A Phase 2, Open-label, Multiple Ascending Dose Study to Evaluate the Efficacy, Safety, Tolerability, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of ALXN1210 Administered Intravenously to Patients With Paroxysmal Nocturnal Hemoglobinuria
Phase: PHASE2
Conditions: Paroxysmal Nocturnal Hemoglobinuria, PNH
Sponsor: Alexion Pharmaceuticals, Inc.

A PHASE 2, OPEN-LABEL, MULTIPLE ASCENDING
DOSE STUDY TO EVALUATE THE EFFICACY, SAFETY, 
TOLERABILITY, IMMUNOGENICITY, 
PHARMACOKINETICS, AND PHARMACODYNAMICS 
OF ALXN1210 ADMINISTERED INTRAVENOUSLY TO 
PATIENTS WITH PAROXYSMAL NOCTURNAL 
HEMOGLOBINURIA
Unique Protocol ID:  
ALXN1210-PNH-201
NCT Number:   
 
NCT02605993
EudraCT Number:   
2015-002674-20
Date of Protocol:  
 
9 May 2018

A L X N 1 2 1 0 -P N H -2 0 1  
  
Ale xi o n P har mace uticals, I nc.  
A me n d me nt 5, 0 9 Ma y 2 0 1 8  
 
TI T L E P A G E  
A L X N 1 2 1 0  
A L X N 1 2 1 0 -P N H -2 0 1  
A P H A S E 2, O P E N -L A B E L, M U L TI P L E A S C E N DI N G D O S E S T U D Y T O 
E V A L U A T E T H E E F FI C A C Y, S A F E T Y, T O L E R A BI L I T Y, 
I M M U N O G E NI CI T Y, P H A RM A C O KI N E TI C S, A N D 
P H A R M A C O D Y N A MI C S O F A L X N 1 2 1 0 A D MI NI S T E R E D 
I N T R A V E N O U S L Y T O P A TI E N T S WI T H P A R O X Y S M AL N O C T U R N A L 
H E M O G L O BI N U RI A  
S p o ns or : 
Ale xi o n P har mace uticals, I nc.  
 
Ne w Ha ve n, C T 0 6 5 1 0  U S A 
S p o ns or C o ntact:  
 
Ass ociate Direct or, Gl o bal Cli nical O perati o ns  
Ale xi o n P har ma G m b H  
 
8 0 4 5 Z uric h  
Tele p h o ne: 
 
E mail: 
 
Me dical M o nit or:  
 M D, P h D 
Direct or, Gl o bal Me dical Scie nces  
Ale xi o n P har mace uticals, I nc.  
  
Ne w Ha ve n, C T 0 6 5 1 0 U S A  
Tele p h o ne: 
 
E mail: 
 
Versi o ns  
Ori gi nal Pr ot oc ol, date d 1 4 J ul 2 0 1 5  
 
A me n d me nt 1, date d 2 2  Mar 2 0 1 6  
 
A me n d me nt 2, date d 0 2 A u g 2 0 1 6  
 
A me n d me nt 2. 1 ( U K), date d 0 4 A u g 2 0 1 6  
 
A me n d me nt 3  ( Gl o bal), 3. 1 ( U K), date d 0 7 Mar 2 0 1 7 
 
A me n d me nt 4  ( Gl o bal), 4. 1 ( U K) , date d 1 8 Dec 2 0 1 7  
 
A me n d me nt 5 ( Gl o bal), 5. 1 ( U K), date d 0 9 Ma y  2 0 1 8  
I N D N u m ber: 
1 2 8 3 6 7  
E u dra C T N u m ber:  
2 0 1 5 -0 0 2 6 7 4 -2 0  
T his pr ot oc ol c o ntai ns c o nfi de ntial i nf or mati o n a n d is pr o vi de d f or e xcl usi ve use of I n vesti gat ors.  T his i nf or mati o n ma y o nl y be 
Pa ge 1 of 8 6  
Ale xi o n C o nfi de ntial  
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
disclosed to those persons involved in this study who have a need to know with the obligation not to further disseminate this 
information. This information may not be disclosed to other individuals unless such disclosure is required by federal or state law 
or regulations subject to the foregoing. These restrictions on disclosure will apply equally to all future oral or written information 
supplied to you by Alexion which is designated as “privileged” or “confidential.” 
Page 2 of 86 
Alexion Confidential 

P P D
P P D

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
INVESTIGATOR’S AGREEMENT 
 
I have received and read the current Investigator’s Brochure for ALXN1210. I have read the 
ALXN1210-PNH-201, Amendment 5 study protocol and agree to conduct the study in 
accordance with this protocol (A Phase 2, Open-label, Multiple Ascending Dose Study to 
Evaluate the Efficacy, Safety, Tolerability, Immunogenicity, Pharmacokinetics, and 
Pharmacodynamics of ALXN1210 Administered Intravenously to Patients with Paroxysmal 
Nocturnal Hemoglobinuria), all applicable government regulations, the principles of the 
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for 
Human Use Guideline for Good Clinical Practice (E6), and the principles of the World Medical 
Association Declaration of Helsinki. I also agree to maintain the confidentiality of all 
information received or developed in connection with this protocol. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Printed Name of Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date 
Page 4 of 86 
Alexion Confidential 

A L X N 1 2 1 0 -P N H -2 0 1  
  
Ale xi o n P har mace uticals, I nc.  
A me n d me nt 5, 0 9 Ma y 2 0 1 8  
P R O C E D U R E S I N C A S E O F E M E R G E N C Y  
 
T a ble 1: 
E mer ge nc y C o nt act I nf or m ati o n  
R ole i n St u d y  
N a me  
A d dress a n d Tele p h o ne N u m ber  
Cli nical Pr oject Lea d  
  
Ass ociate Direct or,  
Gl o bal Cli nical O perati o ns  
Ale xi o n P har ma G m b H  
  
8 0 4 5 Z uric h 
Tele p h o ne: 
  
M o bile: 
 
E mail: 
  
Res p o nsi ble P h ysicia n  
 M D, P h D 
Direct or,  
Gl o bal Me dical Scie nces  
Ale xi o n P har mace uticals, I nc.  
  
Ne w Ha ve n, C T 0 6 5 1 0   
U S A  
Tele p h o n e: 
 
M o bile: 
 
E mail: 
 
 
 
Pa ge 5 of 8 6  
Ale xi o n C o nfi de ntial  
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
1. 
SYNOPSIS 
Name of Sponsor/Company: Alexion Pharmaceuticals, Inc. 
Name of Investigational Product: ALXN1210 
Name of Active Ingredient: ALXN1210 
Title of Study: A Phase 2, Open-label, Multiple Ascending Dose Study to Evaluate the Efficacy, Safety, 
Tolerability, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of ALXN1210 Administered Intravenously 
to Patients with Paroxysmal Nocturnal Hemoglobinuria 
Protocol No: ALXN1210-PNH-201, Amendment 5 
EudraCT Number: 2015-002674-20 
Study Center(s): 
The study will be conducted in patients with paroxysmal nocturnal hemoglobinuria (PNH) at multiple centers in 
multiple countries. 
Studied Period (years):  
Estimated date first patient enrolled: Q4 2015 
Estimated date last patient completed: Q2 2020  
Phase of Development: 2 
 
Objectives:  
Primary: 
• 
To evaluate the efficacy, safety, and tolerability of multiple doses of ALXN1210 administered intravenously 
(IV) to complement inhibitor treatment-naïve patients with PNH 
Secondary: 
• 
To characterize the pharmacokinetic (PK) and pharmacodynamic (PD) effects of multiple doses of 
ALXN1210 administered IV to complement inhibitor treatment-naïve patients with PNH  
• 
To investigate the immunogenicity of ALXN1210 administered IV to complement inhibitor treatment-naïve 
patients with PNH 
Study Rationale: 
This is a dose ranging and dose-regimen ranging study designed based on the PK/PD-safety data generated from the 
single-ascending dose (SAD) and multiple-ascending dose (MAD) studies to help design a dose and dose regimen for 
the Phase 3 study(ies). It is anticipated that the planned starting and maintenance doses in this study will maintain 
drug levels above the current target efficacious trough level in addition to including the higher end of drug exposures 
to accumulate sufficient safety data prior to the start of Phase 3 study(ies). The dose regimens selected for the study 
are based on the emerging PK/PD data from the ongoing studies. 
Dose Rationale: 
Initial analyses supporting dose and dose regimen selection for Study ALXN1210-PNH-201 utilized data from the 
SAD study (ALXN1210-HV-101) in healthy volunteers. The PK data following single subtherapeutic doses (200 mg 
and 400 mg) of ALXN1210 to healthy volunteers (ALXN1210-HV-101) yielded an estimated mean (range) 
elimination half-life of ALXN1210 of ~31 (27-38) days. The initial PK/PD data estimated a target efficacious trough 
level of ≥100 μg/mL to design dose regimens for this study. The targeted efficacious trough level is defined as 
concentration achieving complete complement inhibition (≥ 99%) in all patients (≥ 97.5%). Subsequent population 
PK analyses, utilizing emerging PK data from both healthy volunteers and patients with PNH across a wider range of 
doses, exposures, and durations, suggest the median (95% confidence interval) elimination half-life of ALXN1210 is 
~43 days (39-48). This change in the estimate of elimination half-life of ALXN1210 following multiple dose 
administrations in healthy volunteers and patients with PNH has resulted in an increase in the estimated target trough 
concentrations in Cohorts 1-3 and has presented the opportunity to explore dosing ALXN1210 less frequently. It is 
also desirable to target a trough level that will achieve complete complement inhibition in all PNH patients. 
Therefore, to provide safety and PK/PD support for an optimized Phase 3 dosing regimen characterization, it is 
necessary to evaluate the dose regimen ranging in this protocol from once every month dosing to once every 3 month 
dosing as enabled by the increased estimated elimination half-life, taking into account the current estimates of 
targeted efficacious ALXN1210 trough level.  
It was anticipated that the planned starting and maintenance doses in this study would maintain the drug levels above 
the current target efficacious trough level in addition to including the higher end of drug exposures to accumulate 
sufficient safety data prior to the start of Phase 3 study(ies). The weight-based dosages of ALXN1210 for the 
extension phase are premised on PK/PD data from the induction and maintenance phases of this study as well as from 
Page 6 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
early development studies in healthy adult volunteers and an ongoing Phase 1b study (ALXN1210-PNH-103) in 
patients with PNH. The selection of ALXN1210 dose regimen is based on targeting immediate, complete, and 
sustained inhibition of terminal complement activity in patients with PNH. 
Methodology: 
ALXN1210-PNH-201 is an open-label, multiple ascending dose study to evaluate the efficacy, safety, tolerability, 
immunogenicity, PK, and PD of multiple doses of ALXN1210 administered IV to patients with PNH who have not 
previously been treated with a complement inhibitor.  
Four treatment cohorts and up to 26 patients (at least 6 per cohort) are planned for enrollment, with at least 
20 patients planned for evaluation. All patients are to be screened for study eligibility after providing written 
informed consent to participate. Patients who fail to meet any of the eligibility criteria may be rescreened once for 
study participation, at the discretion of the Investigator. 
Patients enrolled in Cohort 1 will receive induction doses of ALXN1210 of 1400 mg on Day 1 and 1000 mg on 
Day 15. On Day 29 they will receive the first of 8 maintenance doses of 1000 mg of ALXN1210 (administered every 
28 days or 4 weeks) (Table s1). Patients enrolled in Cohort 2 will receive induction doses of ALXN1210 of 2000 mg 
on Day 1 and 1600 mg on Day 22. On Day 43 they will receive the first of 5 maintenance doses of 1600 mg of 
ALXN1210 (administered every 42 days or 6 weeks). Patients enrolled in Cohort 3 will receive induction doses of 
ALXN1210 of 1600 mg on Day 1 and 1600 mg on Day 15. On Day 29 they will receive the first of 4 maintenance 
doses of 2400 mg of ALXN1210 (administered every 56 days or 8 weeks). Patients enrolled in Cohort 4 will receive 
an induction dose of ALXN1210 of 3000 mg on Day 1. On Day 29 they will receive the first of 3 maintenance doses 
of 5400 mg of ALXN1210 (administered every 84 days or 12 weeks). The first 2 patients in Cohort 4 will receive 
their induction dose (3000 mg) at least 1 day apart. The third patient will receive the induction dose at least 7 days 
after the second patient has received the induction dose.  
An independent Data Monitoring Committee (DMC) will review and evaluate the study data for patient safety and 
make recommendations on dose escalation, continuing dosing within the cohort, modification, or termination of the 
study. The DMC will conduct a review of the available safety data at the following scheduled time points:  
• 
Fifteen days after the second patient in Cohort 1 receives the second induction dose to determine whether 
Cohort 2 can be opened.  
• 
Fifteen days after the second patient in Cohort 2 receives the second induction dose to determine whether 
Cohort 3 can be opened.  
• 
Fifteen days after the second patient in Cohort 3 receives the first maintenance dose to determine whether 
Cohort 4 can be opened. 
• 
Approximately 7 days after the second patient in Cohort 4 receives the 3000 mg dose to review safety. 
• 
Approximately 7 days after the second patient in Cohort 4 receives the first 5400 mg dose to review safety. 
If additional patients are screened and are eligible for enrollment before a dose-escalation decision has been made by 
the DMC for any cohort, those patients will be assigned to the active cohort with the lowest dose level.  
On Day 253 patients will continue treatment in a long-term Extension Period of the study, at the same maintenance 
dose and frequency as their final dose of ALXN1210 administered during the Treatment Period and receive 
ALXN1210 until the product is registered or approved (in accordance with country-specific regulations) or for up to 
5 years, whichever occurs first. Beginning on Day 463 for patients in Cohort 2, Day 477 for patients in Cohort 3, and 
Day 533 for patients in Cohort 1, patients will switch from their current dose regimen to a q8w, weight-based 
regimen, as follows: 3000 mg for patients weighing ≥ 40 to < 60 kg, 3300 mg for patients weighing ≥ 60 to < 100 kg, 
and 3600 mg for patients weighing ≥ 100 kg. The dose regimen will not change for patients in Cohort 4. Beginning 
on Day 953 for patients in Cohort 4, Day 981 for patients in Cohort 3, Day 1023 for patients in Cohort 2, and 
Day 1037 for patients in Cohort 1 patients will switch from the 10 mg/mL ALXN1210 unit dose formulation to the 
100 mg/mL ALXN1210 unit dose formulation, while remaining on their current dose regimen. This transition will 
reduce the number of vials needed for each infusion and the duration of the infusion. 
Up to 30 days will be allowed for screening procedures. The total duration of treatment (which includes an Induction 
Period and a Maintenance Period) is approximately 253 days. The total duration of the Extension Period is up to 
Page 7 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
approximately 5 years.  
The dosing schedule is provided in Table s1 and the overall study design is presented in Figure s1. 
Table s1: 
Dosing Schedule 
Cohort 
Patients 
Induction 
Maintenance 
1 
6 
1400 mg on Day 1 
1000 mg on Day 15 
• 
1000 mg on Day 29 and then every 28 days or 4 weeks 
(Days 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365, 
393, 421, 449, 477)  
• 
Weight-baseda dose on Day 533 and then every 8 weeks 
(Days 589, 645, 701, 757, 813, 869, 925, 981, 1037b, 1093, 
1149, 1205, 1261, 1317, 1373, 1429, 1485, 1541, 1597, 1653, 
1709, 1765, 1821, 1877, 1933, 1989, 2045, 2101) 
2  
6 
2000 mg on Day 1 
1600 mg on Day 22 
• 
1600 mg on Day 43 and then every 42 days or 6 weeks 
(Days 85, 127, 169, 211, 253, 295, 337, 379, 421) 
• 
Weight-baseda dose on Day 463 and then every 8 weeks 
(Days 519, 575, 631, 687, 743, 799, 855, 911, 967, 1023b, 1079, 
1135, 1191, 1247, 1303, 1359, 1415, 1471, 1527, 1583, 1639, 
1695, 1751, 1807, 1863, 1919, 1975, 2031, 2087) 
3  
6 
1600 mg on Day 1 
1600 mg on Day 15 
• 
2400 mg on Day 29 and then every 56 days or 8 weeks 
(Days 85, 141, 197, 253, 309, 365, 421)  
• 
Weight-baseda dose on Day 477 and then every 8 weeks 
(Days 533, 589, 645, 701, 757, 813, 869, 925, 981b, 1037, 1093, 
1149, 1205, 1261, 1317, 1373, 1429, 1485, 1541, 1597, 1653, 
1709, 1765, 1821, 1877, 1933, 1989, 2045, 2101) 
4 
6 to 8 
3000 mg on Day 1 
• 
5400 mg on Day 29 and then every 84 days or 12 weeks 
(Days 113, 197, 281, 365, 449, 533, 617, 701, 785, 869, 953b, 
1037, 1121, 1205, 1289, 1373, 1457, 1541, 1625, 1709, 1793, 
1877, 1961, 2045)  
a 
3000 mg for patients weighing ≥ 40 to < 60 kg, 3300 mg for patients weighing ≥ 60 to < 100 kg, and 3600 mg 
for patients weighing ≥ 100 kg. 
b 
Beginning on Day 953 for patients in Cohort 4, Day 981 for patients in Cohort 3, Day 1023 for patients in 
Cohort 2, and Day 1037 for patients in Cohort 1, patients will switch from the 10 mg/mL ALXN1210 unit dose 
formulation to the 100 mg/mL ALXN1210 unit dose formulation, while remaining on their current dose 
regimen. 
 
Page 8 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
Figure s1: 
ALXN1210-PNH-201 Study Schematic 
 
 
a Beginning at Day 463 (Cohort 2), Day 477 (Cohort 3), and Day 533 (Cohort 1), weight-based maintenance doses 
will be administered as follows: 3000 mg for patients weighing ≥ 40 to < 60 kg, 3300 mg for patients weighing ≥ 60 
to < 100 kg, and 3600 mg for patients weighing ≥ 100 kg.  
Number of Patients (planned): 
Up to 26 patients (at least 6 per cohort) are planned for enrollment, with at least 20 patients planned for evaluation. 
Diagnosis and Main Criteria for Inclusion:  
Patients must meet all inclusion and no exclusion criteria. Patients who fail any of the eligibility criteria may be 
rescreened once for participation, at the Investigator’s discretion. 
Inclusion Criteria: 
1. Male or female patients ≥ 18 years of age 
2. PNH diagnosis confirmed by documented high-sensitivity flow cytometry (red blood cells [RBCs] and/or 
granulocytes)  
3. Mean lactate dehydrogenase (LDH) ≥ 3 × upper limit of normal, based on 2 measurements from separate 
blood samples collected at least 1 day apart during screening 
4. Willing and able to give written informed consent and comply with the study visit schedule  
5. Documented meningococcal vaccination not more than 3 years prior to dosing 
6. Female patients who consider themselves postmenopausal must provide evidence at screening of menopause 
status, based on a combination of amenorrhea for at least 1 year and increased serum follicle-stimulating 
hormone level (> 30 IU/L) on at least 2 occasions (eg, in the absence of hormone replacement therapy, 
dietary phytoestrogens) or estradiol concentration < 10 pg/mL. 
7. Female patients of childbearing potential must use highly effective contraception as defined below, starting 
at screening and continuing until at least 8 months after the last dose of ALXN1210. Highly effective 
contraceptive methods are as follows: 
a. 
Combined (estrogen and progestogen) hormonal contraception associated with inhibition of 
ovulation: 
Page 9 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
i. Oral 
ii. Intravaginal 
iii. Transdermal 
b. Progesterone-only hormonal contraception associated with inhibition of ovulation 
i. Oral 
ii. Injectable 
iii. Implantable 
c. 
Intrauterine device 
d. Intrauterine hormone-releasing system 
e. 
Bilateral tubal occlusion 
f. 
Vasectomized partner, provided that the partner is the patient’s sole sexual partner 
g. Sexual abstinence, defined as refraining from heterosexual intercourse during the entire period of 
risk associated with the study treatments; reliability of sexual abstinence needs to be evaluated in 
relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject 
h. Combination of male condom with appropriate barrier methods for the female patient (double 
barrier methods) 
8. Male patients with a female spouse/partner of childbearing potential or a pregnant or breastfeeding spouse 
or partner must agree to use barrier contraception (male condom) during the Treatment Period and for at 
least 8 months after the last dose of ALXN1210. Barrier contraception is required even with documented 
medical assessment of surgical success of a vasectomy. Female spouses/partners of male patients who are of 
childbearing potential must use highly effective contraception (as defined in inclusion criterion #7) or 
acceptable contraception, as defined below, starting at screening and continuing until at least 8 months after 
the last dose of ALXN1210. Male patients must not donate sperm during the Screening and Treatment 
Periods and for at least 8 months after the last dose of ALXN1210. 
a. 
Acceptable contraceptive methods are as follows: 
i. Simultaneous use of male condom and appropriate barrier methods for the female partner 
Exclusion Criteria: 
1. Treatment with a complement inhibitor at any time 
2. Platelet count < 30,000/mm3 (30 × 109 /L) at screening 
3. Absolute neutrophil count < 500/µL (0.5 × 109 /L) at screening 
4. History of bone marrow transplantation 
5. History of Neisseria meningitidis infection or history of unexplained, recurrent infection 
6. Female patients who are planning to become pregnant, or are pregnant or breastfeeding  
7. Positive pregnancy test at screening or Day 1 
8. Patients are excluded if they are taking any of the following medications and are not on a stable regimen (as 
judged by the Investigator) for the time period indicated prior to screening: 
a. 
Erythropoietin or immunosuppressants for at least 8 weeks  
b. Corticosteroids for at least 4 weeks  
c. 
Vitamin K antagonists (eg, warfarin) with a stable international normalized ratio (per Investigator 
discretion) for 4 weeks 
d. Iron supplements or folic acid for at least 4 weeks  
e. 
Low molecular weight heparin for at least 4 weeks  
9. Human immunodeficiency virus (HIV) infection (evidenced by HIV-1 or HIV-2 antibody titer) 
10. Acute or chronic hepatitis B virus infection (evidenced by the presence of hepatitis B surface antigen or 
immunoglobulin M antibodies against hepatitis B core antigen).  
11. Acute or chronic hepatitis C virus infection (evidenced by hepatitis C virus antibody) 
12. Active systemic bacterial, viral, or fungal infection within 14 days prior to dosing on Day 1 
13. Immunization with a live-attenuated vaccine 1 month prior to dosing on Day 1 
14. Participation in an interventional clinical study within 30 days before initiation of dosing on Day 1, or use of 
any experimental therapy within 30 days prior to dosing on Day 1, or within 5 half-lives of the 
investigational product, whichever is greater 
15. Major surgery within 90 days prior to dosing on Day 1 
16. Presence of fever ≥ 38 °C within 2 weeks prior to the first dosing on Day 1 
17. Patients with a history of malignancy within 5 years of screening with the exception of a nonmelanoma skin 
cancer or carcinoma in situ of the cervix that has been treated with no evidence of recurrence.   
18. Known history of severe allergic or anaphylactic reactions to any drug (including vaccines) or allergen 
Page 10 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
19. History of allergy to excipients of ALXN1210 (eg, polysorbate 80)  
20. Known allergy to Chinese hamster ovary cell proteins  
21. History of any clinically significant cardiac, hepatic, immunologic, pulmonary, or rheumatoid disease that, 
in the Investigator’s judgment, would preclude participation 
22. Inability to comply with study requirements 
23. Other unspecified reasons that, in the opinion of the Investigator or Sponsor, make the patient unsuitable for 
enrollment 
Withdrawal from the Study: 
Patients who discontinue dosing or are withdrawn from the study for any reason after receiving any dose of study 
drug should be encouraged to return for the remainder of the scheduled protocol visits. 
Investigational Product, Dosage, and Mode of Administration: 
ALXN1210 is formulated at 10 mg/mL and 100 mg/mL concentrations. Both ALXN1210 formulations are presented 
as sterile, preservative-free solutions for IV administration, will be diluted in 0.9% sodium chloride injection, and 
administered by IV infusion. 
Table s2: 
Composition of Investigational Product 
ALXN1210 Formulation 
Composition 
10 mg/mL concentration  
10 mg/mL ALXN1210 antibody in 10 mM sodium 
phosphate containing 150 mM sodium chloride, 
0.02% polysorbate 80, and pH 7.0 
100 mg/mL concentration  
100 mg/mL ALXN1210 antibody in 50 mM sodium 
phosphate containing 25 mM arginine, 5% sucrose, 
0.05% polysorbate 80, and pH 7.4 
Duration of Treatment: 
Up to 30 days will be allowed for screening procedures. The total duration of treatment (which includes an Induction 
Period and a Maintenance Period) is approximately 253 days. The total duration of the Extension Period is up to 
approximately 5 years. 
Reference Therapy, Dosage, and Mode of Administration: 
None 
Endpoints and Criteria for Evaluation: 
Primary Efficacy: 
• 
Change in LDH levels from baseline to Day 253 
Secondary Efficacy: 
• 
Changes in hemolysis-related hematologic parameters: free hemoglobin, haptoglobin, reticulocyte 
count, PNH red blood cell clone, and D-dimer 
• 
Changes in clinical manifestations: fatigue, abdominal pain, dyspnea, dysphagia, chest pain, and erectile 
dysfunction 
Exploratory Efficacy: 
• 
Change from baseline in the need for blood transfusions 
• 
Change from baseline in disease-associated biomarkers (markers of chronic kidney disease; ie, 
estimated glomerular filtration rate, spot urine albumin:creatinine ratio, and plasma brain natriuretic 
peptide for pulmonary hypertension) 
• 
Change from baseline in quality of life, assessed via the Functional Assessment of Chronic Illness 
Therapy (FACIT)-Fatigue Scale, version 4 and the European Organisation for Research and Treatment 
of Cancer, Quality of Life Questionnaire-Core 30 Scale, version 3.0  
Page 11 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
• 
Change from baseline in major adverse vascular events (MAVEs) 
Immunogenicity: 
• 
Measurement of antidrug antibodies (ADA) 
Pharmacokinetic/Pharmacodynamic: 
• 
Changes in serum ALXN1210 concentration over time  
• 
Changes in cRBC hemolytic activity 
• 
Changes in free and total C5 concentrations 
Safety: 
• 
Changes from baseline in physical examination assessments and vital signs 
• 
Change from baseline in electrocardiogram parameters 
• 
Change from baseline in laboratory assessments 
• 
Incidence of adverse events (AEs) and serious adverse events (SAEs) 
Safety Evaluation: 
Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse 
Events v4.03 grading scale. Laboratory evaluations include chemistry panel, coagulation panel, complete blood count 
with differential, and urinalysis. Potential risks of ALXN1210, specifically the risk of infection, will be reviewed 
with patients at screening and on a regular basis throughout the study. Patients will be contacted by the Investigator 
or designee to discuss potential safety risks of ALXN1210, and the Investigator or designee will address any safety 
concerns the patient has at defined times throughout the study. 
Pharmacokinetic and Pharmacodynamic Evaluations: 
Using noncompartmental PK methods, the serum concentration-versus-time data will be used to derive the following 
PK parameters: maximum observed serum concentration (Cmax) after each dose, time to maximum observed serum 
concentration (tmax), the minimum observed serum concentration (Cmin), the observed serum concentration at the end 
of the dosage interval τ (Ctrough), area under the serum concentration-versus-time curve from time 0 (dosing) to the 
last quantifiable concentration (AUCt) after each dose, area under the concentration-versus-time curve from time 0 
(dosing) to the end of the dosing interval (AUCτ), apparent terminal-phase elimination rate constant (λz), terminal 
elimination half-life (t½), and, if possible, total clearance (CL), and volume of distribution at steady-state (Vss). In 
addition, attainment of steady-state and accumulation at steady-state will be determined. The relationship between 
ALXN1210 exposure and PD markers may be assessed, and dose proportionality and time linearity in PK parameters 
may be assessed.  
Serum concentrations of ALXN1210 and blood samples for analyses of C5 levels (total and free), cRBC hemolysis, 
and quantitative measures of C5 activation will be collected at the time points specified in Table s2. Serum samples 
will be stored for additional PK/PD analyses. Assessments of PK/PD relationships may be explored using data from 
this study or in combination with data from other studies. 
Table s3: 
Collection Time Points for Serum Concentrations of ALXN1210 and Analysis of Hemolytic 
Activity 
Cohort 
Period 
Dose Number and Study Day 
Collection Windows 
1 
Treatment 
Dose 1 on Day 1 
Dose 2 on Day 15 
• 
Predose (up to 0.5 hour before) 
• 
EOI (up to 0.5 hour after) 
• 
4 hours post-SOI (±1 hour) 
• 
Day 22 (±1 day) 
Doses 3 to 11 on Days 29, 57, 85, 113, 
141, 169, 197, 225, and 253 
• 
Predose (up to 0.5 hour before) 
• 
EOI (up to 0.5 hour after) 
• 
4 hours post-SOI (±1 hour) 
Page 12 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
• 
Day 43 (±1 day) 
• 
Days 127 and 211 (±2 days) 
• 
Day 253 (up to 0.5 hour before Dose 11) 
Extension 
Doses 14, 19, 22, 25, 27, 28, 29, 30, 31, 33, 
35, 37, 39, 41, 43, 45, and 47 on Days 337, 
477, 645, 813, 925, 981, 1037, 1093, 1149, 
1261, 1373, 1485, 1597, 1709, 1821, 
1933, and 2045   
• 
Predose (up to 0.5 hour before) 
• 
When a patient discontinues the study or 
at the last study visit (Day 2157) 
2 
Treatment 
Dose 1 on Day 1 
Dose 2 on Day 22 
• 
Predose (up to 0.5 hour before) 
• 
EOI (up to 0.5 hour after) 
• 
4 hours post-SOI (±1 hour) 
• 
Day 29 (±1 day) 
Doses 3 to 8 on Days 43, 85, 127, 169, 
211, and 253 
• 
Predose (up to 0.5 hour before) 
• 
EOI (up to 0.5 hour after) 
• 
4 hours post-SOI (±1 hour) 
• 
Day 57 (±1 day) 
• 
Days 113, 141, 197, and 225 (±2 days) 
• 
Day 253 (up to 0.5 hour before Dose 8) 
Extension 
Doses 10, 14, 17, 20, 22, 23, 24, 25, 26, 28, 
30, 32, 34, 36, 38, 40, and 42 on Days 337, 
519, 687, 855, 967, 1023, 1079, 1135, 
1191, 1303, 1415, 1527, 1639, 1751, 1863, 
1975, and 2087 
• 
Predose (up to 0.5 hour before) 
• 
When a patient discontinues the study or 
at the last study visit (Day 2143) 
3 
Treatment  
Dose 1 on Day 1 
Dose 2 on Day 15 
• 
Predose (up to 0.5 hour before) 
• 
EOI (up to 0.5 hour after) 
• 
4 hours post-SOI (±1 hour) 
• 
Days 22 (±1 day) 
Doses 3 to 7 on Days 29, 85, 141, 197, and 
253 
• 
Predose (up to 0.5 hour before) 
• 
EOI (up to 0.5 hour after) 
• 
4 hours post-SOI (±1 hour) 
• 
Days 43 and 57 (±1 day) 
• 
Days 113, 127, 169, 211, and 225 
(±2 days) 
• 
Day 253 (up to 0.5 hour before Dose 7) 
Extension 
Doses 8, 11, 14, 16, 18, 19, 20, 21, 22, 24, 
26, 28, 30, 32, 34, 36, 38, and 40 on 
Days 309, 477, 645, 757, 869, 925, 981, 
1037, 1093, 1205, 1317, 1429, 1541, 1653, 
1765, 1877, 1989,  and 2101 
• 
Predose (up to 0.5 hour before) 
• 
When a patient discontinues the study or 
at the last study visit (Day 2157) 
4 
Treatment 
Dose 1 on Day 1 
 
• 
Predose (up to 0.5 hour before) 
• 
EOI (up to 0.5 hour after) 
• 
4 hours post-SOI (±1 hour) 
• 
Day 15 (±1 day) 
Doses 2 to 4 on Days 29, 113, and 197 
• 
Predose (up to 0.5 hour before) 
• 
EOI (up to 0.5 hour after) 
• 
6 hours post-SOI (±1 hour) 
• 
Day 57 (±1 day) 
• 
Days 141 and 225 (±2 days) 
• 
Day 253  
Extension 
Doses 5, 7, 9, 11, 12, 13, 14, 16, 18, 20, 22, 
24, and 26 on Days 281, 449, 617, 785, 
869, 953, 1037, 1205, 1373, 1541, 1709, 
1877, and 2045 
• 
Predose (up to 0.5 hour before) 
• 
When a patient discontinues the study or 
at the last study visit (Day 2129) 
Abbreviations: EOI = end of infusion; SOI = start of infusion 
Immunogenicity Evaluation: 
Blood samples for the analyses of ADA to ALXN1210 will be collected at the time points listed in Table s4. Please 
refer to the Laboratory Study Manual for time windows for collection and detailed instructions for collecting, 
processing, storing, and shipping blood samples for immunogenicity analysis. The total volume of blood collected 
per patient for clinical laboratory, PK, PD, and immunogenicity assessments will not exceed 300 mL in any 16-week 
period. All sample analyses will be performed by Alexion or designee. 
Page 13 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
 
 
 
Table s4: 
Collection Time Points for Serum Samples for Immunogenicity Analyses of Antidrug Antibodies 
to ALXN1210 
Cohort 1 
Predose on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 337, 477, 645, 813, 925, 981, 1037, 
1093, 1149, 1261, 1373, 1485, 1597, 1709, 1821, 1933, 2045, and 2157 or ET 
Cohort 2 
Predose on Days 1, 22, 43, 85, 127, 169, 211, 253, 337, 519, 687, 855, 967, 1023, 1079, 1135, 1191, 
1303, 1415, 1527, 1639, 1751, 1863, 1975, 2087, and 2143 or ET 
Cohort 3 
Predose on Days 1, 15, 29, 85, 141, 197, 253, 309, 477, 645, 757, 869, 925, 981, 1037, 1093, 1205, 
1317, 1429, 1541, 1653, 1765, 1877, 1989, 2101, and 2157 or ET 
Cohort 4 
Predose on Days 1, 29, 113, 197, 281, 449, 617, 785, 869, 953, 1037, 1205, 1373, 1541, 1709, 1877, 
2045, and 2129 or ET 
1 This is not a dosing day, therefore collection can occur at any time. 
 
Statistical Methods: 
All data collected in this study will be documented using summary tables, figures, and data listings. For categorical 
variables, frequencies and percentages will be presented for each cohort and for the combined cohorts. For 
continuous variables, descriptive statistics (n, mean, median, standard deviation [SD], minimum, maximum) will be 
presented for each cohort and for the combined cohorts. Safety analyses will be performed on the Safety Set, which 
includes all patients who receive at least 1 dose of ALXN1210. Efficacy analyses will be performed on the Full 
Analysis Set, which includes the Safety Set subset with a baseline and at least 1 postbaseline LDH measurement.  
Immunogenicity: Immunogenicity, as measured by ADA, will be summarized in tabular form by treatment. 
Efficacy: The absolute LDH level, and the change and percent change from baseline will be summarized at all study 
visits. Baseline is defined as the average of all available assessments on or prior to first infusion with ALXN1210. A 
mixed model for repeated measures, with the fixed, categorical effect of visit and fixed, continuous effect of baseline 
LDH levels as covariates will be fit to test whether the changes and percent changes differ from zero at each time 
point. An unstructured covariance analysis will be used to model the within-patient errors. If this analysis fails to 
converge, the following structures will be tested and the final covariance structure will be determined by Akaike’s 
information criterion: first-order autoregressive, compound symmetry, and Toeplitz method. The Kenward-Roger 
approximation will be used to estimate denominator degrees of freedom. The secondary endpoints will be similarly 
analyzed, as appropriate. 
Change from baseline in the quality of life instrument scores, FACIT-Fatigue scale and the EORTC scale, will be 
summarized descriptively at all visits. 
Transfusion rates and the incidence rate of MAVEs will be summarized. 
 
Pharmacokinetics: Mean serum ALXN1210 concentrations versus nominal time and individual serum ALXN1210 
concentrations versus actual time will be graphically presented. Descriptive statistics (mean, SD, coefficient of 
variance [CV], median, minimum, maximum, geometric mean, and geometric percent [CV]) of the serum 
concentrations will be provided, as appropriate.  
Using noncompartmental PK methods, the serum concentration-versus-time data will be used to derive the following 
PK parameters: Cmax after each dose, tmax, Cmin/Ctrough, AUCt after each dose, AUC0-τ, λz, t½, CL, and Vss. 
Descriptive statistics (mean, SD, CV, median, minimum, maximum, geometric mean, and geometric %CV) of the PK 
parameters will be provided, as appropriate. Attainment of steady state and accumulation at steady state also will be 
determined. Additional PK analyses, such as assessment of PK linearity and dose proportionality, may be conducted. 
Safety: The incidence of treatment-emergent adverse events and SAEs will be summarized by System Organ Class 
and Preferred Term overall, by severity, and by relationship to study drug. Changes from baseline in 
electrocardiograms, vital signs, and laboratory assessments (chemistry, hematology, and urinalysis) will be 
summarized. Shifts from baseline in laboratory assessments as well as physical examination findings will be 
summarized for all study visits. 
Pharmacodynamics: The PD effects of ALXN1210 administered IV will be evaluated by assessing changes and 
Page 14 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
percent changes in serum total and/or free C5 concentrations and cRBC hemolysis over time. Exploratory analyses of 
PK/PD parameters may be performed. 
Additional details of statistical analyses will be described in the statistical analysis plan. 
Sample Size Estimation:  
A sample size of 20 patients from the combined cohorts will provide an approximately 95% power to detect a mean 
paired difference in LDH from baseline of –40% at Day 253, with an estimated SD of 45%. This is based on a 
2-sided, paired t-test, with a 5% type I error rate. To account for a possible 15% dropout rate and additional patients 
in screening, up to 26 patients will be enrolled. 
 
Page 15 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
2. 
TABLE OF CONTENTS, LISTS OF TABLES, AND LIST OF 
FIGURES 
TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
1. 
SYNOPSIS ...................................................................................................................6 
2. 
TABLE OF CONTENTS, LISTS OF TABLES, AND LIST OF FIGURES .............16 
3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS .............................21 
4. 
INTRODUCTION ......................................................................................................23 
4.1. 
Background .................................................................................................................23 
4.1.1. 
Clinical Studies ...........................................................................................................23 
4.1.2. 
Nonclinical Studies .....................................................................................................24 
4.1.3. 
Potential Risks ............................................................................................................24 
4.1.3.1. 
Infections (Neisseria meningitidis and other encapsulated organisms) ......................24 
4.1.3.2. 
Immunogenicity and Hypersensitivity ........................................................................25 
4.2. 
Study Rationale ...........................................................................................................25 
5. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................26 
5.1. 
Primary Objective .......................................................................................................26 
5.2. 
Secondary Objectives .................................................................................................26 
5.3. 
Endpoints ....................................................................................................................26 
5.3.1. 
Efficacy Endpoints ......................................................................................................26 
5.3.1.1. 
Primary Efficacy .........................................................................................................26 
5.3.1.2. 
Secondary Efficacy .....................................................................................................26 
5.3.1.3. 
Exploratory Efficacy ...................................................................................................26 
5.3.2. 
Immunogenicity Endpoints .........................................................................................27 
5.3.3. 
Pharmacokinetic/Pharmacodynamic Endpoints .........................................................27 
5.3.4. 
Safety Endpoints .........................................................................................................27 
6. 
OVERALL STUDY DESIGN ....................................................................................28 
6.1. 
Number of Patients .....................................................................................................30 
6.2. 
Dose Rationale ............................................................................................................30 
6.3. 
Criteria for Dose Continuation and Escalation ...........................................................31 
6.4. 
Criteria for Study Termination/Site Termination .......................................................31 
7. 
SCHEDULE OF ASSESSMENTS .............................................................................33 
Page 16 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
8. 
SELECTION AND WITHDRAWAL OF PATIENTS ..............................................50 
8.1. 
Patient Inclusion Criteria ............................................................................................50 
8.2. 
Patient Exclusion Criteria ...........................................................................................51 
8.3. 
Patient Withdrawal Criteria ........................................................................................52 
9. 
TREATMENT OF PATIENTS ..................................................................................54 
9.1. 
Management of Potential Drug Infusion Reactions ....................................................54 
9.2. 
Infection Risk ..............................................................................................................55 
9.3. 
Prior and Concomitant Medications and Procedures ..................................................56 
9.4. 
Treatment Compliance ................................................................................................56 
9.5. 
Randomization and Blinding ......................................................................................57 
10. 
STUDY DRUG MATERIALS AND MANAGEMENT ...........................................58 
10.1. 
Description of Study Drug ..........................................................................................58 
10.2. 
Study Drug Packaging and Labeling ..........................................................................58 
10.3. 
Study Drug Storage .....................................................................................................58 
10.4. 
Study Drug Preparation ..............................................................................................58 
10.4.1. 
ALXN1210 Dose Preparation .....................................................................................59 
10.4.2. 
In-use Shelf Life .........................................................................................................60 
10.5. 
Study Drug Administration .........................................................................................60 
10.6. 
Study Drug Accountability .........................................................................................60 
10.7. 
Study Drug Handling and Disposal ............................................................................61 
11. 
PHARMACOKINETIC AND PHARMACODYNAMIC ASSESSMENTS ............62 
11.1. 
Blood Sample Collection ............................................................................................62 
11.2. 
PK/PD Sample Analysis .............................................................................................63 
12. 
IMMUNOGENICITY ASSESSMENTS ....................................................................64 
12.1. 
Immunogenicity Sample Analysis ..............................................................................64 
13. 
ASSESSMENTS OF EFFICACY ..............................................................................65 
13.1. 
Blood Samples for Pharmacodynamic Analysis .........................................................65 
13.1.1. 
Lactate Dehydrogenase ...............................................................................................65 
13.1.2. 
Biomarkers of PNH ....................................................................................................65 
13.1.3. 
Hemolysis-related Hematological Parameters ............................................................65 
13.2. 
Quality of Life ............................................................................................................65 
13.3. 
PNH Symptomatology ................................................................................................65 
13.4. 
Exploratory Markers of PNH ......................................................................................66 
Page 17 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
13.5. 
Major Adverse Vascular Events .................................................................................66 
14. 
ASSESSMENT OF SAFETY .....................................................................................67 
14.1. 
Safety Parameters .......................................................................................................67 
14.1.1. 
Demographic/Medical History ...................................................................................67 
14.1.2. 
Weight and Height ......................................................................................................67 
14.1.3. 
Physical Examination .................................................................................................67 
14.1.4. 
Vital Signs ..................................................................................................................67 
14.1.5. 
Electrocardiogram .......................................................................................................67 
14.1.6. 
Laboratory Assessments .............................................................................................68 
14.1.6.1. 
Pregnancy Screen ........................................................................................................68 
14.1.6.2. 
Hematology .................................................................................................................68 
14.1.6.3. 
Blood Chemistry .........................................................................................................68 
14.1.6.4. 
Coagulation .................................................................................................................68 
14.1.6.5. 
Urinalysis and Urine Chemistry .................................................................................69 
14.1.6.6. 
Virus Serology ............................................................................................................69 
14.1.6.7. 
Brain Natriuretic Protein .............................................................................................69 
14.1.7. 
Infusion Site Reaction .................................................................................................69 
15. 
ADVERSE EVENT MANAGEMENT ......................................................................70 
15.1. 
Definition of an Adverse Event ..................................................................................70 
15.2. 
Definition of a Serious Adverse Event .......................................................................71 
15.3. 
Severity Assessments ..................................................................................................72 
15.4. 
Causality Assessment .................................................................................................72 
15.5. 
Outcome ......................................................................................................................73 
15.6. 
Recording Adverse Events .........................................................................................73 
15.7. 
Reporting Serious Adverse Event(s) to the Sponsor ..................................................74 
15.8. 
Exposure During Pregnancy and Lactation ................................................................74 
15.9. 
Reporting Requirements .............................................................................................75 
15.9.1. 
Sponsor .......................................................................................................................75 
15.9.2. 
Investigator .................................................................................................................75 
16. 
STATISTICS ..............................................................................................................76 
16.1. 
General Considerations ...............................................................................................76 
16.2. 
Analysis Populations ..................................................................................................76 
16.3. 
Sample Size and Power ..............................................................................................76 
Page 18 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
16.4. 
Demographics, Baseline Characteristics, and Patient Disposition .............................76 
16.5. 
Safety Analysis ...........................................................................................................77 
16.6. 
Efficacy Analysis ........................................................................................................77 
16.7. 
Pharmacokinetic Analysis ..........................................................................................78 
16.8. 
Pharmacodynamic and Immunogenicity Analyses .....................................................78 
17. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS .........................................79 
17.1. 
Study Monitoring ........................................................................................................79 
17.2. 
Audits and Inspections ................................................................................................79 
18. 
ETHICS ......................................................................................................................80 
18.1. 
Data Monitoring Committee .......................................................................................80 
18.2. 
Ethics Review .............................................................................................................80 
18.3. 
Ethical Conduct of the Study ......................................................................................80 
18.4. 
Written Informed Consent ..........................................................................................80 
19. 
DATA HANDLING AND RECORDKEEPING .......................................................82 
19.1. 
Data Collection ...........................................................................................................82 
19.2. 
Inspection of Records .................................................................................................82 
19.3. 
Retention of Records ..................................................................................................82 
20. 
PUBLICATION POLICY ..........................................................................................83 
21. 
LIST OF REFERENCES ............................................................................................84 
22. 
APPENDIX .................................................................................................................85 
APPENDIX A. CLINICAL LABORATORY TESTS ...............................................................86 
 
LIST OF TABLES 
Table 1: 
Emergency Contact Information ...................................................................................5 
Table 2:  
Abbreviations and Special Terms ...............................................................................21 
Table 3: 
Dosing Schedule .........................................................................................................29 
Table 4: 
Schedule of Assessments: Induction and Maintenance Dosing During the 
Treatment Period: Cohort 1 ........................................................................................34 
Table 5: 
Schedule of Assessments: Induction and Maintenance Dosing During the 
Treatment Period: Cohort 2 ........................................................................................36 
Table 6: 
Schedule of Assessments: Induction and Maintenance Dosing During the 
Treatment Period: Cohort 3 ........................................................................................38 
Table 7: 
Schedule of Assessments: Induction and Maintenance Dosing During the 
Treatment Period: Cohort 4 ........................................................................................40 
Page 19 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
Table 8: 
Schedule of Assessments: Extension Period and Early Termination: Cohort 1 .........42 
Table 9: 
Schedule of Assessments: Extension Period and Early Termination: Cohort 2 .........44 
Table 10: Schedule of Assessments: Extension Period and Early Termination: Cohort 3 .........46 
Table 11: Schedule of Assessments: Extension Period and Early Termination: Cohort 4 .........48 
Table 12: Clinical Criteria for Diagnosing Anaphylaxis ............................................................55 
Table 13: Composition of Investigational Product .....................................................................58 
Table 14: Dosing Reference Chart for 10 mg/mL ALXN1210 Formulation Dose 
Preparation ..................................................................................................................59 
Table 15: Weight-based Dosing Reference Chart for 10 mg/mL ALXN1210 
Formulation Dose Preparation Beginning on Day 463 (Cohort 2), Day 477 
(Cohort 3), and Day 533 (Cohort 1) ...........................................................................59 
Table 16: Dosing Reference Chart for 100 mg/mL ALXN1210 Formulation Dose 
Preparation ..................................................................................................................60 
Table 17: Collection Time Points for Serum Concentrations of ALXN1210 and 
Analysis of Hemolytic Activity ..................................................................................62 
Table 18: Collection Time Points for Serum Samples for Immunogenicity Analyses of 
Antidrug Antibodies to ALXN1210 ...........................................................................64 
 
LIST OF FIGURES 
Figure 1: 
ALXN1210-PNH-201 Study Schematic .....................................................................30 
 
 
 
 
 
Page 20 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Table 2:  
Abbreviations and Special Terms  
Abbreviation or 
Term  
Explanation  
λz  
apparent terminal-phase elimination rate constant 
%CV  
percent coefficient of variance  
ADA 
antidrug antibody/ies 
ADCC 
antibody-dependent cell-mediated cytotoxicity 
AE  
adverse event  
Alexion 
Alexion Pharmaceuticals, Inc. 
AUCt  
area under the serum concentration-versus-time curve from time 0 (dosing) to the last 
quantifiable concentration 
AUCτ  
area under the concentration-versus-time curve from time 0 (dosing) to the end of the dosing 
interval 
AUC0-x  
area under the concentration-versus-time curve from time 0 (dosing) to X days postdosing 
AUC∞  
area under the concentration-versus-time curve from time 0 (dosing) extrapolated to infinity 
BMI  
body mass index  
BNP 
brain natriuretic peptide 
BP 
blood pressure 
C5 
complement component 5 
CDC 
complement-dependent cytotoxicity 
CL  
total clearance  
Cmax  
maximum observed serum concentration  
Cmin 
minimum observed serum concentration 
Ctrough 
the serum concentration at the end of the dosage interval τ 
cRBC  
chicken red blood cell 
CTCAE 
Common Terminology Criteria for Adverse Events 
CV 
coefficient of variance 
DMC 
Data Monitoring Committee 
ECG  
electrocardiogram  
eCRF 
electronic case report form 
eGFR 
estimated glomerular filtration rate 
EOI 
end of infusion 
EORTC 
European Organisation for Research and Treatment of Cancer, Quality of Life 
Questionnaire-Core 30 Scale, version 3.0 
FACIT-Fatigue 
Functional Assessment of Chronic Illness Therapy-Fatigue Scale, version 4 
FAS 
Full Analysis Set 
GCP  
Good Clinical Practice  
HIV  
human immunodeficiency virus  
IC99 
99% inhibitory concentration 
ICF  
informed consent form  
ICH  
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for 
Human Use 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
IV  
intravenous(ly)  
LDH 
lactate dehydrogenase 
mAb  
monoclonal antibody  
MAVE 
major adverse vascular event 
PD  
pharmacodynamic(s)  
PEF 
peak expiratory flow 
Page 21 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
Table 2:  
Abbreviations and Special Terms (Continued) 
PNH  
paroxysmal nocturnal hemoglobinuria  
PK  
pharmacokinetic(s)  
QoL 
quality of life 
RBC  
red blood cell  
SAE  
serious adverse event  
SD 
standard deviation 
SOI 
start of infusion 
t½ 
terminal elimination half-life  
tmax  
time to maximum observed serum concentration  
Vss  
volume of distribution at steady state 
Page 22 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
 
4. 
INTRODUCTION 
ALXN1210 is a humanized monoclonal antibody (mAb) that is structurally related to eculizumab 
(Soliris®), and is being developed by Alexion Pharmaceuticals, Inc. (Alexion). ALXN1210 
selectively binds to human complement protein C5, inhibiting its cleavage to C5a and C5b 
during complement activation. This inhibition prevents the release of the proinflammatory 
mediator C5a and the formation of the cytolytic pore-forming membrane attack complex C5b-9 
while preserving the proximal or early components of complement activation (eg, C3 and C3b) 
essential for the opsonization of microorganisms and clearance of immune complexes. The 
mechanism of action of ALXN1210 provides a rationale for the potential therapeutic use in 
diseases where complement activation is involved (eg, paroxysmal nocturnal hemoglobinuria 
[PNH] or atypical hemolytic uremic syndrome). These disorders of uncontrolled complement 
activation are chronic and progressive, with severe morbidities and significant premature 
mortality. 
Paroxysmal nocturnal hemoglobinuria is a condition in which uncontrolled complement activity 
leads to systemic complications, principally through intravascular hemolysis and platelet 
activation (Socie, 1996; Brodsky, 2014) . Persistent intravascular hemolysis may be triggered by 
various stressors such as infection or physical exertion, and this leads to smooth muscle 
contraction (free hemoglobin), chronic anemia, and an increased risk of severe 
thromboembolism. Thromboembolism is the most common cause of mortality in patients with 
PNH, and pulmonary hypertension and end-organ damage of vital organs, such as the liver, 
kidneys, brain, and intestines, are sequelae of such events (Hillmen, 2010) . Due to these adverse 
pathologic processes, patients with PNH have a decreased quality of life (QoL), which may 
include debilitating fatigue, chronic pain, poor physical function, shortness of breath, abdominal 
pain, erectile dysfunction, a need for anticoagulation, blood transfusions and, in some instances, 
need for dialysis (Weitz, 2012) . 
The purpose of the study is to evaluate the efficacy, safety, tolerability, immunogenicity, 
pharmacokinetics (PK), and pharmacodynamics (PD) of multiple doses of ALXN1210 
administered intravenously (IV) to patients with PNH who have not previously been treated with 
a complement inhibitor. 
4.1. 
Background 
Detailed information about the known and expected benefits, risks, and reasonably anticipated 
adverse events (AEs) of ALXN1210 may be found in the current edition of the ALXN1210 
Investigator’s Brochure. 
4.1.1. 
Clinical Studies 
ALXN1210 was administered in single doses of 200 mg and 400 mg IV to healthy volunteers in 
a Phase 1, randomized, blinded, placebo-controlled, single ascending-dose (SAD) study designed 
to evaluate the safety, tolerability, PK, and PD of ALXN1210 (Study ALXN1210-HV-101, 
n=14). There were no drug-related serious adverse events (SAEs) and no AEs leading to study 
discontinuation or individual subject withdrawal. The overall conclusions of the study were as 
follows: 
 
Page 23 of 86 
 
 
 
Alexion Confidential 
 
 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
 
 
• ALXN1210 exhibited prolonged PK exposure with mean geometric half-life estimates of 
32.4 days and 30.8 days following single doses of 200 and 400 mg, respectively.  
• The PK parameters (AUCt, AUC∞, and Cmax) were essentially dose proportional over the 
studied dose range. 
• At the EOI, the mean free C5 serum concentrations and cRBC hemolysis activity were 
inhibited by > 99% and > 97%, respectively. The duration of the effect was dose 
dependent. All subjects were negative for ADA through Day 150.   
ALXN1210 has been administered in multiple doses of 400 mg and 800 mg monthly to healthy 
volunteers in a Phase 1, randomized, blinded, placebo-controlled, multiple ascending dose 
(MAD) study designed to evaluate the safety, tolerability, PK, and PD of ALXN1210 (Study 
ALXN1210-HV-102). The study is currently ongoing.  
ALXN1210 has been administered to patients with PNH in an open-label, intrapatient, dose-
escalation study designed to evaluate the safety, tolerability, PK, and PD of ALXN1210 (Study 
ALXN1210-PNH-103). The study is currently ongoing. 
Please refer to the current edition of the ALXN1210 Investigator’s Brochure for more 
information. 
4.1.2. 
Nonclinical Studies 
The binding characteristics, potency, and effector functions of ALXN1210 have been studied in 
vitro and compared with its parent molecule, eculizumab. ALXN1210, like eculizumab, binds 
with high affinity to human C5, but does not bind to C5 from nonhuman primate or nonprimate 
mammalian species tested or exhibit pharmacological activity in any nonhuman species tested. 
Effector function of ALXN1210 was also studied. Since ALXN1210 is directed against a soluble 
antigen, a direct assessment of the capacity to initiate antibody-dependent cell-mediated 
cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC) is not possible. Instead, 
direct measurements of ALXN1210 binding to Fcgamma receptors (FcγRs) and complement 
component C1q were performed and inferred that in the absence of binding, they cannot mediate 
ADCC or CDC, respectively. Having both a soluble antigen and weak binding to effector 
molecules, ALXN1210 is unlikely to be capable of ADCC or CDC in vivo. Supporting this 
assertion is that no indication of ADCC or CDC was observed in Study ALXN1210-HV-101. 
Please refer to the current edition of the ALXN1210 Investigator’s Brochure for detailed results. 
4.1.3. 
Potential Risks 
4.1.3.1. 
Infections (Neisseria meningitidis and other encapsulated organisms) 
Complement C5 inhibition is known to increase the susceptibility to infections caused by 
encapsulated bacteria, particularly Neisseria meningitidis (N. meningitidis). To address this risk, 
all study participants must be vaccinated against N. meningitidis. Refer to Section 9.2 for further 
details. 
 
Page 24 of 86 
 
 
 
Alexion Confidential 
 
 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
 
4.1.3.2. 
Immunogenicity and Hypersensitivity 
Treatment with any therapeutic protein (human, humanized, chimeric) may induce an immune 
response. Occasionally, this immune response is clinically meaningful. The consequences of an 
immune reaction to a therapeutic protein range from transient appearance of antibodies, without 
any clinical consequence, to severe, life-threatening conditions. Potential clinical consequences 
also 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). 
Some subjects and patients treated with IV infusions of mAbs have experienced concurrent 
infusion-related reactions, with signs or symptoms that can be classified as acute 
allergic/hypersensitivity reactions or cytokine release syndrome (Sampson, 2006). Signs and 
symptoms include headache, fever, facial flushing, pruritus, myalgia, nausea, chest tightness, 
dyspnea, vomiting, erythema, abdominal discomfort, diaphoresis, shivers, hypertension, 
lightheadedness, hypotension, palpitations, and somnolence. Anaphylaxis might occur at any 
time during an infusion. In addition, readministration of some mAbs has been associated with 
serum sickness-like reactions, manifesting 1 to 14 days after drug administration. 
4.2. 
Study Rationale 
This is a dose ranging and dose-regimen ranging study designed based on the PK/PD-safety data 
generated from the single-ascending dose (SAD) and multiple-ascending dose (MAD) studies to 
help design a dose and dose regimen for the Phase 3 study(ies). It is anticipated that the planned 
starting and maintenance doses in this study will maintain drug levels above the current target 
efficacious trough level in addition to including the higher end of drug exposures to accumulate 
sufficient safety data prior to the start of Phase 3 study(ies). The dose regimens selected for the 
study are based on the emerging PK/PD data from the ongoing studies. 
 
Page 25 of 86 
 
 
 
Alexion Confidential 
 
 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
 
5. 
STUDY OBJECTIVES AND ENDPOINTS 
5.1. 
Primary Objective 
The primary objective of this study is to evaluate the efficacy, safety, and tolerability of multiple 
doses of ALXN1210 administered IV to complement inhibitor treatment-naïve patients with 
PNH. 
5.2. 
Secondary Objectives 
The secondary objectives are to characterize the PK and PD effects of multiple doses of 
ALXN1210 administered IV to complement inhibitor treatment-naïve patients with PNH, and to 
investigate the immunogenicity of ALXN1210 administered IV to complement inhibitor 
treatment-naïve patients with PNH. 
5.3. 
Endpoints 
Efficacy, safety, immunogenicity, PK, and PD endpoints are described in the sections to follow. 
Timing of assessments is displayed in the Schedule of Assessments (Section 7). 
5.3.1. 
Efficacy Endpoints  
5.3.1.1. 
Primary Efficacy  
The primary efficacy endpoint is: 
• Change in lactate dehydrogenase (LDH) levels from baseline to Day 253 
5.3.1.2. 
Secondary Efficacy 
The secondary efficacy endpoints are: 
• Changes in hemolysis-related hematologic parameters: free hemoglobin, haptoglobin, 
reticulocyte count, PNH red blood cell (RBC) clone, and D-dimer 
• Changes in clinical manifestations: fatigue, abdominal pain, dyspnea, dysphagia, 
chest pain, and erectile dysfunction 
5.3.1.3. 
Exploratory Efficacy 
The exploratory efficacy endpoints are: 
• Change from baseline in the need for blood transfusions 
• Change from baseline in disease-associated biomarkers (markers of chronic kidney 
disease; ie, estimated glomerular filtration rate [eGFR]; spot urine albumin:creatinine, 
and plasma brain natriuretic peptide [BNP] for pulmonary hypertension) 
• Change from baseline in QoL, assessed via the Functional Assessment of Chronic 
Illness Therapy (FACIT)-Fatigue Scale, version 4 and European Organisation for 
 
Page 26 of 86 
 
 
 
Alexion Confidential 
 
 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
 
Research and Treatment of Cancer, Quality of Life Questionnaire-Core 30 Scale, 
Version 3.0 (EORTC) scales 
• Change from baseline in major adverse vascular events (MAVEs) 
5.3.2. 
Immunogenicity Endpoints 
• Measurement of ADA 
5.3.3. 
Pharmacokinetic/Pharmacodynamic Endpoints 
• Changes in serum ALXN1210 concentration over time 
• Change in cRBC hemolytic activity 
• Change in free and total C5 concentration 
5.3.4. 
Safety Endpoints 
• Changes from baseline in physical examination assessments and vital signs 
• Change from baseline in electrocardiogram (ECG) parameters 
• Change from baseline in laboratory assessments 
• Incidence of AEs and SAEs 
 
Page 27 of 86 
 
 
 
Alexion Confidential 
 
 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
 
6. 
OVERALL STUDY DESIGN 
ALXN1210-PNH-201 is a Phase 2, open-label, multiple ascending dose study to evaluate the 
efficacy, safety, tolerability, immunogenicity, PK, and PD of multiple doses of ALXN1210 
administered IV to patients with PNH who have not been previously treated with a C5 
complement inhibitor.  
Four treatment cohorts and up to 26 patients (at least 6 per cohort) are planned for enrollment, 
with at least 20 patients planned for evaluation. All patients are to be screened for study 
eligibility after providing written informed consent to participate. Patients who fail to meet any 
of the eligibility criteria may be rescreened once for study participation, at the discretion of the 
Investigator.  
Patients enrolled in Cohort 1 will receive induction doses of ALXN1210 of 1400 mg on Day 1 
and 1000 mg on Day 15. On Day 29 they will receive the first of 8 maintenance doses of 
1000 mg of ALXN1210 (administered every 28 days or 4 weeks) (Table 3). Patients enrolled in 
Cohort 2 will receive induction doses of ALXN1210 of 2000 mg on Day 1 and 1600 mg on 
Day 22. On Day 43 they will receive the first of 5 maintenance doses of 1600 mg of ALXN1210 
(administered every 42 days or 6 weeks). Patients enrolled in Cohort 3 will receive induction 
doses of ALXN1210 of 1600 mg on Day 1 and 1600 mg on Day 15. On Day 29 they will receive 
the first of 4 maintenance doses of 2400 mg of ALXN1210 (administered every 56 days or 
8 weeks). Patients enrolled in Cohort 4 will receive an induction dose of ALXN1210 of 3000 mg 
on Day 1. On Day 29 they will receive the first of 3 maintenance doses of 5400 mg of 
ALXN1210 (administered every 84 days or 12 weeks). The first 2 patients in Cohort 4 will 
receive their induction dose (3000 mg) at least 1 day apart. The third patient will receive the 
induction dose at least 7 days after the second patient has received the induction dose.  
An independent Data Monitoring Committee (DMC) will review and evaluate the study data for 
patient safety and make recommendations on dose escalation, continuing dosing within the 
cohort, modification, or termination of the study. The DMC will conduct a review of the 
available safety data at the following scheduled time points:  
• Fifteen days after the second patient in Cohort 1 receives the second induction dose to 
determine whether Cohort 2 can be opened.  
• Fifteen days after the second patient in Cohort 2 receives the second induction dose to 
determine whether Cohort 3 can be opened.  
• Fifteen days after the second patient in Cohort 3 receives the first maintenance dose 
to determine whether Cohort 4 can be opened. 
• Approximately 7 days after the second patient in Cohort 4 receives the 3000 mg dose 
to review safety. 
• Approximately 7 days after the second patient in Cohort 4 receives the first 5400 mg 
dose to review safety. 
If additional patients are screened and are eligible for enrollment before a dose-escalation 
decision has been made by the DMC for any cohort, those patients will be assigned to the active 
cohort with the lowest dose level.  
 
Page 28 of 86 
 
 
 
Alexion Confidential 
 
 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
 
On Day 253, patients will continue treatment in a long-term Extension Period of the study, at the 
same maintenance dose and frequency as their final dose of ALXN1210 administered during the 
Treatment Period and receive ALXN1210 until the product is registered or approved (in 
accordance with country-specific regulations) or for up to 5 years, whichever occurs 
first. Beginning on Day 463 for patients in Cohort 2, Day 477 for patients in Cohorts 3, and Day 
533 for patients in Cohort 1, patients will switch from their current dose regimen to a q8w, 
weight-based regimen, as follows:  3000 mg for patients weighing ≥ 40 to < 60 kg, 3300 mg for 
patients weighing ≥ 60 to < 100 kg, and 3600 mg for patients weighing ≥ 100 kg. The dose 
regimen will not change for patients in Cohort 4. Beginning on Day 953 for patients in Cohort 4, 
Day 981 for patients in Cohort 3, Day 1023 for patients in Cohort 2, and Day 1037 for patients in 
Cohort 1, patients will switch from the 10 mg/mL ALXN1210 unit dose formulation to the 
100 mg/mL ALXN1210 unit dose formulation, while remaining on their current dose regimen. 
This transition will reduce the number of vials needed for each infusion and the duration of the 
infusion. 
Up to 30 days will be allowed for screening procedures. The total duration of treatment (which 
includes an Induction Period and a Maintenance Period) is approximately 253 days. The total 
duration of the Extension Period is up to approximately 5 years (Figure 1).  
All patients will be monitored closely for signs of infection throughout the study. Treatment with 
prophylactic antibiotics will be at the discretion of the Investigator and per the site/country 
standard of care. 
The dosing schedule is provided in Table 3 and the overall study design is presented in Figure 1. 
Table 3: 
Dosing Schedule 
Cohort 
Patients 
Induction 
Maintenance 
1 
6 
1400 mg on Day 1 
1000 mg on Day 15 
• 
1000 mg on Day 29 and then every 28 days or 4 weeks 
(Days 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365, 
393, 421, 449, 477)  
• 
 Weight-baseda dose on Day 533 and then every 8 weeks (Days 
589, 645, 701, 757, 813, 869, 925, 981, 1037b, 1093, 1149, 
1205, 1261, 1317, 1373, 1429, 1485, 1541, 1597, 1653, 1709, 
1765, 1821, 1877, 1933, 1989, 2045, 2101) 
2  
6 
2000 mg on Day 1 
1600 mg on Day 22 
• 
1600 mg on Day 43 and then every 42 days or 6 weeks 
(Days 85, 127, 169, 211, 253, 295, 337, 379, 421) 
• 
Weight-baseda dose on Day 463 and then every 8 weeks (Days 
519, 575, 631, 687, 743, 799, 855, 911, 967, 1023b, 1079, 1135, 
1191, 1247, 1303, 1359, 1415, 1471, 1527, 1583, 1639, 1695, 
1751, 1807, 1863, 1919, 1975, 2031, 2087) 
3  
6 
1600 mg on Day 1 
1600 mg on Day 15 
• 
2400 mg on Day 29 and then every 56 days or 8 weeks 
(Days 85, 141, 197, 253, 309, 365, 421)  
• 
Weight-baseda dose on Day 477 and then every 8 weeks 
(Days 533, 589, 645, 701, 757, 813, 869, 925, 981b, 1037, 
1093, 1149, 1205, 1261, 1317, 1373, 1429, 1485, 1541, 1597, 
1653, 1709, 1765, 1821, 1877, 1933, 1989, 2045, 2101) 
4 
6 to 8 
3000 mg on Day 1 
• 
5400 mg on Day 29 and then every 84 days or 12 weeks 
(Days 113, 197, 281, 365, 449, 533, 617, 701, 785, 869, 953b, 
1037, 1121, 1205, 1289, 1373, 1457, 1541, 1625, 1709, 1793, 
1877, 1961, 2045)  
a 
3000 mg for patients weighing ≥ 40 to < 60 kg, 3300 mg for patients weighing ≥ 60 to < 100 kg, and 3600 mg 
for patients weighing ≥ 100 kg.  
 
Page 29 of 86 
 
 
 
Alexion Confidential 
 
 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
 
b 
Beginning on Day 953 for patients in Cohort 4, Day 981 for patients in Cohort 3, Day 1023 for patients in 
Cohort 2, and Day 1037 for patients in Cohort 1, patients will switch from the 10 mg/mL ALXN1210 unit dose 
formulation to the 100 mg/mL ALXN1210 unit dose formulation, while remaining on their current dose 
regimen. 
 
Figure 1: 
ALXN1210-PNH-201 Study Schematic 
 
 a Beginning at Day 463 (Cohort 2), Day 477 (Cohort 3), and Day 533 (Cohort 1), weight-based maintenance doses 
will be administered as follows: 3000 mg for patients weighing ≥ 40 to < 60 kg, 3300 mg for patients weighing ≥ 60 
to < 100 kg, and 3600 mg for patients weighing ≥ 100 kg. 
6.1. 
Number of Patients 
Up to 26 patients (at least 6 per cohort) are planned for enrollment, with at least 20 patients 
planned for evaluation. 
6.2. 
Dose Rationale 
Initial analyses supporting dose and dose regimen selection for Study ALXN1210-PNH-201 
utilized data from the SAD study (ALXN1210-HV-101) in healthy volunteers. The PK data 
following single sub-therapeutic doses (200 mg and 400 mg) of ALXN1210 to healthy 
volunteers (ALXN1210-HV-101) yielded an estimated mean (range) elimination half-life of 
ALXN1210 of ~31 (27-38) days. The initial PK/PD data estimated a target efficacious trough 
level of ≥100 μg/mL to design dose regimens for this study. The targeted efficacious trough level 
is defined as concentration achieving complete complement inhibition (≥ 99%) in all patients 
(≥ 97.5%). Subsequent population PK analyses, utilizing emerging PK data from both healthy 
volunteers and patients with PNH across a wider range of doses, exposures, and durations, 
 
Page 30 of 86 
 
 
 
Alexion Confidential 
 
 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
 
suggest the median (95% confidence interval) elimination half-life of ALXN1210 is ~43 days 
(39-48). This change in the estimate of elimination half-life of ALXN1210 following multiple 
dose administrations in healthy volunteers and patients with PNH has resulted in an increase in 
the estimated target trough concentrations in Cohorts 1-3 and has presented the opportunity to 
explore dosing ALXN1210 less frequently. It is also desirable to target a trough level that will 
achieve complete complement inhibition in all PNH patients. Therefore, to provide safety and 
PK/PD support for an optimized Phase 3 dosing regimen characterization, it is necessary to 
evaluate the dose regimen ranging in this protocol from once every month dosing to once every 3 
month dosing as enabled by the increased estimated elimination half-life, taking into account the 
current estimates of targeted efficacious ALXN1210 trough level.  
It was anticipated that the planned starting and maintenance doses in this study would maintain 
the drug levels above the current target efficacious trough level in addition to including the 
higher end of drug exposures to accumulate sufficient safety data prior to the start of Phase 3 
study(ies). 
The weight-based dosages of ALXN1210 (Table 15) for the extension phase are premised on 
PK/PD data from the induction and maintenance phases of this study as well as from early 
development studies in healthy adult volunteers and an ongoing Phase 1b study (ALXN1210-
PNH-103) in patients with PNH. The selection of ALXN1210 dose regimen is based on targeting 
immediate, complete, and sustained inhibition of terminal complement activity in patients with 
PNH. 
6.3. 
Criteria for Dose Continuation and Escalation  
An independent DMC will oversee safety monitoring in this study and will operate according to 
a separate DMC charter. This committee will be comprised of experts in relevant biomedical 
fields who have no direct relationship with this study. The DMC will conduct a review of the 
available safety data at the following scheduled time points:  
• Fifteen days after the second patient in Cohort 1 receives the second induction dose to 
determine whether Cohort 2 can be opened.  
• Fifteen days after the second patient in Cohort 2 receives the second induction dose to 
determine whether Cohort 3 can be opened.  
• Fifteen days after the second patient in Cohort 3 receives the first maintenance dose to 
determine whether Cohort 4 can be opened. 
• Approximately 7 days after the second patient in Cohort 4 receives the 3000 mg dose to 
review safety. 
• Approximately 7 days after the second patient in Cohort 4 receives the first 5400 mg dose 
to review safety. 
The DMC will meet quarterly thereafter for the remainder of the study. 
6.4. 
Criteria for Study Termination/Site Termination 
The Sponsor or Competent Authority may terminate the study for reasonable cause. Conditions 
that may warrant termination of the study include, but are not limited to:  
 
Page 31 of 86 
 
 
 
Alexion Confidential 
 
 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
 
• Discovery of an unexpected, serious, or unacceptable risk to patients enrolled in the 
study  
• Sponsor decision to suspend or discontinue testing, evaluation, or development of the 
study drug  
• Failure of the Investigator to comply with the approved protocol, pertinent guidelines, 
and/or regulations  
• Submission of knowingly false information from the Investigator to the Sponsor 
and/or regulatory authorities  
The end of the study will be defined as the date of the last patient’s last visit in the Extension 
Period. 
 
Page 32 of 86 
 
 
 
Alexion Confidential 
 
 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
 
7. 
SCHEDULE OF ASSESSMENTS 
The Schedules of Assessments are provided for Cohorts 1, 2, and 3 and 4, respectively, in 
Table 4, Table 5, Table 6, and Table 7 for Induction and Maintenance dosing, and in 
Table 8, Table 9, Table 10, and Table 11 for the Extension Period and Early Termination. 
 
 
Page 33 of 86 
 
 
 
Alexion Confidential 
 
 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
Table 4: 
Schedule of Assessments: Induction and Maintenance Dosing During the Treatment Period: Cohort 1 
Period 
Screening 
Treatment 
Induction 
Maintenance 
Study Day 
–30 to –1 
1 
7 
15 
22 
29 
43 
57 
85 
113 
127 
141 
169 
197 
211 
225 
253 
Window (day) 
N/A 
±1 
±1 
±1 
±1 
±1 
±1 
±1 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confirmation of 
meningococcal vaccination 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history and 
demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Virus serology 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PNH clone size 
X 
X 
 
 
 
 
 
X 
 
X 
 
 
X 
 
 
X 
X 
Height, weight, BMI 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test 
X 
X 
 
X 
 
X 
 
X 
X 
X 
 
X 
X 
X 
 
X 
X 
PNH symptomatology 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Abbreviated physical exam 
 
X 
 
X 
 
X 
 
X 
X 
X 
 
X 
X 
X 
 
X 
 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-Lead ECG  
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Chemistry, including LDH 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis and urine 
chemistry, spot urine 
X 
X 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
eGFR calculation 
X 
X 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
Brain natriuretic peptide 
 
X 
 
 
 
X 
 
 
X 
 
 
X 
 
X 
 
 
X 
ALXN1210 administration 
 
X 
 
X 
 
X 
 
X 
X 
X 
 
X 
X 
X 
 
X 
X 
PK sampling 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum PD panel 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Immunogenicity (ADA) 
 
X 
 
X 
 
X 
 
X 
X 
X 
 
X 
X 
X 
 
X 
X 
QoL assessments 
 
X 
 
X 
 
 
 
X 
 
X 
X 
 
 
X 
 
X 
X 
Infusion site evaluation 
 
X 
 
X 
 
X 
 
X 
X 
X 
 
X 
X 
X 
 
X 
X 
VAS for infusion site pain 
 
X 
 
X 
 
X 
 
X 
X 
X 
 
X 
X 
X 
 
X 
X 
Review safety card 
   Review continuously    
Concomitant medications 
   Monitor continuously    
Adverse events 
   Monitor continuously    
 
Abbreviations: ADA = antidrug antibody; BMI = body mass index; ECG = electrocardiogram; eGFR = estimated glomerular filtration rate; LDH = lactate 
dehydrogenase; QoL = quality of life; PD = pharmacodynamic; PK = pharmacokinetic; PNH = paroxysmal nocturnal hemoglobinuria; VAS = visual analog 
scale 
Page 34 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
1 All assessments will be performed predose and are part of the Maintenance Period. The dose administered on Day 253 is the first dose in the Extension Period. 
2 Meningococcal vaccination may be completed on Day 1 prior to dosing with ALXN1210. Prophylactic antibiotics must be used if 14 days has not elapsed (see 
Section 9.2). 
3 Hepatitis B and C, human immunodeficiency virus types 1 and 2. 
4 Granulocyte and red blood cell clone size at screening and red blood cell clone size only during the Treatment Period. 
5 Measure height at screening only.  
6 Female patients of childbearing potential only. Serum pregnancy test at screening only; urine pregnancy test at all other time points. A negative urine test result 
is required prior to administering ALXN1210 to female patients on dosing days. 
7 Investigator assessment of the following events: fatigue, abdominal pain, dyspnea, dysphagia, chest pain, and erectile dysfunction. Symptoms of disease burden 
will be captured through the QoL questionnaires. 
8 Abbreviated physical examination consists of a body system relevant examination based upon Investigator judgment and subject symptoms. 
9 Obtain triplicate 12-lead ECGs at screening and prior to the first dose on Day 1, and single 12-lead ECGs on Day 253.  
10 Clinical safety laboratory measurements will be collected predose on dosing days. Follicle-stimulating hormones and estradiol levels will be measured at least 
twice during screening, only in order to confirm postmenopausal status. 
11 At least two samples must be collected at least one day apart during the screening period for LDH testing. 
12 Assessment for safety, as well as the following parameters as secondary endpoints: free hemoglobin, haptoglobin, reticulocyte count, and D-dimer. 
13 Obtain predose on Days 1, 29, 85, 141, 197, and 253.  
14 Please refer to Table 17 for cohort-specific sampling time points. 
15 To include serum for exploratory PD assays; please refer to Table 17 for cohort-specific sampling time points. 
16 Immunogenicity samples will be collected predose on dosing days. Please refer to Table 18 for cohort-specific sampling time points. 
17 Functional Assessment of Chronic Illness Therapy-Fatigue Scale, version 4.0 and European Organisation for Research and Treatment of Cancer, Quality of 
Life Questionnaire-Core 30 Scale, Version 3.0.  
18 An induration or reaction of <10 mm will not be listed as an adverse event unless it persists for more than 24 hours, at which time the patient must inform the 
study staff immediately and proceed to the nearest hospital emergency department. 
19 Patient should assess infusion site pain using a 100 mm VAS. The VAS should be completed as soon as practical after completion of the infusion. 
 
 
Page 35 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
Table 5: 
Schedule of Assessments: Induction and Maintenance Dosing During the Treatment Period: Cohort 2 
Period 
Screening 
Treatment 
Induction 
Maintenance 
Study Day 
–30 to –1 
1 
7 
15 
22 
29 
43 
57 
85 
113 
127 
141 
169 
197 
211 
225 
253 
Window (day) 
N/A 
±1 
±1 
±1 
±1 
±1 
±1 
±1 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confirmation of meningococcal 
vaccination 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history and 
demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Virus serology 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PNH clone size 
X 
X 
 
 
 
 
 
X 
 
X 
 
 
X 
 
 
X 
X 
Height, weight, BMI 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
PNH symptomatology 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Abbreviated physical exam 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-Lead ECG 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Chemistry, including LDH 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis and urine chemistry, 
spot urine 
X 
X 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
eGFR calculation 
X 
X 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
Brain natriuretic peptide 
 
X 
 
 
X 
 
 
 
X 
 
X 
 
X 
 
 
 
X 
ALXN1210 administration 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
PK sampling 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum PD panel 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Immunogenicity (ADA) 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
QoL assessments 
 
X 
 
X 
 
 
 
X 
 
X 
X 
 
 
X 
 
X 
X 
Infusion site evaluation 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
VAS for infusion site pain 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Review safety card 
   Review continuously    
Concomitant medications 
   Monitor continuously    
Adverse events 
   Monitor continuously    
 
Abbreviations: ADA = antidrug antibody; BMI = body mass index; ECG = electrocardiogram; eGFR = estimated glomerular filtration rate; LDH = lactate 
dehydrogenase; QoL = quality of life; PD = pharmacodynamic; PK = pharmacokinetic; PNH = paroxysmal nocturnal hemoglobinuria; VAS = visual analog scale 
1 All assessments will be performed predose and are part of the Maintenance Period. The dose administered on Day 253 is the first dose in the Extension Period. 
Page 36 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
2 Meningococcal vaccination may be completed on Day 1 prior to dosing with ALXN1210. Prophylactic antibiotics must be used if 14 days has not elapsed 
(see Section 9.2). 
3 Hepatitis B and C, human immunodeficiency virus types 1 and 2. 
4 Granulocyte and red blood cell clone size at screening and red blood cell clone size only during the Treatment Period. 
5 Measure height at screening only.  
6 Female patients of childbearing potential only. Serum pregnancy test at screening only; urine pregnancy test at all other time points. A negative urine test result 
is required prior to administering ALXN1210 to female patients on dosing days. 
7 Investigator assessment of the following events: fatigue, abdominal pain, dyspnea, dysphagia, chest pain, and erectile dysfunction. Symptoms of disease burden 
will be captured through the QoL questionnaires. 
8 Abbreviated physical examination consists of a body system relevant examination based upon Investigator judgment and subject symptoms. 
9 Obtain triplicate 12-lead ECGs at screening and prior to the first dose on Day 1, and single 12-lead ECGs on Day 253.  
10 Clinical safety laboratory measurements will be collected predose on dosing days. Follicle-stimulating hormones and estradiol levels will be measured at least 
twice during screening, only in order to confirm postmenopausal status. 
11 At least two samples must be collected at least one day apart during the screening period for LDH testing. 
12 Assessment for safety, as well as the following parameters as secondary endpoints: free hemoglobin, haptoglobin, reticulocyte count, and D-dimer. 
13 Obtain predose on Days 1, 22, 85, 127, 169, and 253. 
14 Please refer to Table 17 for cohort-specific sampling time points. 
15 To include serum for exploratory PD assays; please refer to Table 17 for cohort-specific sampling time points. 
16 Immunogenicity samples will be collected predose on dosing days. Please refer to Table 18 for cohort-specific sampling time points. 
17 Functional Assessment of Chronic Illness Therapy-Fatigue Scale, version 4.0 and European Organisation for Research and Treatment of Cancer, Quality of 
Life Questionnaire-Core 30 Scale, Version 3.0. 
18 An induration or reaction of < 10 mm will not be listed as an adverse event unless it persists for more than 24 hours, at which time the patient must inform the 
study staff immediately and proceed to the nearest hospital emergency department.  
19 Patient should assess infusion site pain using a 100 mm VAS. The VAS should be completed as soon as practical after completion of the infusion. 
 
 
Page 37 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
Table 6: 
Schedule of Assessments: Induction and Maintenance Dosing During the Treatment Period: Cohort 3 
Period 
Screening 
Treatment 
Induction 
Maintenance 
Study Day 
–30 to –1 
1 
7 
15 
22 
29 
43 
57 
85 
113 
127 
141 
169 
197 
211 
225 
253 
Window (day) 
N/A 
±1 
±1 
±1 
±1 
±1 
±1 
±1 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confirmation of 
meningococcal vaccination 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history and 
demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Virus serology 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PNH clone size 
X 
X 
 
 
 
 
 
X 
 
X 
 
 
X 
 
 
X 
X 
Height, weight, BMI 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test 
X 
X 
 
X 
 
X 
 
 
X 
 
 
X 
 
X 
 
 
X 
PNH symptomatology 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Physical examination 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Abbreviated physical exam 
 
X 
 
X 
 
X 
 
 
X 
 
 
X 
 
X 
 
 
 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-Lead ECG 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Chemistry, including LDH 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis and urine 
chemistry, spot urine 
X 
X 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
eGFR calculation 
X 
X 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
Brain natriuretic peptide 
 
X 
 
 
 
X 
 
 
X 
 
 
X 
 
X 
 
 
X 
ALXN1210 administration 
 
X 
 
X 
 
X 
 
 
X 
 
 
X 
 
X 
 
 
X 
PK sampling 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum PD panel 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Immunogenicity (ADA) 
 
X 
 
X 
 
X 
 
 
X 
 
 
X 
 
X 
 
 
X 
QoL assessments 
 
X 
 
X 
 
 
 
X 
 
X 
X 
 
 
X 
 
X 
X 
Infusion site evaluation 
 
X 
 
X 
 
X 
 
 
X 
 
 
X 
 
X 
 
 
X 
VAS for infusion site pain 
 
X 
 
X 
 
X 
 
 
X 
 
 
X 
 
X 
 
 
X 
Review safety card 
   Review continuously    
Concomitant medications 
   Monitor continuously    
Adverse events 
   Monitor continuously    
 
Abbreviations: ADA = antidrug antibody; BMI = body mass index; ECG = electrocardiogram; eGFR = estimated glomerular filtration rate; LDH = lactate 
dehydrogenase; QoL = quality of life; PD = pharmacodynamic; PK = pharmacokinetic; PNH = paroxysmal nocturnal hemoglobinuria; VAS = visual analog scale 
1 All assessments will be performed predose and are part of the Maintenance Period. The dose administered on Day 253 is the first dose in the Extension Period. 
Page 38 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
2 Meningococcal vaccination may be completed on Day 1 prior to dosing with ALXN1210. Prophylactic antibiotics must be used if 14 days has not elapsed (see 
Section 9.2). 
3 Hepatitis B and C, human immunodeficiency virus types 1 and 2. 
4 Granulocyte and red blood cell clone size at screening and red blood cell clone size only during the Treatment Period. 
5 Measure height at screening only. 
6 Female patients of childbearing potential only. Serum pregnancy test at screening only; urine pregnancy test at all other time points. A negative urine test result 
is required prior to administering ALXN1210 to female patients on dosing days. 
7 Investigator assessment of the following events: fatigue, abdominal pain, dyspnea, dysphagia, chest pain, and erectile dysfunction. Symptoms of disease burden 
will be captured through the QoL questionnaires. 
8 Abbreviated physical examination consists of a body system relevant examination based upon Investigator judgment and subject symptoms. 
9 Obtain triplicate 12-lead ECGs at screening and prior to the first dose on Day 1, and single 12-lead ECGs on Day 253.  
10 Clinical safety laboratory measurements will be collected predose on dosing days. Follicle-stimulating hormones and estradiol levels will be measured at least 
twice during screening, only in order to confirm postmenopausal status. 
11 At least two samples must be collected at least one day apart during the screening period for LDH testing. 
12 Assessment for safety, as well as the following parameters as secondary endpoints: free hemoglobin, haptoglobin, reticulocyte count, and D-dimer. 
13 Obtain predose on Days 1, 29, 85, 141, 197, and 253.  
14 Please refer to Table 17 for cohort-specific sampling time points. 
15 To include serum for exploratory PD assays; please refer to Table 17 for cohort-specific sampling time points. 
16 Immunogenicity samples will be collected predose on dosing days. Please refer to Table 18 for cohort-specific sampling time points. 
17 Functional Assessment of Chronic Illness Therapy-Fatigue Scale, version 4.0 and European Organisation for Research and Treatment of Cancer, Quality of 
Life Questionnaire-Core 30 Scale, Version 3.0.  
18 An induration or reaction of < 10 mm will not be listed as an adverse event unless it persists for more than 24 hours, at which time the patient must inform the 
study staff immediately and proceed to the nearest hospital emergency department.  
19 Patient should assess infusion site pain using a 100 mm VAS. The VAS should be completed as soon as practical after completion of the infusion. 
 
 
Page 39 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
Table 7: 
Schedule of Assessments: Induction and Maintenance Dosing During the Treatment Period: Cohort 4 
Period 
Screening 
Treatment 
Induction 
Maintenance 
Study Day 
–30 to –1 
1 
7 
15 
22 
29 
43 
57 
85 
113 
127 
141 
169 
197 
211 
225 
253 
Window (day) 
N/A 
±1 
±1 
±1 
±1 
±1 
±1 
±1 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
±2 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confirmation of 
meningococcal vaccination 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history and 
demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Virus serology 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PNH clone size 
X 
X 
 
 
 
 
 
X 
 
X 
 
 
X 
 
 
X 
X 
Height, weight, BMI 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test 
X 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
PNH symptomatology 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Abbreviated physical exam 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-Lead ECG 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Chemistry, including LDH 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis and urine 
chemistry, spot urine 
X 
X 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
eGFR calculation 
X 
X 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
Brain natriuretic peptide 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
X 
ALXN1210 administration 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
PK sampling 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Serum PD panel 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Immunogenicity (ADA) 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
QoL assessments 
 
X 
 
X 
 
 
 
X 
 
X 
X 
 
 
X 
 
X 
X 
Infusion site evaluation 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
VAS for infusion site pain 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
Review safety card 
   Monitor continuously    
Concomitant medications 
   Monitor continuously    
Adverse events 
   Monitor continuously    
 
Abbreviations: ADA = antidrug antibody; BMI = body mass index; ECG = electrocardiogram; eGFR = estimated glomerular filtration rate; LDH = lactate 
dehydrogenase; QoL = quality of life; PD = pharmacodynamic; PK = pharmacokinetic; PNH = paroxysmal nocturnal hemoglobinuria; VAS = visual analog scale 
Page 40 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
1 All assessments will be performed predose and are part of the Maintenance Period. The last dose administered during Maintenance is on Day 197; the next dose 
administered on Day 281 (see Table 11) is the first dose in the Extension Period. 
2 Meningococcal vaccination may be completed on Day 1 prior to dosing with ALXN1210. Prophylactic antibiotics must be used if 14 days has not elapsed 
(see Section 9.2). 
3 Hepatitis B and C, human immunodeficiency virus types 1 and 2. 
4 Granulocyte and red blood cell clone size at screening and red blood cell clone size only during the Treatment Period. 
5 Measure height at screening only.  
6 Female patients of childbearing potential only. Serum pregnancy test at screening only; urine pregnancy test at all other time points. A negative urine test result 
is required prior to administering ALXN1210 to female patients on dosing days. 
7 Investigator assessment of the following events: fatigue, abdominal pain, dyspnea, dysphagia, chest pain, and erectile dysfunction. Symptoms of disease burden 
will be captured through the QoL questionnaires. 
8 Abbreviated physical examination consists of a body system relevant examination based upon Investigator judgment and subject symptoms. 
9 Obtain triplicate 12-lead ECGs at screening and prior to the first dose on Day 1, and single 12-lead ECGs on Day 253.  
10 Clinical safety laboratory measurements will be collected predose on dosing days. Follicle-stimulating hormones and estradiol levels will be measured at least 
twice during screening, only in order to confirm postmenopausal status. 
11 At least two samples must be collected at least one day apart during the screening period for LDH testing. 
12 Assessment for safety, as well as the following parameters as secondary endpoints: free hemoglobin, haptoglobin, reticulocyte count, and D-dimer. 
13 Obtain predose. 
14 Please refer to Table 17 for cohort-specific sampling time points. 
15 To include serum for exploratory PD assays; please refer to Table 17 for cohort-specific sampling time points. 
16 Immunogenicity samples will be collected predose on dosing days. Please refer to Table 18 for cohort-specific sampling time points. 
17 Functional Assessment of Chronic Illness Therapy-Fatigue Scale, version 4.0 and European Organisation for Research and Treatment of Cancer, Quality of 
Life Questionnaire-Core 30 Scale, Version 3.0. 
18 An induration or reaction of < 10 mm will not be listed as an adverse event unless it persists for more than 24 hours, at which time the patient must inform the 
study staff immediately and proceed to the nearest hospital emergency department.  
19 Patient should assess infusion site pain using a 100 mm VAS. The VAS should be completed as soon as practical after completion of the infusion. 
 
 
Page 41 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
Table 8: 
Schedule of Assessments: Extension Period and Early Termination: Cohort 1 
Period 
Extension 
 
ET1 
Year 1 
Year 2 
Year 3 
Year 4 
 
Year 5 
Year 6 
Study Day 
281 
309 
337 
365 
393 
421 
449 
477 
533 
589 
645 
701 
757 
813 
869 
925 
981 
10372 
1093 
1149 
1205 
1261 
1317 
1373 
1429 
1485 
1541 
1597 
1653 
1709 
1765 
1821 
1877 
1933 
1989 
2045 
2101 
2157 
 
Window (day) 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
 
ALXN1210  administration 
X X X X X X X X X3 X X X X X X X X X X X X X X  X X X X X X X X X X X X X X 
  
 
Weight 
 
 
 
 
 
 
X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
 
PNH clone size4 
 
 
X 
 
 
 
 
X 
 
 X 
 
 X  X  X  X  X  X 
 X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Pregnancy test5 
X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
X 
PNH symptomatology6 
X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
X 
Physical examination 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Abbreviated physical 
examination7 
 
 
X 
 
 
X 
 
X 
 X  
X 
 X  X  X  
X  X  X 
 X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
 
Vital signs 
X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
X 
12-Lead ECG8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Chemistry, including LDH 
X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
X 
Hematology9 
X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
X 
Coagulation 
X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
X 
Urinalysis and urine chemistry 
X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
X 
PK sampling10 
 
 
X 
 
 
 
 
X 
 
 X 
 
 X  X X X X X  
X  X 
 X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Serum PD panel11 
 
 
X 
 
 
 
 
X 
 
 X 
 
 X  X X X X X  X  X 
 X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Immunogenicity (ADA)12 
 
 
X 
 
 
 
 
X 
 
 X 
 
 X  X X X X X  X  X 
 X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
QoL assessments 
 
 
X 
 
 
X 
 
 
X X X 
 
X X  X  X 
 X  X  X 
 X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Infusion site evaluation13 
X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
 
 
VAS for infusion site pain14 
X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
 
 
Review safety card 
   Review continuously    
 
Concomitant medications 
   Monitor continuously    
X 
Adverse events 
   Monitor continuously    
X 
 
Abbreviations: ADA = antidrug antibody; ECG = electrocardiogram; ET = early termination; LDH = lactate dehydrogenase; PD = pharmacodynamic; PK = 
pharmacokinetic; PNH = paroxysmal nocturnal hemoglobinuria; QoL = quality of life; VAS = visual analog scale 
1 The ET visit should only be performed for patients who discontinue or are withdrawn early from the study. 
Page 42 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
2 Beginning on Day 1037, patients in Cohort 1 will switch from the 10 mg/mL ALXN1210 unit dose formulation to the 100 mg/mL ALXN1210 unit dose 
formulation, while remaining on their current dose regimen. 
3 Weight-based maintenance doses of ALXN1210 every 8 weeks (q8w), as follows:  3000 mg for patients weighing ≥ 40 to < 60 kg, 3300 mg for patients 
weighing ≥ 60 to < 100 kg, 3600 mg for patients weighing ≥ 100 kg. The final dose of study drug will be administered on Day 2101. 
4 Red blood cell clone size only during the Extension Period. 
5 Female patients of childbearing potential only. Serum pregnancy test end of study (Day 2157) or ET visit only; urine pregnancy test at all other time points. A 
negative urine test result is required prior to administering ALXN1210 to female patients on dosing days. 
6 Investigator assessment of the following events: fatigue, abdominal pain, dyspnea, dysphagia, chest pain, and erectile dysfunction. Symptoms of disease burden 
will be captured through the QoL questionnaires. 
7 Abbreviated physical examination consists of a body system relevant examination based upon Investigator judgment and subject symptoms. 
8 Obtain triplicate 12-lead ECGs during the end of study (Day 2157) or at ET visit.  
9 Assessment for safety as well as the following parameters as secondary endpoints: free hemoglobin, haptoglobin, reticulocyte count, and D-dimer. 
10 Please refer to Table 17 for cohort-specific sampling time points. 
11 To include serum for exploratory PD assays; please refer to Table 17  for cohort-specific sampling time points. 
12 Immunogenicity samples will be collected predose on dosing days. Please refer to Table 18 for cohort-specific sampling time points. 
13 An induration or reaction of < 10 mm will not be listed as an adverse event unless it persists for more than 24 hours, at which time the patient must inform the 
study staff immediately and proceed to the nearest hospital emergency department.   
14 Patient should assess infusion site pain using a 100 mm VAS. The VAS should be completed as soon as practical after completion of the infusion. 
 
 
Page 43 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
Table 9: 
Schedule of Assessments: Extension Period and Early Termination: Cohort 2 
Period 
Extension 
ET1 
Year 1 
Year 2 
Year 3 
Year 4 
 
Year 5 
 
Year 6 
 
Study Day 
295 
337 
379 
421 
463 
519 
575 
631 
687 
743 
799 
855 
911 
967 
10232 
1079 
1135 
1191 
1247 
1303 
1359 
1415 
1471 
1527 
1583 
1639 
1695 
1751 
1807 
1863 
1919 
1975 
2031 
2087 
2143 
 
Window (day) 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
 
ALXN1210  
administration 
X X X X X3 X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
 
 
Weight 
 
 
 
X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
 
PNH clone size4 
 
X 
 
 
 
X 
 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X X 
 
Pregnancy test5 
X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
X 
PNH symptomatology6 
X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
X 
Physical examination 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Abbreviated physical 
examination7 
 
X 
 
X 
 
X X 
 
X X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X  
X 
 
X 
 
X 
 
X 
 
 
Vital signs 
X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
X 
12-Lead ECG8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Chemistry, including 
LDH 
X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
X 
Hematology9 
X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
X 
Coagulation 
X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
X 
Urinalysis and urine 
chemistry 
X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
X 
PK sampling10 
 
X 
 
 
 
X 
 
 
X 
 
 
X 
 
X X X X X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X X 
X 
Serum PD panel11 
 
X 
 
 
 
X 
 
 
X 
 
 
X 
 
X X X X X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X X 
X 
Immunogenicity (ADA)12 
 
X 
 
 
 
X 
 
 
X 
 
 
X 
 
X X X X X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X X 
X 
QoL assessments 
 
X 
 
X 
 
X X 
 
X X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X X 
X 
Infusion site  
evaluation13 
X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
 
 
VAS for infusion site 
pain14 
X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
 
 
Review safety card 
   Review continuously    
 
Concomitant medications 
   Monitor continuously    
X 
Adverse events 
   Monitor continuously    
X 
Page 44 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
Abbreviations: ADA = antidrug antibody; ECG = electrocardiogram; ET = early termination; LDH = lactate dehydrogenase; PD = pharmacodynamic; PK = 
pharmacokinetic; PNH = paroxysmal nocturnal hemoglobinuria; QoL = quality of life; VAS = visual analog scale 
1 The ET visit should only be performed for patients who discontinue or are withdrawn early from the study.  
2 Beginning on Day 1023, patients in Cohort 2 will switch from the 10 mg/mL ALXN1210 unit dose formulation to the 100 mg/mL ALXN1210 unit dose 
formulation, while remaining on their current dose regimen. 
3 Weight-based maintenance doses of ALXN1210 every 8 weeks (q8w), as follows: 3000 mg for patients weighing ≥ 40 to < 60 kg, 3300 mg for patients 
weighing ≥ 60 to < 100 kg, 3600 mg for patients weighing ≥ 100 kg.  The final dose of study drug will be administered on Day 2087. 
4 Red blood cell clone size only during the Extension Period. 
5 Female patients of childbearing potential only. Serum pregnancy test at end of study (Day 2143) or ET visit only; urine pregnancy test at all other time points. 
A negative urine test result is required prior to administering ALXN1210 to female patients on dosing days. 
6 Investigator assessment of the following events: fatigue, abdominal pain, dyspnea, dysphagia, chest pain, and erectile dysfunction. Symptoms of disease burden 
will be captured through the QoL questionnaires. 
7 Abbreviated physical examination consists of a body system relevant examination based upon Investigator judgment and subject symptoms. 
8 Obtain triplicate 12-lead ECGs during the end of study (Day 2143) or at ET visit.  
9 Assessment for safety as well as the following parameters as secondary endpoints: free hemoglobin, haptoglobin, reticulocyte count, and D-dimer. 
10 Please refer to Table 17 for cohort-specific sampling time points. 
11 To include serum for exploratory PD assays; please refer to Table 17 for cohort-specific sampling time points. 
12 Immunogenicity samples will be collected predose on dosing days. Please refer to Table 18  for cohort-specific sampling time points. 
13 An induration or reaction of <10 mm will not be listed as an adverse event unless it persists for more than 24 hours, at which time the patient must inform the 
study staff immediately and proceed to the nearest hospital emergency department. 
14 Patient should assess infusion site pain using a 100 mm VAS. The VAS should be completed as soon as practical after completion of the infusion. 
 
 
Page 45 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
Table 10: 
Schedule of Assessments: Extension Period and Early Termination: Cohort 3 
Period 
Extension 
ET1 
Year 1 
Year 2 
Year 3 
Year 4 
Year 5 
Year 6 
Study Day 
309 
365 
421 
477 
533 
589 
645 
701 
757 
813 
869 
925 
9812 
1037 
1093 
1149 
1205 
1261 
1317 
1373 
1429 
1485 
1541 
1597 
1653 
1709 
1765 
1821 
1877 
1933 
1989 
2045 
2101 
2157 
 
Window (day) 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
 
ALXN1210 administration 
X X X X3 X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
 
 
Weight 
 
 
X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
 
PNH clone size4 
X 
 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Pregnancy test5 
X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
X 
PNH symptomatology6 
X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
X 
Physical examination 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Abbreviated physical 
examination7 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X  
X 
 
X 
 
X 
 
 
Vital signs 
X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
X 
12-Lead ECG8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Chemistry, including LDH 
X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
X 
Hematology9 
X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
X 
Coagulation 
X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
X 
Urinalysis and urine 
chemistry 
X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
X 
PK sampling10 
X 
 
 
X 
 
 
X 
 
X 
 
X X X X X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X X 
X 
Serum PD panel11 
X 
 
 
X 
 
 
X 
 
X 
 
X X X X X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X X 
X 
Immunogenicity (ADA)12 
X 
 
 
X 
 
 
X 
 
X 
 
X X X X X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X X 
X 
QoL assessments 
 
X 
 
X 
 
X 
 
X X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X X 
X 
Infusion site evaluation13 
X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
 
 
VAS for infusion site pain14 
X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X 
 
 
Review safety card 
   Review continuously    
 
Concomitant medications 
   Monitor continuously    
X 
Adverse events 
   Monitor continuously    
X 
 
Abbreviations: ADA = antidrug antibody; ECG = electrocardiogram; ET = early termination; LDH = lactate dehydrogenase; PD = pharmacodynamic; PK = 
pharmacokinetic; PNH = paroxysmal nocturnal hemoglobinuria; QoL = quality of life; VAS = visual analog scale 
1 The ET visit should only be performed for patients who discontinue or are withdrawn early from the study.  
2 Beginning on Day 981, patients in Cohort 3 will switch from the 10 mg/mL ALXN1210 unit dose formulation to the 100 mg/mL ALXN1210 unit dose 
formulation, while remaining on their current dose regimen. 
Page 46 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
3 Weight-based maintenance doses of ALXN1210 every 8 weeks (q8w), as follows:  3000 mg for patients weighing ≥ 40 to < 60 kg, 3300 mg for patients 
weighing ≥ 60 to < 100 kg, 3600 mg for patients weighing ≥ 100 kg.  The final dose of study drug will be administered on Day 2101. 
4 Red blood cell clone size only during the Extension Period. 
5 Female patients of childbearing potential only. Serum pregnancy test at end of study (Day 2157) or ET visit only; urine pregnancy test at all other time points. 
A negative urine test result is required prior to administering ALXN1210 to female patients on dosing days. 
6 Investigator assessment of the following events: fatigue, abdominal pain, dyspnea, dysphagia, chest pain, and erectile dysfunction. Symptoms of disease burden 
will be captured through the QoL questionnaires. 
7 Abbreviated physical examination consists of a body system relevant examination based upon Investigator judgment and subject symptoms. 
8 Obtain triplicate 12-lead ECGs during the end of study (Day 2157) or at ET visit.  
9 Assessment for safety as well as the following parameters as secondary endpoints: free hemoglobin, haptoglobin, reticulocyte count, and D-dimer. 
10 Please refer to Table 17 for cohort-specific sampling time points. 
11 To include serum for exploratory PD assays; please refer to Table 17 for cohort-specific sampling time points. 
12 Immunogenicity samples will be collected predose on dosing days. Please refer to Table 18 for cohort-specific sampling time points. 
13 An induration or reaction of < 10 mm will not be listed as an adverse event unless it persists for more than 24 hours, at which time the patient must inform the 
study staff immediately and proceed to the nearest hospital emergency department.  
14 Patient should assess infusion site pain using a 100 mm VAS. The VAS should be completed as soon as practical after completion of the infusion. 
 
 
Page 47 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
Table 11: 
Schedule of Assessments: Extension Period and Early Termination: Cohort 4 
Period 
Extension 
 
ET1 
Year 1 
Year 2 
Year 3 
Year 4 
Year 5 
 
Year 6 
 
Study Day 
281 
365 
449 
533 
617 
701 
785 
869 
953 
1037 
1121 
1205 
1289 
1373 
1457 
1541 
1625 
1709 
1793 
1877 
1961 
2045 
2129 
 
Window (day) 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
±5 
 
ALXN1210 administration 
X 
X 
X X X X 
X X X 
X 
X 
X 
X 
 X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
PNH clone size4 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Pregnancy test5 
X 
X 
X X X X 
X X X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PNH symptomatology6 
X 
X 
X X X X 
X X X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Abbreviated physical examination7 
X 
X 
X X X X 
X X X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Vital signs 
X 
X 
X X X X 
X X X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-Lead ECG8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Chemistry, including LDH 
X 
X 
X X X X 
X X X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology9 
X 
X 
X X X X 
X X X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation 
X 
X 
X X X X 
X X X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis and urine chemistry 
X 
X 
X X X X 
X X X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PK sampling10 
X 
 
X 
 
X 
 
X X X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
Serum PD panel11 
X 
 
X 
 
X 
 
X X X 
X 
 
X  
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
Immunogenicity (ADA)12 
X 
 
X 
 
X 
 
X X X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
QoL assessments 
X 
 
X 
 
X 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
Infusion site evaluation13 
X 
X 
X X X X 
X X X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
VAS for infusion site pain14 
X 
X 
X X X X 
X X X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Review safety card 
   Review continuously    
 
Concomitant medications 
   Monitor continuously    
X 
Adverse events 
   Monitor continuously    
X 
 
Abbreviations: ADA = antidrug antibody; ECG = electrocardiogram; ET = early termination; LDH = lactate dehydrogenase; PD = pharmacodynamic; PK = 
pharmacokinetic; PNH = paroxysmal nocturnal hemoglobinuria; QoL = quality of life; VAS = visual analog scale 
1 The ET visit should only be performed for patients who discontinue or are withdrawn early from the study.  
2 Beginning on Day 953, patients in Cohort 4 will switch from the 10 mg/mL ALXN1210 unit dose formulation to the 100 mg/mL ALXN1210 unit dose 
formulation, while remaining on their current dose regimen. 
Page 48 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
3 The final dose of study drug will be administered on Day 2045. 
4 Red blood cell clone size only during the Extension Period. 
5 Female patients of childbearing potential only. Serum pregnancy test at end of study (Day 2129) or ET visit only; urine pregnancy test at all other time points. 
A negative urine test result is required prior to administering ALXN1210 to female patients on dosing days. 
6 Investigator assessment of the following events: fatigue, abdominal pain, dyspnea, dysphagia, chest pain, and erectile dysfunction. Symptoms of disease burden 
will be captured through the QoL questionnaires. 
7 Abbreviated physical examination consists of a body system relevant examination based upon Investigator judgment and subject symptoms. 
8 Obtain triplicate 12-lead ECGs during the end of study (Day 2129) or at ET visit.  
9 Assessment for safety as well as the following parameters as secondary endpoints: free hemoglobin, haptoglobin, reticulocyte count, and D-dimer. 
10 Please refer to Table 17 for cohort-specific sampling time points. 
11 To include serum for exploratory PD assays; please refer to Table 17  for cohort-specific sampling time points. 
12 Immunogenicity samples will be collected predose on dosing days. Please refer to Table 18 for cohort-specific sampling time points. 
13 An induration or reaction of < 10 mm will not be listed as an adverse event unless it persists for more than 24 hours, at which time the patient must inform the 
study staff immediately and proceed to the nearest hospital emergency department.  
14 Patient should assess infusion site pain using a 100 mm VAS. The VAS should be completed as soon as practical after completion of the infusion. 
 
Page 49 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
8. 
SELECTION AND WITHDRAWAL OF PATIENTS 
8.1. 
Patient Inclusion Criteria 
Patients must meet all of the following inclusion criteria in order to be eligible for the study: 
1. Male or female patients ≥ 18 years of age 
2. PNH diagnosis confirmed by documented high-sensitivity flow cytometry (RBCs and/or 
granulocytes)  
3. Mean LDH ≥ 3 × upper limit of normal, based on 2 measurements from separate blood 
samples collected at least 1 day apart during screening 
4. Willing and able to give written informed consent and comply with the study visit 
schedule  
5. Documented meningococcal vaccination not more than 3 years prior to dosing 
6. Female patients who consider themselves postmenopausal must provide evidence at 
screening of menopause status, based on a combination of amenorrhea for at least 1 year 
and increased serum follicle-stimulating hormone level (> 30 IU/L) on at least 
2 occasions (eg, in the absence of hormone replacement therapy, dietary phytoestrogens) 
or estradiol concentration < 10 pg/mL. 
7. Female patients of childbearing potential must use highly effective contraception as 
defined below, starting at screening and continuing until at least 8 months after the last 
dose of ALXN1210. Highly effective contraceptive methods are as follows: 
a. 
Combined (estrogen and progestogen) hormonal contraception associated with 
inhibition of ovulation: 
− 
Oral 
− 
Intravaginal 
− 
Transdermal 
b. Progesterone-only hormonal contraception associated with inhibition of ovulation 
− Oral 
− Injectable 
− Implantable 
c. Intrauterine device 
d. Intrauterine hormone-releasing system 
e. Bilateral tubal occlusion 
f. Vasectomized partner, provided that the partner is the patient’s sole sexual partner 
g. Sexual abstinence, defined as refraining from heterosexual intercourse during the 
entire period of risk associated with the study treatments; reliability of sexual 
abstinence needs to be evaluated in relation to the duration of the clinical trial and 
the preferred and usual lifestyle of the subject 
Page 50 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
h. Combination of male condom with appropriate barrier methods for the female 
patient (double barrier methods) 
8. Male patients with a female spouse/partner of childbearing potential or a pregnant or 
breastfeeding spouse or partner must agree to use barrier contraception (male condom) 
during the Treatment Period and for at least 8 months after the last dose of ALXN1210. 
Barrier contraception is required even with documented medical assessment of surgical 
success of a vasectomy. Female spouses/partners of male patients who are of 
childbearing potential must use highly effective contraception (as defined in inclusion 
criterion #7) or acceptable contraception, as defined below, starting at screening and 
continuing until at least 8 months after the last dose of ALXN1210. Male patients must 
not donate sperm during the Screening and Treatment Periods and for at least 8 months 
after the last dose of ALXN1210. 
Acceptable contraceptive methods are as follows: 
a. Simultaneous use of male condom and appropriate barrier methods for the female 
partner 
8.2. 
Patient Exclusion Criteria 
Patients meeting any of the following exclusion criteria are not eligible to participate in the 
study: 
1. Treatment with a complement inhibitor at any time 
2. Platelet count < 30,000/mm3 (30 × 109 /L) at screening 
3. Absolute neutrophil count < 500/µL (0.5 × 109 /L) at screening 
4. History of bone marrow transplantation 
5. History of N. meningitidis infection or history of unexplained, recurrent infection 
6. Female patients who are planning to become pregnant, or are pregnant or breastfeeding  
7. Positive pregnancy test at screening or Day 1 
8. Patients are excluded if they are taking any of the following medications and are not on a 
stable regimen (as judged by the Investigator) for the time period indicated prior to 
screening:  
a. Erythropoietin or immunosuppressants for at least 8 weeks  
b. Corticosteroids for at least 4 weeks  
c. Vitamin K antagonists (eg, warfarin) with a stable international normalized ratio 
(per Investigator discretion) for at least 4 weeks 
d. Iron supplements or folic acid for at least 4 weeks  
e. Low molecular weight heparin for at least 4 weeks  
9. Human immunodeficiency virus (HIV) infection (evidenced by HIV-1 or HIV-2 antibody 
titer) 
10. Acute or chronic hepatitis B virus infection (evidenced by the presence of hepatitis B 
surface antigen or immunoglobulin M antibodies against hepatitis B core antigen).  
Page 51 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
11. Acute or chronic hepatitis C virus infection (evidenced by hepatitis C virus antibody) 
12. Active systemic bacterial, viral, or fungal infection within 14 days prior to dosing on 
Day 1 
13. Immunization with a live-attenuated vaccine 1 month prior to dosing on Day 1 
14. Participation in an interventional clinical study within 30 days before initiation of dosing 
on Day 1, or use of any experimental therapy within 30 days prior to dosing on Day 1, or 
within 5 half-lives of the investigational product, whichever is greater 
15. Major surgery within 90 days prior to dosing on Day 1 
16. Presence of fever ≥ 38 °C within 2 weeks prior to the first dosing on Day 1 
17. Patients with a history of malignancy within 5 years of screening with the exception of a 
nonmelanoma skin cancer or carcinoma in situ of the cervix that has been treated with no 
evidence of recurrence.  
18. Known history of severe allergic or anaphylactic reactions to any drug (including 
vaccines) or allergen 
19. History of allergy to excipients of ALXN1210 (eg, polysorbate 80)  
20. Known allergy to Chinese hamster ovary cell proteins  
21. History of any clinically significant cardiac, hepatic, immunologic, pulmonary, or 
rheumatoid disease that, in the Investigator’s judgment, would preclude participation 
22. Inability to comply with study requirements 
23. Other unspecified reasons that, in the opinion of the Investigator or Sponsor, make the 
patient unsuitable for enrollment 
8.3. 
Patient Withdrawal Criteria 
A patient may withdraw from the study at any time at his/her own request, or may be withdrawn 
at any time at the discretion of the Investigator. Patients who discontinue dosing will be 
instructed to return for follow-up visits, as described in the Schedule of Assessments (Section 7), 
unless they withdraw consent and/or are lost to follow-up. 
• If the patient withdraws consent, the Early Termination visit should be completed as 
soon as possible.   
• If the patient is withdrawn from ALXN1210, the Early Termination visit should occur 
prior to initiation of complement-targeted therapy. 
• If the patient is withdrawn from ALXN1210, the patient should be encouraged to 
return for the remainder of his or her scheduled protocol visits until starting a 
different complement-targeted therapy. 
Patients should be permanently discontinued from ALXN1210 treatment if any of the following 
occur during the study: 
Page 52 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
• Serious infusion reaction (such as bronchospasm with wheezing or requiring 
ventilator support or symptomatic hypotension, refer to Section 9.1) 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 deem it is in the best interest of the 
patient. 
Page 53 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
9. 
TREATMENT OF PATIENTS 
9.1. 
Management of Potential Drug Infusion Reactions 
Some patients treated with IV infusions of mAbs have experienced concurrent infusion-related 
reactions with signs or symptoms that can be classified as acute allergic 
reactions/hypersensitivity reactions or cytokine release syndrome. The signs and symptoms 
include headache, fever, facial flushing, pruritus, myalgia, nausea, chest tightness, dyspnea, 
vomiting, erythema, abdominal discomfort, diaphoresis, shivers, hypertension, lightheadedness, 
hypotension, palpitations, and somnolence. Anaphylaxis might occur at any time during an 
infusion and patients will be monitored closely prior to and through 1 hour following the end of 
the infusion of ALXN1210. All AEs which may indicate an infusion-related response will be 
graded according to criteria from the National Cancer Institute Common Terminology Criteria 
for Adverse Events (CTCAE) v4.0.3. 
Before infusion is started, the treating physician and other appropriate personnel, medication 
(adrenaline, inhaled beta agonists, antihistamines, and corticosteroids), and other requirements to 
treat anaphylaxis must be readily available. 
The infusion will be stopped immediately if ≥ Grade 2 allergic/hypersensitivity reaction 
(including drug fever) or ≥ Grade 3 cytokine release syndrome/acute infusion reaction occurs. 
Alexion must be notified within 24 hours of any infusion reaction requiring interruption of study 
drug. 
Patients experiencing a reaction during the administration of study drug should be treated 
according to institutional guidelines.  
For a Grade 1 or Grade 2 infusion-related reaction, the infusion should be stopped, and 
medication with antihistamine (eg, with diphenhydramine, 25 to 50 mg orally or equivalent) and 
acetaminophen (650 mg orally or equivalent) may be considered. If the signs and symptoms have 
resolved with the above medications, the infusion may be restarted. If the infusion is slowed, the 
total infusion time should not exceed 5 hours, including any interruptions for safety or technical 
reasons. The study drug should be stopped if the infusion reaction recurs. Patients experiencing 
an infusion reaction should be observed in the clinic until resolution of the reaction, or in the 
Investigator’s best judgment.  
If an event of anaphylaxis occurs, according to the criteria listed in Table 12 then subcutaneous 
epinephrine (1/1000, 0.3 to 0.5 mL or equivalent) should be considered. In the case of 
bronchospasm, inhaled beta agonist also should be considered. Patients administered 
antihistamine for the study drug or prevention of infusion reactions should be given appropriate 
warnings about drowsiness and impairment of driving ability prior to discharge. 
Patients who experience a severe reaction during administration of study drug resulting in 
discontinuation of study drug should undergo all scheduled safety, PK, and PD evaluations 
required by the protocol. 
Page 54 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
Table 12: 
Clinical Criteria for Diagnosing Anaphylaxis 
Anaphylaxis is highly likely when any one of the following 3 criteria are fulfilled: 
1. Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both 
(eg, generalized hives, pruritus or flushing, swollen lips-tongue-uvula) 
AND AT LEAST ONE OF THE FOLLOWING: 
a. 
Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia) 
b. Reduced BP or associated symptoms of end-organ dysfunction (eg, hypotonia [collapse], syncope, 
incontinence) 
2. Two or more of the following that occur rapidly after exposure to a likely allergen for that patient (minutes 
to several hours): 
a. 
Involvement of the skin-mucosal tissue (eg, generalized hives, itch-flush, swollen lips-tongue-uvula) 
b. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia) 
c. 
Reduced BP or associated symptoms (eg, hypotonia [collapse], syncope, incontinence) 
d. Persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting) 
3. Reduced BP after exposure to known allergen for that patient (minutes to several hours): 
a. 
Systolic BP of less than 90 mm Hg or greater than 30% decrease from that person’s baseline 
Abbreviations: BP = blood pressure; PEF = peak expiratory flow  
Source: Adapted from Sampson, 2006 
9.2. 
Infection Risk 
Due to its mechanism of action, the use of ALXN1210 increases the patient’s susceptibility to 
meningococcal infection (N. meningitidis). Patients might be at risk of disease by uncommon 
serogroups (such as X), although meningococcal disease due to any serogroup may occur. To 
reduce the risk of infection, all patients must be vaccinated prior to receiving ALXN1210. 
Patients who are treated with ALXN1210 less than 2 weeks after receiving a meningococcal 
vaccine must receive treatment with appropriate prophylactic antibiotics until 2 weeks after 
vaccination. Vaccines against serotypes A, C, Y, W135, and B, where available, are 
recommended to prevent common pathogenic meningococcal serotypes. Patients must be 
vaccinated or revaccinated according to current national vaccination guidelines or local practice 
for vaccination use with complement inhibitors (eg, eculizumab).  
Vaccination may not be sufficient to prevent meningococcal infection. Consideration should be 
given per official guidance and local practice on the appropriate use of antibacterial agents. All 
patients should be monitored for early signs of meningococcal infection, evaluated immediately 
if infection is suspected, and treated with appropriate antibiotics, if necessary. 
To increase risk awareness and promote quick disclosure of any potential signs or symptoms of 
infection experienced by the patients during the course of the study, patients will be provided a 
safety card to carry with them at all times. Additional discussion and explanation of the potential 
Page 55 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
risks, signs, and symptoms will take place at specific time points as part of the review of the 
patient safety card and throughout the study as described in the Schedule of Assessments 
(Section 7). 
9.3. 
Prior and Concomitant Medications and Procedures 
Prior medications (including vitamins and herbal preparations), including those discussed in the 
exclusion criteria (Section 8.2) and/or procedures (any therapeutic intervention, such as 
surgery/biopsy or physical therapy) the patient takes or undergoes within 28 days (or 3 years for 
documentation of meningococcal vaccination) prior to signing the informed consent form (ICF) 
until the first dose of ALXN1210 will be recorded on the patient’s electronic case report form 
(eCRF).  
All medication use during the study will be recorded in the patient’s source/chart and eCRF. This 
record will include all prescription drugs, herbal products, vitamins, minerals, over-the-counter 
medications, and current medications for PNH. Any changes in concomitant medications also 
will be recorded in the patient’s source/chart and eCRF. Any concomitant medication deemed 
necessary for the patient’s standard of care treatment during the study, or for the treatment of any 
AE, along with the allowed medications described below may be given at the discretion of the 
Investigator. However, it is the responsibility of the Investigator to ensure that details regarding 
the medication are recorded in full in the patient’s source/chart. 
The following concomitant medications are allowed if the following apply, and dose adjustments 
are not expected during the Treatment Period: 
• Patients are taking erythropoietin on a stable dose for at least 8 weeks prior to 
screening. 
• Patients are taking immunosuppressants on a stable dose for at least 8 weeks prior to 
screening. 
• Patients are taking corticosteroids on a stable dose for at least 4 weeks prior to 
screening. 
• Patients are allowed to take vitamin K antagonists (eg, warfarin) but must have had a 
stable international normalized ratio level (per Investigator discretion) for 4 weeks 
prior to screening. 
• Patients are taking iron supplements or folic acid on a stable dose for at least 4 weeks 
prior to screening. 
• Patients are allowed to take low molecular weight heparin on a stable dose for at least 
4 weeks prior to screening. 
Adjustments in the frequency or level of dosing 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 patient. 
9.4. 
Treatment Compliance 
Patients will be administered ALXN1210 in a controlled setting under the Investigator’s 
supervision, thereby ensuring compliance with ALXN1210 administration. Study coordinators at 
Page 56 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
the investigative site will ensure that all patients are adequately informed on the specific 
ALXN1210 dosing regimen required for compliance with the study protocol. 
Alexion or its designee will periodically monitor study sites to ensure compliance with the 
protocol, and communicate with sites on a regular basis regarding study protocol deviations. All 
protocol deviations will be appropriately documented by the Investigator or designee and study 
monitors. 
Unless otherwise specified, procedures, data collection, and evaluation will be conducted as per 
the clinical site’s standard operating procedures. 
9.5. 
Randomization and Blinding 
This is an open-label study. Up to 26 patients will be enrolled in the study. The first 2 eligible 
patients who meet the inclusion/exclusion criteria will be assigned to Cohort 1. The DMC will 
conduct a review of the available safety data as described in Section 6.3 to determine whether the 
next cohort may be opened. If additional patients are screened and are eligible for enrollment 
before a dose-escalation decision has been made by the DMC for any cohort, those patients will 
be assigned to the active cohort with the lowest dose level.  
Page 57 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
10. 
STUDY DRUG MATERIALS AND MANAGEMENT 
10.1. 
Description of Study Drug 
ALXN1210 is formulated at 10 mg/mL and 100 mg/mL concentrations with a pH of 7.0 and 7.4, 
respectively (Table 13).  Both ALXN1210 formulations are presented as sterile, preservative-free 
solutions for IV administration and are supplied in single-use vials. ALXN1210 will be provided 
by the Sponsor and is suitable for human use and manufactured under current Good 
Manufacturing Practices. 
Further details are provided in the Investigator’s Brochure and in the Pharmacy Manual. 
 
Table 13: 
Composition of Investigational Product 
Name of Ingredient 
10 mg/mL 
Concentration (IV) 
100 mg/mL 
Concentration (IV) 
Function 
ALXN1210 antibody 
10 mg/mL 
100 mg/mL 
Active Ingredient 
Sodium phosphate monobasic 
3.34 mM 1 
(0.46 mg/mL) 
33.1 mM 2 
(4.42 mg/mL) 
Buffering Agent 
Sodium phosphate dibasic 
6.63 mM 1 
(1.78 mg/mL) 
16.5 mM 2 
(4.42 mg/mL) 
Buffering Agent 
Sodium chloride 
150 mM 
(8.77 mg/mL) 
NA 
Tonicity 
L-Arginine 
NA 
25 mM 
(4.33 mg/mL) 
Stabilizer 
Sucrose 
NA 
50 mg/mL 
Tonicifying agent and 
stabilizer 
Polysorbate 80  
0.02% w/v 
0.05% w/v 
Surfactant 
Water for Injection 
QS 
QS 
Solvent 
Abbreviations: IV = intravenous; NA = not applicable; QS = quantum sufficiat (sufficient quantity). 
1 The sodium phosphate concentration is approximately 10 mM, which is comprised of sodium phosphate 
monobasic and the sodium phosphate dibasic.  
2 The sodium phosphate concentration is approximately 50 mM, which is comprised of sodium phosphate 
monobasic and the sodium phosphate dibasic. 
 
10.2. 
Study Drug Packaging and Labeling 
ALXN1210 will be supplied in a one-vial-per-kit configuration. Each vial and carton will be 
labeled according to specific country or region regulatory requirements. 
10.3. 
Study Drug Storage 
ALXN1210 vials must be stored in refrigerated conditions at 2°C to 8°C (36°F to 46°F) and 
protected from light. ALXN1210 vials should not be frozen or shaken. 
10.4. 
Study Drug Preparation 
Preparation of ALXN1210 doses must be performed in accordance with site-specific local 
standards by qualified and study-trained pharmacy personnel. 
Page 58 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
Handling and preparation of materials used to prepare and administer study drug must be carried 
out using aseptic techniques for sterile products.  
Pharmacy personnel will prepare doses in accordance with the dose assignment. 
Please refer to the Pharmacy Manual for additional dose preparation instructions. 
10.4.1. 
ALXN1210 Dose Preparation 
ALXN1210 will be diluted in 0.9% sodium chloride injection (country-specific pharmacopeia) 
and administered by IV infusion at a fixed rate by dose, as indicated in Table 14. 
For each patient, doses will be prepared as required for each dose cohort, as indicated in 
Table 14. 
Table 14: 
Dosing Reference Chart for 10 mg/mL ALXN1210 Formulation Dose 
Preparation  
Dose (mg) 
Infusion Volume (mL) 
Maximum Infusion Rate 
(mL/hour) 
Minimum Infusion Duration 
minutes (hours) 
1000 
200 
333 
36.0 (0.6) 
1400 
280 
333 
50.4 (0.8) 
1600 
320 
333 
57.6 (1.0) 
2000 
400 
333 
72.1 (1.2) 
2400 
480 
333 
86.4 (1.4) 
3000 
600 
333 
108.1 (1.8) 
5400* 
1080 
333 
194.6 (3.2) 
*To be given in divided dose. 
Please refer to the Pharmacy Manual for additional dose preparation instructions. 
These dosing rates apply to patients ≥ 50 kg; for patients < 50 kg, please refer to the pharmacy manual.   
Beginning on Day 463 for patients in Cohort 2, Day 477 for patients in Cohorts 3, and Day 533 
for patients in Cohort 1, patients will switch from their current dose regimen to a q8w, weight-
based regimen, as shown in Table 15. The dose regimen will not change for patients in Cohort 4. 
Table 15: 
Weight-based Dosing Reference Chart for 10 mg/mL ALXN1210 
Formulation Dose Preparation Beginning on Day 463 (Cohort 2), Day 477 
(Cohort 3), and Day 533 (Cohort 1) 
Body Weight 
(kg)a 
Dose  
(mg) 
ALXN1210 
Volume (mL) 
Total  
Volume (mL) 
Maximum Infusion  
Rate (mL/hr) 
Minimum Infusion  
Duration in minutes (hr) 
≥ 40 to < 60 
3000 
300 
600 
250 
140 (2.4) 
≥ 60 to < 100 
3300 
330 
660 
330 
120 (2.0) 
≥ 100 
3600 
360 
720 
328 
132 (2.2) 
Note: For patients weighing < 40 kg, please see Pharmacy Manual. 
a Dose regimen will be based on the last recorded study visit body weight. If the study drug is prepared the night 
before a visit, the weight from the most recent study visit should be used. 
Beginning on Day 953 for patients in Cohort 4, Day 981 for patients in Cohort 3, Day 1023 for 
patients in Cohort 2, and Day 1037 for patients in Cohort 1, patients will switch from the 
10 mg/mL ALXN1210 unit dose formulation to the 100 mg/mL ALXN1210 unit dose 
formulation (Table 16), while remaining on their current dose regimen.  
Page 59 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
Table 16: 
Dosing Reference Chart for 100 mg/mL ALXN1210 Formulation Dose 
Preparation    
Dose (mg) 
ALXN1210 
Volume (mL) 
Total  
Volume (mL) 
Maximum Infusion Rate 
(mL/hour) 
Minimum Infusion 
Duration minutes 
(hours) 
3000 
30 
60 
65 
55 (0.92) 
3300 
33 
66 
98 
40 (0.67) 
3600 
36 
72 
144 
30 (0.50) 
5400 
54 
108 
67 
95 (1.6) 
Please refer to the Pharmacy Manual for additional dose preparation instructions. 
These dosing rates apply to patients ≥ 50 kg; for patients < 50 kg, please refer to the Pharmacy Manual. 
Please refer to the Pharmacy Manual for additional dose preparation instructions. 
10.4.2. 
In-use Shelf Life 
ALXN1210 will be diluted with 0.9% sodium chloride injection (country-specific pharmacopeia) 
before administration (dosing solution). The dosing solution is stable for 6 hours at room 
temperature 15°C to 25°C (59°F to 77°F) or for 24 hours when refrigerated at 2°C to 8°C (36°F 
to 46°F). The expiration date and time of the dosing solution is calculated from breach of the 
first vial. The dose must be administered within the expiration date and time. 
10.5. 
Study Drug Administration 
All doses of ALXN1210 will be administered by IV infusion using a programmable IV infusion 
pump and IV sets with in-line filters. Infusion rates are presented in Section 10.4.1. Infusion 
volume and duration and further information regarding the preparation and administration of 
study drug are provided in the Pharmacy Manual. 
During the Induction and Maintenance Periods (up to Day 253), patients will remain seated or 
semi-reclined for the duration of ALXN1210 administration and remain in the clinic for an 
additional 2 hours for safety observations.  
Time of dosing (t = 0) will be defined as ALXN1210 start of infusion. All procedures will be 
performed in relation to SOI or EOI as described in the Schedules of Assessments (Section 7). 
10.6. 
Study Drug Accountability 
The study site must maintain accurate records demonstrating dates and amount of study drug 
received from Alexion, to whom dispensed (patient-by-patient accounting), and accounts of any 
study drug accidentally or deliberately destroyed. 
Accountability logs will be provided to assist the pharmacist in maintaining current and accurate 
inventory records covering receipt, dispensation, and disposition of the study drug.  
The study monitor will examine the inventory during the study. Accountability records must be 
readily available and may be subject to regulatory authority review by the local regulatory 
agency, or an independent auditor’s inspection, at any time. 
Unless otherwise notified, empty vials and vials with residual materials should be kept for 
inspection and accountability by the study monitor prior to their destruction or handled per local 
site pharmacy standard operating procedures for clinical study drugs. At the end of the study, a 
Page 60 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
final reconciliation must be made between the amount of study drug supplied, dispensed, and 
subsequently destroyed or returned to Alexion. 
A written explanation will be provided for any discrepancies. After reconciliation, the 
Investigator must destroy or return to Alexion all unused vials of study drug as instructed by 
Alexion. 
Refer to the Pharmacy Manual for detailed instructions on receipt, storage, preparation, 
administration, destruction, and return of study drug. 
10.7. 
Study Drug Handling and Disposal 
At the completion of the study, to satisfy regulatory requirements regarding drug accountability, 
all remaining study drug inventory will be reconciled and retained or destroyed according to 
applicable provincial and federal regulations. 
For handling instructions, please refer to the Pharmacy Manual. 
Page 61 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
11. 
PHARMACOKINETIC AND PHARMACODYNAMIC 
ASSESSMENTS 
11.1. 
Blood Sample Collection 
The total volume of blood collected per patient for clinical laboratory, PK, PD, and 
immunogenicity assessments will not exceed 300 mL in any 16-week period. 
Please refer to the Laboratory Study Manual for details on sample collection, including blood 
volume requirements. 
After administration of ALXN1210, blood samples for determination of serum ALXN1210 
concentrations will be collected at the time points indicated in the Schedule of Assessments 
(Section 7), with the actual blood sampling dates and times being recorded and used in PK 
calculations. The timing of PK sample collection may be altered based on initial PK results to 
ensure appropriate PK monitoring. The number of PK sampling time points for any given patient 
will not exceed the currently planned number of time points.  
Serum concentrations of ALXN1210 and blood samples for analyses of C5 levels (total and 
free), cRBC hemolysis, and quantitative measures of C5 activation will be collected at the time 
points specified in (Table 17). Serum samples will be stored for additional PK/PD analyses. 
Table 17: 
Collection Time Points for Serum Concentrations of ALXN1210 and 
Analysis of Hemolytic Activity 
Cohort 
Period 
Dose Number and Study Day 
Collection Windows 
1 
Treatment 
Dose 1 on Day 1 
Dose 2 on Day 15 
• Predose (up to 0.5 hour before) 
• EOI (up to 0.5 hour after) 
• 4 hours post-SOI (±1 hour) 
• Day 22 (±1 day) 
Doses 3 to 11 on Days 29, 57, 85, 113, 
141, 169, 197, 225, and 253 
• Predose (up to 0.5 hour before) 
• EOI (up to 0.5 hour after) 
• 4 hours post-SOI (±1 hour) 
• Day 43 (±1 day) 
• Days 127 and 211 (±2 days) 
• Day 253 (up to 0.5 hour before Dose 
11) 
Extension 
Doses 14, 19, 22, 25 27, 28, 29, 30, 31, 
33, 35, 37, 39, 41, 43, 45, and 47 on Days 
337, 477, 645, 813, 925, 981, 1037, 1093, 
1149, 1261, 1373, 1485, 1597, 1709, 
1821, 1933, and 2045 
• Predose (up to 0.5 hour before) 
• When a patient discontinues the study 
or at the last study visit (Day 2157) 
2 
Treatment 
Dose 1 on Day 1 
Dose 2 on Day 22 
• Predose (up to 0.5 hour before) 
• EOI (up to 0.5 hour after) 
• 4 hours post-SOI (±1 hour) 
• Day 29 (±1 day) 
Doses 3 to 8 on Days 43, 85, 127, 169, 
211, and 253 
• Predose (up to 0.5 hour before) 
• EOI (up to 0.5 hour after) 
• 4 hours post-SOI (±1 hour) 
• Day 57 (±1 day) 
• Days 113, 141, 197, and 225 (±2 days) 
• Day 253 (up to 0.5 hour before Dose 
8) 
Page 62 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
Cohort 
Period 
Dose Number and Study Day 
Collection Windows 
Extension 
Doses 10, 14, 17, 20, 22, 23, 24, 25, 26, 
28, 30, 32, 34, 36, 38, 40, and 42 on Days 
337, 519, 687, 855, 967, 1023, 1079, 
1135, 1191, 1303, 1415, 1527, 1639, 
1751, 1863, 1975, and 2087 
• Predose (up to 0.5 hour before) 
• When a patient discontinues the study 
or at the last study visit (Day 2143) 
3 
Treatment  
Dose 1 on Day 1 
Dose 2 on Day 15 
• Predose (up to 0.5 hour before) 
• EOI (up to 0.5 hour after) 
• 4 hours post-SOI (±1 hour) 
• Days 22 (±1 day) 
Doses 3 to 7 on Days 29, 85, 141, 197, 
and 253 
• Predose (up to 0.5 hour before) 
• EOI (up to 0.5 hour after) 
• 4 hours post-SOI (±1 hour) 
• Days 43 and 57 (±1 day) 
• Days 113, 127, 169, 211, and 225 
(±2 days) 
• Day 253 (up to 0.5 hour before 
Dose 7) 
Extension 
Doses 8, 11, 14, 16, 18, 19, 20, 21, 22, 24, 
26, 28, 30, 32, 34, 36, 38, and 40 on 
Days 309, 477, 645, 757, 869, 925, 981, 
1037, 1093, 1205, 1317, 1429, 1541, 
1653, 1765, 1877, 1989, and 2101 
• Predose (up to 0.5 hour before) 
• When a patient discontinues the study 
or at the last study visit (Day 2157) 
4 
Treatment 
Dose 1 on Day 1 
 
• Predose (up to 0.5 hour before) 
• EOI (up to 0.5 hour after) 
• 4 hours post-SOI (±1 hour) 
• Day 15 (±1 day) 
Doses 2 to 4 on Days 29, 113, and 197 
• Predose (up to 0.5 hour before) 
• EOI (up to 0.5 hour after) 
• 6 hours post-SOI (±1 hour) 
• Day 57 (±1 day) 
• Days 141 and 225 (±2 days) 
• Day 253  
Extension 
Doses 5, 7, 9, 11, 12, 13, 14,  16, 18, 20, 
22, 24, and 26 on Days 281, 449, 617, 
785, 869, 953, 1037, 1205, 1373, 1541, 
1709, 1877, and 2045 
• Predose (up to 0.5 hour before) 
• When a patient discontinues the study 
or at the last study visit (Day 2129) 
Abbreviations: EOI = end of infusion; SOI = start of infusion 
11.2. 
PK/PD Sample Analysis 
Samples for PK/PD analysis should not be drawn from the same arm as the infusion on dosing 
days. Detailed instructions on the procedures for collection, processing, storage, and shipment of 
blood samples for PK and PD analyses will be provided in the Laboratory Study Manual. All 
sample analysis will be performed by Alexion or designee. 
Page 63 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
12. 
IMMUNOGENICITY ASSESSMENTS 
Blood samples for the analyses of ADA to ALXN1210 will be collected at the time points 
specified in Table 18.  
Table 18: 
Collection Time Points for Serum Samples for Immunogenicity Analyses of 
Antidrug Antibodies to ALXN1210 
Cohort 1 
Predose on Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 337, 477, 645, 813, 925, 981, 
1037, 1093, 1149, 1261, 1373, 1485, 1597, 1709, 1821, 1933, 2045, and 2157 or ET 
Cohort 2 
Predose on Days 1, 22, 43, 85, 127, 169, 211, 253, 337, 519, 687, 855, 967, 1023, 1079, 1135, 
1191, 1303, 1415, 1527, 1639, 1751, 1863, 1975, 2087, and 2143 or ET 
Cohort 3 
Predose on Days 1, 15, 29, 85, 141, 197, 253, 309, 477, 645, 757, 869, 925, 981, 1037, 1093, 
1205, 1317, 1429, 1541, 1653, 1765, 1877, 1989, 2101, and 2157 or ET  
Cohort 4 
Predose on Days 1, 29, 113, 197, 281, 449, 617, 785, 869, 953, 1037, 1205, 1373, 1541, 1709, 
1877, 2045, and 2129 or ET 
1 This is not a dosing day, therefore collection can occur at any time. 
12.1. 
Immunogenicity Sample Analysis 
Please refer to the Laboratory Study Manual for time windows for collection and detailed 
instructions for collecting, processing, storing, and shipping blood samples for immunogenicity 
analysis.  
The total volume of blood collected per patient for clinical laboratory, PK, PD, and 
immunogenicity assessments will not exceed 300 mL in any 16-week period. All sample 
analyses will be performed by Alexion or designee. 
Page 64 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
13. 
ASSESSMENTS OF EFFICACY  
The following assessments will be performed during the study to evaluate the efficacy of 
ALXN1210 therapy. 
13.1. 
Blood Samples for Pharmacodynamic Analysis 
13.1.1. 
Lactate Dehydrogenase 
Lactate dehydrogenase levels will be analyzed at the time points specified in the Schedule of 
Assessments (Section 7). 
Detailed instructions on the procedure for collection, processing, storage, and shipment of the 
blood samples for LDH analysis will be provided in the Laboratory Study Manual. All sample 
analysis will be performed by Alexion or designee. 
13.1.2. 
Biomarkers of PNH 
A serum PD panel will be collected for analyses of C5 levels (total and free) and cRBC 
hemolysis at the time points specified in Table 17. In addition, serum samples will be stored for 
potential additional analyses. 
13.1.3. 
Hemolysis-related Hematological Parameters 
Hemolysis-related hematological parameters will be assessed by measurements of free 
hemoglobin, haptoglobin, reticulocyte count, PNH clone size (%), and D-dimer. 
Hematology assessments will be obtained at the time points specified in the Schedule of 
Assessments (Section 7). 
13.2. 
Quality of Life 
The FACIT-Fatigue scale, version 4, is a collection of QoL questionnaires targeted to the 
management of fatigue symptoms due to a chronic illness. 
The EORTC Quality of Life Questionnaire-Core 30 Scale, Version 3.0, is a questionnaire 
developed to assess the QoL of cancer patients. 
Both scales will be administered at the time points specified in the Schedule of Assessments 
(Section 7). Sample FACIT-Fatigue and EORTC scales will be provided in the Study Manual. 
13.3. 
PNH Symptomatology 
The Investigator will assess patients for the following events: fatigue, abdominal pain, dyspnea, 
dysphagia, chest pain, and erectile dysfunction. Symptoms of disease burden will be captured 
through the QoL questionnaire. 
Investigator assessment of clinical symptoms related to PNH will be made at the time points 
specified in the Schedule of Assessments (Section 7). 
Page 65 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
13.4. 
Exploratory Markers of PNH 
Markers of PNH symptoms and comorbidities (ie, chronic kidney disease by urinary spot 
albumin:creatinine ratio and eGFR, and BNP for pulmonary hypertension) will be evaluated in 
the study as exploratory efficacy endpoints. Evaluation for changes in kidney function will be 
based on Investigator assessment and laboratory results of serum and urinary creatinine and 
eGFR. The estimated glomerular filtration rate will be calculated using the Modification of Diet 
in Renal Disease formula at the same time blood is drawn for chemistry assessments; specified in 
the Schedule of Assessments (Section 7). In addition, total serum LDH levels may be further 
analyzed as individual LDH isozymes (LDH1-5). 
13.5. 
Major Adverse Vascular Events 
Major adverse vascular events (MAVEs) will be assessed as part of the planned evaluation for 
AEs as described in Section 15. The definition of MAVE is provided below. 
The description of event, location, method of diagnosis (magnetic resonance imaging, 
ultrasound, angiogram, or other), date of diagnosis and date resolved (or ongoing) will be 
collected in the eCRF as part of the patient’s medical history and during the study. 
A MAVE can only be one of the following events: 
• Thrombophlebitis/deep vein thrombosis 
• Pulmonary embolus 
• Myocardial infarction 
• Transient ischemic attack 
• Unstable angina 
• Renal vein thrombosis 
• Acute peripheral vascular occlusion 
• Amputation (non-traumatic; non-diabetic) 
• Mesenteric/visceral vein thrombosis or infarction 
• Mesenteric/visceral arterial thrombosis or infarction 
• Hepatic/portal vein thrombosis (Budd-Chiari syndrome) 
• Dermal thrombosis  
• Gangrene (non-traumatic; non-diabetic) 
• Cerebral arterial occlusion/cerebrovascular accident 
• Cerebral venous occlusion 
• Renal arterial thrombosis 
• Other, specify 
Page 66 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
14. 
ASSESSMENT OF SAFETY 
14.1. 
Safety Parameters 
Patients will meet with the Investigator or designee to discuss the potential safety risks of 
ALXN1210 and to allow for the Investigator to address any of the patient’s safety concerns at the 
time points specified in the Schedule of Assessments (Section 7). 
Collection of AEs, including SAEs and MAVEs, will be monitored from the time informed 
consent is obtained until study completion. Investigators are instructed to follow any AEs 
through to their conclusion; in the event of patient discontinuation from the study, AE 
monitoring should continue through the last study visit if possible.  
Clinical and laboratory assessments will be performed to assess ALXN1210. Timing of the 
assessments is specified in the Schedule of Assessments (Section 7). Any abnormal results 
should be followed until resolution or stabilization. 
14.1.1. 
Demographic/Medical History 
A review of demographic parameters, including age, gender, race, and ethnicity will be 
performed, as specified in the Schedule of Assessments (Section 7). A complete medical history 
will be taken and documented. 
14.1.2. 
Weight and Height 
Weight, height, and body mass index will be recorded, as described in the Schedule of 
Assessments (Section 7). 
14.1.3. 
Physical Examination 
A physical examination assessing general appearance, skin, head/eyes/ears/nose/throat, neck, 
lymph nodes, chest, heart, abdominal cavity, limbs, central nervous system, and musculoskeletal 
will be performed at the time points specified in the Schedule of Assessments (Section 7). An 
abbreviated physical examination consists of a body system relevant examination based upon 
Investigator judgment and subject symptoms. 
14.1.4. 
Vital Signs 
Vital sign measurements will be taken after the patient has been resting in the supine position for 
at least 5 minutes, and will include oral or tympanic temperature (°C), respiratory rate, supine 
blood pressure, and pulse rate. The timing of vital sign assessments is provided in the Schedule 
of Assessments (Section 7). Out-of-range blood pressure or pulse measurements will be repeated 
at the Investigator’s discretion. Any confirmed, clinically significant vital sign measurements 
will be recorded as AEs. 
14.1.5. 
Electrocardiogram  
The ECG will be obtained after the patient has been resting in a supine position for at least 
5 minutes. A triplicate 12-lead ECG will be obtained at screening, prior to the first dose of 
ALXN1210 on Day 1, and at the end of study (Day 2157 for Cohorts 1 and 3, Day 2143 for 
Page 67 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
Cohort 2, and Day 2129 for Cohort 4) or Early Termination visit. A single ECG will be obtained 
at the other time points specified in the Schedule of Assessments (Section 7).  
Heart rate, PR, QRS, RR (when available), and QT will be measured, and corrected QTcF 
intervals (Fridericia’s formula) will be calculated. 
14.1.6. 
Laboratory Assessments 
Blood samples for analysis of hematology, clinical chemistry, coagulation, BNP, urinalysis/urine 
chemistry, and virus serology parameters will be collected as specified in the Schedule of 
Assessments (Section 7). A list of parameters is provided in Appendix A. 
Abnormal results should be followed, as appropriate. Handling and shipping of clinical 
laboratory samples will be outlined in the Laboratory Study Manual. A central laboratory will be 
used to evaluate all laboratory assessments. If a screening laboratory sample is cancelled by the 
central laboratory due to hemoglobin interference in a grossly hemolyzed specimen, a local retest 
may be performed and the results entered into the EDC system. Any on-treatment laboratory 
samples cancelled centrally will be reviewed by Alexion Medical to determine if local retesting 
is needed. Sites will be notified if local laboratory retesting is required during a patient’s 
treatment. 
14.1.6.1. Pregnancy Screen  
Serum pregnancy testing (beta human chorionic gonadotropin) will be performed in all female 
patients of childbearing potential at screening and end of study/Early Termination. Urine 
pregnancy testing (with a minimum human chorionic gonadotropin detection limit of 25 IU/L) 
will be performed at the time points specified in the Schedule of Assessments (Section 7). 
14.1.6.2. Hematology 
Blood will be analyzed for the parameters listed in Appendix A and will be performed at the time 
points specified in the Schedule of Assessments (Section 7). 
14.1.6.3. Blood Chemistry 
Blood samples will be analyzed for the parameters listed in Appendix A. Considering that 
indirect bilirubin is calculated from total and direct bilirubin values, indirect bilirubin results will 
not be available if direct bilirubin is below the limit of quantification. 
Serum follicle-stimulating hormone level and estradiol concentrations will be measured at least 
twice during screening for postmenopausal female patients to confirm their postmenopausal 
status. 
Chemistry assessments will be performed at the time points specified in the Schedule of 
Assessments (Section 7). 
14.1.6.4. Coagulation 
Blood samples will be analyzed for the parameters listed in Appendix A. 
Coagulation assessments will be performed at the time points specified in the Schedule of 
Assessments (Section 7). 
Page 68 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
14.1.6.5. Urinalysis and Urine Chemistry 
Urine samples will be analyzed for the parameters listed in Appendix A. 
Urine samples will also be analyzed to measure proteins and creatinine in order to calculate the 
urine protein:creatinine ratio. 
Urinalysis and urine chemistry assessments will be performed at the time points specified in the 
Schedule of Assessments (Section 7). 
14.1.6.6. Virus Serology 
Blood samples will be analyzed for the parameters listed in Appendix A and will be performed at 
the time points specified in the Schedule of Assessments (Section 7). 
14.1.6.7. Brain Natriuretic Protein 
Blood samples for BNP analysis will be performed at the time points specified in the Schedule of 
Assessments (Section 7). 
14.1.7. 
Infusion Site Reaction 
Patients will be evaluated for infusion site reactions at the time points specified in the Schedule 
of Assessments (Section 7). Infusion site reactions will be recorded as an AE using the 
appropriate coding terms. 
An induration or reaction of < 10 mm will not be listed as an AE unless it persists for more than 
24 hours, at which time, the patient must inform the study staff immediately and proceed to the 
nearest hospital emergency department. Pain at the site of infusion will be assessed using a 
100 mm visual analog scale (VAS). The VAS should be completed as soon as practical after 
completion of the infusion. 
Page 69 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
15. 
ADVERSE EVENT MANAGEMENT 
The Investigator is responsible for detecting, assessing, documenting and reporting all AEs. All 
AEs will be recorded from the signing of informed consent until study completion. There is no 
time limit for SAEs that are considered causally related. 
All observed or volunteered AEs, regardless of causal relationship, must be reported and 
recorded in the eCRF. Adverse events reported by the patient and/or parent or legal guardian, 
and/or identified in response to an open-ended question from study personnel, or revealed by 
observation, physical examination, or other study procedures must be collected and recorded. 
15.1. 
Definition of an Adverse Event 
An AE is defined as any unfavorable and unintended sign (eg, including an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of a medicinal product or 
procedure, whether or not considered related to the medicinal product or procedure, which 
occurs during the course of the clinical study. 
Exacerbations of a chronic or intermittent pre-existing condition, including either an increase in 
frequency and/or intensity of the condition, are all to be considered AEs. 
Abnormal test findings may be considered AEs. If an abnormal laboratory value is identified, 
Investigators are strongly encouraged to report a diagnosis, or a sign or symptom, rather than an 
isolated abnormal test value. An abnormal test finding should be documented as an AE if any of 
the following conditions are met: 
• Is associated with a sign or symptom 
• Requires additional diagnostic testing (repeat tests are not considered additional 
testing) 
• Requires a medical or surgical intervention 
• Leads to a change in study dosing outside of the protocol-defined dosing or leads to 
discontinuation from the study 
• Requires significant additional treatment 
• Does not meet any of the conditions above; however, the Investigator or Sponsor 
considers the result clinically significant or meeting the definition of an AE. 
This definition also includes the signs or symptoms resulting from: 
• Drug overdose 
• Drug withdrawal 
• Drug misuse 
• Drug interactions 
• Extravasation 
• Exposure during pregnancy 
Page 70 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
• Exposure via breastfeeding 
• Medication error 
• Occupational exposure 
An AE does not necessarily include the following: 
• Medical or surgical procedures (eg, surgery, endoscopies, tooth extraction, 
transfusion); the condition that leads to the procedure is the AE (eg, laparoscopic 
cholecystectomy is the procedure or treatment for an SAE of necrotic gall bladder) 
• Pre-existing diseases or conditions present or detected prior to the screening 
evaluation that do not worsen 
• Situations where an untoward medical occurrence has not occurred (eg, 
hospitalization for elective surgery if planned prior to the start of the study, social 
and/or convenience admissions) 
15.2. 
Definition of a Serious Adverse Event  
Any AE that fulfills any one of the criteria listed below must be recorded as an SAE. 
An SAE is described as any untoward medical occurrence that, at any dose: 
• Results in death 
• Is life threateninga 
• Requires hospitalization or prolongation of hospitalizationb. Hospitalization does not 
necessarily include the following: 
o Rehabilitation/hospice/nursing facility 
o Emergency room visit less than 24 hours 
o Elective or preplanned admission/surgery/day surgery 
o Protocol-specified admission 
o Admission for a pre-existing condition not associated with either a new AE 
or with worsening of a pre-existing AE 
• Results in persistent or significant disability/incapacity 
• Is a congenital anomaly/birth defect 
• Is an important medical eventc 
a The term “life threatening” in the definition of “serious” refers to an event in which the patient was at risk of death at the time of the event; it 
does not refer to an event which hypothetically might have caused death if it were more severe. 
b Hospitalization requires inpatient admission or prolongation of an existing hospitalization. The AEs that are associated with hospitalization or 
prolongation of hospitalization are considered SAEs. 
c  Important medical event: Medical and scientific judgment should be exercised in deciding whether expedited reporting is appropriate in other 
situations, such as important medical events that may not be immediately life threatening, or result in death or hospitalization, but may 
jeopardize the patient or may require intervention to prevent one of the other outcomes listed in the definition above. These should also 
Page 71 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
usually be considered serious. Examples of such events are 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. 
Severity and seriousness must be differentiated. Severity describes the intensity of an AE, while 
the term seriousness refers to an AE that has met the criteria for an SAE, as described above. 
15.3. 
Severity Assessments 
All AEs will be graded according to criteria from CTCAE v4.03, published 14 June 2010.  
• 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 
Changes in the severity of an AE should be documented to allow an assessment of the AE 
duration at each level of intensity to be evaluated. Adverse events characterized as intermittent 
require documentation of onset and duration of each episode, if the severity of the intermittent 
event changes. 
15.4. 
Causality Assessment 
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. 
Definitions for causality assessments are as follows: 
• Not related (unrelated): This relationship suggests that there is no association between 
the investigational product and the reported event. 
• Unlikely related: This relationship suggests that the clinical picture is highly 
consistent with a cause other than the investigational product, but attribution cannot 
be made with absolute certainty, and a relationship between the investigational 
product and the AE cannot be excluded with complete confidence. 
• Possibly related: This relationship suggests that treatment with the investigational 
product may have caused or contributed to the AE, ie, the event follows a reasonable 
temporal sequence from the time of drug administration, and/or follows a known 
response pattern to the investigational product, but could also have been produced by 
other factors. 
• Probably related: This relationship suggests that a reasonable temporal sequence of 
the event with the investigational product administration exists, as well as the likely 
association of the event with the investigational product. This will be based upon the 
known pharmacological action of the investigational product, known or previously 
reported adverse reactions to the investigational product or class of drugs, or 
judgment based on the Investigator’s clinical experience. 
Page 72 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
• Definitely related: Temporal relationship to the investigational product. Other 
conditions (concurrent illness, concurrent medication reaction, or 
progression/expression of disease state) do not appear to explain event, corresponds 
with the known pharmaceutical profile, improvement on discontinuation, 
reappearance on rechallenge. 
15.5. 
Outcome 
For all AEs, regardless of causal relationships, the Investigator must follow up regarding the 
outcome of the event until the event or sequelae either resolve or stabilize. Adverse event 
outcomes must be recorded in the eCRF and on any additional forms, as appropriate. 
If a patient experiences an SAE with an outcome of death, the following procedures are to be 
performed: 
• The SAE resulting in death should have an outcome documented as death/fatal, with 
an end date being the date of death. 
• If the patient had additional AE/SAEs that were ongoing at the time of death, these 
events would be documented as ongoing with no end date. 
• Only 1 event should have an outcome of death/fatal, unless an autopsy report or 
Investigator states otherwise. 
15.6. 
Recording Adverse Events 
All observed or volunteered AEs, regardless of dose level or causal relationship, must be 
reported as described in Section 15. 
For all AEs, the Investigator must do the following: 
• Determine the AE outcome 
• Determine if the event meets criteria for an SAE 
• Assess AE severity 
• Determine AE causality 
Adverse events must be documented in clear, unambiguous medical terms. Study personnel are 
advised not to use abbreviations or acronyms. 
For each AE, record in the eCRF only the diagnosis; do not report the characteristic signs and 
symptoms of the diagnosis as additional AEs. 
If a diagnosis is not available, record each sign and symptom as an AE; when a diagnosis 
becomes available, study personnel are to update the source document and the eCRF with the 
relevant diagnosis only. 
For medical or surgical procedures (eg, surgery, endoscopies, tooth extraction, transfusion), the 
condition/diagnosis that leads to the procedure should be recorded as the AE (eg, laparoscopic 
cholecystectomy is the procedure or treatment for an SAE of necrotic gall bladder). 
Page 73 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
All AEs that later increase in frequency and or severity (medical and scientific judgment should 
be exercised by the Investigator) will be considered new AEs, and will be recorded on a new line 
in the eCRF. 
Withdrawal due to an AE or SAE must be clearly differentiated from withdrawal due to other 
reasons. 
15.7. 
Reporting Serious Adverse Event(s) to the Sponsor 
All AEs must be assessed by the Investigator to determine if they meet criteria for an SAE. All 
SAEs must be reported to Alexion or designee immediately, or within 24 hours of the 
Investigator and/or study site staff becoming aware of the event, regardless of the presumed 
relationship to ALXN1210. 
The Investigator must verify the accuracy of the information recorded on the SAE pages of the 
eCRF with the corresponding source documents, and submit the SAE electronically via the 
Safety Gateway. In the event that the eCRF is not available or the Investigator is unable to 
submit the SAE electronically, the Investigator must complete the Safety Gateway Contingency 
form, sign and date the paper SAE pages, and send a copy via e-mail or fax to the contact 
information provided below: 
E-mail: ClinicalSAE@alexion.com 
Fax: + 1 203.439.9347 
Additional follow-up information, if required or available, should be entered into the eCRF and 
sent to the Sponsor or designee within 24 hours of the Investigator or study site staff becoming 
aware of this additional information. These reporting timelines should be followed for all initial 
and follow-up SAEs. 
For all SAEs, the Investigator must provide the following: 
• Appropriate and requested follow-up information in the time frame detailed above 
• Causality of the serious event(s) 
• Outcome of the serious event(s) 
• Medical records and laboratory/diagnostic information 
15.8. 
Exposure During Pregnancy and Lactation 
Pregnancy data will be collected during this study for all patients. Exposure during pregnancy, 
also called exposure in utero, can be the result of either maternal exposure or transmission of 
drug product via semen following paternal exposure. 
For all Alexion products, both in development or postapproval, exposure during pregnancy must 
be recorded and followed. If a female patient participating in this study, or a male patient’s 
female partner becomes or is found to be pregnant while being treated or exposed to study drug, 
the Investigator must submit the “Pregnancy Reporting and Outcome/Breastfeeding Form” to 
Alexion or designee via the same method as SAE reporting. Female patients who become 
pregnant will be discontinued from dosing, but will continue to be followed for safety where 
Page 74 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
feasible. Male patients may continue in the study if an accidental pregnancy of their female 
partner occurs, despite adequate contraception. 
The female patient should be followed until the outcome of the pregnancy is known 
(spontaneous miscarriage, elective termination, normal birth, or congenital abnormality), even if 
the patient discontinues ALXN1210 treatment or discontinues from the study. When the 
pregnancy outcome becomes known, the pregnancy reporting form should be updated and 
returned to Alexion or designee. If additional follow-up is required, the Investigator will be 
requested to provide the information. 
Pregnancy in itself is not regarded as an AE unless there is a suspicion that investigational 
product may have interfered with the effectiveness of a contraceptive medication. However, 
complications of pregnancy and abnormal outcomes of pregnancy are AEs, and many may meet 
criteria for an SAE. Complications of pregnancy and abnormal outcomes of pregnancy, such as 
ectopic pregnancy, spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital 
anomaly, would meet the criteria of an SAE and therefore should be reported as an SAE. 
Elective abortions without complications should not be handled as an AE. 
Exposure of an infant to an Alexion product during breastfeeding should also be reported on the 
“Pregnancy Reporting and Outcome/Breast Feeding Form.” Any AEs an infant experiences 
following breastfeeding are to be reported to Alexion or designee. 
15.9. 
Reporting Requirements 
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. 
15.9.1. 
Sponsor 
The Sponsor or legal representative is responsible for notifying relevant regulatory authorities of 
SAEs meeting the reporting criteria. 
15.9.2. 
Investigator 
The Investigator must fulfill all local regulatory requirements for Investigators conducting 
clinical studies. It is the Investigator’s responsibility to notify the Institutional Review Board 
(IRB) or Independent Ethics Committee (IEC) of all reportable SAEs that occur. Alexion will 
notify Investigators of all unexpected, serious, drug-related events (7/15 Day Safety Reports) that 
occur during the clinical study. The Investigator is responsible for notifying the IRB or IEC of 
these additional SAEs. Adverse events are recorded in the eCRF, and are retrieved by or 
submitted to the Sponsor at regular monthly intervals, or more frequently during the course of 
the investigation. 
Page 75 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
16. 
STATISTICS 
16.1. 
General Considerations 
All data collected in this study will be documented using summary tables, figures, and data 
listings. For categorical variables, frequencies and percentages will be presented for each cohort, 
and for the combined cohorts. For continuous variables, descriptive statistics (n, mean, median, 
SD, minimum, maximum) will be presented for each cohort, and for the combined cohorts. 
Descriptive statistics for PK parameters will include the number of observations, mean, SD, 
coefficient of variance (CV), median, minimum, maximum, geometric mean, and geometric 
%CV. 
A clinical study report will be produced after the end of the Maintenance Period and will include 
safety, efficacy, immunogenicity, PK, and PD analyses. A final clinical study report will be 
produced at study completion and will include data on all patients in the study through the end of 
the Extension Period. Additional analyses may be performed for the 100 mg/mL formulation. 
All calculations will be performed by Alexion or its designee. Additional details of statistical 
analyses will be described in the statistical analysis plan. 
16.2. 
Analysis Populations 
The safety population will consist of all patients who receive at least 1 dose of study drug (Safety 
Set). Patients in this population will be used for the safety analyses. 
The full analysis set (FAS) will consist of all patients in the safety population who had a baseline 
LDH measurement and at least 1 postbaseline LDH measurement. The FAS will be used for all 
efficacy analyses. 
The PK population will consist of all patients who have sufficient serum concentration data to 
enable the calculation of PK parameters. The PK population will be used for PK summaries. 
The immunogenicity population will consist of all patients who have a predose and postdose 
immunogenicity sample collected. 
16.3. 
Sample Size and Power 
A sample size of 20 patients from the combined cohorts will provide approximately 95% power 
to detect a mean paired difference in LDH from baseline of –40% at Day 253, with an estimated 
SD of 45%. This is based on a 2-sided paired t-test, with 5% type I error rate. To account for a 
possible 15% dropout rate and additional patients in screening, up to 26 patients will be enrolled.  
16.4. 
Demographics, Baseline Characteristics, and Patient Disposition 
All patients will be included in the summaries of patient disposition, which will describe the 
frequency and percentage of patients screened and treated and who completed or discontinued 
from the study, along with reason for discontinuation, by cohort. Demographics and baseline 
characteristics will be summarized for all patients by each cohort and overall. 
Page 76 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
16.5. 
Safety Analysis 
Safety analyses will be performed on the Safety Set, which consists of all patients who receive at 
least 1 dose of ALXN1210, and will be reported by cohort and overall. Safety analyses will 
include all AEs, ECGs, clinical laboratory data, physical examinations, and vital sign 
measurements, and will be presented using descriptive statistics. No inferential statistical 
analyses are planned on safety parameters. The incidence of treatment-emergent adverse events 
and SAEs will be summarized by System Organ Class and Preferred Term for each cohort and 
overall, by severity, and by relationship to ALXN1210. Adverse events will be coded using the 
Medical Dictionary for Regulatory Activities, Version 18.0 or higher. Serious AEs and AEs 
resulting in withdrawal from the study will be listed. Patients having multiple AEs within a 
category (eg, overall, System Organ Class, Preferred Term) will be counted once in that 
category. For severity tables, a patient’s most severe event within a category will be counted. 
Changes from baseline in vital signs and laboratory assessments (chemistry, complete blood 
count with differential, and urinalysis) will be summarized by cohort. Shift tables of clinical 
laboratory tests using criteria from CTCAE v4.03 will be produced by cohort. Graphical displays 
will be presented, as appropriate. 
The ECG parameters will be measured at the specified time points, including heart rate, PR, RR, 
QRS, QT, and corrected QTcF intervals. The average of the triplicate ECG readings at the time 
points collected will be calculated, and changes from pretreatment baseline values will be 
assessed by cohort. 
All concomitant medications will be coded using the World Health Organization Drug 
Dictionary, and the frequency and percentage of concomitant medications will be summarized. 
16.6. 
Efficacy Analysis 
Efficacy analyses will be performed on the FAS, which include the Safety Set subset with a 
baseline and at least 1 postbaseline LDH measurement. 
Absolute LDH levels, and the change and percent change from baseline will be summarized at 
all study visits. Baseline is defined as the average of all available assessments on or prior to the 
first ALXN1210 infusion. A mixed model for repeated measures (MMRM) with the fixed, 
categorical effect of visit and fixed, continuous effect of baseline LDH levels as covariates will 
be fit to test whether changes and percent changes differ from zero at each time point. An 
unstructured covariance analysis will be used to model the within-patient errors. If this analysis 
fails to converge, the following structures will be tested and the final covariance structure will be 
determined by Akaike’s information criterion: first-order autoregressive, compound symmetry, 
and Toeplitz method. The Kenward-Roger approximation will be used to estimate denominator 
degrees of freedom. As a sensitivity analysis, changes and percent changes from baseline will be 
analyzed, using the Wilcoxon signed-rank test. Graphical displays will be presented, as 
appropriate. 
The percentage of patients with clinical symptoms will be summarized for all study visits. 
Changes in hematologic measures will be similarly analyzed using an MMRM and Wilcoxon 
signed-rank test. 
Page 77 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
Scoring guidelines for the FACIT-Fatigue and EORTC scales will be used to calculate QoL 
scores. Changes from baseline in FACIT-Fatigue and EORTC scale scores will be summarized 
descriptively for all study visits, and analyzed using MMRM and Wilcoxon signed rank test.  
Transfusion rates and the incidence rate of MAVEs will be summarized. 
16.7. 
Pharmacokinetic Analysis 
Individual serum concentration data for ALXN1210-treated patients, with actual sampling dates 
and times, will be used to derive the PK parameters by noncompartmental analyses, using 
Phoenix® WinNonlin® (Pharsight Corporation, St Louis, Missouri) Version 6.3 or higher. The 
PK samples collected on or after Day 1149 for Cohort 1, Day 1135 for Cohort 2, Day 1093 for 
Cohort 3, or Day 1121 for Cohort 4 will be stored and may be assayed if considered necessary 
for the purpose of medical monitoring.   
The following PK parameters will be estimated: maximum observed serum concentration (Cmax) 
after each dose, time to maximum observed serum concentration (tmax), minimum observed 
serum concentration (Cmin), the observed serum concentration at the end of the dosage interval τ 
(Ctrough), area under the serum concentration-versus-time curve from time 0 (dosing) to the last 
quantifiable concentration (AUCt), area under the concentration-versus-time curve from time 0 
(dosing) to the end of the dosing interval (AUCτ), apparent terminal-phase elimination rate 
constant (λz), terminal elimination half-life (t½), and, if possible, total clearance (CL) and 
volume of distribution at steady state (Vss). Attainment of steady state and accumulation at 
steady state also will be determined. Dose proportionality and time linearity in PK parameters 
may be assessed. 
Mean serum ALXN1210 concentrations versus nominal time and individual serum ALXN1210 
concentrations versus actual time will be graphically presented. Descriptive statistics (mean, SD, 
CV, median, minimum, maximum, geometric mean, and geometric %CV) of the serum 
concentration and PK parameter summaries will be provided, as appropriate.  
16.8. 
Pharmacodynamic and Immunogenicity Analyses 
The PD effects of ALXN1210 administered IV will be evaluated by assessing changes and 
percent changes in serum total and/or free C5 concentrations and cRBC hemolysis over time. 
Assessments of PK-PD relationships may be explored using data from this study or in 
combination with data from other studies. 
Immunogenicity, as measured by ADA, will be summarized in tabular form by treatment.  
The PD and ADA samples collected on or after Day 1149 for Cohort 1, Day 1135 for Cohort 2, 
Day 1093 for Cohort 3, or Day 1121 for Cohort 4 will be stored and may be assayed if 
considered necessary for the purpose of medical monitoring. 
Page 78 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
17. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
17.1. 
Study Monitoring 
Before an investigational site can enter a patient into the study, a representative of Alexion 
(Sponsor) will visit the investigational study site to: 
• Determine the adequacy of the facilities; 
• Discuss with the Investigator(s) and other personnel their responsibilities with regard 
to protocol adherence, and the responsibilities of the Sponsor or designee. 
During the study, a monitor from the Sponsor or the Sponsor’s designee will have regular contact 
with the investigational site, for the following: 
• Provide information and support to the Investigator 
• Confirm that facilities remain acceptable 
• Confirm that the investigational team is adhering to the protocol, that data are being 
accurately recorded in the eCRF, and that ALXN1210 accountability checks are being 
performed 
• Perform source data verification. This includes a comparison of the data in the eCRF 
with the patient’s medical records, and other records relevant to the study. This will 
require direct access to all original records for each patient (eg, clinic charts) 
• Record and report any protocol deviations not previously sent to the Sponsor or 
designee 
• Confirm AEs and SAEs have been properly documented in the eCRF, and confirm 
any SAEs have been forwarded to the Sponsor or the Sponsor’s designee, and those 
SAEs that meet criteria for reporting have been forwarded to the IRB/IEC 
The monitor will be available between visits if the Investigator(s) or other staff needs 
information or advice. 
17.2. 
Audits and Inspections 
Authorized representatives of the Sponsor or designee, a regulatory authority, or an IRB/IEC 
may visit the site to perform audits or inspections, including source data verification. The 
purpose of an audit or inspection is to systematically and independently examine all 
study-related activities and documents, to determine whether these activities were conducted, 
and data were recorded, analyzed, and accurately reported, according to the protocol, Good 
Clinical Practice (GCP) guidelines of the International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use (ICH), and any applicable regulatory 
requirements. The Investigator should contact the Sponsor or designee immediately if contacted 
by a regulatory agency about an inspection. 
Page 79 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
18. 
ETHICS 
18.1. 
Data Monitoring Committee 
An independent DMC comprised of experts in relevant biomedical fields who have no direct 
relationship with the study will be appointed by the Sponsor. The DMC will review and evaluate 
the accumulated study data for patient safety and make recommendations on dose escalation, 
continuing dosing within the cohort, modification, or termination of the study. The DMC will 
review study information as outlined in the DMC charter, which is maintained separately from 
the study protocol.  
Final decisions regarding the conduct of the study will be made by the Sponsor after consultation 
with the DMC. All appropriate regulatory authorities and Ethics Committees will be notified of 
any significant action.  
Each member of the DMC will be required to sign a contract agreement, which includes a 
confidentiality and financial disclosure statement, assuring no conflicts of interest as a condition 
for membership on the board. 
18.2. 
Ethics Review 
The final study protocol and the final version of the ICF must be approved or given a favorable 
opinion in writing by an IRB/IEC, as appropriate. The Investigator must submit written approval 
to the Sponsor or the Sponsor’s designee prior to enrolling any patient into the study. 
The Investigator is responsible for informing the IRB/IEC of any amendment to the protocol, in 
accordance with local regulatory requirements. In addition, the IRB/IEC must approve all 
advertising used to recruit patients for the study. The protocol must be reapproved by the 
IRB/IEC upon receipt of amendments and annually, as local regulations require. 
The Investigator is also responsible for providing the IRB/IEC with reports of any serious 
adverse drug reactions from any other study conducted with ALXN1210. The Sponsor or the 
Sponsor’s designee will provide this information to the Investigator. 
Progress reports and notifications of serious adverse drug reactions will be provided to the 
IRB/IEC, according to local regulations and guidelines. 
18.3. 
Ethical Conduct of the Study 
The study will be performed in accordance with ethical principles that have their origin in the 
Declaration of Helsinki and are consistent with ICH, GCP, applicable regulatory requirements, 
and the Alexion policy on bioethics. 
18.4. 
Written Informed Consent 
The Investigator will ensure that the patient is given full and adequate oral and written 
information about the nature, purpose, possible risk, and benefit of the study. Patients must also 
be notified that they are free to discontinue from the study at any time. The patient should be 
given the opportunity to ask questions and allowed time to consider the information provided. 
Page 80 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
The patient’s signed and dated informed consent form (ICF) must be obtained before conducting 
any study procedures, and documented in the patient’s study record. 
The Investigator must retain the original version of the signed ICF. If the ICF is amended, the 
original, signed, amended version must also be retained. A copy of the signed ICF must be given 
to the patient. 
Page 81 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
19. 
DATA HANDLING AND RECORDKEEPING 
19.1. 
Data Collection 
To ensure compliance with GCP and all applicable regulatory requirements, the Sponsor or the 
Sponsor’s designee may conduct a quality assurance audit. Please see Section 17.2 for more 
details regarding the audit process. 
All required clinical data will be recorded promptly and accurately, electronically into the study 
electronic data capture (EDC) system, Medidata RAVE. All source documents will be preserved 
in order to maintain data integrity. The Investigator or designee will assume the responsibility of 
ensuring completeness, accuracy, and timeliness of the clinical data entry into the EDC system. 
At each scheduled monitoring visit, the Investigator or designee will cooperate with the 
Sponsor’s representative(s) for the periodic review of study source documents to ensure the 
accuracy and completeness of the data contained within the EDC system. 
Electronic checks and manual review will be performed to identify any errors or inconsistencies 
in the data provided in the EDC system. Queries will be raised in the EDC system to the 
respective study sites, as applicable. 
The Investigator or designee will prepare and maintain adequate and accurate source documents 
(medical records, ECGs, AE and concomitant medication reporting, and raw data collection 
forms) designed to record all observations and other pertinent data for each patient in the study. 
The Investigator will allow Sponsor representatives, contract designees, authorized regulatory 
authority inspectors, and the IRB/IEC to have direct access to all documents pertaining to the 
study. 
19.2. 
Inspection of Records 
The Sponsor or the Sponsor’s designee will be allowed to conduct site visits to the investigation 
facilities for the purpose of monitoring any aspect of the study. The Investigator agrees to allow 
the monitor to inspect the drug storage area, study drug stocks, drug accountability records, 
patient charts and study source documents, and other records relative to study conduct. 
19.3. 
Retention of Records 
The Investigator must maintain all documentation relating to the study for a period of 2 years 
after the last marketing application approval, or if not approved 2 years following the 
discontinuance of the test article for investigation. If it becomes necessary for the Sponsor or the 
Sponsor’s designee or the Regulatory Authority to review any documentation relating to the 
study, the Investigator must permit access to such records. 
Page 82 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
20. 
PUBLICATION POLICY 
The terms for publication are outlined in the Clinical Study Agreement, Statement of Agreement, 
or the Master Clinical Study Agreement. Refer to these documents for further details and 
information. 
Page 83 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
21. 
LIST OF REFERENCES 
Brodsky RA. Paroxysmal nocturnal hemoglobinuria. Blood 2014 Oct 30;124(18):2804-11. 
Casadevall N, Nataf J, Viron B, Kolta A, Kiladjian JJ, Martin-Dupont P, Michaud P, Papo T, 
Ugo V, Teyssandier I, et al. Pure red-cell aplasia and antierythropoietin antibodies in patients 
treated with recombinant erythropoietin. N.Engl.J.Med. 2002 Feb 14;346(7):469-75. 
Hillmen P, Elebute M, Kelly R, Urbano-Ispizua A, Hill A, Rother RP, Khursigara G, Fu CL, 
Omine M, Browne P, et al. Long-term effect of the complement inhibitor eculizumab on kidney 
function in patients with paroxysmal nocturnal hemoglobinuria. Am.J.Hematol. 2010 
Aug;85(8):553-9. 
Li J, Yang C, Xia Y, Bertino A, Glaspy J, Roberts M, Kuter DJ. Thrombocytopenia caused by 
the development of antibodies to thrombopoietin. Blood 2001 Dec 1;98(12):3241-8. 
Sampson HA, Munoz-Furlong A, Campbell RL, Adkinson NF, Jr., Bock SA, Branum A, Brown 
SG, Camargo CA, Jr., Cydulka R, Galli SJ, et al. Second symposium on the definition and 
management of anaphylaxis: summary report--Second National Institute of Allergy and 
Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J.Allergy Clin.Immunol. 
2006 Feb;117(2):391-7. 
Socie G, Mary JY, de GA, Rio B, Leporrier M, Rose C, Heudier P, Rochant H, Cahn JY, 
Gluckman E. Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic 
factors. French Society of Haematology. Lancet 1996 Aug 31;348(9027):573-7. 
Weitz IC, Razavi P, Rochanda L, Zwicker J, Furie B, Manly D, Mackman N, Green R, Liebman 
HA. Eculizumab therapy results in rapid and sustained decreases in markers of thrombin 
generation and inflammation in patients with PNH independent of its effects on hemolysis and 
microparticle formation. Thromb.Res. 2012 Sep;130(3):361-8. 
Page 84 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
22. 
APPENDIX 
Page 85 of 86 
Alexion Confidential 

ALXN1210-PNH-201 
  
Alexion Pharmaceuticals, Inc. 
Amendment 5, 09 May 2018 
APPENDIX A. CLINICAL LABORATORY TESTS 
Chemistry Testing 
 
Alanine aminotransferase 
 
Albumin 
 
Alkaline phosphatase 
 
Aspartate aminotransferase 
 
Bicarbonate 
 
Blood urea nitrogen 
 
Chloride 
 
Creatinine 
 
Gamma-glutamyltransferase 
 
Glucose 
 
Lactate dehydrogenase 
 
Magnesium 
 
Phosphorus 
 
Potassium 
 
Sodium 
 
Total bilirubin (direct and indirect) 
 
Total calcium 
 
 
Total protein 
 
Uric acid 
 
Hematology Testing 
 
Haptoglobin 
 
Reticulocyte count 
 
Free hemoglobin 
 
Hematocrit 
 
Hemoglobin 
 
Mean corpuscular hemoglobin  
  
Platelet count  
 
Red blood cell distribution width 
 
Red blood cell mean corpuscular volume 
 
Red blood cell count  
 
White blood cell count  
 
White blood cell differential 
Urinalysis 
 
Albumin 
 
Appearance 
 
Bilirubin 
 
Blood 
 
Creatinine 
 
Glucose 
 
Ketone 
 
Nitrite 
 
pH 
 
Protein 
 
Specific gravity 
 
Urobilinogen 
 
Coagulation Panel 
 
International normalized ratio 
 
Prothrombin time  
 
Partial thromboplastin time 
 
D-dimer 
 
Virus Serology 
 
Hepatitis B core antibody (HBcAb)  
 
Hepatitis B surface antigen (HBsAg) 
 
Hepatitis B surface antibody (HBsAb) 
 
Hepatitis C virus antibody 
 
HIV-1 
 
HIV-2 
 
 
Other 
Serum follicle-stimulating hormone 
(postmenopausal female patients only) 
Brain natriuretic peptide 
Estradiol concentrations (postmenopausal female 
patients only) 
Beta human chorionic gonadotropin (female 
patients only) 
PNH clone size (granulocyte or red blood cell 
assay at screening, red blood cell only at all other 
time points)  
 
 
 
Page 86 of 86 
Alexion Confidential