Amendment History ................................................................80 
11. 
REFERENCES ...........................................................................................................81 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 8 of 82 
Alexion Confidential 
LIST OF TABLES 
Table 1: 
Schedule of Study Visits and Assessments: Screening Visit Through 
Confirmation Visit ......................................................................................................12 
Table 2: 
Schedule of Study Visits and Assessments: Confirmation Visit Through 
Follow-up ....................................................................................................................14 
Table 3: 
Schedule of Study Visits and Assessments: q6w Dosing ...........................................17 
Table 4: 
Dosing Reference Chart for Ravulizumab Dose Preparation .....................................31 
Table 5: 
Dosing Guidance for Patients with Breakthrough Hemolysis ....................................34 
Table 6: 
Protocol-Required Safety Laboratory Assessments ...................................................54 
Table 7: 
Potential Risks and Mitigation Measures due to COVID-19 .....................................75 
Table 8: 
Potential Risks and Mitigation Measures due to COVID-19 Vaccine .......................77 
 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 9 of 82 
Alexion Confidential 
1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: 
Phase 4, Single-Arm Study of Ravulizumab in Adult Participants with Paroxysmal Nocturnal 
Hemoglobinuria Currently Treated with High-Dose Eculizumab 
Short Title: 
Ravulizumab in Adult Participants with Paroxysmal Nocturnal Hemoglobinuria Currently 
Treated with High-Dose Eculizumab 
Rationale: 
To assess the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of 
ravulizumab in participants who are prescribed and are receiving a higher than approved dose of 
Soliris® (eculizumab) to treat paroxysmal nocturnal hemoglobinuria (PNH) 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
 
• To evaluate the prevalence of free complement 
component 5 (C5)-associated breakthrough 
hemolysis (BTH) in participants on high-dose 
eculizumab who switch to ravulizumab (per 
approved dose regimen) 
• Proportion of participants who experience free C5-
associated BTH through Day 351. Free C5-
associated BTH is defined as BTH concurrent with 
free C5 concentrations ≥ 0.5 μg/mL. BTH is 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], MAVE, including 
thrombosis, dysphagia, or erectile dysfunction) in 
the presence of elevated LDH ≥ 2 × ULN. 
Secondary 
 
• To evaluate efficacy by other measures in 
participants on high-dose eculizumab who switch to 
ravulizumab 
• Proportion of participants who experience BTH 
through Day 351 
• Hemolysis as directly measured by LDH-PCHG 
from baseline to Day 351  
• Proportion of participants who receive a transfusion, 
from baseline to Day 351  
• Proportion of participants with stabilized 
hemoglobin, defined as avoidance of a ≥ 2 g/dL 
decrease in hemoglobin level from baseline in the 
absence of transfusion from baseline to Day 351  

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 10 of 82 
Alexion Confidential 
Objectives 
Endpoints 
Exploratory 
 
 
To evaluate Patient-Reported Outcomes over time for 
those who switch to Ravulizumab from high-dose 
eculizumab 
• Patient-reported PNH Symptoms (PRS) at baseline, 
Day 183 and Day 351 
• Healthcare Resource Utilization (HRU) at baseline, 
Day 183 and Day 351 
Safety 
 
• To evaluate the safety and tolerability of 
ravulizumab in participants on high-dose eculizumab 
who switch to ravulizumab 
• Physical examinations, vital signs, and laboratory 
assessment results, and incidence of adverse events 
(AEs) and serious adverse events (SAEs) 
• Proportion of participants who develop 
(ravulizumab) antidrug antibodies (ADAs) 
PK/PD  
 
• To characterize the PK/PD of ravulizumab in 
participants on high-dose eculizumab who switch to 
ravulizumab 
• Change in serum ravulizumab concentration over 
time 
• Change in serum free and total C5 concentrations 
over time 
Abbreviations: ADA = antidrug antibody; AE – adverse event; BTH = breakthrough hemolysis; C5 = complement 
component C5; LDH-PCHG = lactate dehydrogenase percent change; MAVE = major adverse vascular event; 
PD = pharmacodynamic; PK = pharmacokinetic; SAE = serious adverse event 
Overall Design 
This is a Phase 4, single-arm, open-label study to evaluate the efficacy and safety of ravulizumab 
in adult participants with PNH who switch from eculizumab 1200 mg every 2 weeks (q2w; ie, 
above the recommended dose) to ravulizumab (at the recommended dose). 
The study will consist of a Screening Period of approximately 3 months and a Treatment Period 
of 351 days. All participants must provide informed consent prior to any procedures at the first 
Screening visit. All participants must have been prescribed and are receiving a stable dose of 
eculizumab 1200 mg q2w for at least 3 months prior to screening. During Screening, eculizumab 
may be administered at the participant’s home at the discretion of the Investigator. During 
screening, participants will continue to receive eculizumab 1200 mg q2w, and blood samples 
will be collected for PD parameters and lactate dehydrogenase (LDH) levels. 
Eligible participants will receive a loading dose of ravulizumab on Day 1, followed by 
maintenance doses on Day 15 and every 8 weeks (q8w), administered by intravenous (IV) 
infusion. Ravulizumab loading and maintenance doses will be based on participants’ body 
weight per approved dose regimen. Ravulizumab dosing will be administered in the clinic by a 
trained member of the site study team; patients may have the option to receive study drug 
remotely at a medical facility that is located near the patient’s home or at the patient’s home by a 
qualified healthcare personnel. 
The schedule of study visits and assessments is shown in Section 1.3. 
An interim analysis will be performed on Day 183. 
Disclosure Statement: This is a single-arm, open-label study. 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 11 of 82 
Alexion Confidential 
Number of Participants: 
Approximately 20 participants will be enrolled. 
Treatment Groups and Duration: 
This single-arm study will consist of a 3-month Screening Period and a 351-day Treatment 
Period. All eligible participants will receive ravulizumab according to approved dose regimen 
during the Treatment Period. 
Data Monitoring Committee: No 
1.2. 
Schema 
 
 
a. Ravulizumab loading dose is 2400 mg for patients weighing ≥ 40 to < 60 kg, 2700 mg for patients weighing ≥ 60 
to < 100 kg, or 3000 for participants weighing ≥ 100 kg. 
b. Ravulizumab maintenance dose is 3000 mg for patients weighing ≥ 40 to < 60 kg, 3300 mg for patients weighing 
≥ 60 to < 100 kg, or 3600 mg for participants weighing ≥ 100 kg. 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 12 of 82 
Alexion Confidential 
1.3. 
Schedules of Activities 
Table 1: 
Schedule of Study Visits and Assessments: Screening Visit Through Confirmation Visit 
Period 
Screening 
Notes 
Study Day 
-85 
-71 
-57 
-43 
-29 
-15 
 
Window (day) 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
All study assessments for a given Study Day must be 
completed on the same day as the study visit. The 
window of ± 2 days is relative to Day 1 and allows for 
the Study Visit to occur ± 2 days from the indicated 
study day 
Informed consent 
X 
 
 
 
 
 
 
Inclusion and exclusion criteria 
X 
 
 
 
 
 
 
Confirmation of 
meningococcal vaccination 
X 
Refer to Section 6.5.1 for details 
Abbreviated physical 
examination 
X 
 
X 
 
X 
 
Refer to Section 8.2.1 for details 
Height 
X 
 
 
 
 
 
 
Weight 
X 
  
X 
  
X 
  
 
Medical history including PNH 
and eculizumab dosing history 
X 
 
 
 
 
 
 
Serum or urine pregnancy test  
X 
  
X 
  
X 
  
Refer to Section 8.3.5 for details. Serum pregnancy test at Day -85, 
Urine pregnancy test at all other visits 
HIV testing 
X 
 
 
 
 
 
 
Chemistry including LDH 
X 
 
X 
 
X 
 
Sample to be collected within 24 hours of or immediately prior to a 
scheduled dose of study drug (trough) and not from a heparinized line. 
Hematology including free 
hemoglobin and coagulation 
X 
 
X 
 
X 
 
Blood will be collected predose and not from a heparinized line. 
Urinalysis and urine chemistry 
X 
  
X 
  
X 
  
Urine will be collected predose on dosing days.  
Safety 12-lead ECG 
X 
 
 
 
 
 
Participants must be supine for approximately 5 to 10 minutes before 
ECG collection and remain supine but awake during ECG collection. 
Refer to Section 8.2.3 for details 
Vital signs 
X 
  
X 
  
X 
  
Will be measured after the participant has been resting for at least 5 
minutes. Refer to Section 8.2.2 for details 
PNH clone size 
X 
 
 
 
 
 
WBC (granulocyte and monocyte) and RBC clone size measured by 
high-sensitivity flow cytometry at Screening; RBC clone size only at 
Screening  
Record transfusions and 
transfusion parameters 
X 
X 
X 
X 
X 
X 
Transfusions given during and between visits will be recorded. This 
can be optionally performed by a phone call on Days -71, -43, and -15 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 13 of 82 
Alexion Confidential 
Table 1: 
Schedule of Study Visits and Assessments: Screening Visit Through Confirmation Visit 
Period 
Screening 
Notes 
Study Day 
-85 
-71 
-57 
-43 
-29 
-15 
 
Window (day) 
± 2 
± 2 
± 2 
± 2 
± 2 
± 2 
All study assessments for a given Study Day must be 
completed on the same day as the study visit. The 
window of ± 2 days is relative to Day 1 and allows for 
the Study Visit to occur ± 2 days from the indicated 
study day 
PNH symptomatology 
X 
X 
X 
X 
X 
X 
Investigator assessed and reported. Refer to Section 8.1.3 for details. 
This can be optionally performed by a phone call on Days -71, -43, and 
-15 
PD sampling 
 
 
X 
 
X 
 
PD sampling is measurement of serum free C5 and total C5 
concentration. Refer to Sections 8.5 and 8.6 for details 
Review safety card 
X 
X 
X 
X 
X 
X 
 
BTH 
←Monitor continuously→ 
If a BTH event occurs during the Screening Period, the participant will 
be ineligible for the study. To confirm BTH, LDH, PK, and PD 
samples will be collected and analyzed. If the suspected event of BTH 
does not occur at a scheduled visit, an unscheduled visit should occur 
for evaluation of the participant and collection of the required LDH, 
PK, and PD samples.  
Concomitant medications 
←Monitor continuously→ 
 
Adverse events 
←Monitor continuously→ 
 
Confirmation of eculizumab 
dose 
X 
X 
X 
X 
X 
X 
At the Investigator’s discretion and preference of the patient, 
eculizumab may be administered at the participant’s home (except at 
Visits -57 and -29) by a trained qualified staff member (Section 8)  
Abbreviations: ADA = antidrug antibody; AE = adverse event; BTH = breakthrough hemolysis; C5 = complement component C5; ECG = electrocardiogram; HIV = human 
immunodeficiency virus; LDH = lactate dehydrogenase; LDH-PCHG = lactate dehydrogenase percent change; PD = pharmacodynamic; PK = pharmacokinetic; RBC = red 
blood cell; SAE = serious adverse event; WBC = white blood cell. 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 14 of 82 
Alexion Confidential 
Table 2: 
Schedule of Study Visits and Assessments: Confirmation Visit Through Follow-up 
Period 
Confirmation 
Visit 
Evaluation Period 
Unscheduled 
Visits 
Follow-
up call 
Notes 
Study Day 
1 
15 
71 
127 
183 
239 
295 
351/ 
ET 
NA 
 
407 
 
Window (day) 
NA 
± 2 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
 
± 7 
 
Inclusion and 
exclusion criteria 
X 
 
 
 
 
 
 
 
 
 
LDH and hematologic criteria 
assessed  
Physical 
examination 
X 
 
 
 
 
 
 
X 
 
 
 
Abbreviated 
physical 
examination 
 
X 
X 
X 
X 
X 
X 
 
X 
 
Refer to Section 8.2.1 for details 
Weight 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Serum or urine 
pregnancy test  
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Refer to Section 8.3.5 for details. 
Serum pregnancy test at Day 1, and 
Day 351/ET.; Urine pregnancy test at 
all other visits 
Chemistry 
including LDH 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Sample to be collected within 24 hours 
of or immediately prior to a scheduled 
dose of study drug (trough) and not 
from a heparinized line. 
Hematology 
including free 
hemoglobin and 
coagulation 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Blood will be collected predose on 
dosing days and not from a 
heparinized line. 
Urinalysis and 
urine chemistry 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Urine will be collected predose on 
dosing days.  
Safety 12-lead 
ECG 
 
 
 
 
 
 
 
X 
 
 
Refer to Section 8.2.3 for details 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Will be measured after the participant 
has been resting for at least 5 minutes. 
Refer to Section 8.2.2 for details 
PNH clone size 
X 
 
 
X 
 
 
 
X 
 
 
WBC (granulocyte and monocyte) and 
RBC clone size measured by high-
sensitivity flow cytometry at Day 1; 
RBC clone size only at Day 127 and 
Day 351/ET 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 15 of 82 
Alexion Confidential 
Table 2: 
Schedule of Study Visits and Assessments: Confirmation Visit Through Follow-up 
Period 
Confirmation 
Visit 
Evaluation Period 
Unscheduled 
Visits 
Follow-
up call 
Notes 
Study Day 
1 
15 
71 
127 
183 
239 
295 
351/ 
ET 
NA 
 
407 
 
Window (day) 
NA 
± 2 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
 
± 7 
 
PRS and HRU 
X 
 
 
 
X 
 
 
X 
 
 
Questionnaires at the confirmation 
visit administered prior to first dosing 
of Ravulizumab. 
PRS completed by the participant 
Refer to Section 8.10 for details 
Record 
transfusions and 
transfusion 
parameters 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Transfusions given during and 
between visits will be recorded 
PNH 
symptomatology 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Investigator assessed and reported 
Refer to Section 8.1.3 for details 
PK/PD sampling 
X 
X 
X 
X 
X 
 
 
X 
X 
 
Refer to Section 8.5 and Section 8.6 
for details 
Immunogenicity 
(ADA) 
X 
 
X 
 
X 
 
 
X 
X 
 
Samples will be collected predose 
Review safety 
card 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
BTH 
←Monitor continuously→ 
 
If a suspected event of BTH occurs, 
LDH, PK, and PD samples will be 
collected and analyzed . If the 
suspected event of BTH does not 
occur at a scheduled visit, an 
unscheduled visit should occur for 
evaluation of the participant and 
collection of the required LDH, PK, 
and PD samples.  
Concomitant 
medications 
←Monitor continuously→ 
 
Adverse events 
←Monitor continuously→ 
 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 16 of 82 
Alexion Confidential 
Table 2: 
Schedule of Study Visits and Assessments: Confirmation Visit Through Follow-up 
Period 
Confirmation 
Visit 
Evaluation Period 
Unscheduled 
Visits 
Follow-
up call 
Notes 
Study Day 
1 
15 
71 
127 
183 
239 
295 
351/ 
ET 
NA 
 
407 
 
Window (day) 
NA 
± 2 
± 7 
± 7 
± 7 
± 7 
± 7 
± 7 
 
± 7 
 
Ravulizumab 
administration 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
The dose of ravulizumab is based on 
the participant’s last recorded study 
visit body weight as per approved dose 
regimen. Refer to Section 6.1.1  
At the Investigator’s discretion and in 
accordance with the local regulations, 
ravulizumab may be administered at 
the patient’s home or at a medical 
facility close to the patient's home by a 
qualified healthcare personnel (see 
Section 8.11).  
Abbreviations: ADA = antidrug antibody; AE = adverse event; BTH = breakthrough hemolysis; C5 = complement component C5; ECG = electrocardiogram; ET = early 
termination; LDH = lactate dehydrogenase; LDH-PCHG = lactate dehydrogenase percent change; NA = not applicable; PD = pharmacodynamic; PK = pharmacokinetic; 
RBC = red blood cell; SAE = serious adverse event; WBC = white blood cell. 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 17 of 82 
Alexion Confidential 
Table 3: 
Schedule of Study Visits and Assessments: q6w Dosing 
 
Starting 
Visit  
Example 
Visit  
EOS/ET 
Unscheduled 
visit 
Follow-
up call 
Notes 
Study Day 
q6w Day 1 
q6w Day 
43 
Day XX 
NA 
 
EOS/ET 
+ 56 days 
All subsequent q6w visits up to EOS/ET to follow 
the assessments shown in the example visit  
 
Window (day) 
NA 
± 7 
± 7 
 
± 7 
 
Physical 
examination 
 
 
X 
 
 
 
Abbreviated 
physical 
examination 
X 
X 
 
X 
 
Refer to Section 8.2.1 for details 
Weight 
X 
X 
X 
X 
 
 
Serum or urine 
pregnancy test  
X 
X 
X 
X 
 
Refer to Section 8.3.5 for details 
Chemistry 
including LDH 
X 
X 
X 
X 
 
Sample to be collected within 24 hours of or immediately prior to 
a scheduled dose of study drug (trough) and not from a 
heparinized line. 
Hematology 
including free 
hemoglobin and 
coagulation 
X 
X 
X 
X 
 
Blood will be collected predose on dosing days and not from a 
heparinized line. 
Urinalysis and 
urine chemistry 
X 
X 
X 
X 
 
Urine will be collected predose on dosing days.  
Safety 12-lead 
ECG 
X 
 
X 
 
 
Refer to Section 8.2.3 for details 
Vital signs 
X 
X 
X 
X 
 
Will be measured after the participant has been resting for at least 
5 minutes. Refer to Section 8.2.2 for details 
PNH clone size 
X 
X 
X 
 
 
WBC (granulocyte and monocyte) and RBC clone size measured 
by high-sensitivity flow cytometry at Day 1; RBC clone size only 
at Day 127 and Day 351/ET 
Record 
transfusions and 
transfusion 
parameters 
X 
X 
X 
X 
 
Transfusions given during and between visits will be recorded 
PNH 
symptomatology 
X 
X 
X 
X 
 
Investigator assessed and reported. Refer to Section 8.1.3 for 
details 
PK/PD sampling 
X 
X 
X 
X 
 
Refer to Section 8.5 and Section 8.6 for details 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 18 of 82 
Alexion Confidential 
Table 3: 
Schedule of Study Visits and Assessments: q6w Dosing 
 
Starting 
Visit  
Example 
Visit  
EOS/ET 
Unscheduled 
visit 
Follow-
up call 
Notes 
Study Day 
q6w Day 1 
q6w Day 
43 
Day XX 
NA 
 
EOS/ET 
+ 56 days 
All subsequent q6w visits up to EOS/ET to follow 
the assessments shown in the example visit  
 
Window (day) 
NA 
± 7 
± 7 
 
± 7 
 
Immunogenicity 
(ADA) 
X 
X 
X 
X 
 
Samples will be collected predose 
Review safety card 
X 
X 
X 
X 
 
 
BTH 
←Monitor continuously→ 
 
If a suspected event of BTH occurs, LDH, PK, and PD samples 
will be collected and analyzed. If the suspected event of BTH 
does not occur at a scheduled visit, an unscheduled visit should 
occur for evaluation of the participant and collection of the 
required LDH, PK, and PD samples.  
Concomitant 
medications 
←Monitor continuously→ 
 
Adverse events 
←Monitor continuously→ 
 
Ravulizumab 
administration 
X 
X 
 
X 
 
The dose of ravulizumab is based on the participant’s last 
recorded study visit body weight as per approved dose regimen. 
Refer to Section 6.1.1  
At the Investigator’s discretion and in accordance with the local 
regulations, ravulizumab may be administered at the 
patient’s home or at a medical facility close to the patient's 
home by a qualified healthcare personnel (see Section 8.11) 
 
Abbreviations: ADA = antidrug antibody; AE = adverse event; BTH = breakthrough hemolysis; C5 = complement component C5; ECG = electrocardiogram; ET = early 
termination; LDH = lactate dehydrogenase; LDH-PCHG = lactate dehydrogenase percent change; NA = not applicable; PD = pharmacodynamic; PK = pharmacokinetic; 
RBC = red blood cell; SAE = serious adverse event; WBC = white blood cell. 
 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 19 of 82 
Alexion Confidential 
2. 
INTRODUCTION 
2.1. 
Study Rationale 
Some patients are prescribed a higher dose of eculizumab than the approved dose in order to 
achieve complete blockade of complement component 5 (C5) (Kelly, 2008). The main purpose 
of this study is to provide clinical evidence that participants on high dose eculizumab can be 
switched to ravulizumab without a change in the benefit/risk profile. 
2.2. 
Background 
Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra-rare and life-threatening acquired 
hemolytic disorder caused by uncontrolled activation of the terminal complement pathway 
(Brodsky, 2014; 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 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 together result 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 (Brodsky, 2014; Hill, 2013). 
A substantial proportion of patients with PNH experience renal dysfunction and pulmonary 
hypertension (Hill, 2013; Hill, 2012; Hillmen, 2010). Patients also experience venous or arterial 
thrombosis in diverse sites, including the abdomen or central nervous system (Brodsky, 2014). 
Approved treatments for PNH include eculizumab and ravulizumab. Eculizumab and 
ravulizumab are humanized monoclonal antibodies (mAb) that specifically bind to the 
complement protein C5 with high affinity. They have no known off-target interactions with other 
proteins in vitro or in vivo. In addition, eculizumab and ravulizumab are 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 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 20 of 82 
Alexion Confidential 
attributes underlie the established safety and therapeutic efficacy profile of eculizumab and 
ravulizumab in the treatment of PNH, demonstrated in clinical studies and supported by 
subsequent postmarketing experience. 
Patients treated with eculizumab are required to receive maintenance infusions q2w. 
Ravulizumab 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), allowing for maintenance infusions every 8 weeks (q8w). 
Ravulizumab and eculizumab share > 99% sequence homology, as ravulizumab was derived 
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 ravulizumab for C5; the other two are in the Fc binding region which improves recycling of 
ravulizumab into the vascular space instead of degrading. These changes were specifically 
designed (and have subsequently been proven) to increase the half-life of ravulizumab 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 recommended eculizumab maintenance dose of 900 mg every 14 days is sufficient to 
maintain inhibition of hemolysis in most patients with PNH. However, approximately 11% to 
27% of patients experience BTH during treatment with the approved dose of eculizumab and 
require the dosing interval to be shortened to < 14 days or the dosage to be increased (Hill, 2005; 
Peffault de Latour, 2015). 
In this Phase 4 open-label study, the efficacy and safety of ravulizumab will be assessed in 
participants with PNH who are clinically stable, having been treated with eculizumab 1200 mg 
q2w for at least the past 3 months prior to study entry. The choice of study design is further 
discussed in Section 4.2. 
More information about the PK, mechanism of action, known and expected benefits, risks, and 
reasonably anticipated safety profile of ravulizumab may be found in the current edition of the 
Investigator’s Brochure (IB). 
2.3. 
Benefit/Risk Assessment 
2.3.1. 
Risk Assessment  
Risks of Clinical 
Significance 
Summary of Data/ 
Rationale for Risk 
Mitigation Strategy 
Identified Risk 
Meningococcal infection 
Complement C5 inhibition is known 
to increase the susceptibility to 
infections caused by Neisseria 
meningitidis. 
Participants must be vaccinated or 
revaccinated according to current 
national vaccination guidelines for 
vaccination use prior to or at the time of 
initiating dosing with complement 
inhibitors (eg, eculizumab or 
ravulizumab). 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 21 of 82 
Alexion Confidential 
Risks of Clinical 
Significance 
Summary of Data/ 
Rationale for Risk 
Mitigation Strategy 
Potential Risks 
Serious hemolysis after drug 
discontinuation 
This potential disease-associated risk 
is based on a theoretical possibility, 
associated with abrupt ravulizumab 
discontinuation, resulting in a so-
called rebound effect. Rebound effect 
is described for many biologicals but 
has not been observed in ravulizumab 
clinical trials. 
The effects are most likely not 
completely preventable, but their 
severity can be minimized by avoiding 
abrupt drug discontinuation. 
Participants who discontinue the drug 
will be followed up for 16 weeks if 
participants remain in the study. 
Serious infection 
This potential risk is a based on the 
mode of action of ravulizumab and 
experience with the use of eculizumab. 
Since the relevance of serious 
infection with ravulizumab therapy 
has not been confirmed in clinical 
trials, this remains a potential risk. 
Increased awareness of healthcare 
professionals and participant about the 
potential risk of serious Infection. 
Monitoring for signs and symptoms of 
serious infections will be conducted as 
part of routine safety assessments for 
this study. 
Malignancies and 
hematologic abnormalities 
The natural evolution of PNH disease 
makes PNH patients more prone to 
development of hematologic 
abnormalities or malignancies as 
approximately 30-70% of PNH 
patients eventually develop aplastic 
anemia or myelodysplastic syndrome. 
The potential role of ravulizumab in 
the risk of such abnormalities or 
malignancies (if any) is unknown 
Monitoring as part of routine safety 
assessments for this study. 
Immunogenicity  
Treatment with any therapeutic protein 
has the potential to induce an immune 
response. Potential clinical 
consequences may include severe 
hypersensitivity type reactions, 
decrease in efficacy and induction of 
autoimmunity, including antibodies to 
the endogenous form of the protein 
(Casadevall, 2002; Li, 2001). 
Protein therapies administered IV have 
the potential risk of causing local 
(infusion-site reactions) and systemic 
reactions (infusion-associated 
reactions). 
In the ALXN1210-PNH-103 and 
ALXN1210-PNH-201 studies, no 
participants have returned a positive 
ADA sample. ADA will be assessed. 
Monitoring for infusion reactions will 
be conducted as part of routine safety 
assessments for this study. 
Pregnancy 
exposure/lactation 
No studies of ravulizumab have been 
conducted in pregnant women. There 
are no data available on excretion of 
ravulizumab in breast milk. 
Pregnant or nursing female participants 
are excluded from the clinical trial. 
Participants enrolled in the study, and 
their spouses/partners, must use a 
highly effective or acceptable method 
of contraception for a period of 8 
months following the last dose of 
ravulizumab. Breastfeeding should be 
discontinued during treatment and up to 
8 months after treatment with 
ravulizumab. 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 22 of 82 
Alexion Confidential 
2.3.2. 
Benefit Assessment 
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; Socié, 1996). Chronic intravascular hemolysis due to continuous activation of 
the complement pathway leads to the release of free hemoglobin, NO 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, 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 dosing regimen for eculizumab for PNH involves 4 
weekly induction doses, followed by maintenance doses administered q2w 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 may be unable to comply with the treatment frequency of 
eculizumab. Practice survey research supports the assumption that less frequent infusions 
associated with ravulizumab will have a positive impact on daily life for patients and their 
caregivers. 
Ravulizumab (ALXN1210) is a recombinant, humanized mAb derived through minimal targeted 
engineering of eculizumab by introducing 4 unique amino acid substitutions. Ravulizumab 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. 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 LDH levels, a direct measure of hemolytic activity 
that is of comparable magnitude to that seen in studies of eculizumab. 
The benefit to this population includes less-frequent dosing which creates less burden on the 
patient and will allow greater access to care for those patients who may not initiate treatment or 
may discontinue eculizumab due to the frequency of dosing. Additionally, the substantially 
longer half-life of ravulizumab is expected to produce sustained terminal complement inhibition 
during a longer dosing interval. 
2.3.3. 
Overall Benefit/Risk Conclusion 
Taking into account the measures taken to minimize risk to participants in this study, the 
potential risks identified in association with ravulizumab are justified by the anticipated benefits 
that may be afforded to patients with PNH. 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 23 of 82 
Alexion Confidential 
3. 
OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary 
 
• To evaluate the prevalence of free C5-associated 
BTH in participants on high-dose eculizumab who 
switch to ravulizumab (per approved dose regimen) 
• Proportion of participants who experience free 
C5-associated BTH through Day 351. Free 
C5-associated BTH is defined as BTH concurrent 
with free C5 concentrations ≥ 0.5 μg/mL. BTH is 
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], MAVE, 
including thrombosis, dysphagia, or erectile 
dysfunction) in the presence of elevated LDH ≥ 2 × 
ULN. 
Secondary 
 
• To evaluate efficacy by other measures in 
participants on high-dose eculizumab who switch to 
ravulizumab 
• Proportion of participants who experience BTH 
through Day 351 
• Hemolysis as directly measured by LDH-PCHG 
from baseline to Day 351  
• Proportion of participants who receive a transfusion, 
from baseline to Day 351  
• Proportion of participants with stabilized 
hemoglobin, defined as avoidance of a ≥ 2 g/dL 
decrease in hemoglobin level from baseline in the 
absence of transfusion from baseline to Day 351  
Exploratory 
 
 
To evaluate patient-reported outcomes over time for 
those who switch to Ravulizumab from high-dose 
eculizumab 
• Patient-reported PNH Symptoms (PRS) at baseline, 
Day 183 and Day 351 
• Healthcare Resource Utilization (HRU) at baseline, 
Day 183 and Day 351 
Safety 
 
• To evaluate the safety and tolerability of 
ravulizumab in participants on high-dose eculizumab 
who switch to ravulizumab 
• Physical examinations, vital signs, and laboratory 
assessment results, and incidence of adverse events 
(AEs) and serious adverse events (SAEs) 
• Proportion of participants who develop antidrug 
antibodies (ADAs) to ravulizumab 
PK/PD  
 
• To characterize the PK/PD of ravulizumab in 
participants on high-dose eculizumab who switch to 
ravulizumab 
• Change in serum ravulizumab concentration over 
time 
• Change in serum free and total C5 concentrations 
over time 
Abbreviations: ADA = antidrug antibody; AE = adverse event; BTH = breakthrough hemolysis; C5 = complement 
component C5; LDH-PCHG = lactate dehydrogenase percent change; MAVE = major adverse vascular event; 
PD = pharmacodynamic; PK = pharmacokinetic; SAE = serious adverse event; ULN = upper limit of normal 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 24 of 82 
Alexion Confidential 
4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a Phase 4, multicenter, single-arm, open-label study to evaluate safety and efficacy of 
ravulizumab in adult participants with PNH who switch from eculizumab 1200 mg q2w to 
ravulizumab. 
The study will consist of a Screening Period of approximately 3 months and a Treatment Period 
of 351 days. 
Approximately 20 participants will be enrolled. Eligible participants will be administered 
eculizumab 1200 mg q2w optionally at home at the discretion of the Investigator, and preference 
of the patient (see Section 8) during the Screening Period followed by a loading dose of 
ravulizumab on Day 1, and maintenance treatment with ravulizumab on Day 15 and q8w 
thereafter until Day 351. Ravulizumab loading and maintenance doses will be based on the 
participant's body weight measured at the prior visit, per approved dosing regimen. Ravulizumab 
dosing will be administered in the clinic by a trained member of the site study team; patients may 
have the option to receive study drug remotely at a medical facility that is located near the 
patient’s home or at the patient’s home through a qualified healthcare personnel 
(see Section 8.11). The schedule of study visits and assessments is shown in Section 1.3. 
An interim analysis will be performed on Day 183. 
4.2. 
Scientific Rationale for Study Design 
The purpose of this study is to evaluate the safety and efficacy of ravulizumab q8w in adult 
participants with PNH who are currently receiving maintenance treatment with eculizumab 
1200 mg q2w, a dosage that is higher than the approved maintenance dose of eculizumab 
(900 mg q2w). Use of this higher dose has been reported in the literature to prevent the 
occurrence of BTH in some patients (Peffault de Latour, 2015). Some patients require a 
shortened dosing interval to completely block serum hemolytic activity despite sufficient levels 
of eculizumab (Hill, 2005). They may benefit from the longer half-life and less frequent dosing 
interval with ravulizumab. 
A Phase 3 study demonstrated the safety and efficacy of ravulizumab in eculizumab-experienced 
participants (Kulasekararaj, 2019). However, this study excluded participants on eculizumab 
1200 mg q2w therefore, the current study is designed to demonstrate the safety and efficacy in 
these participants. 
The safety parameters being evaluated are commonly used in clinical studies per International 
Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use 
(ICH) and Good Clinical Practice (GCP) guidances. 
4.3. 
Justification for Dose 
The ravulizumab dose regimen in this study is the approved dose for the treatment of PNH in 
adult participants. 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 25 of 82 
Alexion Confidential 
4.4. 
End of Study Definition 
The end of the study is defined as the date of the last participant’s last visit. 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 26 of 82 
Alexion Confidential 
5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
Age 
1. Participant must be 18 years of age or older, at the time of signing the informed consent. 
Type of Participant and Disease Characteristics 
2. Documented diagnosis of PNH, confirmed by high-sensitivity flow cytometry evaluation 
of RBCs and WBCs, with granulocyte or monocyte clone size of ≥ 5%. 
3. Received 1200 mg eculizumab every 12 to 16 days (q2w) for at least 3 months prior to 
Screening. 
4. Lactate dehydrogenase (LDH) ≤ 2 x upper limit of normal (ULN) according to central 
laboratory, at screening. Sample must be obtained within 24 hours of or immediately 
prior to a schedule eculizumab dose administration (ie, at trough eculizumab level). 
5. To reduce the risk of meningococcal infection (N. meningitidis), all participants must be 
vaccinated against meningococcal infections within 3 years prior to initiating study drug. 
Weight 
6. Body weight ≥ 40 kg. 
Sex 
7. Male or female 
Contraceptive use by men or women should be consistent with local regulations 
regarding the methods of contraception for those participating in clinical studies. 
a. Male participants: 
• Male participants must agree to use contraception as detailed in the protocol during 
the treatment period and for at least 8 months after last dose of study drug and refrain 
from donating sperm during this period. 
b. Female participants: 
A female participant is eligible to participate if she is not pregnant, not breastfeeding, and 
at least 1 of the following conditions applies: 
• Not a woman of childbearing potential (WOCBP) 
OR 
• Is a WOCBP and using a highly effective or acceptable contraceptive method as 
described in Appendix 4 during the treatment period and for at a minimum of 8 
months after the last dose of study drug. 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 27 of 82 
Alexion Confidential 
− The investigator should evaluate the effectiveness of the contraceptive method in 
relationship to the first dose of study drug. A WOCBP must have a negative 
highly sensitive pregnancy test (serum pregnancy test) within 24 hours before the 
first dose of study drug. Additional requirements for pregnancy testing during and 
after study drug are described in Section 10.4. The investigator is responsible for 
review of medical history, menstrual history, and recent sexual activity to 
decrease the risk for inclusion of a woman with an early undetected pregnancy. 
Informed Consent 
8. Capable of giving signed informed consent as described in Section 10.1.3 which includes 
compliance with the requirements and restrictions listed in the informed consent form 
(ICF) and in this protocol. 
5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
Medical Conditions 
1. History of major adverse vascular events (MAVEs) within 6 months of Day 1. 
2. History of bone marrow transplantation. 
3. History of N. meningitidis infection 
4. History of unexplained, recurrent infection. 
5. Active systemic bacterial, viral, or fungal infection within 14 days prior to study drug 
administration on Day 1. 
6. Presence of fever ≥ 38°C (100.4°F) within 7 days prior to study drug administration on 
Day 1. 
7. History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease (eg, 
active hepatitis) that, in the opinion of the Investigator or Alexion, precludes the 
participant’s participation in an investigational clinical trial. 
8. Unstable medical conditions (eg, myocardial ischemia, active gastrointestinal bleed, 
severe congestive heart failure, anticipated need for major surgery within 6 months of 
Day 1, coexisting chronic anemia unrelated to PNH) that would make them unlikely to 
tolerate the requirements of the protocol. 
9. Hypersensitivity to the active substance or to any of the excipients. 
10. Known or suspected history of drug or alcohol abuse or dependence within 1 year prior to 
the start of Screening. 
11. Known medical or psychological condition(s) or risk factor that, in the opinion of the 
Investigator or Alexion, might interfere with the participant’s full participation in the 
study, pose any additional risk for the participant, or confound the assessment of the 
participant or outcome of the study. 
12. Clinically significant multiple or severe drug allergies, intolerance to topical 
corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 28 of 82 
Alexion Confidential 
limited to, erythema multiforme major, linear immunoglobulin A dermatosis, toxic 
epidermal necrolysis, and exfoliative dermatitis). 
13. Lymphoma, leukemia, myelodysplastic syndrome, or any malignancy within the past 5 
years except for basal cell or squamous epithelial carcinomas of the skin that have been 
resected with no evidence of metastatic disease for 3 years. 
14. Major surgery within 90 days prior to dosing on Day 1. 
Prior/Concomitant Therapy 
15. Concomitant use of anticoagulants is prohibited if not on a stable regimen for at least 2 
weeks prior to Day 1. 
16. Concomitant use of any of the following medications and not on a stable regimen (as 
judged by the investigator) for the time period indicated prior to Screening: 
• Erythropoietin or immunosuppressants for at least 8 weeks 
• Systemic corticosteroids for at least 4 weeks 
• Vitamin K antagonists (eg, warfarin) with a stable international normalized ratio 
(INR) level for at least 4 weeks 
• Iron supplements or folic acid for 4 weeks 
17. Live vaccine(s) within 1 month prior to Screening or plans to receive such vaccines 
during the study. 
Prior/Concurrent Clinical Study Experience 
18. 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. 
Diagnostic Assessments 
19. More than one LDH value > 2 × ULN within the 6 months prior to Day 1. 
20. Platelet count < 30,000/mm3 (30 × 109/L) at Screening. 
21. Absolute neutrophil count < 500/µL (0.5 × 109/L) at Screening. 
22. Positive human immunodeficiency virus (HIV) antibody test. 
Other Exclusions 
23. Females who plan to become pregnant, are currently pregnant or breastfeeding, or are 
sexually active and unwilling to use effective birth control for the duration of the study. 
5.3. 
Lifestyle Considerations 
No restrictions are required. 
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently entered in the study. A minimal set of screen failure information is required to 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 29 of 82 
Alexion Confidential 
ensure transparent reporting of screen failure participants to meet the Consolidated Standards of 
Reporting Trials (CONSORT) publishing requirements (Schulz, 2010) and to respond to queries 
from regulatory authorities. Minimal information includes demography, screen failure details 
(eg, failed eligibility criteria), and any AEs or SAEs occurring during the Screening Period. 
Individuals who do not meet the criteria for participation in this study (screen failure) due to a 
reason that is expected to resolve or has resolved may be rescreened based on discussion and 
agreement between the Investigator and Medical Monitor. 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 30 of 82 
Alexion Confidential 
6. 
STUDY TREATMENTS 
Study drug is defined as any investigational drug(s), marketed product(s), placebo, or medical 
device(s) intended to be administered to a study participant according to the study protocol. 
6.1. 
Study Drug(s) Administered 
Ravulizumab is a humanized, anti-C5a mAb. Ravulizumab was derived through minimal 
targeted engineering of eculizumab by introducing 4 unique amino acid substitutions to its heavy 
chain. Ravulizumab and eculizumab share over 99% primary sequence identity and have very 
similar pharmacology. 
Ravulizumab drug product is supplied for clinical studies as a 10-mg/mL solution in a 30-mL 
single-use vial and is designed for infusion by diluting into commercially available saline (0.9% 
sodium chloride injection; country-specific pharmacopeia) for administration via IV infusion. 
Each vial of ravulizumab drug product includes a nominal overfill to ensure that 30 mL (300 mg 
of the ravulizumab antibody) of solution can be withdrawn for IV administration. 
ARM Name 
Ravulizumab 
Drug Name 
Ravulizumab 
Type  
Biologic 
Dose Formulation 
Concentrated sterile, preservative-free aqueous solution 
Unit Dose Strength(s) 
300 mg (10 mg/mL concentrated solution) 
Dosage Level(s) 
Doses based on participant weight 
Route of Administration 
IV infusion 
Use 
Experimental 
IMP and NIMP 
IMP  
Sourcing 
Provided centrally by Alexion or contracted manufacturing organization. 
Packaging and Labeling 
Study drug will be provided in glass vials and stoppered with a butyl rubber 
stopper with an aluminum overseal and a flip-off cap. Study drug will be supplied 
in kits and labeled as required per country requirement. 
Abbreviations: IMP = investigational medicinal product; IV = intravenous; NIMP = non-investigational medicinal 
product 
6.1.1. 
Ravulizumab Dosing 
The approved body weight-based ravulizumab dosing is shown in Table 4. 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 31 of 82 
Alexion Confidential 
Table 4: 
Dosing Reference Chart for Ravulizumab Dose Preparation 
Dose Type 
Body Weight 
(kg)a 
Dose 
(mg) 
Ravulizuma
b Volume 
(mL) 
Saline 
Volume 
(mL) 
Total 
Volume 
(mL) 
Minimum 
Infusion 
Duration 
minutes 
(hours) 
Maximum 
Infusion 
Rate 
(mL/hour) 
Loading 
≥ 40 to < 60 
2400 
240 
240 
480 
114 (1.9) 
253 
≥ 60 to < 100 
2700 
270 
270 
540 
102 (1.7) 
318 
≥ 100 
3000 
300 
300 
600 
108 (1.8) 
333 
Maintenance 
≥ 40 to < 60 
3000 
300 
300 
600 
 140 (2.4) 
250 
≥ 60 to < 100 
3300 
330 
330 
660 
120 (2.0) 
330 
≥ 100 
3600 
360 
360 
720 
132 (2.2) 
328 
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. 
6.2. 
Preparation/Handling/Storage/Accountability 
Upon arrival of the study drug at the study site, study drug kits should be removed from the 
shipping container and stored in their original cartons under refrigerated conditions at 2°C to 8°C 
(35°F to 47°F) and protected from light. Ravulizumab should not be frozen. 
Study drug must be stored in a secure, limited-access storage area with temperature monitored 
daily. 
Infusions of study drug should be prepared using aseptic technique. Ravulizumab will be further 
diluted in a 1:1 ratio with compatible diluent. Ravulizumab will be filtered with a 0.2 micron 
filter during infusion. Study drug will be prepared and administered by a trained member of the 
site study team. 
1. The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study drug received and any discrepancies are reported 
and resolved before use of the study drug. 
2. Only participants enrolled in the study may receive study drug and only authorized site 
staff may supply or administer study drug. All study drug must be stored in a secure, 
environmentally controlled, and monitored (manual or automated) area in accordance 
with the labeled storage conditions with access limited to the investigator and authorized 
site staff. 
3. The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study drug accountability, reconciliation, and record maintenance (ie, 
receipt, reconciliation, and final disposition records). 
4. For detailed instruction on study drug preparation, handling, storage, and accountability, 
refer to the Pharmacy Manual. Further guidance and information for the final disposition 
of unused study drug are provided in the Pharmacy Manual. 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 32 of 82 
Alexion Confidential 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
This is an open-label study. All study participants, site personnel, Alexion staff, designees, and 
all staff directly associated with the conduct of the trial will be unblinded to participant 
treatment. 
6.4. 
Study Drug Compliance 
Study drug will be administered in a controlled setting under the supervision of the Investigator 
or designee, thereby ensuring compliance with study drug administration. 
The date and time of each dose administered in the clinic will be recorded in the source 
documents and recorded in the electronic case report form (eCRF). The dose of study drug and 
study participant identification will be confirmed at the time of dosing by a member of the study 
site staff other than the person administering the study drug. 
6.5. 
Concomitant Therapy 
Any medication including over-the-counter or prescription medicines, vitamins, and/or herbal 
supplements that the participant is receiving at the time of enrollment or receives during the 
study must be recorded along with: 
• Reason for use 
• Dates of administration including start and end dates 
• Dosage information including dose and frequency 
Prior medications (including vitamins and herbal preparations), including those discussed in the 
exclusion criteria (Section 5.2) and procedures (any therapeutic intervention, such as 
surgery/biopsy or physical therapy) the participant takes or undergoes within 28 days prior to the 
start of Screening until the first dose of study drug, will be recorded in the participant’s case 
report forms. In addition, history of meningococcal vaccination must be collected for the 3 years 
prior to first dose of study drug. 
Transfusions of packed red blood cells received within 1 year prior to first study drug 
administration will be recorded in the participant’s eCRF. 
All medications or therapies and procedures undertaken during the study will be recorded in the 
participant’s source document/medical chart and eCRF. This record will include all prescription 
drugs, herbal products, vitamins, minerals, over-the-counter medications, and current 
medications for PNH. Concomitant medications will be recorded from the first infusion of study 
drug through 30 days after the participant’s last dose of study drug. Any changes in concomitant 
medications also will be recorded in the participant’s source document/medical chart and eCRF. 
Any concomitant medication deemed necessary for the participant’s standard of care during the 
study, or for the treatment of any AE, along with the allowed medications described below may 
be given at the discretion of the investigator. 
The following concomitant medications are allowed if the following conditions apply, and dose 
adjustments are not expected during the treatment period: 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 33 of 82 
Alexion Confidential 
• Erythropoietin, if the participant has been receiving a stable dose for at least 8 weeks 
before Screening. 
• Immunosuppressants, if the participant has been receiving a stable dose for at least 8 
weeks before Screening. 
• Corticosteroids, if the participant has been receiving a stable dose for at least 4 weeks 
before Screening. 
• Vitamin K antagonists (eg, warfarin), if the participant has had a stable INR level (per 
investigator’s discretion) for at least 4 weeks before Screening. 
• Iron supplements or folic acid, if the participant has been receiving a stable dose for 
at least 4 weeks before Screening. 
Adjustments in the frequency or dose level in any of the above medications can be made if the 
Alexion Medical Monitor or the Investigator deems it is in the best interest of the participant. 
The Medical Monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
Participants must abstain from taking prescription or nonprescription drugs (including vitamins 
and dietary or herbal supplements) within 7 days (or 14 days if the drug is a potential enzyme 
inducer) or 5 half-lives (whichever is longer) before the start of study drug until completion of 
the follow-up visit, unless, in the opinion of the Investigator and Alexion, the medication will not 
interfere with the study. 
Other concomitant medication may be considered on a case-by-case basis by the Investigator in 
consultation with the Medical Monitor, if required. 
6.5.1. 
Meningococcal Vaccination 
As with any terminal complement antagonist, the use of ravulizumab increases the participant’s 
susceptibility to meningococcal infection (N. meningitidis). To reduce the risk of meningococcal 
infection, all participants must have been vaccinated against meningococcal infections within 
3 years prior to initiating study drug. 
Vaccines against serotypes A, C, Y, W135, and B, where available, are recommended to prevent 
common pathogenic meningococcal serotypes. Participants must be vaccinated or revaccinated 
according to current national vaccination guidelines or local practice for vaccination use with 
complement inhibitors (eg, eculizumab). Participant’s vaccination status will be confirmed. 
Vaccination may not be sufficient to prevent meningococcal infection. Consideration should be 
given per official guidance and local practice on the appropriate use of antibacterial agents. All 
participants 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 participants during the course of the study, participants will be 
provided a safety card to carry with them at all times. Additional discussion and explanation of 
the potential risks, signs, and symptoms will occur at specific time points as part of the review of 
the participant safety card and throughout the study as described in the Schedule of Activities 
(SoA [Section 1.3]). 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 34 of 82 
Alexion Confidential 
6.5.2. 
Rescue Medicine 
Not applicable. 
6.6. 
Dose Modification 
6.6.1. 
Supplemental Dosing  
If a BTH event occurs during the Screening Period, the participant will be ineligible for the 
study. If a participant experiences BTH during maintenance treatment with ravulizumab, an 
additional weight-based maintenance dose of ravulizumab may be administered or the next 
scheduled maintenance dose may be accelerated as per Table 5 at the Investigator’s discretion 
after discussion with the Medical Monitor. 
Table 5: 
Dosing Guidance for Patients with Breakthrough Hemolysis 
 
 
 
Timing of Subsequent Dose after Next 
Maintenance Dose 
Time of BTH 
Supplemental 
Dosing 
Next Maintenance 
Dose 
if free C5 is 
< 0.5μg/mL 
if free C5 is 
≥ 0.5 μg/mL 
≤ 2 weeks 
after previous 
dose 
Decision to be made 
based on results of 
Free C5 at 
Investigator’s 
discretion 
As per SoAa  
As per SoAa 
6 weeks after the last 
maintenance doseb 
>2 to < 6 
weeks after 
previous dose 
Supplemental dose  
As per SoAa 
As per SoAa 
6 weeks after the last 
maintenance doseb 
≥ 6 weeks 
after previous 
dose 
Not applicable 
Accelerate next 
dose at 
Investigator’s 
discretion 
As per SoAa 
6 weeks after the last 
maintenance doseb 
aTiming of next dose will be per SoA (Section 1.3) 
b  See Section 6.6.2  
Abbreviations: BTH = breakthrough hemolysis; C5 = complement component 5; SoA = Schedule of Activities 
6.6.2. 
Permitted Change in Dosing Interval 
If a participant experiences a free C5-related BTH during maintenance treatment with 
ravulizumab, shortening the dosing interval to every 6 weeks (q6w) is permitted at the discretion 
of the Investigator after discussion with Alexion’s Medical Monitor. For these participants, the 
assessments performed at the first q6w visit would be those indicated in the SoA (Section 1.3). 
Subsequent q6w visit assessments would continue to be aligned to the example visit illustrated in 
Table 3, with the EOS/ET visit being on/after Day 351. Between the SoA-specified visits 
occurring at 6-week dosing frequency and the EOS/ET visit, any additional visits are to be 
classified as unscheduled visits and would follow the study procedures for unscheduled visits 
(Table 3). 
6.7. 
Intervention after the End of the Study 
At the end of the study, participants will be transitioned to standard of care. 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 35 of 82 
Alexion Confidential 
All participants will be followed for safety for an additional 16 weeks after the last dose of study 
drug if they discontinue from the study early. 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 36 of 82 
Alexion Confidential 
7. 
DISCONTINUATION OF STUDY DRUG AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of Study Drug 
In rare instances, it may be necessary for a participant to permanently discontinue (definitive 
discontinuation) the study drug. If the study drug is definitively discontinued, the participant 
should remain in the study to be evaluated for safety follow up. See the SoA (Section 1.3) for 
data to be collected at the time of discontinuation of the study drug and follow-up and for any 
further evaluations that need to be completed. 
Participants should be considered for discontinuation from study drug if any of the following 
occur during the study: 
1. Serious hypersensitivity reaction 
2. Use of disallowed medication as defined in Section 6.5 
3. Alexion or the Investigator deems it is necessary for the participant 
4. Withdrawal of consent. 
Participants who become pregnant must have study drug discontinued. 
7.2. 
Participant Discontinuation/Withdrawal from the Study 
All efforts should be made to ensure participants are willing to comply with study participation 
prior to conducting the screening procedures. The study staff should notify their site monitor and 
Alexion of all study withdrawals as soon as possible. The reason for participant discontinuation 
must be recorded in the source documents and eCRF. 
If a participant withdraws consent, the assessments specified for the Early Termination (ET) visit 
(as shown in the SoA, Section 1.3) will be performed and Alexion and site monitor notified as 
soon as possible. Participants who withdraw from the study will not be replaced. 
Participants should be permanently discontinued from ravulizumab 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) 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 is in the best interest of 
the participant. 
The Investigator should speak with the Medical Monitor prior to discontinuing a participant’s 
study treatment. If a participant is discontinued from study drug, the participant should be 
encouraged to return for the remainder of his or her scheduled protocol visits until starting a 
different complement-targeted therapy. 
If a participant is discontinued from the study with an ongoing AE or an unresolved laboratory 
result that, in the opinion of the Investigator, is significantly outside of the reference range and 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 37 of 82 
Alexion Confidential 
clinically significant (Section 10.3), the Investigator will attempt to provide follow-up until a 
satisfactory clinical resolution of the laboratory result or adverse event is achieved. 
If a female participant is permanently discontinued from ravulizumab treatment due to 
pregnancy, the Investigator will attempt to follow-up until the outcome of the pregnancy 
(Section 10.4). 
• A participant may withdraw from the study at any time at his/her own request or may 
be withdrawn at any time at the discretion of the Investigator for safety, behavioral, 
compliance, or administrative reasons. This is expected to be uncommon. 
• If the participant withdraws consent for disclosure of future information, Alexion may 
retain and continue to use any data collected before such a withdrawal of consent. 
• If a participant withdraws from the study, he/she may request destruction of any 
samples taken and not tested, and the Investigator must document this in the site 
study records. 
7.3. 
Lost to Follow up 
If a participant fails to return, or is otherwise unavailable, for a scheduled visit within the 
acceptable visit window (Section 1.3), the site study staff must make a reasonable attempt to 
contact the participant to determine the reason for missing the appointment. 
Participants who fail to return for a scheduled visit must be contacted by the site’s study staff to 
determine the reason for missing the appointment. As it is vital to obtain any participant’s 
missing visit information to ensure the missed appointment was not due to an AE or potential 
relapse, every effort must be made to undertake protocol-specified safety follow-up procedures. 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study. 
• Before a participant is deemed lost to follow up, the Investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record. 
• Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
Discontinuation of specific sites or of the study as a whole are handled as part of Section 10.1.8. 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 38 of 82 
Alexion Confidential 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
• Study procedures and their timing are summarized in the SoA (Section 1.3). 
• Immediate safety concerns should be discussed with Alexion immediately upon 
occurrence or awareness to determine if the participant should receive the study drug. 
• Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct. 
• During Screening, eculizumab may be administered at the participant’s home at the 
discretion of the Investigator and preference of the patient, in accordance with the 
local procedures and Standard Operating Procedures at the site. These visits will be 
conducted by a trained qualified staff member. During a home administration visit, all 
assessments will be performed according to the SoA (Table 1). Patients must return to 
the study site for any visit at which PD sampling (Day –57 and Day –29) is 
scheduled, as specified in the SoA (Table 1). 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 
• All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The Investigator will maintain a screening log 
to record details of all participants screened and to confirm eligibility or record 
reasons for screening failure, as applicable. 
• Procedures conducted as part of the participant’s routine clinical management (eg, 
blood count) and obtained before signing of the ICF may be utilized for screening or 
baseline purposes provided the procedures met the protocol-specified criteria and 
were performed within the time frame defined in the SoA. 
8.1. 
Efficacy Assessments 
8.1.1. 
Transfusions 
Administration of a pRBC transfusion, including the hemoglobin result and symptoms that 
triggered the transfusion and the number of units transfused, will be documented in the eCRF. 
8.1.2. 
Lactate Dehydrogenase and Other Disease-Related Laboratory Parameters 
Blood and urine samples will be collected at the times indicated in the SoA (Section 1.3) and as 
indicated in Section 10.2. 
The following disease-related laboratory parameters will be measured during the study (refer to 
Section 8.5 and Section 8.6 for PK/PD assessments): 
• LDH 
• free hemoglobin 
• occult blood, urine 
• haptoglobin 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 39 of 82 
Alexion Confidential 
• reticulocyte count 
• PNH RBC clone size evaluated by high-sensitivity flow cytometry (Borowitz, 2010) 
• estimated glomerular filtration rate (calculated using the Schwartz formula) 
8.1.3. 
Paroxysmal Nocturnal Hemoglobinuria Symptomatology 
The Investigator or designee will record for each participant the presence or absence of the 
following signs and symptoms of PNH: fatigue, chest pain, hemoglobinuria, abdominal pain, 
dyspnea, dysphagia, erectile dysfunction, and red/dark urine or hemoglobinuria. 
8.1.4. 
Major Adverse Vascular Events 
Major adverse vascular events will be assessed as part of the planned evaluation for AEs as 
described in Section 8.3. 
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 participant’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 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 40 of 82 
Alexion Confidential 
8.2. 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA (Section 1.3). 
8.2.1. 
Physical Examinations 
• A complete physical examination will include, at a minimum, assessments of the 
cardiovascular, respiratory, gastrointestinal and neurological systems. Height and 
weight will also be measured and recorded. 
• An abbreviated physical examination will include, at a minimum, assessments of the 
skin, lungs, cardiovascular system, and abdomen (liver and spleen). 
• Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 
• Additional physical examinations can be performed as medically indicated during the 
study at the Investigator’s discretion. 
8.2.2. 
Vital Signs 
• Oral temperature, pulse rate, respiratory rate, and blood pressure will be assessed. 
• Blood pressure and pulse measurements will be assessed with an automated device. 
Manual techniques will be used only if an automated device is not available. 
• Vital sign measurements will be taken after the participant has been resting for at 
least 5 minutes and will include systolic and diastolic blood pressure (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. 
8.2.3. 
Electrocardiograms 
• A single 12-lead electrocardiogram (ECG) will be obtained as outlined in the SoA 
(see Section 1.3) using an ECG machine that automatically calculates the heart rate 
and measures PR, QRS, QT, and QTc intervals. 
• Participants must be supine for approximately 5 to 10 minutes before ECG collection 
and remain supine but awake during ECG collection. 
• The Investigator or qualified 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 recorded in the source 
documents and the eCRF. 
8.2.4. 
Clinical Safety Laboratory Assessments 
• Detailed instructions on the procedure for collection, processing, storage, and 
shipment of the samples for laboratory analyses will be provided in the Laboratory 
Study Manual. All sample analyses will be performed by Alexion or its designee. 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 41 of 82 
Alexion Confidential 
• See Section 10.2 for the clinical laboratory tests to be performed and the SoA 
(Section 1.3) for their timing and frequency. 
• If a suspected event of BTH occurs, LDH, PK, and PD samples will be collected and 
analyzed. If the suspected event of BTH does not occur at a scheduled visit, an 
unscheduled visit should be conducted for evaluation of the participant and collection 
of the required LDH, PK, and PD samples. 
• The Investigator must review the laboratory report, document this review, and record 
any clinically relevant changes occurring during the study in the AE section of the 
eCRF. The laboratory reports must be filed with the source documents. Clinically 
significant abnormal laboratory findings are those which are not associated with the 
underlying disease, unless judged by the Investigator to be more severe than expected 
for the participant’s condition. 
• All laboratory tests with values considered clinically significantly abnormal during 
participation in the study should be discussed by the Investigator and Medical 
Monitor. 
− If such values do not return to normal/baseline within a period of time judged 
reasonable by the Investigator, the etiology should be identified, and Alexion 
notified. 
− All protocol-required laboratory assessments, as defined in Section 10.2, must be 
conducted in accordance with the laboratory manual and the SoA. 
− If laboratory values from non-protocol specified laboratory assessments 
performed at the institution’s local laboratory require a change in participant 
management or are considered clinically significant by the Investigator (eg, SAE 
or AE or dose modification), then the results must be recorded in the CRF. 
8.3. 
Adverse Events and Serious Adverse Events 
The definitions of AEs and SAEs are specified in Section 10.3. 
AEs will be reported to the Investigator or qualified designee by the participant (or when 
appropriate, by a caregiver, surrogate, or the participant’s legally authorized representative). 
The Investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up of AEs that are serious, considered related to the study drug or study procedures, or that 
caused the participant to discontinue the study drug (see Section 7). 
Definitions and procedures for recording, evaluating, follow-up, and reporting AEs and SAEs are 
outlined in Section 10.3 (Appendix 3). 
8.3.1. 
Time Period and Frequency for Collecting Adverse Event and Serious Adverse 
Event Information 
All AEs will be collected from the signing of the Informed Consent Form until the follow-up 
call. 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 42 of 82 
Alexion Confidential 
All SAEs will be recorded and reported to Alexion or designee within 24 hours of awareness, as 
indicated in Section 10.3. The Investigator will submit any updated SAE data to Alexion within 
24 hours of it being available. 
Investigators are not obligated to actively seek AEs or SAEs after conclusion of the study 
participation. However, if the Investigator learns of any SAE, including a death, at any time after 
a participant has exited the study, and he/she considers the event to be reasonably related to the 
study drug, the Investigator must promptly notify Alexion. 
8.3.2. 
Method of Detecting AEs and SAEs 
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Section 10.3. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences. 
8.3.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs and AEs of special interest (AESI) (as defined 
in Section 8.3.6), will be followed until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.3). Further information on follow-
up procedures is provided in Section 10.3. 
8.3.4. 
Regulatory Reporting Requirements for SAEs 
• Prompt notification by the Investigator to Alexion of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the 
safety of a study drug under clinical investigation are met. 
• Alexion has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study drug under clinical investigation. 
Alexion will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, Institutional Review Board (IRB)/Independent 
Ethics Committee (IEC), and investigators. 
• Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSARs) according to local regulatory requirements and sponsor policy 
and forwarded to Investigators as necessary. 
• An Investigator who receives an investigator safety report describing a SAE or other 
specific safety information (eg, summary or listing of SAEs) from Alexion will 
review, sign a document stating they have reviewed it, and then file it along with the 
IB and will notify the IRB/IEC, if appropriate according to local requirements. 
8.3.5. 
Pregnancy 
Pregnancy testing must be performed on all WOCBP at protocol-specified timepoints in the SoA 
(Section 1.3). Serum samples will be collected at Day 85, Day 1, and Day 351/ET. At all other 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 43 of 82 
Alexion Confidential 
time points urine samples will be collected for pregnancy test. Pregnancy tests (urine or serum) 
may also be performed at any time during the study at the Investigator’s discretion. 
A negative pregnancy test is required for WOCBP before study drug administration. 
• Details of all pregnancies in female participants and, if indicated, female partners of 
male participants will be collected after the start of study drug and until the 
termination of the pregnancy. 
• If a pregnancy is reported, the Investigator should inform Alexion within 24 hours of 
learning of the pregnancy and should follow the procedures outlined in Section 10.4. 
• Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs. Pregnancy alone is 
not considered an AE. 
If a participant becomes pregnant, the study drug must be immediately discontinued, and 
Alexion must be notified as per Section 10.4. Each pregnancy will be followed to term and 
Alexion notified regarding the outcome. 
8.3.6. 
Adverse Events of Special Interest  
Meningococcal infections will be collected as AESI. 
8.4. 
Treatment of Overdose 
For this study, any dose of study drug greater than that specified in the label will be considered 
an overdose. 
Accidental overdose without any association with laboratory abnormalities or clinical symptoms 
should not be considered as an AE. Overdose must be reported by the Investigator within 
24 hours to Alexion regardless of its association with or without an AE. 
Alexion does not recommend specific treatment for an overdose. 
In the event of an overdose, the Investigator should: 
1. Contact the Medical Monitor immediately. 
2. Closely monitor the participant for any AE/SAE. 
3. Obtain a serum sample for PK analysis if requested by the Medical Monitor (determined 
on a case-by-case basis). 
4. Document the quantity of the excess dose as well as the timing of the overdose in the 
eCRF. 
Decisions regarding dose interruptions will be made by the Investigator in consultation with the 
Medical Monitor based on the clinical evaluation of the participant. 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 44 of 82 
Alexion Confidential 
8.5. 
Pharmacokinetics/Pharmacodynamics Sampling 
8.5.1. 
Sample Collection During the Screening Period 
Serum samples will be collected for free and total C5 analyses (before eculizumab dosing) 
during Screening on Day ­57 and Day ­29. The predose (within 0.5 hours prior to the start of 
infusion) free C5 sample may be drawn through the venous access created for the dose infusion, prior 
to administration of the dose. All collection times will be recorded in the eCRF. In the event of 
BTH, a serum sample for PK/PD analysis will be collected. 
In the event of an unscheduled visit, PK and PD blood sample will be collected as soon as 
possible. 
8.5.2. 
Sample Collection during Confirmation Visit Through Follow-up 
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 as specified in the SoA 
(Section 1.3). The predose (within 0.5 hours prior to the start of infusion) PK/PD sample may be 
drawn through the venous access created for the dose infusion, prior to administration of the dose. 
End-of-infusion (within 0.5 hours after the end of infusion) PK/PD samples will be drawn from the 
participant’s opposite, non-infused arm. All collection times will be recorded in the eCRF. In the 
event of BTH, a serum PK/PD sample will be collected. 
8.6. 
Pharmacodynamics 
Changes in serum free C5 and total C5 concentrations over time will be assessed. 
8.7. 
Genetics 
No samples will be collected for genetic analyses. 
8.8. 
Biomarkers 
Biomarkers will not be evaluated in this study. 
8.9. 
Immunogenicity Assessments 
Antibodies to ravulizumab will be evaluated in serum samples collected predose (within 5 to 
90 minutes prior to the start of infusion of study drug) from all participants according to the SoA 
(Section 1.3). 
Additionally, serum samples will be collected at the final visit from participants who discontinue 
study drug or are withdrawn from the study. 
In the event of a BTH, serum samples for ADA analysis will be collected per SoA (Table 1). 
Serum samples will be screened for antibodies binding to ravulizumab and the titer of confirmed 
positive samples will be reported. Other analyses may be performed to verify the stability of 
antibodies to ravulizumab and/or further characterize the immunogenicity of ravulizumab. 
The detection and characterization of antibodies to ravulizumab will be performed using a 
validated assay method by or under the supervision of Alexion. Samples may be further 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 45 of 82 
Alexion Confidential 
characterized to determine the titer and the presence of neutralizing antibodies if deemed 
necessary. Samples may be stored for a maximum duration according to local regulations 
following the last participant’s last study visit at a facility selected by Alexion. 
8.10. 
Patient-Reported Symptoms and Health Resource Utilization 
questionnaires 
Patient-reported PNH symptoms (PRS) and Health Resource Utilization (HRU) data, will be 
collected at Day 1 (baseline), Day 183 and Day 351/ET in the eCRF by the Investigator and 
study-site personnel for all participants throughout the study. Protocol-mandated procedures, 
tests, and encounters are excluded. 
For PRS, each participant will record the presence or absence of the signs and symptoms of 
PNH: fatigue, chest pain, abdominal pain, dyspnea, dysphagia, headache, confusion, erectile 
dysfunction (if applicable), discoloration of urine, discoloration of eyes (see Appendix 10.5.1). 
For HRU, the Investigator or designee will record for each participant the number of clinic visits, 
emergency services utilized, hospitalization, missed work and also record the number of times 
the participant had darkened urine (see Appendix  10.5.2). 
8.11. 
Visits during COVID-19 Pandemic 
To ensure patient safety and treatment continuity during the COVID-19 pandemic, the following 
will apply until patients are able to resume study visits at the site. 
Patients may have an opportunity to receive ravulizumab administration (see Section 1.3 for 
SoA) remotely at a medical facility that is located near the patient’s home or at the patient’s 
home with the permission of the Investigator in accordance with all national, state, and local 
laws or regulations of the pertinent regulatory authorities. 
Remote visit options may be at the Investigator’s discretion and oversight, in accordance with 
the local regulations, and conducted by a qualified healthcare personnel. Information about AEs 
concomitant medications, samples for protocol-defined laboratory parameters must be sent to the 
Investigator’s site for evaluation on the day of the remote visit. 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 46 of 82 
Alexion Confidential 
9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical Hypotheses 
This is an estimation study; no formal statistical hypotheses will be tested. 
9.2. 
Sample Size Determination 
The proposed sample size for this estimation study is approximately 20 participants. The range 
of possible proportions of participants experiencing free C5-associated BTH during the 
Treatment Period (with 95% exact confidence intervals) is as follows: 
Proportion of BTH (participants with BTH/total 
population) 
95% CI 
95% (19/20) 
75%, 100% 
75% (15/20) 
51%, 91% 
50% (10/20) 
27%, 73% 
25% (5/20) 
9%, 49% 
10% (2/20) 
1%, 32% 
5% (1/20) 
0%, 25% 
0% (0/20) 
0%, 17% 
9.3. 
Populations for Analyses 
Efficacy analyses will be performed on the Full Analysis Set (FAS). The FAS is the primary 
population for all efficacy analyses. The FAS will include all participants who receive at least 1 
dose of ravulizumab. 
Safety analyses will be performed on the Safety Set, defined as all participants who receive at 
least 1 dose of ravulizumab. 
Pharmacokinetic analyses will be performed on the PK analysis set, defined as all participants 
who receive at least 1 dose of study drug and who have evaluable PK data. 
9.4. 
Statistical Analyses 
Details of the statistical analyses described below will be specified in a separate Statistical 
Analysis Plan (SAP) before first database lock and analysis, including procedures for accounting 
for missing data. Any change to the data analysis methods described in the protocol will require 
an amendment only if it changes the primary or secondary objectives or the study conduct. Any 
other change to the data analysis methods described in the protocol or SAP, and the justification 
for making the change, will be described in the clinical study report (CSR). Additional analyses 
of the data to address the impact of COVID-19 may be conducted as deemed appropriate. 
All data collected will be presented using summary tables, figures, and data listings. All data, as 
well as any outcomes derived from the data, will be presented in detailed data listings. Graphical 
displays may also be provided, when appropriate. 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 the 
number of observations, and mean, standard deviation, median, minimum, and maximum values. 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 47 of 82 
Alexion Confidential 
Categorical variables will be summarized by frequency counts and the percentage of participants. 
All statistical tests performed will be based on a 2-sided 5% level of significance unless 
otherwise specified. 
A CSR to summarize efficacy, safety, PK, PD, and immunogenicity data will be produced at 
study completion. 
9.4.1. 
Efficacy Analyses 
The primary efficacy endpoint is proportion of participants who experience free C5-associated 
BTH. The proportion along with a two-sided 95% exact CI will be calculated. The same 
approach will be employed for proportion of participants who experience BTH and stabilized 
hemoglobin. 
The percentage change in LDH will be analyzed using a mixed model for repeated measures 
(MMRM) (Mallinckrodt, 2001; Mallinckrodt, 2004) with the fixed categorical effects of study 
visit, and the continuous fixed covariate of baseline LDH. Baseline is defined as the average of 
all assessments analyzed by the central laboratory prior to first study drug administration. The 
Kenward-Roger approximation will be used to estimate denominator degrees of freedom. A 
p-value testing whether percent changes differ from zero at each visit will be calculated. 
Transfusion rates will be summarized. 
Exploratory data of PRS and HRU will be summarized descriptively. 
9.4.2. 
Safety Analyses 
All safety data will be summarized using the Safety Set. 
9.4.2.1. 
Analysis of Adverse Events 
The analysis and reporting of AEs will be based on treatment-emergent adverse events (TEAEs), 
defined as AEs with onset on or after the first dose of ravulizumab. The incidence of TEAEs will 
be summarized by system organ class (SOC) and preferred term (PT), with additional summaries 
showing severity, relationship to study drug, TEAEs leading to study drug discontinuation, and 
TEAEs resulting in death. Summaries of treatment-emergent serious adverse events (TESAEs) 
will also be summarized by SOC and PT, with an additional summary showing relationship to 
study drug. All AEs will be coded using the latest MedDRA version. 
9.4.2.2. 
Analysis of Clinical Laboratory Parameters, Vital Sign Measurements and 
Electrocardiogram Parameters 
Laboratory measurements as well as their changes from baseline at each visit and shift from 
baseline, if applicable, will be summarized. Data on ECGs, including ECG interpretation heart 
rate, PR, QRS, QT, and QTc intervals, and vital signs will also be summarized. 
9.4.3. 
Demographics and Baseline Characteristics 
Participant demographic and baseline characteristics will be summarized by treatment group, 
using the Safety Set. Summary statistics will be presented. No formal hypothesis testing will be 
performed. 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 48 of 82 
Alexion Confidential 
9.4.4. 
Participant Disposition 
The number of participants screened, treated, completing the study, discontinued from the study, 
reasons for discontinuation, and those included in each analysis set will be summarized. 
Important protocol deviations will be summarized by prespecified deviation categories. 
9.4.5. 
Prior and Concomitant Medications 
Any medication taken up to 28 days prior to the start of Screening or are ongoing at the first dose 
of study drug will be considered prior medications or concomitant medications. Prior and 
concomitant medications will be summarized for all participants in the Safety Analysis Set, 
including immunosuppressant therapies for relapse prevention and acute relapse treatment. 
Medications will be coded using the World Health Organization Drug Dictionary based on the 
most current version available at the time of the analyses. 
9.4.6. 
Pharmacokinetics and Pharmacodynamics Analyses 
Individual serum concentration data for all participants who receive at least 1 dose of 
ravulizumab and who have evaluable PK data will be used to derive PK parameters for 
ravulizumab. 
Graphs of mean serum concentration-time profiles will be constructed. Graphs of serum 
concentration-time profiles for individual participants may also be provided. Actual dose 
administration and sampling times will be used for all calculations. Descriptive statistics will be 
calculated for serum concentration data at each sampling time, as appropriate. Assessment of 
population-PK may be considered using data from this study or in combination with data from 
other studies. 
Pharmacodynamic analyses will be performed for all participants who receive at least 1 dose of 
ravulizumab and who have evaluable PD data. 
Descriptive statistics will be presented for all ravulizumab PD endpoints at each sampling time 
(Section 1.3). The PD effects of ravulizumab administered IV will be evaluated by assessing the 
absolute values and changes and percentage changes from baseline in total and free C5 serum 
concentrations over time, as appropriate. 
Immunogenicity analyses and subgroup and sensitivity analyses will be described in the SAP and 
finalized before database lock. 
9.5. 
Interim Analyses 
An interim analysis will be conducted on accrued data through Day 183 for publication purposes. 
The SAP will describe the planned interim analyses in greater detail. 
9.6. 
Data Monitoring Committee 
This study will not include a Data Monitoring Committee (DMC). 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 49 of 82 
Alexion Confidential 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
• This study will be conducted in accordance with the protocol and with the following: 
− Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
− Applicable ICH GCP Guidelines 
− Applicable laws and regulations 
• The protocol, protocol amendments, ICF, IB, and other relevant documents (eg, 
advertisements) must be submitted to an IRB/IEC by the Investigator and reviewed 
and approved by the IRB/IEC before the study is initiated. 
• Any amendments to the protocol will require IRB/IEC approval before 
implementation of changes made to the study design, except for changes necessary to 
eliminate an immediate hazard to study participants. 
• The Investigator will be responsible for the following: 
− Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC 
− Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
− Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local 
regulations 
10.1.2. 
Financial Disclosure 
Investigators and sub-investigators will provide Alexion with sufficient, accurate financial 
information as requested to allow Alexion to submit complete and accurate financial certification 
or disclosure statements to the appropriate regulatory authorities. Investigators are responsible 
for providing information on financial interests during the course of the study and for 1 year after 
completion of the study. 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 50 of 82 
Alexion Confidential 
10.1.3. 
Informed Consent Process 
• The Investigator or his/her representative will explain the nature of the study to the 
participant or his/her legally authorized representative and answer all questions 
regarding the study. 
• Participants must be informed that their participation is voluntary. Participants or 
their legally authorized representative, defined according to local and country 
regulations where the study is taking place, will be required to sign a statement of 
informed consent that meets the requirements of 21 CFR 50, local regulations, ICH 
guidelines, Health Insurance Portability and Accountability Act requirements, where 
applicable, and the IRB/IEC or study center. 
• The medical record must include a statement that written informed consent was 
obtained before the participant was screened in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent must 
also sign the ICF(s). 
• Participants must be re-consented to the most current version of the ICF(s) during 
their participation in the study. 
• A copy of the ICF(s) must be provided to the participant or the participant’s legally 
authorized representative. 
10.1.4. 
Data Protection 
• Participants will be assigned a unique identifier by Alexion. Any participant records 
or datasets that are transferred to Alexion will contain the identifier only; participant 
names or any information which would make the participant identifiable will not be 
transferred. 
• The participant must be informed that his/her personal study-related data will be used 
by Alexion in accordance with local data protection law. The level of disclosure must 
also be explained to the participant who will be required to give consent for their data 
to be used as described in the informed consent. 
• The participant must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by 
Alexion, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities. 
10.1.5. 
Dissemination of Clinical Study Data 
Study-related information and study results may be posted on publicly accessible clinical study 
databases (eg, the US website www.clinicaltrials.gov or the EU website 
www.clinicaltrialsregister.eu), as appropriate, and in accordance with national, regional, and 
local regulations. 
10.1.6. 
Data Quality Assurance 
• All participant data relating to the study will be recorded on a printed or eCRF unless 
transmitted to Alexion or designee electronically (eg, laboratory data). The 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 51 of 82 
Alexion Confidential 
investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the CRF. 
• The Investigator must maintain accurate documentation (source data) that supports 
the information entered in the eCRF. 
• The Investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents. 
• Alexion or designee is responsible for the data management of this study including 
quality checking of the data. 
• Study monitors will perform ongoing source data verification to confirm that data 
entered into the eCRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of participants are being 
protected; and that the study is being conducted in accordance with the currently 
approved protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements. 
• Records and documents, including signed ICFs, pertaining to the conduct of this 
study must be retained by the Investigator for 2 years after the last marketing 
application approval, or if not approved, 2 years following the discontinuance of the 
test article for investigation, unless local regulations or institutional policies require a 
longer retention period. No records may be destroyed during the retention period 
without the written approval of Alexion. No records may be transferred to another 
location or party without written notification to Alexion. 
10.1.7. 
Source Documents 
• Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. The Investigator or designee will 
prepare and maintain adequate and accurate source documents (eg, medical records, 
ECGs, AE and concomitant medication reporting, raw data collection forms) 
designed to record all observations and other pertinent data for each participant. 
• Data entered in the eCRF that are transcribed from source documents must be 
consistent with the source documents or the discrepancies must be explained. The 
Investigator may need to request previous medical records or transfer records, 
depending on the study. Also, current medical records must be available. Source 
documents are filed at the Investigator’s site. 
10.1.8. 
Study and Site Start and Closure 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
The first act of recruitment is the first site open and will be the study start date. 
Alexion or designee reserves the right to close the study site or terminate the study at any time 
for any reason at the sole discretion of Alexion. Study sites will be closed upon study 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 52 of 82 
Alexion Confidential 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The Investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by Alexion or Investigator may include but are not 
limited to: 
• Failure of the Investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, Alexion-s procedures, or GCP guidelines 
• Inadequate recruitment of participants by the Investigator 
• Discontinuation of further study drug development 
If the study is prematurely terminated or suspended, Alexion shall promptly inform the 
Investigators, the IECs/IRBs, the regulatory authorities, and any contract research 
organization(s) used in the study of the reason for termination or suspension, as specified by the 
applicable regulatory requirements. The Investigator shall promptly inform the participant and 
should assure appropriate therapy and/or follow-up. 
10.1.9. 
Publication Policy 
The full terms regarding publication of the results of this study are outlined in the applicable 
Clinical Study Agreement. 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 53 of 82 
Alexion Confidential 
10.2. 
Appendix 2: Clinical Laboratory Tests 
• The tests detailed in Table 6 will be performed by both the central laboratory and the 
local laboratory. 
• Local laboratory results are only required in the event that the central laboratory 
results are not available in time for either study drug administration and/or response 
evaluation. If a local sample is required, it is important that the sample for central 
analysis is obtained at the same time. Additionally, if the local laboratory results are 
used to make either a study drug decision or response evaluation, the results must be 
entered into the eCRF. 
• Protocol-specific requirements for inclusion or exclusion of participants are detailed 
in Section 5 of the protocol. 
• Additional tests may be performed at any time during the study as determined 
necessary by the Investigator or required by local regulations. 
• Pregnancy Testing (see Section 10.4.3) 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 54 of 82 
Alexion Confidential 
Table 6: 
Protocol-Required Safety Laboratory Assessments 
Hematology 
Free hemoglobin 
Haptoglobin 
Hematocrit 
Hemoglobin 
Mean corpuscular hemoglobin 
Platelet count  
RBC count  
RBC distribution width 
RBC mean corpuscular volume 
Reticulocyte count 
WBC count  
WBC differential 
 
Coagulation Panel 
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 (women of 
childbearing potential only) 
Free and total C5 
Pharmacokinetic assay  
PNH clone size 
Serum follicle-stimulating hormone (postmenopausal 
females only) 
Investigators must document their review of each laboratory safety report. 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 55 of 82 
Alexion Confidential 
10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
Adverse Event Definition 
• 
An AE is any untoward medical occurrence in a participant or clinical study participant, temporally 
associated with the use of study drug, whether or not considered related to the study drug. 
• 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of 
study drug. 
 
Events Meeting the AE Definition  
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other safety 
assessments (eg, ECG, radiological scans, vital signs measurements), including those that worsen from 
baseline, considered clinically significant in the medical and scientific judgment of the Investigator (ie, 
not related to progression of underlying disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an increase in 
frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after study drug administration even though it may have been 
present before the start of the study. 
• 
Signs, symptoms, or clinical sequelae whether or not related to a suspected drug-drug interaction. 
• 
"Lack of efficacy" or "failure of expected pharmacological action" per se will not be reported as an AE 
or SAE. Such instances will be captured in the efficacy assessments. However, the signs, symptoms, 
and/or clinical sequelae resulting from lack of efficacy will be reported as AE or SAE if they fulfil the 
definition of an AE or SAE.  
 
 
Events NOT Meeting the AE Definition  
• 
Any clinically significant abnormal laboratory findings or other abnormal safety assessments which are 
associated with the underlying disease, unless judged by the Investigator to be more severe than 
expected for the participant’s condition. 
• 
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to the 
procedure is the AE. 
• 
Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital). 
• 
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. 
Serious Adverse Event Definition 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (eg, hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease). 
An SAE is defined as an AE that, at any dose: 
1. Results in death 
2. Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the participant was at risk 
of death at the time of the event. It does not refer to an event, which hypothetically might have caused 
death, if it were more severe. 
3. Requires inpatient hospitalization or prolongation of existing hospitalization 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 56 of 82 
Alexion Confidential 
An SAE is defined as an AE that, at any dose: 
In general, hospitalization signifies that the participant has been detained (usually involving at least an 
overnight stay) at the hospital or emergency ward for observation and/or treatment that would not have 
been appropriate in the physician’s office or outpatient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfills any other serious criteria, the 
event is serious. When in doubt as to whether “hospitalization” occurred or was necessary, the AE should 
be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from baseline is not 
considered an AE. 
4. Results in persistent disability/incapacity 
• 
The term disability means a substantial disruption of a person’s ability to conduct normal life 
functions. 
• 
This definition is not intended to include experiences of relatively minor medical significance such as 
uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma (eg, sprained 
ankle) which may interfere with or prevent everyday life functions but do not constitute a substantial 
disruption. 
5. Is a congenital anomaly/birth defect 
6. Other situations: 
• 
Medical or scientific judgment should be exercised in deciding whether SAE reporting is appropriate 
in other situations such as important medical events that may not be immediately life-threatening or 
result in death or hospitalization but may jeopardize the participant or may require medical or surgical 
drug to prevent one of the other outcomes listed in the above definition. These events should usually 
be considered serious. 
• 
Examples of such events include invasive or malignant cancers, intensive treatment in an emergency 
room or at home for allergic bronchospasm, blood dyscrasias or convulsions that do not result in 
hospitalization, or development of drug dependency or drug abuse. 
Recording and Follow-Up of Adverse Event and/or Serious Adverse Event 
Adverse Event and Serious Adverse Event Recording 
• 
When an AE/SAE occurs, it is the responsibility of the Investigator to review all documentation (eg, 
hospital progress notes, laboratory reports, and diagnostics reports) related to the event. 
• 
The Investigator will then record all relevant AE or SAE information in the eCRF. 
• 
It is not acceptable for the Investigator to send photocopies of the participant’s medical records to 
Alexion in lieu of completion of the AE/SAE eCRF page. 
• 
There may be instances when copies of medical records for certain cases are requested by Alexion. In 
this case, all participant identifiers, with the exception of the participant number, will be redacted on 
the copies of the medical records before submission to Alexion. 
• 
The Investigator will attempt to establish a diagnosis of the event based on signs, symptoms, and/or 
other clinical information. Whenever possible, the diagnosis (not the individual signs/symptoms) will 
be documented as the AE/SAE. 
Assessment of Intensity 
The Investigator will make an assessment of intensity for each AE and SAE reported during the study and 
assign it to 1 of the following categories from National Cancer Institute CTCAE v5.0, published 27 Nov 
2017:  
• 
Grade 1: Mild (awareness of sign or symptom, but easily tolerated) 
• 
Grade 2: Moderate (discomfort sufficient to cause interference with normal activities) 
• 
Grade 3: Severe (incapacitating, with inability to perform normal activities) 
• 
Grade 4: Life-threatening 
• 
Grade 5: Fatal 
 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 57 of 82 
Alexion Confidential 
Assessment of Causality 
• 
The Investigator is obligated to assess the relationship between the study drug and each occurrence 
of each AE or SAE. An Investigator causality assessment must be provided for all AEs (both 
nonserious and serious). This assessment must be recorded in the eCRF and on any additional 
forms, as appropriate. The definitions for the causality assessments are as follows: 
− 
Not related: There is no reasonable possibility the study intervention caused the 
adverse event. 
 
The adverse event has a more likely alternative etiology; it may be due to 
underlying or concurrent illness, complications, concurrent treatments, or 
effects of another concurrent drug. 
 
The event does not follow a reasonable temporal relationship to 
administration of the study intervention. 
− 
Related: There is a reasonable possibility the study intervention caused the adverse 
event. 
 
The adverse event has a temporal relationship to the administration of the 
study intervention. 
 
The event does not have a likely alternative etiology. 
 
The event corresponds with the known pharmaceutical profile of the study 
intervention. 
− 
There is improvement on discontinuation and/or reappearance on rechallenge. 
• 
The Investigator will use clinical judgment to determine the relationship. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, as 
well as the temporal relationship of the event to study drug administration will be considered and 
investigated. 
• 
This protocol will use the current Investigator’s Brochure as the Reference Safety Document. The 
expectedness and reporting criteria of an SAE will be determined by Alexion, based on the 
Reference Safety Document. The Investigator will also consult the Investigator’s Brochure (IB) in 
his/her assessment. 
• 
For each AE/SAE, the Investigator must document in the medical notes that he/she has reviewed 
the AE/SAE and has provided an assessment of causality. 
− 
There may be situations in which an SAE has occurred, and the Investigator has minimal 
information to include in the initial report to Alexion. However, it is very important 
that the Investigator always makes an assessment of causality for every event before 
the initial transmission of the SAE data to Alexion or designee. 
• 
The Investigator may change his/her opinion of causality in light of follow-up information and 
send a SAE follow-up report with the updated causality assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements.  
 
Follow-up of Adverse Events and Serious Adverse Events 
• 
The Investigator is obligated to perform or arrange for the conduct of supplemental measurements 
and/or evaluations as medically indicated or as requested by Alexion to elucidate the nature and/or 
causality of the AE or SAE as fully as possible. This may include additional laboratory tests or 
investigations, histopathological examinations, or consultation with other health care professionals. 
• 
New or updated information will be recorded in the originally completed eCRF. 
• 
The Investigator will submit any updated SAE data to Alexion within 24 hours of receipt of the 
information. 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 58 of 82 
Alexion Confidential 
10.4. 
Appendix 4: Pregnancy Information 
10.4.1. 
Definitions 
10.4.1.1. Woman of Childbearing Potential 
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile (see below). 
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study drug, additional evaluation should be considered. 
10.4.1.2. Women in the following categories are not considered WOCBP 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
• Documented hysterectomy 
• Documented bilateral salpingectomy 
• Documented bilateral oophorectomy 
• For individuals with permanent infertility due to an alternate medical cause other than the 
above, (eg, mullerian agenesis, androgen insensitivity), Investigator discretion should be 
applied to determining study entry. 
• Note: Documentation can come from the site personnel’s: review of the participant’s 
medical records, medical examination, or medical history interview. 
3. Postmenopausal female 
• A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
− A high follicle stimulating hormone (FSH) level in the postmenopausal range may 
be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the absence 
of 12 months of amenorrhea, confirmation with more than one FSH measurement 
is required. 
• Females on HRT and whose menopausal status is in doubt will be required to use one 
of the non-estrogen hormonal highly effective contraception methods if they wish to 
continue their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment. 
10.4.2. 
Contraception Guidance 
Before receiving study drug, female participants 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 FSH level (> 30 IU/L). 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 59 of 82 
Alexion Confidential 
Women 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 are: 
1. Intrauterine device in place for at least 6 weeks prior to first dose of study drug. 
2. Progestogen-only hormonal contraception associated with inhibition of ovulation (either 
oral, injectable, or implantable) for at least 6 weeks prior to first dose of study drug. 
3. Intrauterine progestogen releasing system for at least 6 weeks prior to first dose of study 
drug. 
4. Bilateral tubal occlusion for at least 6 weeks prior to first dose of study drug. 
5. Combined (estrogen- and progestogen-containing) hormonal contraception (either oral, 
intravaginal, or transdermal) for at least 6 weeks prior to first dose of study drug. 
6. Surgical sterilization of the male partner (medical assessment of azoospermia is required 
if vasectomy was performed within the prior 6 months prior to the first dose of study 
drug). Male partner is still required to use condom during sexual intercourse. 
7. Sexual abstinence for female participants: 
• Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse. In this study, abstinence is only acceptable 
if consistent with the participant’s preferred and usual lifestyle. Abstinent female 
participants must refrain from heterosexual intercourse for at least 8 months after the 
final dose of study drug. 
Other methods of contraception that are not considered highly effective for female participants 
but are acceptable birth control methods that result in a failure rate of more than 1% per year 
include: 
• Progestogen-only oral hormonal contraception, where inhibition of ovulation is not 
the primary mode of action 
• Male or female condom with or without spermicide 
• Cap, diaphragm, or sponge with spermicide 
• A combination of male condom with cap, diaphragm, or sponge with spermicide 
(double-barrier methods) 
Female participants must not donate ova from the Day 1 Visit at least until 8 months after their 
final dose of study drug. 
The following methods of contraception are considered unacceptable in this study: 
• Periodic abstinence (calendar, symptothermal, or post ovulation methods) 
• Withdrawal (coitus interruptus) 
• Spermicides only 
• Lactational amenorrhea method 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 60 of 82 
Alexion Confidential 
• Female condom and male condom should not be used together 
10.4.3. 
Pregnancy Testing 
Participants of childbearing potential should only be included after a menstrual period and a 
negative highly sensitive serum pregnancy test. 
Additional pregnancy testing should be performed per the time points specified in the SoA 
(Section 1.3). 
Pregnancy testing will be performed whenever a menstrual cycle is missed or when pregnancy is 
otherwise suspected. 
10.4.4. 
Collection of Pregnancy Information 
10.4.4.1. Male Participants with Partners who Become Pregnant 
• The Investigator will attempt to collect pregnancy information on any male 
participant’s female partner who becomes pregnant while the male participant is in 
this study. This applies only to male participants who receive study drug. 
• After obtaining the necessary signed informed consent from the pregnant female 
partner directly, the Investigator will record pregnancy information on the appropriate 
form and submit it to Alexion within 24 hours of learning of the partner’s pregnancy. 
The female partner will also be followed to determine the outcome of the pregnancy. 
Information on the status of the mother and child will be forwarded to Alexion. 
Generally, the follow-up of the baby will be no longer than 3 months after the birth of 
the baby. Any termination of the pregnancy will be reported regardless of fetal status 
(presence or absence of anomalies) or indication for the procedure. 
10.4.4.2. Female Participants who Become Pregnant 
• The Investigator will collect pregnancy information on any female participant who 
becomes pregnant while participating in this study. The initial Information will be 
recorded on the appropriate form and submitted to Alexion within 24 hours of 
learning of a participant's pregnancy. 
• The participant will be followed to determine the outcome of the pregnancy. The 
Investigator will collect follow-up information on the participant and the neonate and 
the information will be forwarded to Alexion. Generally, follow-up of the baby will 
occur at 3 months after birth. Any termination of pregnancy will be reported, 
regardless of fetal status (presence or absence of anomalies) or indication for the 
procedure. 
• While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be 
reported as an AE or SAE. A spontaneous abortion (occurring at < 22 weeks 
gestational age) or still birth (occurring at > 22 weeks gestational age) is always 
considered to be an SAE and will be reported as such. Any post-study pregnancy 
related SAE considered reasonably related to the study drug by the Investigator will 
be reported to Alexion as described in Section 8.3.5. While the investigator is not 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 61 of 82 
Alexion Confidential 
obligated to actively seek this information in former study participants, he or she may 
learn of an SAE through spontaneous reporting. 
• Any female participant who becomes pregnant while participating in the study will 
discontinue study drug, and each pregnancy will be followed to term and Alexion 
notified regarding the outcome.

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 62 of 82 
Alexion Confidential 
10.5. 
Appendix 5: Questionnaires PNH Symptoms and Health Resource 
Utilization 
10.5.1. 
PNH Patient-Reported Symptoms questionnaire 
 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 63 of 82 
Alexion Confidential 
 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 64 of 82 
Alexion Confidential 
 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 65 of 82 
Alexion Confidential 
 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 66 of 82 
Alexion Confidential 
 
 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 67 of 82 
Alexion Confidential 
 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 68 of 82 
Alexion Confidential 
 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 69 of 82 
Alexion Confidential 
 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 70 of 82 
Alexion Confidential 
 
 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 71 of 82 
Alexion Confidential 
 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 72 of 82 
Alexion Confidential 
 
 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 73 of 82 
Alexion Confidential 
 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 74 of 82 
Alexion Confidential 
10.5.2. 
Health Resource Utilization questionnaire 
 
 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 75 of 82 
Alexion Confidential 
10.6. 
Appendix 6: 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-401 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 7. Depending on the availability of approved COVID-19 
vaccines and country-specific and/or local recommendations, a participant may have been 
vaccinated against COVID-19. 
Table 7: 
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 is also 
evaluated for the capacity to 
perform remote monitoring 
visits and remote source data 
verification. 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 76 of 82 
Alexion Confidential 
Table 7: 
Potential Risks and Mitigation Measures due to COVID-19 
Risks Category 
Summary of Data/ 
Rationale for Risk 
Mitigation Strategy 
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; SARS-CoV-2 = severe acute respiratory syndrome 
coronavirus 2. 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 77 of 82 
Alexion Confidential 
10.7. 
Appendix 7: 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 6.5.1. 
Vaccination may further activate complement. As a result, patients with complement-mediated 
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 8.  
Table 8: 
Potential Risks and Mitigation Measures due to COVID-19 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). 
Abbreviations: COVID-19 = coronavirus disease 2019; eCRF: electronic case report form 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 78 of 82 
Alexion Confidential 
10.8. 
Appendix 8: Abbreviations 
Abbreviation 
Definition 
ADA 
antidrug antibody 
AE 
adverse event 
AESI 
adverse event of special interest 
BTH 
breakthrough hemolysis 
C5 
component C5 
CDR 
complementarity determining region 
CFTG 
Clinical Trials Facilitation and Coordination Group 
CIOMS 
Council for International Organizations of Medical Sciences  
CONSORT 
Consolidated Standards of Reporting Trials  
COVID-19 
Coronavirus Disease 2019 
CSR 
clinical study report 
DMC 
Data Monitoring Committee 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
ET 
early termination 
FAS 
full analysis set 
FSH 
follicle stimulating hormone  
GCP 
Good Clinical Practice 
GPI 
glycophosphatidylinositol 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
human immunodeficiency virus 
HRT 
hormonal replacement therapy  
HRU 
Health Resource Utilization 
IB 
Investigator's Brochure 
ICH 
International Conference on Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use 
IEC 
Independent Ethics Committee 
IgA 
immunoglobulin A 
INR 
international normalized ratio  
IRB 
Institutional Review Board 
IST 
immunosuppressant therapy 
IV 
Intravenous 
LDH 
lactate dehydrogenase 
LDH-PCHG 
lactate dehydrogenase percent change 
mAb 
monoclonal antibody 
MAVE 
major adverse vascular events  
MMRM 
mixed model for repeated measures  
N. meningitidis  
Neisseria meningitidis  
NO 
nitric oxide 
PD 
Pharmacodynamics 
PK 
Pharmacokinetics 
PNH 
Paroxysmal Nocturnal Hemoglobinuria 
PRS 
PNH Patient-Reported Symptoms 
PT 
Preferred Term 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 79 of 82 
Alexion Confidential 
Abbreviation 
Definition 
q2w 
every 2 weeks 
q8w 
every 8 weeks 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SoA 
Schedule of Activities 
SOC 
system organ class 
SUSARs 
suspected unexpected serious adverse reactions  
TEAE 
treatment-emergent adverse event 
TESAE 
treatment-emergent serious adverse event 
ULN 
upper limit of normal 
WHODrug 
World Health Organization Drug Dictionary  
WOCBP 
woman of childbearing potential 
 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 80 of 82 
Alexion Confidential 
10.9. 
Appendix 9: Protocol Amendment History 
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the Table of Contents (TOC). 
Amendment 1 (29 Jan 2020) 
Overall Rationale for the Amendment: 
The main rationale for this Amendment was to allow administration of eculizumab at the 
participant’s home at the discretion of the Investigator during Screening to reduce the burden of 
clinical visits. In addition, 2 specific patient-reported outcomes (Patient-Reported Symptoms 
[PRS] and Healthcare Resource Utilization [HRU]) are being included for exploratory data 
analysis. 
Other changes implemented through this Amendment constitute minor editorial corrections and 
fixing inconsistencies. 
Amendment 2 (15 Feb 2021) 
Overall Rationale for the Amendment: 
The main rationale for this Amendment was to allow treatment continuity and ensure patient 
safety during the Coronavirus Disease 2019 (COVID-19) pandemic by introducing the option for 
patients to receive ravulizumab administration from a qualified healthcare personnel at the 
patient’s home or at a medical facility that is located near the patient’s home. 
Other changes implemented through the Protocol Amendment constituted updating the 
contraception guidance based on the most recent Clinical Trials Facilitation and Coordination 
Group (CFTG) requirements. 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 81 of 82 
Alexion Confidential 
11. 
REFERENCES 
Borowitz MJ, et al. Guidelines for the diagnosis and monitoring of paroxysmal nocturnal 
hemoglobinuria and related disorders by flow cytometry. Cytometry Part B: Clinical Cytometry. 
2010;78B(4):211-230. 
Brodsky RA. Paroxysmal nocturnal hemoglobinuria. Blood. 2014;124(18):2804-2811. 
Brodsky RA. Complement in hemolytic anemia. Blood. 2015;126(22):2459-2465. 
 
Casadevall N, et al. Pure red-cell aplasia and antierythropoietin antibodies in patients treated 
with recombinant erythropoietin. N Engl J Med. 2002;346(7):469-475. 
Hill A, Kelly RJ, Hillmen P. Thrombosis in paroxysmal nocturnal hemoglobinuria. Blood. 
2013;121(25):4985-4996. 
Hill A, et al. Sustained response and long-term safety of eculizumab in paroxysmal nocturnal 
hemoglobinuria. Blood. 2005;106(7):2559-2565. 
Hill A, et al. Under-recognized complications in patients with paroxysmal nocturnal 
haemoglobinuria: raised pulmonary pressure and reduced right ventricular function. Br J 
Haematol. 2012;158(3):409-414. 
Hillmen P, 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. 
Kelly R, et al. Modification of the eculizumab dose to successfully manage intravascular 
breakthrough hemolysis in patients with paroxysmal nocturnal hemoglobinuria. Blood. 
2008;112(11):3441. 
Kulasekararaj AG, et al. Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor–experienced 
adult patients with PNH: the 302 study. Blood. 2019;133(6):540-549. 
Li J, et al. Thrombocytopenia caused by the development of antibodies to thrombopoietin. 
Blood. 2001;98(12):3241-3248. 
Mallinckrodt CH, Clark WS, David SR. Accounting for dropout bias using mixed-effects 
models. J Biopharm Stat. 2001;11(1-2):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. Clin Trials. 
2004;1(6):477-489. 
Matis LA, Rollins SA. Complement-specific antibodies: Designing novel anti-inflammatories. 
Nat Med. 1995;1(8):839-842. 
Peffault de Latour R, et al. Assessing complement blockade in patients with paroxysmal 
nocturnal hemoglobinuria receiving eculizumab. Blood. 2015;125(5):775-783. 
Prodinger W, Wurzner R, Erdei A, Dierich M. Complement. In: William PE, editor. 
Fundamental Immunology. 4th ed. Philadelphia: Lippincott-Raven; 1999. p. 967-995. 
Schulz KF, Altman DG, Moher D, Group C. CONSORT 2010 Statement: Updated Guidelines 
for Reporting Parallel Group Randomized Trials. Ann Int Med. 2010;152(11):726-732. 

Protocol ALXN1210-PNH-401 
Alexion Pharmaceuticals, Inc. 
Amendment 3.0 07 May 2021 
Page 82 of 82 
Alexion Confidential 
Socié G, et al. Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic 
factors. The Lancet. 1996;348(9027):573-577.