Conditions: Paroxysmal Nocturnal Hemoglobinuria
Keywords: Marchiafava-Micheli Syndrome Paroxysmal Cold Hemoglobinuria
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 42
Healthy volunteers: no

Brief summary:
This is a randomized, double-blind, active-controlled phase 3 study of ABP 959 in participants with paroxysmal nocturnal hemoglobinuria.

Detailed description:

Arms:
arm 1: ABP 959 for 52 weeks in Period 1 followed by eculizumab for 26 weeks in Period 2 arm 2: Eculizumab for 52 weeks in Period 1 followed by ABP 959 for 26 weeks in Period 2

Interventions: intervention 1: ABP 959 intervention 2: Eculizumab
Intervention descriptions: intervention 1: intravenous infusion intervention 2: intravenous infusion

Protocol document:
SAP_002.pdf: 
Sponsor: Amgen Inc.
Statistical Analysis Plan  
Protocol no: 20150168 
Version Date: 26-January-2022
Page 1 of 33
Strictly Confidential.  © 2017, PRA Health Sciences.  All rights reserved.
Statistical Analysis Plan
A Randomized, Double-blind, Active-controlled Phase 3 Study Evaluating the Efficacy and 
Safety of ABP 959 Compared With Eculizumab in Adult Subjects With Paroxysmal 
Nocturnal Hemoglobinuria (PNH)
Test Drug: ABP 959
Sponsor:
Amgen Inc.
Protocol No:
20150168 
PRA Project Id:
AMGAB959-ABP959
SAP Version Date:
26 January-2022
SAP Version No.:
2.0 Final
1.0 Approvals
Sponsor
Sponsor Name:
Amgen Inc.
Representative/ Title:
 MS / Biostatistics  Senior Manager
Signature /Date:
Representative/ Title:
, MD / Executive Medical Director
Signature /Date:
PRA
Project Manager/Title:
/ Project Director
Signature /Date:
Biostatistician / Title
(Owner):
 MS, MD / Senior Principal Biostatistician
Signature /Date:
00(00) 
Stronger together. The new ICON 
.,§ 
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allys/gn9dby:
Reason: I am approving this 
document 
Data: Jan 28, 2022 09:17 EST 
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 Mt> 
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: I am approving tNs 
-"' 
Date: Jan 27, 2022 14:43 PST 
I 
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Electronically signed by:
 
Reason: I am approving this 
__ , 
Date: Jan 28. 2022 10:4-0 EST 
 
Electronically signed by:
Reason: I am approving this 
document 
Date: Jan 27, 2022 19:18 EST 
Page 2 of 92
Date: 
ABP 959
Clinical Study Report:  20150168 Final Analysis
Confidential
20 September 2022
Page 2
NCT Number: NCT03818607
This NCT number has been applied to the document for
purposes of posting on Clinicaltrials.gov


Sponsor: Amgen Inc.
Statistical Analysis Plan  
Protocol no: 20150168 
Version Date: 26-January-2022
Page 2 of 33
Strictly Confidential.  © 2017, PRA Health Sciences.  All rights reserved.
Table of Contents
1.0 Approvals.....................................................................................................................................................................1
Table of Contents.............................................................................................................................................................2
2.0 Purpose........................................................................................................................................................................4
3.0 Scope.............................................................................................................................................................................4
4.0 Introduction................................................................................................................................................................4
4.1 Change from Protocol .........................................................................................................................................4
5.0 Study Objectives........................................................................................................................................................4
5.1 Primary Objective.................................................................................................................................................4
5.2 Secondary Objectives..........................................................................................................................................4
6.0 Study Design...............................................................................................................................................................4
6.1 Sample Size Considerations..............................................................................................................................5
6.2 Randomization......................................................................................................................................................6
7.0 Study Variables..........................................................................................................................................................6
7.1 Primary Variables.................................................................................................................................................6
7.2 Secondary Variables............................................................................................................................................6
7.3 Safety Variables.....................................................................................................................................................6
7.4 Predetermined Covariates and Prognostic Factors...................................................................................7
8.0 Definitions...................................................................................................................................................................7
8.1 General.....................................................................................................................................................................7
8.2 Efficacy..................................................................................................................................................................10
8.3 Safety.....................................................................................................................................................................10
8.4 Pharmacokinetic................................................................................................................................................11
8.5 Full Analysis Set.................................................................................................................................................12
8.6 Modified Full Analysis Set...............................................................................................................................12
8.7 Per Protocol Sets................................................................................................................................................12
8.7.1 Per-protocol Analysis Set for the Primary Endpoint of Lactate Dehydrogenase at Week 27 
for the Parallel Comparison..............................................................................................................................12
8.7.2 Per-protocol Analysis Set for the Primary Endpoint of AUEC for the Crossover 
Comparison............................................................................................................................................................12
8.8 Safety Analysis Set............................................................................................................................................13
8.9 Pharmacokinetic Analysis Sets.....................................................................................................................13
8.9.1 Pharmacokinetic Concentration Analysis Set..................................................................................13
8.9.2 Pharmacokinetics Parameter Analysis Set........................................................................................13
9.0 LDH Review..............................................................................................................................................................13
10.0 Interim Analyses..................................................................................................................................................13
11.0 Statistical Methods..............................................................................................................................................14
11.1 Subject Disposition.........................................................................................................................................14
11.2 Protocol Deviations........................................................................................................................................14
11.3 Treatments........................................................................................................................................................15
11.3.1 Extent of Study Drug Exposure..........................................................................................................15
11.3.2 Concomitant Medications....................................................................................................................15
11.4 Demographic and Baseline Characteristics............................................................................................15
11.5 Efficacy Analyses.............................................................................................................................................15
11.5.1 Primary Endpoints.................................................................................................................................15
11.5.2 Secondary Endpoints.............................................................................................................................17
11.6 Pharmacokinetics...........................................................................................................................................18
11.7 Safety Analyses................................................................................................................................................18
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Date: 
ABP 959
Clinical Study Report:  20150168 Final Analysis
Confidential
20 September 2022
Page 3


Sponsor: Amgen Inc.
Statistical Analysis Plan  
Protocol no: 20150168 
Version Date: 26-January-2022
Page 3 of 33
Strictly Confidential.  © 2017, PRA Health Sciences.  All rights reserved.
11.7.1 Adverse Events........................................................................................................................................18
11.7.2 Fatal and Serious Adverse Events.....................................................................................................19
11.7.3 Laboratory Data......................................................................................................................................19
11.7.4 Vital Signs and Physical Examination...............................................................................................20
11.7.5 Immunogenicity......................................................................................................................................20
11.7.6 Imputation for Partial or Missing Dates..........................................................................................20
12.0 Validation...............................................................................................................................................................22
13.0 References.............................................................................................................................................................22
Appendix 1 Glossary of Abbreviations...................................................................................................................23
Appendix 2 MedDRA Query SMQ - COVID-19......................................................................................................25
Appendix 3 Baseline Gradings for ALT, AST, Total Bilirubin and Alkaline Phosphatase.......................26
Appendix 4 List of Post-text Tables, Figures, and Listings and Supportive SAS Output Appendices.27
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Date: 
ABP 959
Clinical Study Report:  20150168 Final Analysis
Confidential
20 September 2022
Page 4


Sponsor: Amgen Inc.
Statistical Analysis Plan  
Protocol no: 20150168 
Version Date: 26-January-2022
Page 4 of 33
Strictly Confidential.  © 2017, PRA Health Sciences.  All rights reserved.
2.0 Purpose
The statistical analysis plan (SAP) describes the statistical methods to be used during the reporting and 
analyses of data collected under Amgen Inc. Protocol 20150168 dated 05 March 2020, Version 4.0.
3.0 Scope
The SAP outlines the following:
Study objectives
Study design
Variables analyzed and analysis sets
Applicable study definitions
Statistical methods regarding important protocol deviations, study drug exposure, efficacy analysis, 
concomitant medications, adverse event handling, laboratory data, pharmacokinetics, and 
immunogenicity
4.0 Introduction
This SAP should be read in conjunction with the study protocol and case report form (CRF). This version 
of the plan has been developed using the protocol dated 05 March 2020, Version 4.0 and CRF dated 
09 October 2019, Version 3.0. Any further changes to the protocol or CRF may necessitate updates to the 
SAP.
The SAP will be finalized and approved prior to the database lock and unblinding for the primary analysis
of the study (which is the primary analysis for the parallel comparison of the study).
4.1 Change from Protocol
The protocol states that the disposition summaries will include a summary of the number and percentage 
of subjects on study at each visit. This summary is not included in the SAP.
5.0 Study Objectives
5.1 Primary Objective
The primary objective for this study is to evaluate the efficacy of ABP 959 compared with that of eculizumab 
based on control of intravascular hemolysis.
5.2 Secondary Objectives
The secondary objective is to assess the safety, pharmacokinetics (PK), and immunogenicity of ABP 959 
compared with that of eculizumab.
6.0 Study Design
This is a randomized, double-blind, active-controlled, 2-period crossover study in adult subjects with 
paroxysmal nocturnal hemoglobinuria (PNH).
Approximately 40 subjects will be randomized (1:1) to 1 of the 2 treatment sequences, either treatment T 
followed by treatment R (TR) or treatment R followed by treatment T (RT). Treatments will be administered 
over 2 periods. Period 1 will be 52 weeks in duration; Period 2 will start at week 53, with a crossover in 
treatment, and will be 26 weeks in duration. Randomization will occur within 8 days before the first dose of 
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Clinical Study Report:  20150168 Final Analysis
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Sponsor: Amgen Inc.
Statistical Analysis Plan  
Protocol no: 20150168 
Version Date: 26-January-2022
Page 5 of 33
Strictly Confidential.  © 2017, PRA Health Sciences.  All rights reserved.
IP administration and will be stratified by red blood cell (RBC) transfusion receivedwithin the last 12 months 
before randomization (yes vs. no).
The treatment sequences will be as shown in Figure 1:
Sequence TR: ABP 959 for 52 weeks in Period 1 followed by eculizumab for 26 weeks in Period 2, each at 
a dose of 900 mg administered as an intravenous (IV) infusion every 14 ± 2 days
Sequence RT: Eculizumab for 52 weeks in Period 1 followed by ABP 959 for 26 weeks in Period 2, each 
at a dose of 900 mg administered as an IV infusion every 14 ± 2 days.
Subjects will remain on the treatment phase until 14 days after the last planned dose of IP in Period 2 (i.e, 
at week 79).
Figure 1 Study Diagram
The primary analysis for the parallel comparison of the study will be conducted when all subjects have
completed or have had the chance to complete the week 53 visit or have completed the EOS visit prior to 
week 53. After the database for the primary analysis for the parallel comparison has been locked, identified 
personnel from Amgen and PRA will be unblinded to the study randomization schedule and to the aggregate 
results of the analyses. Members of the study operation and data management team will remain blinded to 
the individual randomization schedule and to the aggregated results unless otherwise identified. Subjects 
and investigators will remain blinded throughout the study. Details on how to disseminate data and results 
of the primary analysis for the parallel comparison while maintaining integrity of the ongoing blinded study 
will be documented in a data dissemination plan. The primary analysis for the crossover comparison of the 
study will be conducted when all subjects have completed the EOS visit.   
6.1 Sample Size Considerations
The sample size of 40 was chosen to provide approximately 87% power to demonstrate noninferiority (NI)
at a 1-sided significance level of 0.025 on the primary endpoint of week 27 LDH for the parallel comparison, 
assuming an inter-subject coefficient of variation (CV) of 130% for ABP 959 and eculizumab, a true 
geometric mean ratio (GMR) of 1 between ABP 959 and eculizumab, an NI margin of 2.873, and a 10% 
dropout rate. The 2.873 margin is considered appropriate to rule out a potential clinically relevant difference, 
as it essentially equates to a mean LDH in the ABP 959 arm of less than 1.5-fold of the mean LDH in the 
eculizumab arm.
The sample size of 40 will also provide greater than 95% power to demonstrate similarity at a 2-sided 
significance level of 0.05 on the primary endpoint of time-adjusted area under the effect curve (AUEC) of 
LDH from week 13 to week 27, from week 39 to week 53, and from week 65 to week 79 for the crossover 
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PERIOD 1 
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Page 6 of 92
Date: 
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Clinical Study Report:  20150168 Final Analysis
Confidential
20 September 2022
Page 6


Sponsor: Amgen Inc.
Statistical Analysis Plan  
Protocol no: 20150168 
Version Date: 26-January-2022
Page 6 of 33
Strictly Confidential.  © 2017, PRA Health Sciences.  All rights reserved.
comparison, assuming an intra-subject CV of 34%, a true GMR of 1 between ABP 959 and eculizumab, a 
similarity margin of (0.77, 1.30), and a 10% dropout rate.
Blinded assessments of the inter-subject CV of LDH and the intra-subject CV of time-adjusted AUEC of 
LDH will be performed. If the aggregated intra-subject CV of AUEC is greater than 44%, additional subjects 
will be enrolled if feasible. If the aggregated inter-subject CV of LDH is greater than 130%, the primary 
endpoint of parallel comparison of LDH at week 27 will be replaced by crossover comparison of LDH at 
week 53 and week 79. Refer to section 10 for details on the interim analysis.
6.2 Randomization
Subjects will be randomized 1:1 to receive ABP 959 and eculizumab in 1 of 2 treatment sequences in a 2-
period crossover design.  Randomization will be performed using an interactive voice/web randomization 
system (IXRS).  Randomization will occur within 8 days before the first dose of investigational product (IP)
administration and will be stratified by RBC transfusion received within the last 12 months before 
randomization (yes vs. no).  The randomization schedule will be prepared by a statistician not otherwise 
involved in the conduct of the study.
7.0 Study Variables
7.1 Primary Variables
The primary efficacy endpoint for the parallel comparison is hemolysis as measured by LDH at week 27. 
The primary endpoint for the crossover comparison is hemolysis, as measured by the time-adjusted AUEC 
of LDH from week 13 to week 27, week 39 to week 53, and from week 65 to week 79.
7.2 Secondary Variables
The secondary efficacy endpoints are:
Total complement, total hemoglobin, serum-free hemoglobin, haptoglobin, bilirubin, degree of 
hemoglobinuria, and type III erythrocytes at week 27, week 39, week 53, and post-crossover week 
65 and week 79.
Crossover comparison of hemolysis as measured by LDH at week 53 and week 79
Lactate dehydrogenase-time profile
Red blood cell transfusion
The secondary PK endpoints are: 
Total and unbound pharmacokinetic area under the curve (AUC) of ABP 959 and eculizumab from 
week 13 to week 15, and trough PK.
7.3 Safety Variables
The safety endpoints include the following:
Treatment-emergent adverse events
Treatment-emergent serious adverse events
Treatment-emergent events of interest
Incidence of antidrug antibodies
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Date: 
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Clinical Study Report:  20150168 Final Analysis
Confidential
20 September 2022
Page 7


Sponsor: Amgen Inc.
Statistical Analysis Plan  
Protocol no: 20150168 
Version Date: 26-January-2022
Page 7 of 33
Strictly Confidential.  © 2017, PRA Health Sciences.  All rights reserved.
7.4 Predetermined Covariates and Prognostic Factors
Unless stated otherwise, the stratification factor RBC transfusion received within the last 12 months before 
randomization (yes vs. no) will be adjusted as a covariate in the model, will be used as a stratification 
variable in stratified analysis, and will be used to examine efficacy in subgroups. 
Analyses that are intended to evaluate the treatment effect and include the stratification variable as a 
covariate in the model will be based on the eCRF stratification value, regardless of the subject’s IXRS 
stratification value, to provide unbiased estimates of the effects of treatment and stratification variable 
without loss of efficiency (Ke et al, 2017).
In addition, the following covariates may be used for further exploration in subgroups or as covariates:
Sex
Age group ( 54 years vs. > 54 years)
Packed RBC units received within 12 months prior to randomization
8.0 Definitions
8.1 General
Actual Treatment Received
The actual dose for each period will be defined according to the majority of actual doses of the IP received, 
regardless of what the subject was randomized to. The actual treatment sequence received for the entire 
study will be based on the combination of the actual treatment received for each period. In cases where a 
subject is not treated in period 2, the actual treatment sequence received for the entire study will be 
determined by the actual treatment of period 1 and the intended treatment of the second period per protocol. 
The actual treatment sequence for the study will be unplanned if the actual treatment is the same for both 
periods. 
Period 1
Period 1 is defined as the date of first dose of study IP through first dose of the crossover treatment. 
If subjects discontinue before receiving the cross-over treatment, the end of Period 1 is end of study.
Period 2
Period 2 is defined as the date of first IP dose of the crossover treatment through the end of study or data 
cutoff date, whichever is earlier.
Change From Baseline
Change from baseline is defined as (value at post-baseline visit – value at study baseline).
Completed Period 1 IP Dosing
A subject is considered to have completed Period 1 IP dosing if they have received a dose of IP between 
study day 349 (targeted Week 51 dosing date – 2 day window) and the end date of Period 1. 
Completed Study
A subject is considered to have completed the study if they indicated they completed study on the EOS 
eCRF at the Week 79 visit.
Concomitant Medication
Concomitant medications are defined as any medications ongoing at the start of IP treatment or with a start 
date on or after the first dose date. 
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Clinical Study Report:  20150168 Final Analysis
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Sponsor: Amgen Inc.
Statistical Analysis Plan  
Protocol no: 20150168 
Version Date: 26-January-2022
Page 8 of 33
Strictly Confidential.  © 2017, PRA Health Sciences.  All rights reserved.
Duration on Eculizumab Prior to Enrollment 
The duration of eculizumab prior to enrollment is the number of months from the eculizumab start date on 
the PNH history eCRF to the date of randomization, which will be derived based on the table below.  No 
imputation will be done for missing eculizumab start date (Year, Month, Day), but to avoid a duration of 
zero, 1 month may be added.
Table 1. Calculation for Duration on Eculizumab Prior to Enrollment
Observed Portion
Missing Portion
Formula to Calculate Duration
Year, Month, Day
(Date of Randomization – Eculizumab Start Date + 1)*12/365.25
Year, Month
Day
[Year (Date of Randomization) – Year (Eculizumab Start 
Date)]*12 
+ [Month (Date 
of Randomization) –
Month 
(Eculizumab Start Date)]*
Year
Month, Day
[Year (Date of Randomization) – Year (Eculizumab Start 
Date)]*12*
*If the duration equals 0, add 1 month.
Duration of IP exposure
Overall duration of IP exposure in weeks will be defined as (minimum of ( end of study [EOS] date, cutoff 
date) – date of first dose of IP + 1) / 7. Duration of IP exposure in Period 1 will be defined as (Period 1 end 
date – Period 1 start date + 1) / 7. Duration of IP exposure in Period 2 will be defined as (Period 2 end date
– Period 2 start date + 1) / 7. 
End of Study Date
The end of study (EOS) date for a subject is the EOS date from the EOS eCRF.  
Study Baseline 
The study baseline is defined as the last non-missing assessment taken prior to the first dose of IP. In 
cases where baseline assessments are taken on the same day as IP, and either no times are reported, or 
the IP and assessment times are the same, it will be assumed that these assessments are taken prior to 
IP being administered. For subjects who arerandomized but not dosed after the randomization, the baseline 
is defined as the last non-missing assessment prior to or on the date of randomization.
Days On-study 
Study Start Day (Day 1) is defined as the first day that IP is administered to the subject.  
Days On-study is defined as the number of days from Study Start Day (Day 1).
Days before Study Start Day (Day 1) are computed as follows: 
Days Before Study Start Day = (Date of Interest – Date of Study Start Day 1)
Days On-study are computed as follows:
Days On-study = (Date of Interest – Date of Study Start Day 1) + 1:
Therefore, the day prior to Study Day 1 is -1.  
For randomized subjects who do not receive any study IP, Day 1 is defined as the randomization date.
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Statistical Analysis Plan  
Protocol no: 20150168 
Version Date: 26-January-2022
Page 9 of 33
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Study Investigational Product
Study IP is referred to as ABP 959 or eculizumab.
Study Randomization
Study randomization is defined as when the subject receives a random treatment allocation via the IXRS 
system.
Study Analysis Visit 
Since the actual visit for a subject may not exactly coincide with their scheduled visit date, the actual visit 
date is mapped to the study analysis visit. 
In general, if more than one actual visit (including unscheduled visits) falls within the same defined window
(e.g., within same defined interval dates), the visit closest to the target day with non-missing data will be 
considered for analysis. If two actual visit dates are at the same distance from the target day, the latest visit 
with non-missing data will be considered for analysis. 
Time Since Original Diagnosis
The time since original diagnosis is the number of months from the date of original diagnosis of PNH to the 
date of randomization, which will be derived based on the table below.  No imputation will be done for 
missing disease diagnosis date (Year, Month, Day), but to avoid a disease duration of zero, 1 month may 
be added.
Table 2. Calculation for Time Since Original Diagnosis
Observed Portion
Missing Portion
Formula to Calculate Duration
Year, Month, Day
(Date of Randomization – Date of Diagnosis + 1)*12/365.25
Year, Month
Day
[Year (Date of Randomization) – Year (Date of Diagnosis)]*12 + 
[Month (Date of Randomization) – Month (Date of Diagnosis)]*
Year
Month, Day
[Year (Date of Randomization) – Year (Date of Diagnosis)]*12*
*If the duration equals 0, add 1 month.
Age at PNH Diagnosis
The age at PNH diagnosis is the number of years from the date of birth to the date of diagnosis of PNH, 
which will be derived based on the table below.  No imputation will be done for missing disease diagnosis 
date (Year, Month, Day).
Table 3. Calculation for Age at PNH Diagnosis
Observed Portion
Missing Portion
Formula to Calculate Duration
Year, Month, Day
(Date of Diagnosis – Date of Birth + 1)/365.25
Year, Month
Day
[Year (Date of Diagnosis) – Year (Date of Birth)] + [Month (Date 
of Diagnosis) – Month (Date of Birth)]/12
Year
Month, Day
[Year (Date of Diagnosis) – Year (Date of Birth)]
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Statistical Analysis Plan  
Protocol no: 20150168 
Version Date: 26-January-2022
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8.2 Efficacy
Area Under the Effect Curve of LDH
The area under the effect curve (AUEC) of LDH will be calculated for the following time periods:
Week 13 to week 27 (study day 78 to study day 189), week 39 to week 53 (study day 260 to study 
day 371, only using results prior to first IP dose date in Period 2)
Week 65 to week 79 (study day 442 to study day 553)
AUEC of LDH for each subject will be calculated by time period using all LDH results in the corresponding 
time periods, except those determined to be elevated due to confounding events by the LDH review 
committee (see section 9.0). The start and end dates for the AUEC for each time period will be the dates 
of the first and last LDH results, respectively, within the given 14-week time period. The AUEC for a given 
time period will only be calculated if there are at least 3 LDH measurements within the time period. The 
AUEC for each time interval t1 to t2 will be calculated using the following equation:
AUEC(t1-t2) = (t1-t2) x (LDH1+LDH2)/2 
where LDH1 and LDH2 are the LDH results at t1 and t2 respectively (t1 and t2 are days from first dose of 
(t1-t2) = (t2-t1) calculated in days.
The AUEC over the entire time period will be obtained by summing the AUEC calculated for each time 
interval in the time period.
Time-adjusted AUEC of LDH
The time-adjusted AUEC of LDH for each individual subject for each time period will be calculated by 
dividing the AUEC for the given time period by the total duration of observed LDH data (in weeks) within 
the 14-week assessment period. For example, the total duration for the week 39 to week 53 time period will 
be calculated as the (date of latest LDH assessment between study day 260 and study day 371) – (date of 
earliest LDH assessment between study day 260 and study day 371). The result will be divided by 7 (days) 
to express AUEC per week.
8.3 Safety
Event of Interest (EOI)
An EOI is defined as a noteworthy treatment-emergent adverse event for a particular product or class of 
products that a sponsor may wish to monitor carefully. It could be serious or non-serious, and could include 
events that might be potential precursors or prodromes for more serious medical conditions in susceptible 
individuals (Council for International Organizations of Medical Sciences (CIOMS) VI, 2005). The EOIs for 
ABP 959/eculizumab are defined below and analyzed from the clinical database:
EOI
Name
Category
Scope 
Details
Serious 
infections
(Meningococcus, 
aspergillus, and 
other 
serious 
infections/sepsis)
Infections and 
Infestations
SOC
Broad
all SAEs and AEs 
with toxicity of grade 
3 or higher
Infusion 
reactions
Hypersensitivity
Infusion reactions
Standard MedDRA 
Query (SMQ)
Amgen MedDRA 
Query
Broad
Broad
all events that occur 
with start date same 
as, or one day after, 
IP administration 
start date
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Statistical Analysis Plan  
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Version Date: 26-January-2022
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Subject Incidence Rate
For adverse event summaries, subject incidence rate for a given event is defined as the number of subjects 
with at least 1 reported occurrence of the event divided by the number of subjects that received the given 
treatment. For subjects with multiple occurrences of the same event while on the given treatment, the event 
will only be counted once per subject.
Treatment-emergent Adverse Event
A treatment-emergent AE (TEAE) is defined as an AE that begins or increases in severity or frequency on 
or after the date of first IP and up to the EOS visit. If the AE starts on the same day as the first dose of IP 
then the flag indicating whether the AE started prior to the first dose on the adverse event CRF page will 
be used. In the event that the flag is missing, the AE that starts on the same day as the first dose of IP will 
be considered a TEAE. If the AE starts on the same day as the EOS visit, the AE will be considered as a 
TEAE. 
A TEAE will be assigned to Period 1 if the start date was on or after the first IP dose date and before the 
Period 1 end date. If the AE starts on the same day as the first dose of IP then the flag indicating whether 
the AE started prior to the first dose on the AE CRF page will be used. A TEAE will be assigned to Period 
2 if the start date was after the first IP dose date in Period 2. If the AE started on the first IP dose date in 
Period 2 (week 53 visit) and the checkbox on the week 53 AE CRF page indicates the TEAE started before 
the start of infusion, the TEAE will be assigned to Period 1. If the week 53 AE CRF page indicates the TEAE 
started after the start of infusion, the TEAE will be assigned to Period 2.
A TEAE will be assigned to the 14-week assessment period between week 13 to week 27 if the start date 
was on or after study day 78 and on or before the study day 189. A TEAE will be assigned to the final 14 
weeks of Period 1 (i.e. weeks 39 to 53) if the start date was on or after study day 260 and on or before the 
minimum of study day 371 and Period 1 end date. A TEAE will be assigned to the final 14 weeks of Period 
2 (i.e. weeks 65 to 79) if the start date was on or after study day 442 and on or before study day 553. These 
windows are defined to be consistent with the efficacy evaluation windows.
Treatment-emergent Adverse Event Leading to Discontinuation of IP
AEs leading to discontinuation of IP are those with an action taken with Investigational Medicinal Product 
of “dose discontinued”. If an AE leads to multiple actions taken with IP, only the last action will be captured 
on the eCRF.
Treatment-emergent Adverse Event Leading to Study Discontinuation
AEs leading to discontinuation from the study are those with another action taken of “discontinued from 
study”.    
Presumed COVID-19 Start Date 
The presumed start date of COVID-19 is the date of the earliest COVID-19 Standardized MedDRA Query 
(SMQ) defined preferred term.
8.4 Pharmacokinetic
Area Under the Curve (week 13 to week 15)
The area under the curve (AUC) from week 13 to week 15 will be calculated using both the total and 
unbound (concentrations at the following 4 time points: week 13 pre-dose, week 13 post-dose, week 14, 
week 15 pre-dose. The AUC for each time interval t1 to t2 will be calculated using the following equation:
AUC(t1-t2) = (t1-t2) x (C1+C2)/2 
where C1 and C2 are the concentrations at t1 and t2 respectively (t1 and t2 are days from first dose of IP 
(t1-t2) = (t2-t1) calculated in days (precision will be in hours based on 
actual sampling time).
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The AUC from week 13 to week 15 will be obtained by summing the AUC calculated for each of the time 
intervals defined by the available PK concentration values between week 13 and week 15. AUC from week 
13 to week 15 will be calculated for subjects if (1) week 13 pre-dose and week 13 post-dose PK 
concentrations are available and (2) week 14 PK concentration or week 15 pre-dose PK concentration is 
available. In the calculation of AUC, concentration values below the limit of quantification (BLQ) will be 
substituted with zero.
Study Analysis Visit for PK Summaries
For the pre-dose PK analysis visits, the actual visit date is mapped to the study analysis visit using the 
analysis visit window that is defined as target day with +6/-7 days window, and the target day is defined as 
study week visit  x 7 – 6.
Predose PK samples recorded as collected post-dose will be excluded. In instances where the dose start 
and/or stop times are missing, the pre-infusion or post-infusion checkbox from the PK CRF will be used if 
available. 
For the calculation of AUC from week 13 to week 15, the week 13 visit must also fall in the window of study 
day 78 to 91. The week 13 post-infusion PK will be excluded if the collection timing does not occur at or 
after the prior dose stop time.
8.5 Full Analysis Set
The full analysis set (FAS) will consist of all randomized subjects, with treatment as the randomized
treatment sequence, regardless of treatment actually received.   
8.6 Modified Full Analysis Set 
The Modified Full Analysis Set (mFAS)will consist of all randomized subjects who have an LDH-time profile 
evaluable for the time-adjusted AUEC within at least one of the following 14-week assessment periods: 
week 13 to week 27, week 39 to week 53, and week 65 to week 79, according to treatment per the 
randomized sequence regardless of treatment actually received. The LDH-time profile within weeks 13 to 
27 is considered evaluable if there are at least 3 LDH values between study day 78 and study day 189. The 
LDH-time profile within weeks 39 to 53 is considered evaluable if there are at least 3 LDH values between 
study day 260 and study day 371. The LDH-time profile within weeks 65 to 79 is considered evaluable if 
there are at least 3 LDH values between study day 442 and study day 553.    
8.7 Per Protocol Sets
8.7.1 Per-protocol Analysis Set for the Primary Endpoint of Lactate Dehydrogenase at 
Week 27 for the Parallel Comparison
The per-protocol analysis set for the primary endpoint of LDH at week 27 for the parallel comparison (PPP) 
will be a subset of the FAS, which includes subjects who did not experience an important protocol deviation 
between week 13 and week 27 (study day 78 to 189) that affects their primary efficacy evaluation for the 
parallel comparison.  The protocol deviations that affect primary efficacy evaluation will be determined 
based on a blinded data review prior to database snapshot for the primary analysis of week 27 LDH for the 
parallel comparison.  Analyses for the PPP analysis set will be based on actual treatment received.
8.7.2 Per-protocol Analysis Set for the Primary Endpoint of AUEC for the Crossover 
Comparison
The per-protocol analysis set for the primary endpoint of time-adjusted AUEC for the crossover comparison 
(PPC) will be a subset of the mFAS, which includes subjects who did not experience an important protocol 
deviation during week 13 to week 27 (study day 78 to 189), week 39 to week 53 (study day 260 to 371) and 
week 65 to week 79 (study day 442 to 553) that affects their primary efficacy evaluation for the crossover 
comparison. The protocol deviations that affect primary efficacy evaluation will be determined based on a 
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Statistical Analysis Plan  
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blinded data review prior to database lock for the crossover comparison. Analyses for the PPC analysis set 
will be based on actual treatment received.
8.8 Safety Analysis Set
The safety analysis set will consist of all treated subjects with treatment assignment based on actual 
treatment received.
8.9 Pharmacokinetic Analysis Sets
8.9.1 Pharmacokinetic Concentration Analysis Set
The Pharmacokinetics Concentration Analysis Set will be defined as the subset of subjects in the safety 
analysis set who have at least 1 serum concentration (including results below the quantifiable limit) of ABP 
959 or eculizumab. Analyses for the PK Concentration Analysis Set will be based on actual treatment 
received.  
8.9.2 Pharmacokinetics Parameter Analysis Set
The Pharmacokinetics Parameter Analysis will be defined as a subset of subjects in the safety analysis set 
who have an evaluable ABP 959 or eculizumab serum concentration time profile from week 13 to 
week 15. Subjects to be excluded from the PK Parameter Analysis Set will be determined based on a 
blinded data review prior to the database lock for the primary analysis if one of the evaluability criteria is 
not met: receiving the full scheduled dose (900 mg) at week 13, having 4 PK samples with valid results 
between week 13 and week 15, not receiving an additional dose between weeks 13 and 15 (e.g. due to a 
break through event), and a valid PK sample collected in the week 15 analysis visit window if the week 15 
dose was withheld. Analyses for the PK parameter analysis set will be based on actual treatment received. 
9.0 LDH Review
The LDH Review Committee will review blinded data and identify LDH values impacted by confounding 
events (e.g. acute infection, or trauma including surgery), unrelated to efficacy of IP that trigger dose 
adjustment for exclusion in the primary analysis of LDH and AUEC of LDH. Details on the LDH review 
committee and related processes can be found in the LDH Review Charter. The final LDH review results 
(one record for each LDH result with a flag indicating if the result should be excluded from analysis) will be 
used in the programming of the LDH-related analyses. Unless otherwise specified, LDH results flagged to 
be excluded will be excluded from all derivations and analysis models.
10.0 Interim Analyses
Blinded assessments of the inter-subject coefficient of variation (CV) of LDH and the intra-subject CV of 
time-adjusted AUEC of LDH will be performed.
The first blinded interim check of CV will take place prior to the end of enrollment. If the aggregated intra-
subject CV of AUEC is greater than 44%, additional subjects will be enrolled if feasible. The AUEC will be 
calculated for week 1 to week 15 and for week 15 to week 29 (if available) for each subject. All non-missing 
AUECs for the two time intervals will be included in the calculation of the aggregated intra-subject CV.
The second blinded interim check of CV will take place when approximately all subjects complete their 
week 27 visit. If the aggregated inter-subject CV of LDH is greater than 130%, the primary endpoint of 
parallel comparison of LDH at week 27 will be replaced by crossover comparison of LDH at week 53 and 
week 79.
An independent data monitoring committee (DMC) will perform safety reviews of unblinded data 
approximately every 6 months (or as determined by the DMC) throughout the study. Details regarding the 
DMC are provided in the DMC Charter. In DMC meeting #4 and future DMC meetings, a table and a listing 
of SAEs occurring on or after the start date of COVID-19 infection were added for review. Adverse event 
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Statistical Analysis Plan  
Protocol no: 20150168 
Version Date: 26-January-2022
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Strictly Confidential.  © 2017, PRA Health Sciences.  All rights reserved.
data collected on the adverse events eCRF is used to identify the subset of subjects diagnosed with COVID-
19 using the search strategy of the COVID-19 SMQ. 
11.0 Statistical Methods
The data cut for the primary analysis for the parallel comparison will be performed when all subjects have 
completed the Week 53 visit or had the EOS visit prior to Week 53. All data collected by the time of the 
data cut will be included in this analysis. The primary analysis for the crossover comparison (which is also 
considered the final analysis for the study) will be performed when all subjects have completed the EOS 
visit.
All statistical analyses will be performed using SAS® Version 9.4 or higher. 
Unless otherwise specified, descriptivedata summaries will be tabulated by treatment for all endpoints. For 
continuous outcomes, the descriptive statistics include number of subjects with observations (n), mean, 
standard deviation, median, 25th percentile (Q1), 75th percentile (Q3), minimum, and maximum. The mean, 
median, Q1, and Q3, will be presented to one decimal place greater than the original data, standard 
deviation will be to two decimal places greater than the original data, and the minimum and maximum will 
have the same number of decimal places as the original data. Geometric mean will have 1 decimal place 
more than the raw data. CV(%) and Geometric CV(%) will have 1 decimal place. Geometric mean ratio and 
associated CI will have 4 decimal places. Confidence intervals (CIs) will be provided when specified. 
Categorical outcomes will be summarized by number and percent of subjects falling into each category. 
Confidence intervals (CIs) will be provided when specified. Percentages will be rounded to one decimal 
place. 
11.1 Subject Disposition
The following information will be summarized for subject disposition and accountability:
Subject disposition (including number of subjects who were treated with IP in each period and 
overall, completed each period IP dosing, discontinued IP during each period with reason for 
discontinuation, discontinued IP during each period with COVID-19 related reasons for 
discontinuation, completed the study and discontinued the study early with reason for 
discontinuation, discontinued the study early with COVID-19 related reason for discontinuation
Randomization by stratification factor (RBC transfusion within 12 months before randomization)
Number of randomized subjects by country and site
Summaries of analysis populations with reason for exclusion
Randomization list of subjects and their actual versus randomized treatment sequence (for the 
FAS)
Listing of subject analysis sets
11.2 Protocol Deviations
Protocol deviations (PD) data will be entered into the Clinical Trials Management System (CTMS). The 
study team will conduct on-going reviews of the PD data from CTMS and the resulting set of subjects to be 
included in the PPP and PPC analysis sets throughout the study, adjusting the PD criteria as seems 
appropriate. The subjects to be included in the PPP analysis set will be finalized prior to the database lock 
for the primary analysis of the parallel comparison. The subjects to be included in the PPC analysis set will 
be finalized prior to database lock.
Based on the PD data entered CTMS, a summary of important PDs (IPDs) will be tabulated using number 
and percentage of subjects with important PD by deviation type and randomized treatment sequence and 
whether the IPDs are related to COVID-19. A summary table of deviations of the inclusion/exclusion criteria 
will also be tabulated. A listing of subjects with important PDs and deviations of the inclusion/exclusion 
00(00) 
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• 
• 
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Statistical Analysis Plan  
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criteria will be provided (with a flag indicating whether the deviation leads to exclusion fromthe PPP or PPC 
analysis sets). In addition, COVID-19 related PDs will be tabulated using number and percentage of 
subjects by deviation type and randomized treatment sequence, and a listing of COVID-19 related PDs will 
be provided. 
11.3 Treatments
All analyses in this section will be performed on the safety analysis set based on a subject’s actual treatment 
received.
11.3.1 Extent of Study Drug Exposure
Study drug exposure will be summarized separately for Period 1, Period 2 and overall. Summary statistics 
will be provided for the total number of IP doses administered, cumulative dose, and duration of IP 
exposure. The number of subjects with at least one dose interruption and the number of subjects with at 
least one dose delay/not administered as well as the reasons will be tabulated by study period. Separate 
rows show the frequency related to COVID-19 reasons. The number of subjects with at least one increase 
in dose and/or frequency will also be summarized by study period.
A listing of the lot number(s) for IP for each subject and a listing of unique manufacturing lot numbers will 
be provided.  
11.3.2 Concomitant Medications
Concomitant medications include all medications and therapies during the study except for planned IP 
administration. Concomitant medications will be coded by the current version of the World Health 
Organization Drug Dictionary (WHO-DD). The numbers and percentages of subjects will be summarized 
by preferred term and actual treatment group for Period 1, Period 2, and overall for the study. Medications 
with a stop date before study day 1 will not be summarized. For subjects who return to eculizumab or other 
PNH treatment after EOS, their PNH medications with a start date on or after theEOS date will beexcluded 
from the summaries. For subjects who will not receive eculizumab or other PNH treatment after EOS, 
medications received on the same as the EOS visit will be included in the summaries.
11.4 Demographic and Baseline Characteristics
The following demographic and baseline characteristics will be summarized for FAS, mFAS, PPP, PPC, 
and safety analysis sets: age (in years, at time of signing informed consent), age group ( 54 years versus
>54 years), age at time of PNH diagnosis (in years), race, sex, ethnicity, height, and weight. Study baseline 
characteristics including time since original diagnosis (months), time since start of eculizumab (months), 
and baseline LDHand hemoglobin values will also besummarized. The number and percentage of subjects 
having RBC transfusion within 12 months before randomization (as entered on the eCRF) will be tabulated.
A summary of the number of packed RBC units received within 12 months before randomization will also 
be included.
Medical conditions at screening will be summarized by preferred term (PT) and primary system organ class 
(SOC) separately by status (unresolved versus resolved) for the FAS. 
11.5 Efficacy Analyses
11.5.1 Primary Endpoints
11.5.1.1 Parallel Comparison
11.5.1.1.1 Primary Analysis
The primary endpoint for the parallel comparison is hemolysis, as measured by LDH at week 27. The 
primary analysis for the parallel comparison will be conducted on the FAS. It will be analyzed when all 
subjects have completed or have had the chance to complete their week 53 visits. 
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The clinical similarity of the week 27 LDH between treatments will be assessed by comparing the 1-sided 
97.5% upper confidence interval (CI) limit for the GMR of the LDH at week 27 between ABP 959 and 
eculizumab treatment with a NI margin of 2.873. The point estimate of the mean difference in the 
log-transformed LDH and the corresponding 1-sided 97.5% upper CI limit will be estimated from a linear 
mixed effects model with treatment, stratification factor, week 1 LDH value, time (as a continuous variable) 
and treatment by time interaction term as fixed effects, and subject as a random effect. An unstructured 
covariance structure will be used. If convergence criteria is not met, then use compound symmetry option. 
The point estimate and the upper CI limit for the GMR will then be calculated by transforming back to the 
original scale. Lactate dehydrogenase values from all assessed time points from week 13 to week 27 (i.e. 
study day 78 to study day 189) will be included in the mixed model. LDH values impacted by confounding 
events unrelated to efficacy of IP, as determined by the LDH review committee, will be excluded from the 
analysis (see section 9.0 for more details). 
11.5.1.1.2 Secondary Analysis
To assess the robustness of the primary parallel comparison, the parallel comparison will also be conducted 
in the PPP population.
The parallel comparison of LDH at week 27 will also be examined in subgroups by the levels of the
stratification factor per the eCRF value and levels of baseline covariates, including age ( 54 vs > 54 years 
old) and gender. The statistical model for the analysis of baseline covariate subgroups will not include the
stratification factor as a covariate.
11.5.1.2 Crossover Comparison
11.5.1.2.1 Primary Analysis
The primary endpoint for the crossover comparison is hemolysis, as measured by the time-adjusted AUEC 
of LDH from week 13 to week 27, week 39 to week 53, and from week 65 to week 79. The primary analysis 
for the crossover comparison will be conducted on the mFAS. See section 8.4 for details on derivation of 
AUEC of LDH.LDH values that are determined to be elevated due to confounding events by the LDH review 
committee will be excluded.
The clinical similarity of the AUEC between treatments will be assessed by comparing the 2-sided 90% CI 
for the GMR of the time-adjusted AUEC of LDH (week 13 to week 27, week 39 to week 53, and week 65 to 
week 79) between ABP 959 and eculizumab treatment with a similarity margin of (0.77, 1.30). The point 
estimate of the mean difference in the log-transformed time-adjusted AUEC and the corresponding 2-sided 
90% CI will be calculated from a linear mixed effects model with treatment, stratification factor, period, and 
sequence as fixed effects, and subject as a random effect. An unstructured covariance structure will be 
used. If convergence criteria is not met, then compound symmetry option will be used The point estimate 
and CI for the GMR will then be calculated by transforming back to the original scale.
11.5.1.2.2 Secondary Analysis
To assess the robustness of the primary crossover comparison, the crossover comparison will also be 
conducted in the PPC population. 
The crossover comparison AUEC of LDH will also be examined in subgroups by the levels of the 
stratification factor per the eCRF value and levels of baseline covariates, including age ( 54 vs > 54 years 
old) and gender.  
11.5.1.3 Methods for Handling Dropouts and Missing Data
Missing LDH values will not be imputed.
11.5.1.4 Multiplicity
The primary analysis for the parallel comparison and the primary analysis for the crossover comparison are 
for separate regulatory agencies; therefore, no adjustment for multiplicity is needed.
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11.5.1.5 Pooling of Sites
All sites will be pooled together for all analyses.
11.5.2 Secondary Endpoints
11.5.2.1 Secondary Efficacy Lab Endpoints
Total complement, total hemoglobin, serum-free hemoglobin, haptoglobin, bilirubin, degree of 
hemoglobinuria, and type III erythrocytes (%) will be summarized descriptively at week 27, week 39, week 
53, week 65, and week 79 in the FAS. For continuous endpoints, the values and the change from baseline 
will be summarized by treatment at each of the specified visits. For categorical endpoints, the number and 
percent of subjects falling into each category will be presented by treatment. Analysis visit windows for the 
relevant time points will be defined as below:
Study Analysis Visit 
Target Day 
Range of Study Day 
Interval (days)
Week 27 
183
176 – 189
14
Week 39 
267
260 – 273
14
Week 53 
365
358 – 371
14
Week 65
449
442 – 455
14
Week 79
547
540 – 553
14
A mean (+/- SD) plot of total complement at each analysis visit (target day with +6/-7 days window) will be 
presented in the FAS. In general, the target day is defined as (study week visit  x 7 – 6).
11.5.2.2 Crossover Comparison of LDH at Week 53 and Week 79
The secondary endpoint of the crossover comparison of LDH at week 53 and week 79 will be evaluated 
descriptively in the FAS. The point estimate of the mean difference in the log-transformed LDH between 
treatments and the corresponding 1-sided 97.5% upper CI limit will be calculated from a linear mixed effects 
model with treatment, stratification factor, period, and sequence as fixed effects and subject as a random 
effect..The point estimate and 1-sided 97.5% upper CI limit for the GMR will then be calculated by 
transforming back to the original scale. LDH values impacted by confounding events unrelated to efficacy 
of IP, as determined by the LDH review committee, will be excluded from the analysis (see section 9.0 for 
more details). 
The week 53 LDH result is the last LDH result prior to the first dose of IP in Period 2. The week 79 LDH 
result is the last LDH result on study. Subjects missing both the week 53 and week 79 LDH results will be 
excluded from this analysis.
11.5.2.3 Lactate Dehydrogenase-time Profile
A descriptive summary of LDH at each time point through the EOS visit will be presented for the FAS. 
Individual and mean LDH with one standard deviation at each analysis visit (target day with +6/-7 days 
window) through the EOS visit will also be presented graphically. LDH values impacted by confounding 
events unrelated to efficacy of IP, as determined by the LDH review committee, will be excluded from the 
analysis (see section 9.0 for more details). 
11.5.2.4 Red Blood Cell Transfusion
Summary statistics for the number of packed RBC units transfused per month will be presented separately 
for Period 1 and Period 2. For each subject, the number of packed RBC units transfused per month for 
Period 1 is calculated as the total number of units transfused from week 13 to week 53 (study day 78 to 
Period 1 end date) divided by the time in months from study day 78 to Period 1 end date. For each subject, 
the number of packed RBC units transfused per month for Period 2 is calculated as the total number of 
units transfused from week 65 (study day 442) to Period 2 end date divided by the time in months from 
study day 442 to the Period 2 end date.
00(00) 
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Statistical Analysis Plan  
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Version Date: 26-January-2022
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11.6 Pharmacokinetics
PK concentrations will be reviewed by a PK scientist and some concentrations may be flagged as not 
evaluable prior to unblinding for the analysis. 
The point estimate and 90% CI for geometric mean ratio (GMR) of ABP 959 to eculizumab for total and 
unbound PK AUC from week 13 to week 15 in the PK parameter analysis set will be estimated using an 
ANOVA. The ratio of the geometric means for the treatment comparison will be obtained by exponentiating 
the difference of the means on the log scale. The 90% CI will be obtained by back-transforming the CI for 
the difference between the means on the log scale. 
Total and unbound serum ABP 959 and eculizumab trough concentrations will be summarized descriptively 
in the PK concentration analysis set by visit through the EOS visit. 
A boxplot of the total and unbound trough serum concentrations at each pre-dose PK visit will be presented
for the PK concentration analysis set. Mean serum concentrations from week 13 to week 15 will be plotted 
for subjects in the PK parameter analysis set. A listing of both total and unbound PK concentration values
from week 13 to week 15 along with the AUC will also be presented for subjects in the PK parameter 
analysis set.
Subjects whose PK AUC between week 13 and week 15 are derived with either week 14 PK concentration 
or week 15 pre-dose PK concentration missing (and hence are not in the PK parameter analysis set) will 
be flagged in the dataset.
11.7 Safety Analyses
All safety analyses will be performed on the safety analysis set based on a subject’s actual treatment 
received.
11.7.1 Adverse Events
All reported treatment emergent adverse events (TEAE) will be summarized. Each reported TEAE will be 
coded to the appropriate SOC and PT according to the most current version of Medical Dictionary for 
Regulatory Activities (MedDRA), and the severity of each TEAE will be graded per Common Terminology 
Criteria for Adverse Events (CTCAE) v5.0 criteria. 
Subject incidence of the following TEAEs will be tabulated by treatment for the entire study through the 
EOS visit, for period 1, for period 2, and for each of the 14 week assessment periods (i.e. week 13 to 
week 27, weeks 39 to 53, and weeks 65 to 79):
Overall summary of treatment-emergent AEs
TEAEs by PT
TEAEs by SOC, PT, and maximum CTCAE grade
TEAEs by SOC and PT
Grade 3 TEAEs by PT
Treatment-emergent AEs leading to discontinuation from study/IP by PT
Overall summary of treatment-emergent EOIs
Subject incidence of the following TEAEs will be tabulated by treatment for the entire study through the 
EOS visit, for period 1, and for period 2:
Treatment Emergent COVID-19 AEs by PT   
Each treatment-emergent EOI category by PT
Each treatment-emergent EOI category by PT and maximum CTCAE grade.
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An overall summary of treatment-emergent AEs will also be provided by treatment sequence for the study 
through the EOS visit, in which subjects experiencing events in both treatment periods, subjects 
experiencing an event in Period 1 only, subjects experiencing an event in Period 2 only, and subjects not 
experiencing an event in either period will be summarized.
Counting of TEAEs will be by subject, and subjects will be counted only once within each SOC or PT. For 
tables categorized by severity, subjects with multiple events within a SOC or PT will be counted under the 
category of their most severe event within that SOC or preferred term. 
In addition to summarizing the subject incidence of EOI by category, the risk difference with 95% CI of each 
EOI category between treatment groups will be provided. The 95% CI will be calculated by exact method
for Period 1 and Period 2 using SAS proc freq with method= fmscore in the exact statement.For the overall 
summary through EOS the risk difference (ABP 959 - eculizumab) and 95% CI are calculated by the 
generalized estimating equation (GEE) method using SAS proc genmod with treatment and period as fixed 
effects, and subject as a random effect. A within subject variance-covariance structure of exchangeable is 
used.
All treatment-emergent AEs will be listed by treatment group separately.
11.7.2 Fatal and Serious Adverse Events
Subject incidence of the following TEAEs will be tabulated by treatment for the entire study through the 
EOS visit, for period 1, and for period 2 and for each of the 14 week assessment periods (i.e. week 13 to 
week 27, weeks 39 to 53, and weeks 65 to 79): 
Treatment-emergent serious adverse events (SAEs) by PT
Treatment-emergent SAEs by SOC and PT
Treatment-emergent SAEs by SOC, PT and maximum CTCAE grade 
Fatal Treatment-emergent AEs by PT
Adverse event data collected on the adverse events eCRF is used to identify the subset of subjects 
diagnosed with COVID-19 using the search strategy of the COVID-19 SMQ. Subject incidence of treatment 
emergent serious adverse events occurring on or after presumed start date of COVID-19 infection will be 
presented by preferred term for Period 1, Period 2 and the complete study by treatment. A listing of SAEs 
on or after presumed start date of COVID-19 infection, as defined for the incidence table, is also presented.
11.7.3 Laboratory Data
Laboratory test results will be reported in International System of Units (SI) units.
Laboratory values and change from baseline will be summarized using descriptive statistics at each 
analysis visit (target day with +6/-7 days window) by treatment. 
Based on CTCAE v5.0, laboratory tables for shift from baseline grade or category (if baseline grade is not 
available, see Appendix 3) to maximum post-baseline grade will be presented by treatment group. Shift 
summaries will be presented separately for Period 1 and Period 2. Period 1 baseline values are from the 
latest laboratoryresults before the first IP treatment in Period 1. Period 2 baseline values are from the latest 
laboratory results before the first IP treatment in Period 2. All post-baseline laboratory assessments will be 
included in the determination of maximum post-baseline grade. 
Standard ranges will be used for the laboratory analysis. In addition, subject incidence of grade 
3 
laboratory toxicities will be summarized by treatment.
Lab assessments will be grouped for summary as follows:
Hematology – white blood cell parameters: white blood cell count and absolute neutrophil count
Hematology – red blood cell parameters: red blood cell count, hemoglobin and packed cell volume 
or hematocrit 
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Hematology – other parameters: platelets
Hematology – hemolysis-related parameters: Type III cells (erythrocytes, monocytes, and 
granulocytes) and serum-free hemoglobin.
Total complement (CH50) 
Serum chemistry – hepatobiliary parameters: alanine aminotransferase, aspartate 
aminotransferase, total bilirubin, alkaline phosphatase, LDH, haptoglobin
Serum chemistry – renal function tests: creatinine, blood urea nitrogen, uric acid, potassium
11.7.4 Vital Signs and Physical Examination
Vital sign assessments include pulse, respirationrate, temperature, and blood pressure (BP).  Change from 
baseline in vital signs will be summarized by treatment group. Descriptive statistics will be shown for 
baseline, and the change from baseline at each analysis visit (target day with +6/-7 days window).
11.7.5 Immunogenicity
The number and percentage of subjects developing binding, neutralizing, and treatment boosted anti-drug 
antibody (ADA)will be tabulated for each treatmentforPeriod 1 and for the studythrough EOSby treatment 
sequence using the safety analysis set. The overall antibody incidence will also be tabulated. Pre-existing 
antibody incidence (on or before the first dose of study IP) and developing antibody incidence (including 
transient antibody incidence)will be summarized.  Pre-existing antibody incidence is defined as the number 
of subjects with a positive antibody result at study baseline divided by the number of subjects with a result 
at study baseline.  Developing antibody incidence through Period 1 is defined as the number of subjects 
with a binding negative or no antibody result at study baseline and a positive antibody result at any
post-baseline time point before Period 1 end date divided by the number of subjects with any postbaseline 
result before Period 1 end date.  Developing antibody incidence through EOS is defined as the number of 
subjects with a binding negative or no antibody result at study baseline and a positive antibody result at 
any post-baseline time point divided by the number of subjects with any postbaseline result. A transient 
antibody result is defined as a positive post-baseline result with a negative result at the subject’s last 
timepoint tested within the study period. 
Treatment boosted ADA is defined as total number and percentage of subjects with a positive immunoassay 
result at baseline and at least 1 post-baseline immunoassay result that is >=4x magnitude of baseline result. 
Developing antibody incidence through specific study visits will also be presented. Developing antibody 
incidence at a given study visit week is defined as the number of subjects with a binding negative or no 
antibody result at study baseline and positive antibody result at any timepoint up to the given visit divided 
by the number of subjects with any postbaseline result up to the given visit. Transient status is not defined 
for given study visit week summaries. For determining developing incidence “by week x”, the following 
window upper limits will be used
Visit 
Target Day 
Upper Limit 
by Week 7
43
49
by Week 27
183
189
by Week 39
267
273
by Week 53
365
371
by Week 65
449
455
11.7.6 Imputation for Partial or Missing Dates 
Partial or missing admission and discharge dates for hospitalizations will not be imputed.
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If dates are missing or incomplete for an AE (including deaths) or concomitant medication, the following 
algorithm will be used for imputation: 
Table 4. Imputation Rules for Partial or Missing Start Dates
Start Date
Stop Date
Complete: 
yyyymmdd
Partial: yyyymm
Partial: yyyy
missing
<1st
dose
st dose
<1st dose 
yyyymm
st dose 
yyyymm
<1st dose 
yyyy
st dose 
yyyy
Partial: 
yyyymm
= 1st dose 
yyyymm
2
1
n/a
1
n/a
1
1
st dose 
yyyymm
2
2
2
2
2
2
Partial: 
yyyy
= 1st dose 
yyyy
3
1
3
1
n/a
1
1
st dose 
yyyy
3
3
3
3
3
Missing
4
1
4
1
4
1
1
1 = Impute the date of first dose
2 = Impute the first of the month
3 = Impute January 1 of the year
4 = Impute January 1 of the stop year
Note: If the start date imputation leads to a start date that is after the stop date, then do not impute the start 
date.
Imputation rules for partial or missing stop dates:
1.
Initial imputation
a.
For partial stop date “mmyyyy”, impute the last day of the month.
b.
For partial stop date “yyyy”, impute December 31 of the year.
c.
For completely missing stop date, do not impute.
2.
If the stop date imputation leads to a stop date that is after the death date, then impute the stop 
date as the death date.
3.
If the stop date imputation leads to a stop date that is before the start date, then there is a data 
error and do not impute the stop date (i.e. set the stop date as missing).
Imputation rules for partial or missing death dates:
1.
If death year and month are available but day is missing:
a.
If “mmyyyy” for last contact date = “mmyyyy” for death date, set death date to the day after 
the last contact date.
b.
If “mmyyyy” for last contact date < “mmyyyy” for death date, set death date to the first day 
of the death month.
c.
If “mmyyyy” for last contact date > “mmyyyy” for death date, data error and do not impute.
2.
If both month and day are missing for death date or a death date is totally missing, set death date 
to the day after the last contact date.
The imputed dates will be used to assess whether AEs should be considered as treatment-emergent and 
if concomitant medications should be included in the safety summaries, however the original, partial dates 
will be included in data listings.
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.?1 
.?1 
>1 
:#1 
:# 1 
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12.0 Validation
The programming (including quality control) of the analysis datasets and tables, figures, and listings (TFLs)
will be conducted under PRA's standard processes PRS 050 and documented accordingly. The entire set 
of TFL will be checked for completeness and consistency prior to its delivery to the client by the lead 
statistician and a senior level statistician, or above, who is not a member of the project team.
The PRA validation process is repeated any time TFL are redelivered using different data. Execution of this 
validation process is documented through the study Table of Programs that is provided to the client at study 
conclusion.
13.0 References
Ke C, Wang J, Zhang C, Jiang Q, Snapinn S. On errors in stratified randomization. Statistics in 
Biopharmaceutical Research 2017; 9 (2): 225-33.
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Appendix 1 Glossary of Abbreviations
Glossary of Abbreviations:
ADA
Anti-drug Antibody
AE
Adverse Event
AUC
Area Under the Curve
AUEC
Area Under the Effect Curve
BLQ
Below Limit of Quantification
BP
Blood Pressure 
CDISC
Clinical Data Interchange Standards Consortium
CI
Confidence Interval 
CIOMS
Council for International Organizations of Medical Sciences
CTCAE
Common Terminology Criteria for Adverse Events
CTMS
Clinical Trials Management System
CV
Coefficient of Variation
DMC
Data Monitoring Committee
EAIR
Exposure-adjusted Incidence Rate
eCRF
Electronic Case Report Form
EOI
Event of Interest
EOS
End of Study
FAS
Full Analysis Set
GMR
Geometric Mean Ratio
IP
Investigational Product
IV
Intravenous
IXRS
Interactive Voice/Web Response System
LDH
Lactate Dehydrogenase
MedDRA
Medical Dictionary for Regulatory Activities
mFAS
Modified Full Analysis Set
NI
Noninferiority
PD
Protocol Deviation
PK
Pharmacokinetic
PNH
Paroxysmal Nocturnal Hemoglobinuria
PPC
Per-protocol Analysis Set for the Crossover Comparison
PPP
Per-protocol Analysis Set for the Parallel Comparison
PT
Preferred Term
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P-Y
Patient-Year
Q1
25th Percentile
Q3
75th Percentile
RBC
Red Blood Cell
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
SI
International System of Units
SMQ
Standard MedDRA Query
SOC
System Organ Class
TEAE
Treatment-emergent Adverse Event
TFL
Tables, Figures, and Listings
WHO-DD
World Health Organization Drug Dictionary
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Appendix 2 MedDRA Query SMQ - COVID-19
Methodology: The PT's related to the COVID-19 MedDRA SMQ dictionary will be used to define subjects 
with presumed COVID-19 infection. For the search the narrow criteria of the SMQ query definitions will be 
used.
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Appendix 3 Baseline Gradings for ALT, AST, Total Bilirubin and 
Alkaline Phosphatase
For the lab parameters ALT, AST total bilirubin and alkaline phosphatase the CTCAE v5.0 grading are not 
defined for baseline. The following definitions will be used for baseline categories:
Lab Parameter
Baseline Categories
AST and ALT
Missing
      
      
      > 3x ULN
Total bilirubin 
Alkaline phosphatase
      Missing
      
> 1x ULN
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.,§ 
!, 1x ULN 
> 1x ULN to !, 3x ULN 
!, 1x ULN 
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Appendix 4 List of Post-text Tables, Figures, and Listings and 
Supportive SAS Output Appendices
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Statistical Analysis Plan  
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•'( 
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Statistical Analysis Plan  
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Version Date: 26-January-2022
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Statistical Analysis Plan  
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Version Date: 26-January-2022
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Statistical Analysis Plan  
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Version Date: 26-January-2022
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Statistical Analysis Plan  
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Version Date: 26-January-2022
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Statistical Analysis Plan  
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Version Date: 26-January-2022
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TABLE OF CONTENTS
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__ 
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___ 
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Prot_000.pdf: 
Product: ABP 959
Clinical Study Protocol: 20150168
Date: 05 March 2020
Page 1 of 71
Confidential
1
TITLE PAGE
A RANDOMIZED, DOUBLE-BLIND, ACTIVE-CONTROLLED PHASE 3 STUDY 
EVALUATING THE EFFICACY AND SAFETY OF ABP 959 COMPARED WITH 
ECULIZUMAB IN ADULT SUBJECTS WITH PAROXYSMAL NOCTURNAL
HEMOGLOBINURIA (PNH)
Test Drug:
ABP 959
Protocol Number:
20150168
EudraCT number:  2017-001418-27
Study Phase:
3
Date and Version:
05 March 2020, version 4.0
Key Contacts:
Amgen Inc.:
Senior Manager
Global Study Management 
Amgen Inc.
One Amgen Center Drive 
Thousand Oaks, CA USA 
91320
Phone:
Email: 
Clinical Research Organization (CRO):
Project Director
PRA Health Sciences
995 Research Park Blvd. Suite 300 
Charlottesville, VA  USA
22911
Phone:
Email: 
Safety Contacts:
PRA Drug Safety Center
North America and South America 
Phone: +1-800-772-2215/1-434-951-3489 
Fax: 
+1-888-772-6919/1-434-951-3482 
Email: CHOSafety@prahs.com/
SAOSafety@prahs.com
Europe, Asia, and Pacific Region 
Phone: +49-621-878-2154
Fax: 
+44-179-252-5720 
Email: MHGSafety@prahs.com
This study will be conducted in compliance with the protocol, Good Clinical Practice 
(GCP) as set forth in the International Conference for Harmonisation (ICH) guidelines 
on GCP (ICH E6), and applicable local regulatory requirements.
CONFIDENTIAL
This document is a confidential communication of Amgen, Inc. Acceptance of this document constitutes 
agreement by the recipient that no unpublished information contained herein shall be published or 
disclosed without prior written approval, except that this document may be disclosed to the appropriate
Institutional Review Board(s)/Independent Ethics Committee(s) under the condition that they keep it 
confidential.
Approved
NCT Number: NCT03818607
This NCT number has been applied to the document for
purposes of posting on Clinicaltrials.gov


Product: ABP 959 
Clinical Study Protocol: 20150168 
Date: 05 March 2020 
SIGNATURES 
Page 2 of 71 
Representatives of Sponsor and Clinical Research Organization 
I have read and agree to the protocol, 20150168, titled "A Randomized, Double-blind, 
Active-controlled Phase 3 Study Evaluating the Efficacy and Safety of ABP 959 Compared 
With Eculizumab in Adult Subjects With Paroxysmal Nocturnal Hemoglobinuria (PNH)." I 
am aware of my responsibilities under the guidelines of GCP, local regulations (as 
applicable), and the study protocol. I agree to conduct the study according to these 
responsibilities. 
Accepted for the Sponsor - Amgen Inc.: 
 
Medical Director, Amgen 
Print Name 
Signature 
Title 
Date 
Accepted for the Clinical Research Organization - PRA: 
 
Medical Director, PRA 
Print Name 
Title 
Date 
r---'-'.: ............ ,-.1 
Approved


Product: ABP 959
Clinical Study Protocol: 20150168
Date: 05 March 2020
Page 3 of 71
Confidential
Investigator
I have read and agree to the protocol, 20150168, entitled “A Randomized, Double-blind, 
Active-controlled Phase 3 Study Evaluating the Efficacy and Safety of ABP 959 Compared 
With Eculizumab in Adult Subjects With Paroxysmal Nocturnal Hemoglobinuria (PNH).” I
am aware of my responsibilities as an investigator under the guidelines of GCP, local 
regulations (as applicable), and the study protocol. I agree to conduct the study according 
to these responsibilities and to appropriately direct and assist the staff under my control, 
who will be involved in the study.
Clinical Site: 
Site Number:
Site Principal Investigator:
Print Name
Title
Signature
Date
Coordinating Investigator Signature (if applicable):
Print Name
Title
Institution/ Country
Signature
Date
Approved 
 
 


Product: ABP 959 
Clinical Study Protocol: 20150168 
Date: 05 March 2020 
Page 4 of 71 
Confidential 
 
2 
SYNOPSIS 
NAME OF SPONSOR: Amgen Inc. 
PROTOCOL No.: 20150168 
NAME OF STUDY TREATMENT: ABP 959 
TITLE OF STUDY: A Randomized, Double-blind, Active-controlled, Phase 3 Study Evaluating the 
Efficacy and Safety of ABP 959 Compared With Eculizumab in Adult Subjects With Paroxysmal 
Nocturnal Hemoglobinuria (PNH) 
STUDY CENTERS:  Approximately 45 sites globally 
STUDY PERIODS:  Subjects will be treated in 2 study 
periods.  Period 1 will be 52 weeks in duration.  Period 2 
will be 26 weeks in duration. 
PHASE OF DEVELOPMENT:  
Phase 3 
PLANNED STUDY DATES:  The planned duration of the clinical study is approximately 
30 months (approximately 12 months for enrollment and approximately 18 months for treatment), 
from approximately Q1 2019 to Q3 2021. 
OBJECTIVES:  
Primary Objective:  The primary objective for this study is to evaluate the efficacy of ABP 959 
compared with that of eculizumab based on control of intravascular hemolysis. 
Secondary Objective:  The secondary objective is to assess the safety, pharmacokinetics (PK), 
and immunogenicity of ABP 959 compared with that of eculizumab. 
STUDY DESIGN AND METHODOLOGY:  This is a randomized, double-blind, active-controlled, 
2-period crossover study in adult subjects with PNH.  Approximately 40 subjects will be 
randomized (1:1) to receive each investigational product (IP) in 1 of 2 sequences, either 
treatment T followed by treatment R (TR) or treatment R followed by treatment T (RT).  Treatment 
will be administered over 2 periods: Period 1 will be 52 weeks in duration; Period 2 will start at 
week 53 with a crossover in treatment and will be 26 weeks in duration.  Randomization will occur 
within 8 days before the first dose of IP administration and will be stratified by red blood cell 
(RBC) transfusion received within the last 12 months before randomization (yes vs no). 
Period 1 (week 1 to week 53): 
Treatment T:  ABP 959 at a dose of 900 mg intravenously (IV) every 14 ± 2 days for 52 weeks 
Treatment R:  eculizumab at a dose of 900 mg IV every 14 ± 2 days for 52 weeks 
 
Period 2: (week 53 to week 79) 
Treatment T:  ABP 959 at a dose of 900 mg IV every 14 ± 2 days for 26 weeks 
Treatment R:  eculizumab at a dose of 900 mg IV every 14 ± 2 days for 26 weeks 
Subjects may require dose adjustments for IP based on signs and symptoms of intravascular 
hemolysis, including lactate dehydrogenase (LDH) levels.  Upon investigator’s determination of 
resolution of symptoms, subjects should resume the 900 mg dose within the recommended 
dosing schedule ie, every 14 ± 2 days.  If a subject requires extended dose adjustments of IP 
indicating that the subject is no longer adequately responding to the treatment regimen, the 
subject will be discontinued from study.   
Subjects will remain in the treatment phase until 14 days after the last planned dose of IP in 
Period 2 (ie, at week 79).    
An independent data monitoring committee (DMC) will evaluate the safety data throughout the 
study.  
Approved 
 
 


Product: ABP 959
Clinical Study Protocol: 20150168
Date: 05 March 2020
Page 5 of 71
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STUDY POPULATION AND MAIN CRITERIA FOR INCLUSION/EXCLUSION: 
INCLUSION CRITERIA:
The study will enroll subjects with PNH who are stable on eculizumab treatment. Subjects cannot 
be enrolled or randomized before all inclusion criteria (including test results) are confirmed:
1.
Men and women ≥18 years of age
2.
Historical diagnosis of PNH by documented flow cytometry (eg, type III erythrocyte cells 
≥10%)
3.
Administration of eculizumab for ≥6 months and currently receiving 900 mg of eculizumab 
every 14 ± 2 days
4.
Hemoglobin ≥9.0 g/dL for at least 6 weeks before randomization
5.
Lactate dehydrogenase (LDH) < 1.5 × the upper limit of normal at screening
6.
Platelet count ≥50 × 109/L
7.
Absolute neutrophil count ≥0.5 x 109/L (500/μL)
8.
Subjects must have been vaccinated against Neisseria meningitidis. Subjects must be 
vaccinated or revaccinated according to current national guidelines for vaccination use.
9.
Subjects must sign an institutional review board/independent ethics committee-approved 
informed consent form before participation in any procedures.
EXCLUSION CRITERIA:
If any of the following apply, the subject MUST NOT enter the study:
1.
Known or suspected hereditary complement deficiency
2.
Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, 
symptomatic congestive heart failure [New York Heart Association ≥Class III], serious 
uncontrolled cardiac arrhythmia), peripheral vascular disease, cerebrovascular accident, or 
transient ischemic attack in the previous 6 months
3.
Evidence of acute thrombosis (liver Doppler ultrasound of hepatic and portal veins)
4.
Known to be positive for human immunodeficiency virus
5.
Woman who is pregnant or breastfeeding
6.
Woman of childbearing potential who does not consent to use a highly effective method of 
birth control (eg, true abstinence, sterilization, birth control pills, Depo Provera injections, or 
contraceptive implants) during treatment and for an additional 5 months after the last 
administration of protocol-specified treatment
7.
Man with a partner of childbearing potential who does not consent to use a highly effective 
method of birth control (eg, true abstinence, vasectomy, or a condom in combination with 
hormonal birth control or barrier methods used by the woman) during treatment and for an 
additional 5 months after the last administration of protocol-specified treatment
8.
Subject is currently enrolled in or has not yet completed at least 30 days since ending other 
investigational device or drug study(s), or subject is receiving other investigational agent(s).
9.
Subject has known sensitivity to any constituent of the products to be administered during the 
study, including mammalian cell-derived drug products.
10. History or evidence of clinically significant disorder, condition, or disease that, in the opinion 
of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or 
interfere with the study evaluation, procedures, or completion
11. History of meningococcal infection
12. Presence or suspicion of active bacterial infection, or recurrent bacterial infection
13. History of bone marrow transplantation
14. Red blood cell transfusion required within 12 weeks before randomization
15. Subject experienced ≥2 breakthrough events, (ie, signs and symptoms of intravascular 
hemolysis, that require dose and/or schedule adjustments of eculizumab) in the previous 
12 months before screening.
Approved 
 
 


Product: ABP 959
Clinical Study Protocol: 20150168
Date: 05 March 2020
Page 6 of 71
Confidential
NUMBER OF SUBJECTS: Approximately 40 subjects will be randomized 1:1 to 1 of the 
2 treatment sequences. The sample size of 40 was chosen to provide approximately 87% power 
to demonstrate non-inferiority (NI) at a 1-sided significance level of 0.025 on the primary endpoint 
of week 27 LDH for the parallel comparison, assuming an inter-subject coefficient of variation
(CV) of 130% for ABP 959 and eculizumab, a true geometric mean ratio (GMR) of 1 between 
ABP 959 and eculizumab, an NI margin of 2.873, and a 10% dropout rate. The 2.873 margin is 
considered appropriate to rule out a potential clinically relevant difference, as it essentially 
equates to a mean LDH in the ABP 959 arm of less than 1.5-fold of the mean LDH in the 
eculizumab arm. The sample size of 40 will also provide greater than 95% power to
demonstrate similarity at a 2-sided significance level of 0.05 on the primary endpoint of time-
adjusted area under the effect curve (AUEC) of LDH from week 13 to week 27, from week 39 to 
week 53, and from week 65 to week 79 for the crossover comparison, assuming an intra-
subject CV of 34%, a true GMR of 1 between ABP 959 and eculizumab, a similarity margin of 
(0.77, 1.30), and a 10% dropout rate. Blinded assessments of the inter-subject CV of LDH and 
the intra-subject CV of time-adjusted AUEC of LDH will be performed. If the aggregated intra-
subject CV of AUEC is greater than 44%, additional subjects will be enrolled if feasible. If the 
aggregated inter-subject CV of LDH is greater than 130%, the primary endpoint of parallel 
comparison of LDH at week 27 will be replaced by crossover comparison of LDH at week 53 and 
week 79.
STUDY TREATMENTS:
Test Product, Dose and Mode of Administration:
ABP 959 administered at a dose of 900 mg IV every 14 ± 2 days
Reference Therapy, Dose and Mode of Administration:
Eculizumab administered at a dose of 900 mg IV every 14 ± 2 days
DURATION OF TREATMENT: Study participation consists of a screening period of up to 
4 weeks, followed by Period 1 (treatment every 14 ± 2 days for a total of 52 weeks), followed by 
Period 2 (treatment every 14 ± 2 days for a total of 26 weeks), and an end of study (EOS) visit
2 weeks (± 2 days) after the last dose of IP. The total duration of study treatment is up to 78 
weeks.
STUDY EVALUATIONS:
Primary Endpoint for Parallel Comparison: 

Hemolysis, as measured by LDH at week 27
Primary Endpoint for Crossover Comparison: 

Hemolysis, as measured by the time-adjusted AUEC of LDH from week 13 to week 27, from
week 39 to week 53, and from week 65 to week 79 
Secondary Endpoints:

Total complement (CH50), total hemoglobin, serum-free hemoglobin, haptoglobin, bilirubin, 
degree of hemoglobinuria, and type III erythrocytes at week 27, week 39, week 53, and 
post-crossover week 65 and week 79

Crossover comparison of hemolysis as measured by LDH at week 53 and week 79

Lactate dehydrogenase-time profile

Red blood cell transfusion

Pharmacokinetic area under the curve (AUC) of ABP 959 and eculizumab from week 13 to 
week 15, and trough PK
Safety Endpoints:

Treatment-emergent adverse events

Treatment-emergent serious adverse events

Treatment-emergent events of interest (EOIs)

Incidence of anti-drug antibodies (ADAs)
STATISTICAL METHODS: 
The primary analysis of the primary endpoint of week 27 LDH for the parallel comparison will be 
conducted on the Full Analysis Set (FAS), consisting of all randomized subjects, with treatment 
as randomized in Period 1 regardless of treatment actually received. Sensitivity analyses, such 
as per-protocol, will also be performed. 
Approved 
 
 


Product: ABP 959
Clinical Study Protocol: 20150168
Date: 05 March 2020
Page 7 of 71
Confidential
The clinical similarity of the week 27 LDH between treatments will be assessed by comparing the 
1-sided 97.5% upper confidence interval (CI) limit for the GMR of the LDH at week 27 between 
ABP 959 and eculizumab treatment with an NI margin of 2.873. The point estimate of the mean 
difference in the log-transformed LDH and the corresponding 1-sided 97.5% upper CI limit will be 
estimated from a linear mixed effects model with treatment, stratification factor, week 1 LDH 
value, time (as a continuous variable), and treatment by time interaction term as fixed effects, and 
subject as a random effect. Lactate dehydrogenase values from all assessed time points from 
week 13 to week 27 will be included in the mixed model.  The point estimate and the upper CI
limit for the GMR will then be calculated by transforming back to the original scale.
The primary analysis of the primary endpoint of time-adjusted AUEC of LDH for the crossover 
comparison will be conducted on the Modified Full Analysis Set (mFAS), consisting of all 
randomized subjects who have an LDH-time profile evaluable for the time-adjusted AUEC within
at least one of the following 14-week assessment periods: week 13 to week 27, week 39 to 
week 53, and week 65 to week 79, according to treatment per the randomized sequence 
regardless of treatment actually received. Sensitivity analyses, such as per-protocol, will also be 
performed.
The linear trapezoidal rule will be used to derive the AUEC of LDH from week 13 to week 27,
from week 39 to week 53, and from week 65 to week 79 for each subject.  The time-adjusted 
AUEC will be calculated by dividing the AUEC by the total duration of observed LDH data (in 
weeks) for each individual subject within each 14-week assessment period.  
The clinical similarity of the AUEC between treatments will be assessed by comparing the 2-sided 
90% CI for the GMR of the time-adjusted AUEC of LDH (week 13 to week 27, week 39 to week
53, and week 65 to week 79) between ABP 959 and eculizumab treatment with a similarity 
margin of (0.77, 1.30). The point estimate of the mean difference in the log-transformed time-
adjusted AUEC and the corresponding 2-sided 90% CI will be calculated from a linear mixed 
effects model with treatment, stratification factor, assessment period, and sequence as fixed 
effects, and subject as a random effect. The point estimate and CI for the GMR will then be 
calculated by transforming back to original scale.
The analysis of secondary endpoints (except for PK) will be conducted on the Full Analysis Set
(FAS). Total complement, total hemoglobin, serum-free hemoglobin, haptoglobin, bilirubin, 
degree of hemoglobinuria, and type III erythrocytes (%) at weeks 27, 39, 53, 65, and 79 will be 
summarized descriptively. For the endpoint of RBC transfusions, summary statistics for the 
number of packed red cells transfused per month after week 13 will be presented. A descriptive 
summary of LDH at each time point through the EOS visit will be presented. Individual and mean 
LDH-time profiles through the EOS visit will also be presented graphically.
The secondary endpoint of crossover comparison of LDH at week 53 and week 79 will be 
evaluated descriptively.  The point estimate of the mean difference in the log-transformed LDH 
between treatments and the corresponding 1-sided 97.5% upper CI limit will be calculated from a 
linear mixed effects model with treatment, stratification factor, period, and sequence as fixed 
effects, and subject as a random effect. The point estimate and 1-sided upper 97.5% CI limit for 
the GMR will then be calculated by transforming back to original scale.  
The PK Concentration Analysis Set will be defined as the subset of subjects in the Safety 
Analysis Set who have at least 1 serum concentration of ABP 959 or eculizumab.  Serum ABP 
959 and eculizumab trough concentrations will be summarized descriptively on the PK 
Concentration Analysis Set for the study through the EOS visit by actual treatment (ABP 959 or 
eculizumab) and by visit within each period. 
The PK Parameter Analysis Set will be defined as the subset of subjects in the Safety Analysis 
Set who have an evaluable ABP 959 or eculizumab serum concentration-time profile from week 
13 to week 15.  Pharmacokinetic AUC from week 13 to week 15 will be analyzed on the PK 
Parameter Analysis Set according to the actual treatment received with GMR and 90% CI 
provided descriptively. 
Safety will be assessed for the study through the EOS visit in the Safety Analysis Set, consisting 
of all treated subjects with treatment assignment based on actual treatment received. Safety 
Approved 
 
 


Product: ABP 959
Clinical Study Protocol: 20150168
Date: 05 March 2020
Page 8 of 71
Confidential
endpoints will be summarized descriptively. All reported adverse events will be assigned the 
system organ class and preferred term according to the Medical Dictionary for Regulatory 
Activities and graded by the National Cancer Institute (US) Common Terminology Criteria for 
Adverse Events, version 5.0. The number and percentage of subjects reporting adverse events
(all, serious, and fatal) and EOIs will be tabulated by treatment (ABP 959 vs eculizumab) for the 
study through the EOS visit, for each study period, and for each 14-week assessment period (ie, 
week 13 to week 27, week 39 to week 53, and week 65 to week 79). Vital signs and laboratory 
data will also be summarized similarly by visit and treatment. The number and percentage of 
subjects developing ADAs will be tabulated by visit and treatment (ABP 959 vs eculizumab) for 
Period 1 and by treatment sequence for the study through the EOS visit using the Safety Analysis 
Set. 
Independent safety reviews will be performed by the DMC approximately every 6 months 
throughout the study. Blinded study data will also be monitored on an ongoing basis by the 
clinical study team. 
DATE AND VERSION: 05 March 2020, version 4.0
Approved 
 
 


Product: ABP 959
Clinical Study Protocol: 20150168
Date: 05 March 2020
Page 9 of 71
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3
TABLE OF CONTENTS
1
TITLE PAGE........................................................................................... 1
2
SYNOPSIS ............................................................................................. 4
3
TABLE OF CONTENTS ......................................................................... 9
4
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS................. 12
5
ETHICS................................................................................................. 14
5.1
Ethics Committee.................................................................................. 14
5.2
Ethical Conduct of the Study................................................................. 14
5.3
Subject Information and Consent .......................................................... 14
6
INTRODUCTION .................................................................................. 16
6.1
Disease Review .................................................................................... 16
6.2
Eculizumab ........................................................................................... 16
6.3
Compound Review................................................................................ 16
6.4
Study Rationale..................................................................................... 17
7
STUDY OBJECTIVES .......................................................................... 18
7.1
Primary Study Objective........................................................................ 18
7.2
Secondary Study Objective................................................................... 18
8
INVESTIGATIONAL PLAN................................................................... 19
8.1
Overall Study Design and Plan ............................................................. 19
8.2
Discussion of Study Design................................................................... 20
8.3
Study Duration ...................................................................................... 20
8.3.1
End of Study Definition.......................................................................... 20
8.4
Study Population................................................................................... 21
8.4.1
Inclusion Criteria ................................................................................... 21
8.4.2
Exclusion Criteria.................................................................................. 21
8.4.3
Withdrawal and Replacement of Subjects............................................. 22
8.4.3.1
Criteria for Subject Withdrawal.............................................................. 22
8.4.3.2
Evaluations at Withdrawal..................................................................... 23
8.4.3.3
Replacement of Subjects ...................................................................... 23
8.5
Treatment ............................................................................................. 23
8.5.1
Treatments Administered ...................................................................... 23
8.5.2
Study Treatment Formulation................................................................ 25
8.5.2.1
Study Drug............................................................................................ 25
8.5.2.2
Comparator........................................................................................... 25
8.5.3
Study Treatment Labeling and Packaging............................................. 25
8.5.4
Blinding of Study Medication................................................................. 25
8.5.5
Study Treatment Storage and Accountability ........................................ 26
8.5.5.1
Study Treatment Storage ...................................................................... 26
8.5.5.2
Study Treatment Accountability............................................................. 26
8.5.6
Dose Adjustments and Dose Escalation................................................ 26
8.5.7
Prior and Concomitant Therapy ............................................................ 27
8.5.8
Treatment Compliance.......................................................................... 28
8.5.9
Assignment to Treatment...................................................................... 28
8.5.10
Unblinding Procedures.......................................................................... 28
8.6
Efficacy and Safety Variables................................................................ 29
8.6.1
Efficacy and Safety Measurements Assessed....................................... 29
8.6.1.1
Efficacy Measurements......................................................................... 35
Approved 
 
 


Product: ABP 959
Clinical Study Protocol: 20150168
Date: 05 March 2020
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8.6.1.2
Safety Measurements ........................................................................... 35
9
STUDY EVALUATIONS BY VISIT........................................................ 36
9.1
Screening (28 Days Before Randomization)....................................... 36
9.1.1
Screen Failures..................................................................................... 36
9.2
Treatment Period 1 ............................................................................... 37
9.2.1
Period 1 Visits....................................................................................... 37
9.3
Visit 27 (Week 53)/Crossover................................................................ 38
9.4
Treatment Period 2 ............................................................................... 38
9.4.1
Period 2 Visits....................................................................................... 38
9.4.2
Visit 40 (Week 79)/End of Study ........................................................... 39
10
METHODS OF ASSESSMENT............................................................. 41
10.1
Physical Examination............................................................................ 41
10.2
Vital Signs and Weight.......................................................................... 41
10.3
Medical History ..................................................................................... 41
10.4
Adverse Event Assessments................................................................. 41
10.5
Concomitant Medication Assessments.................................................. 41
10.6
Blood Transfusion Data Collection ........................................................ 42
10.7
Pregnancy Test..................................................................................... 42
10.8
Clinical Laboratory Testing.................................................................... 42
10.9
Blood Samples for Pharmacokinetic Analysis ....................................... 43
10.10
Liver Doppler Ultrasound ...................................................................... 44
11
SAFETY DATA COLLECTION, RECORDING, AND REPORTING...... 45
11.1
Adverse Events..................................................................................... 45
11.1.1
Definition of Adverse Events ................................................................. 45
11.1.2
Reporting Procedures for Adverse Events ............................................ 45
11.2
Serious Adverse Events........................................................................ 46
11.2.1
Definition of Serious Adverse Events .................................................... 46
11.2.2
Reporting Procedures for Serious Adverse Events ............................... 47
11.3
Events of Interest.................................................................................. 49
11.4
Pregnancy Reporting ............................................................................ 49
12
DATA MANAGEMENT AND STATISTICAL ANALYSIS...................... 51
12.1
Data Management ................................................................................ 51
12.2
Sample Size Estimation ........................................................................ 51
12.3
Statistical Analysis Plan ........................................................................ 52
12.4
Randomization...................................................................................... 52
12.5
Analysis Sets ........................................................................................ 52
12.5.1
Full Analysis Set ................................................................................... 52
12.5.2
Modified Full Analysis Set ..................................................................... 52
12.5.3
Per-protocol Analysis Sets .................................................................... 53
12.5.3.1
Per-protocol Analysis Set for the Primary Endpoint of Lactate 
Dehydrogenase at Week 27 for the Parallel Comparison...................... 53
12.5.3.2
Per-protocol Analysis Set for the Primary Endpoint of AUEC for the 
Crossover Comparison ......................................................................... 53
12.5.4
Safety Analysis Set ............................................................................... 53
12.5.4.1
Pharmacokinetic Concentration Analysis Set........................................ 53
12.5.4.2
Pharmacokinetics Parameter Analysis Set............................................ 53
12.6
Statistical Methods................................................................................ 54
12.6.1
Missing Data......................................................................................... 54
12.6.2
Demographic and Baseline Data........................................................... 54
Approved 
 
 


Product: ABP 959
Clinical Study Protocol: 20150168
Date: 05 March 2020
Page 11 of 71
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12.6.3
Subject Disposition ............................................................................... 54
12.6.4
Primary Endpoints................................................................................. 54
12.6.4.1
Parallel Comparison.............................................................................. 54
12.6.4.2
Crossover Comparison ......................................................................... 55
12.6.5
Secondary Endpoints............................................................................ 56
12.6.6
Safety Endpoints................................................................................... 56
12.6.6.1
Adverse Events..................................................................................... 57
12.6.6.2
Immunogenicity..................................................................................... 57
12.6.6.3
Investigational Product Administration .................................................. 57
12.6.6.4
Concomitant Medications...................................................................... 57
12.6.6.5
Clinical Laboratory Tests....................................................................... 58
12.6.6.6
Vital Signs and Physical Examinations.................................................. 58
12.6.7
Interim Analyses ................................................................................... 58
12.6.8
Data Monitoring Committee................................................................... 58
13
MONITORING PROCEDURES (QUALITY ASSURANCE)................... 60
13.1
Routine Monitoring................................................................................ 60
13.2
Inspections and Auditing Procedures.................................................... 60
14
STUDY MANAGEMENT AND MATERIALS......................................... 62
14.1
Electronic Case Report Forms .............................................................. 62
14.2
Data Collection...................................................................................... 62
14.3
Source Documents Maintenance .......................................................... 63
14.4
Record Maintenance............................................................................. 63
14.5
Confidentiality ....................................................................................... 64
15
ADMINISTRATION PROCEDURES..................................................... 65
15.1
Regulatory Approval ............................................................................. 65
15.2
Protocol Amendments........................................................................... 65
15.3
Protocol Adherence and Deviations ...................................................... 66
15.4
Publication Policy.................................................................................. 66
15.5
Clinical Study Report............................................................................. 67
15.6
Contractual and Financial Details.......................................................... 67
15.7
Compensation....................................................................................... 67
15.8
Discontinuation of the Study.................................................................. 67
15.9
Study Center File Management............................................................. 67
16
REFERENCE LIST ............................................................................... 69
17
APPENDICES....................................................................................... 71
17.1
Appendix 1: Elements of Informed Consent .......................................... 71
LIST OF TABLES
Table 1.  Schedule of Assessments and Procedures – Screening to Period 1 
Week 25........................................................................................... 30
Table 2. Schedule of Assessments and Procedures – Period 1 Week 27 to 
Week 53........................................................................................... 32
Table 3. Schedule of Assessments and Procedures – Period 2 Week 53 to End 
of Study Visit (Week 79)................................................................. 33
LIST OF FIGURES
Figure 1.  Study Diagram ...................................................................................... 20
Approved 
 
 


Product: ABP 959
Clinical Study Protocol: 20150168
Date: 05 March 2020
Page 12 of 71
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4
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS
Term
Definition
ADA
anti-drug antibody
ANC
absolute neutrophil count
AUC
area under the curve
AUEC
area under the effect curve
BP
blood pressure
BUN
blood urea nitrogen
CFR
Code of Federal Regulations
CI
confidence interval
CRO
clinical research organization
CSR
clinical study report
CTCAE
Common Terminology Criteria for Adverse Events
CV
coefficient of variation 
DMC
data monitoring committee
eCRF
electronic case report form
EDC
electronic data capture
EMA
European Medicines Agency
EOI
event of interest
EOS
end of study 
EU
European Union
FAS
Full Analysis Set
FDA
Food and Drug Administration
FSH
follicle stimulating hormone
GCP
Good Clinical Practice
GMR
geometric mean ratio 
HRT
hormonal replacement therapy 
ICF
informed consent form
ICH
International Council for Harmonisation
IEC
independent ethics committee
Ig
Immunoglobulin
IP
investigational product
INR
international normalized ratio
IRB
institutional review board
IV
intravenous
IXRS
interactive voice and web response system
LDH
lactate dehydrogenase
Approved 
 
 


Product: ABP 959
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Term
Definition
MedDRA
Medical Dictionary for Regulatory Activities
mFAS
modified full analysis set
NCI
National Cancer Institute
NI
non-inferiority
PD
pharmacodynamic(s)
PIN
Personal Identification Number
PK
pharmacokinetic(s)
PNH
paroxysmal nocturnal hemoglobinuria
PPC
per-protocol (crossover comparison)
PPP
per-protocol (parallel comparison)
RBC
red blood cell
SAP
Statistical Analysis Plan
SOC
system organ class
SUSAR
suspected unexpected serious adverse reaction
US/USA
United States of America
WHO
World Health Organization
WOCBP
woman of childbearing potential
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5
ETHICS
5.1
Ethics Committee
This study will be conducted in compliance with institutional review board 
(IRB)/independent ethics committee (IEC) and International Council for
Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines - including Title 21 
Part 56 of the United States (US) Code of Federal Regulations (CFR) relating to 
IRBs/IECs and GCP as described in the US Food and Drug Administration (FDA) 
CFR (21 CFR § 50, 56, 312) - in accordance with applicable ICH regulations 
regarding clinical safety data management (E2A, E2B[R3]), European Community 
directives 2001/20, 2001/83, 2003/94, and 2005/28 as enacted into local law, and 
with ICH guidelines regarding scientific integrity (E4, E8, E9, and E10).  In addition,
this study will adhere to all local regulatory requirements and requirements for data 
protection.
Before initiating a trial/study, the investigator/institution must have written and dated 
approval/favorable opinion from the IRB/IEC for the study protocol/amendment(s), a 
written informed consent form (ICF), any consent form updates, subject recruitment 
procedures (eg, advertisements), any written information to be provided to subjects,
and a statement from the IRB/IEC that these materials comply with GCP 
requirements.  The IRB/IEC approval must identify the protocol version as well as the 
documents reviewed.
5.2
Ethical Conduct of the Study
This study will be conducted in accordance with the Note for Guidance on GCP 
(ICH Harmonised Tripartite Guideline E6 (R1); FDA CFR (21 CFR § 50, 56, 312)), 
the general principles indicated in the Declaration of Helsinki, and all applicable 
regulatory requirements.
5.3
Subject Information and Consent
The investigator will explain the benefits and risks of participation in the study to each 
subject or the subject’s legally acceptable representative and obtain written informed 
consent. Written informed consent must be obtained prior to the subject entering the 
study and before initiation of any study-related procedure (including administration of 
investigational product [IP]). 
The sponsor will provide a sample ICF, based on the elements of informed consent
in Section 17.1. The final version-dated form must be agreed to by the sponsor and 
the IRB/IEC and will contain all elements in the sample form, in language readily 
understood by the subject. Each subject’s original consent form, personally signed 
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and dated by the subject or by the subject’s legally acceptable representative and by 
the person who conducted the informed consent discussion, will be retained by the 
investigator. The investigator will supply all enrolled subjects with a copy of their signed 
ICF.
The ICF may need to be revised during the study should important new information 
become available that may be relevant to the safety of the subject. In this instance,
approval should always be given by the IRB/IEC, and existing subjects should always 
be informed of the changes and re-consented. This is documented in the same way 
as previously described.
The investigator should, with the consent of the subject, inform the subject’s primary 
physician about participation in the clinical study as needed.
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6
INTRODUCTION
6.1
Disease Review
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening, bone marrow 
disorder characterized by intravascular hemolytic anemia, bone marrow failure, and
thrombo-embolic episodes, and is associated with a significant increase in mortality, 
development of arterial and venous thrombo-embolic episodes, visceral organ 
damage, and rapid deterioration in quality of life (Kelly et al, 2009; Hill et al, 2007; 
Hillmen et al, 2006; Rother et al, 2005). The disease is caused by the expansion of a 
clone of hematopoietic cells lacking glycosylphosphatidylinositol-anchored 
membrane proteins (eg, CD 55 and CD 59), which leads to chronic, complement-
mediated intravascular hemolysis. The clinical symptoms of the chronic complement 
activity and hemolysis include abdominal pain, chest pain, dyspnea, and 
hemoglobinuria, and life-threatening complications include thromboembolism, 
pulmonary hypertension, and impaired renal function (Hill et al, 2007). Laboratory 
evidence of intravascular hemolysis includes high lactate dehydrogenase (LDH) and 
bilirubin, and low or undetectable serum haptoglobin. Lactate dehydrogenase is a 
sensitive biochemical marker of intravascular hemolysis and can be more than 
25 times the normal concentration during periods of severe hemolysis (Rother et 
al, 2005). 
6.2
Eculizumab
Eculizumab, the active ingredient in Soliris® (Alexion Pharmaceuticals), is a 
monoclonal antibody that specifically binds with high affinity to the complement 
protein C5, thereby inhibiting its cleavage to C5a and C5b and preventing the 
generation of the terminal complement complex C5b-9. Eculizumab inhibits terminal 
complement-mediated intravascular hemolysis in patients with PNH, atypical 
hemolytic uremic syndrome, and refractory generalized myasthenia gravis (Soliris®
Summary of Product Characteristics, 2018). 
6.3
Compound Review
ABP 959 is being developed as a biosimilar to Soliris® (eculizumab), for the treatment 
of PNH and other indications.  The active ingredient of ABP 959 is an anti-C5
monoclonal antibody that has the same amino acid sequence as eculizumab and 
equivalent nonclinical pharmacologic function, based on comprehensive bioanalytical 
assays.  ABP 959 has the same pharmaceutical form, dosage strength, route of 
administration, and dosing regimen as US- and European Union (EU)-licensed 
eculizumab.
Refer to the investigator’s brochure for additional information. 
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6.4 
Study Rationale
The similarity of ABP 959 to eculizumab has been shown using bioanalytical 
methods and nonclinical studies (refer to the investigator’s brochure for additional 
information).  As outlined in the guideline on similar biological medicinal products 
containing monoclonal antibodies (EMA/CHMP/BMWP/403543/2010), applicants are 
expected to provide data on similarity of pharmacokinetics/pharmacodynamics
(PK/PD), safety, and efficacy.  
In the US, EU, and much of the world, laws, regulations, and guidances have been or 
are being put in place to increase availability of biological treatments by developing 
and licensing biosimilar products (CHMP/437/04 Rev 1;
EMEA/CHMP/BWP/247713/2012; EMEA/CHMP/BMWP/42832/2005 Rev 1; US FDA 
2012a; US FDA 2012b).  A biosimilar product, generally, is one that is highly similar 
to a licensed biologic reference product notwithstanding minor differences in clinically 
inactive components, and there are no clinically relevant differences between the 
biosimilar and reference product in terms of safety, purity, and potency.  Biosimilarity 
is demonstrated by the totality of the evidence, including quality, nonclinical, and 
clinical evidence.  The quality and nonclinical data for ABP 959 and eculizumab are 
summarized in the investigator’s brochure.  The current study is designed to 
demonstrate that there is no clinically relevant difference between ABP 959 and 
eculizumab in terms of efficacy, PD, PK, safety, and immunogenicity in adult subjects 
with PNH.
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7
STUDY OBJECTIVES
7.1
Primary Study Objective
The primary objective for this study is to evaluate the efficacy of ABP 959 compared 
with that of eculizumab, based on control of intravascular hemolysis.
7.2
Secondary Study Objective
The secondary objective is to assess the safety, PK, and immunogenicity of ABP 959 
compared with that of eculizumab.
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8
INVESTIGATIONAL PLAN
8.1
Overall Study Design and Plan
This is a randomized, double-blind, active-controlled, 2-period crossover study in 
adult subjects with PNH.  
The study will be run in approximately 45 sites globally.
Approximately 40 subjects will be randomized (1:1) to 1 of the 2 treatment 
sequences, either treatment T followed by treatment R (TR) or treatment R followed 
by treatment T (RT). Treatments will be administered over 2 periods.  Period 1 will 
be 52 weeks in duration; Period 2 will start at week 53, with a crossover in treatment, 
and will be 26 weeks in duration.  Randomization will occur within 8 days before the 
first dose of IP administration (defined as day 1) and will be stratified by red blood 
cell (RBC) transfusion received within the last 12 months before randomization (yes 
vs no).
The treatment sequences will be as shown in Figure 1:
Sequence TR: ABP 959 for 52 weeks in Period 1 followed by eculizumab for 
26 weeks in Period 2, each at a dose of 900 mg administered as an intravenous (IV) 
infusion every 14 ± 2 days
Sequence RT: Eculizumab for 52 weeks in Period 1 followed by ABP 959 for 
26 weeks in Period 2, each at a dose of 900 mg administered as an IV infusion every 
14 ± 2 days.
Subjects will remain on the treatment phase until 14 days after the last planned dose 
of IP in Period 2 (ie, at week 79).  
An independent data monitoring committee (DMC) will perform safety reviews
approximately every 6 months throughout the study (Section 12.6.8).  Blinded study 
data will also be monitored on an ongoing basis by the clinical study team. 
The study endpoints will be analyzed as described in Section 12.6.
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Figure 1.  Study Diagram
8.2
Discussion of Study Design
This study is randomized to prevent bias in treatment sequence allocation. The
assessment of the primary endpoint for the parallel comparison of the study will be 
based on LDH at week 27, and the assessment of the primary endpoint for the 
crossover comparison will be based on the time-adjusted area under the effect curve 
(AUEC) of LDH from week 13 to week 27, from week 39 to week 53, and from week 
65 to week 79.  The primary analysis for the parallel comparison of the study will be 
performed when the last subject has completed or has had the chance to complete
the week 53 evaluations. The primary analysis for the crossover comparison of the 
study will be performed when the last subject has completed the week 79
evaluations.
8.3
Study Duration
Study participation consists of a screening period of up to 4 weeks, followed by 
Period 1 (treatment every 14 ± 2 days for a total of 52 weeks), followed by Period 2 
(treatment every 14 ± 2 days for a total of 26 weeks), and an end of study (EOS) 
visit, 2 weeks after the last dose of IP.  The total duration of study treatment is up to 
78 weeks.
The planned duration of the clinical study is approximately 30 months (approximately 
12 months for enrollment and approximately 18 months for treatment), from 
approximately Q1 2019 to Q3 2021. 
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8.3.1
End of Study Definition
The end of the study will be defined as the date the last subject completes the 
week 79 visit or the date of the last subject’s last completed scheduled 
procedure.
8.4
Study Population
8.4.1
Inclusion Criteria
The study will enroll subjects with PNH who are stable on eculizumab treatment.  
Subjects cannot be enrolled or randomized before all inclusion criteria (including test 
results) are confirmed:
1. Men and women ≥18 years of age
2. Historical diagnosis of PNH by documented flow cytometry (eg, type III 
erythrocyte cells of ≥ 10%)
3. Administration of eculizumab for ≥ 6 months and currently receiving 900 mg of
eculizumab every 14 ± 2 days
4. Hemoglobin ≥ 9.0 g/dL for at least 6 weeks before randomization
5. Lactate dehydrogenase < 1.5 × the upper limit of normal at screening
6. Platelet count ≥ 50 × 109/L
7. Absolute neutrophil count (ANC) ≥0.5 x 109/L (500/μL)
8. Subjects must have been vaccinated against Neisseria meningitidis.  Subjects 
must be vaccinated or revaccinated according to current national guidelines for 
vaccination use.
9. Subjects must sign an IRB/IEC-approved ICF before participation in any 
procedures.
8.4.2
Exclusion Criteria
If any of the following apply, the subject MUST NOT enter the study:
1. Known or suspected hereditary complement deficiency
2. Clinically significant cardiovascular disease (including myocardial infarction, 
unstable angina, symptomatic congestive heart failure [New York Heart 
Association ≥Class III], serious uncontrolled cardiac arrhythmia), peripheral 
vascular disease, cerebrovascular accident, or transient ischemic attack in the 
previous 6 months
3. Evidence of acute thrombosis (liver Doppler ultrasound of hepatic and portal 
veins)
4. Known to be positive for human immunodeficiency virus
5. Woman who is pregnant or breastfeeding
6. Woman of childbearing potential (WOCBP) who does not consent to use a highly 
effective method of birth control (eg, true abstinence, sterilization, birth control 
pills, Depo Provera injections, or contraceptive implants) during treatment and for 
an additional 5 months after the last administration of protocol-specified treatment
WOCBP is defined as a woman who is fertile, following menarche, and until 
becoming postmenopausal unless permanently sterile. Permanent sterilization 
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methods include hysterectomy, bilateral salpingectomy, and bilateral 
oophorectomy.
A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. A high follicle stimulating hormone (FSH) level in the 
postmenopausal range may be used to confirm a postmenopausal state in 
women not using hormonal contraception or hormonal replacement therapy
(HRT). However, in the absence of 12 months of amenorrhea, a single FSH 
measurement is insufficient.
Females on HRT and whose menopausal status is in doubt will be required to 
use 1 of the non-hormonal highly effective contraception methods if they wish to 
continue their HRT during the study.  Otherwise, they must discontinue HRT to 
allow confirmation of postmenopausal status before study enrollment.
7. Man with a partner of childbearing potential who does not consent to use a highly 
effective method of birth control (eg, true abstinence, vasectomy, or a condom in 
combination with hormonal birth control or barrier methods used by the woman) 
during treatment and for an additional 5 months after the last administration of 
protocol-specified treatment
8. Subject is currently enrolled in or has not yet completed at least 30 days since 
ending other investigational device or drug study(s), or subject is receiving other 
investigational agent(s).
9. Subject has known sensitivity to any constituent of the products to be 
administered during the study, including mammalian cell-derived drug products.
10. History or evidence of clinically significant disorder, condition, or disease that, in 
the opinion of the investigator or Amgen physician, if consulted, would pose a risk 
to subject safety or interfere with the study evaluation, procedures, or completion
11. History of meningococcal infection
12. Presence or suspicion of active bacterial infection, or recurrent bacterial infection
13. History of bone marrow transplantation
14. Red blood cell transfusion required within 12 weeks before randomization
15. Subject experienced ≥ 2 breakthrough events, (ie, signs and symptoms of 
intravascular hemolysis, that require dose and/or schedule adjustments of 
eculizumab) in the previous 12 months before screening.
8.4.3
Withdrawal and Replacement of Subjects
8.4.3.1
Criteria for Subject Withdrawal
Subjects have the right to withdraw from the study at any time and for any reason 
without prejudice to future medical care by the physician or at the institution.
Subjects (or a legally acceptable representative) can decline to continue receiving IP
and/or other protocol-required procedures at any time during the study.  If this 
occurs, the investigator is to discuss with the subject the appropriate processes for 
discontinuation of treatment with the IP.  Additionally, the subject should be followed 
and complete the EOS visit, 2 weeks (± 2 days) after the last dose of IP and prior to 
starting commercial eculizumab or other PNH treatment.
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Withdrawal of consent for a study means that the subject does not wish to receive 
further protocol-required therapies or procedures, and the subject does not wish to or 
is unable to continue further study participation.  Subject data up to withdrawal of 
consent will be included in the analysis of the study, and, where permitted, publicly 
available data can be included after withdrawal of consent.  The investigator is to 
discuss with the subject appropriate procedures for withdrawal from the study.
Reasons for removal of a subject from the study might include:

Worsening of PNH

Subject request to end IP(s) administration

Safety concern (eg, due to an adverse event, failure to follow contraception
requirements, and/or noncompliance with protocol requirements)

Pregnancy

Withdrawal of consent to participate in study

Meningococcal infection

Decision by sponsor
8.4.3.2
Evaluations at Withdrawal
For any subject who is withdrawn before completing all treatment visits, the 
investigator should do all of the following:

Perform all procedures scheduled for the EOS visit (ie, week 79 visit 
[Section 9.4.2]). These assessments will be performed 2 weeks (± 2 days)
after the last dose of IP (unless the subject withdraws consent to do so).

Complete all appropriate electronic case report form (eCRF) screens, 
providing the date of and explanation for the subject’s 
withdrawal/discontinuation.

If a subject discontinues IP and will not receive commercial eculizumab, or 
another PNH treatment, the subject will be monitored for at least 8 weeks to 
detect serious hemolysis and other reactions as detailed in Section 9.4.2.
8.4.3.3
Replacement of Subjects
Subjects who are withdrawn will not be replaced. 
8.5
Treatment
8.5.1
Treatments Administered
The investigator must ensure that the IP will be used only in accordance with the
protocol.  ABP 959 and eculizumab will be considered the IPs.
Subjects will be randomly assigned to 1 of 2 treatment sequences in a 1:1 ratio.  
Treatments will be administered over 2 periods: Period 1 will be 52 weeks in 
duration; Period 2 will start at week 53 with a crossover in treatment and will be 
26 weeks in duration. Randomization will be stratified by RBC transfusion received
within the last 12 months before randomization (yes vs no).
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Investigational product will be administered after all other procedures have been 
completed for each visit.
Investigational product will be administered according to local practice for 
administration of eculizumab therapy, ie, as an IV infusion over 25 to 45 minutes.  
Investigational product must not be administered as an IV push or bolus.
Subjects should be monitored for 1 hour following the IP infusion.  If an adverse 
event occurs during the administration of IP, the infusion may be slowed or stopped 
at the discretion of the investigator.  If the infusion is slowed, the total infusion time 
may not exceed 2 hours.
As with all protein products, administration of IP may result in infusion reactions, 
including anaphylaxis or other hypersensitivity reactions.  In clinical trials of
eculizumab, no subjects experienced an infusion reaction that required 
discontinuation.  Hypersensitivity reactions should be managed according to 
institutional guidelines.
Subjects should be educated about the signs and symptoms of meningococcal 
infection and strongly advised to seek immediate medical attention if any of these 
signs or symptoms occur.  These signs and symptoms are as follows:

Moderate to severe headache with:
o
nausea or vomiting
o
fever
o
stiff neck or stiff back

Fever of 103°F (39.4°C) or higher

Fever and a rash

Confusion

Severe muscle aches with influenza-like symptoms and eyes sensitive to light
Subjects will be provided with a Patient Safety Card, which they will be instructed to 
carry with them at all times.  This card describes symptoms that, if experienced, 
should prompt the subject to immediately seek medical evaluation.
Subjects will be discontinued from the study and treated per standard of care if they 
develop a meningococcal infection or become pregnant.
Additionally, subjects may experience increased signs and symptoms of PNH, such 
as hemolysis when subjects are revaccinated against Neisseria meningitidis. 
Therefore, subjects should be closely monitored for disease symptoms after 
recommended vaccination.
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Refer to the investigator’s brochure for ABP 959 or the package insert or Summary of 
Product Characteristics for eculizumab to obtain additional information regarding the 
IPs.
8.5.2
Study Treatment Formulation
8.5.2.1
Study Drug
The test product, ABP 959, is a humanized recombinant immunoglobulin (Ig)G2/4 
monoclonal antibody that binds to the human C5 complement protein. ABP 959 has 
the identical amino acid sequence as eculizumab.  Both ABP 959 and eculizumab 
are produced by recombinant DNA technology and are purified by a process that 
includes specific viral inactivation and filtration steps.  ABP 959 is expressed in a 
Chinese hamster ovary cell line system and has a molecular weight of 
148 kilodaltons.
ABP 959 is supplied as a sterile, clear, colorless, preservative-free 10-mg/mL
solution for IV infusion in 30-mL single-use vials.  Each sterile vial contains 30 mL 
deliverable volume of 10 mg/mL ABP 959 formulated in 10 mM acetate, 5% sorbitol, 
0.01% polysorbate 80, at pH 5.2.
8.5.2.2
Comparator
Eculizumab is a genetically engineered chimeric murine/human monoclonal IgG1-
kappa antibody directed against the complement protein C5. Eculizumab has an 
approximate molecular weight of 148 kilodaltons, is produced by murine myeloma
cell culture, and is purified by standard bioprocess technology. 
Eculizumab is supplied as a sterile, clear, colorless, preservative-free liquid 
concentrate for IV administration and is supplied at a concentration of 10 mg/mL in 
30-mL single-use vials. The product is formulated at pH 7, and each vial contains 
300 mg eculizumab, sodium phosphate monobasic (0.46 mg/mL), sodium phosphate 
dibasic (1.78 mg/mL), sodium chloride (8.77 mg/mL), polysorbate 80 (0.22 mg/mL), 
and Water for Injection.
8.5.3
Study Treatment Labeling and Packaging
A manual containing detailed information regarding the labeling, packaging, storage, 
preparation, and administration of each IP is provided separately in the Pharmacy 
Guide.
8.5.4
Blinding of Study Medication
This is a double-blind study.  Since the IP containers are different for ABP 959 and 
eculizumab, IP (ABP 959 or eculizumab) will be prepared by an unblinded 
pharmacist, or designee, into a common IV preparation for administration to the 
subject. Subjects, Amgen, designated PRA, and other clinical site staff will be blinded 
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to the IP allocation for each subject. Select PRA staff (eg, clinical research 
associate), not involved in the monitoring or the daily operations of the study, will be 
unblinded to subject IP allocation in order to perform IP accountability.
At randomization, randomization numbers will be assigned to each subject by the 
interactive voice and web response system (IXRS). ABP 959 and eculizumab will be 
provided for IV infusion in 30-mL single-use vials identified by codes that can only be 
broken in the case of emergency unblinding (Section 8.5.10).
8.5.5
Study Treatment Storage and Accountability
It is forbidden to use IP for purposes other than as defined in this protocol.
8.5.5.1
Study Treatment Storage
ABP 959 and eculizumab vials should be stored in a secure limited-access location, 
protected from direct sunlight at 2°C to 8°C, and according to the storage and 
expiration information (where required) provided on the label that is affixed to the 
package containing the IP.  Do not freeze or shake.
8.5.5.2
Study Treatment Accountability
All supplies of IPs will be accounted for in accordance with GCP.  There will be an 
individual study drug accountability record for each subject, and the pharmacist, or 
designee, should maintain accurate records of the disposition of all IP supplies 
received during the study.  These records should include the amounts and dates 
clinical drug supplies were received and destroyed/returned to Amgen or its 
designee. If errors or damages in the clinical drug supply shipments occur, the 
investigator should contact Amgen or its designee immediately.  The study monitor 
will periodically check the supplies of IP held by the investigator or pharmacist to 
verify accountability of the IP used. Copies of the IP accountability records will be 
provided by each investigator for inclusion in the Trial Master File during and at the 
end of the trial.  
The investigator will administer the medication only to the identified subjects of this 
study, according to the procedures described in this study protocol.  After the end of 
the study, all unused medication and all medication containers should be destroyed 
on site or returned to Amgen or its designee, as appropriate, for destruction. In either 
instance, complete documentation will be returned to the sponsor.
8.5.6
Dose Adjustments and Dose Escalation
Subjects may require dose adjustments for IP based on signs and symptoms of 
intravascular hemolysis, including LDH levels.  Upon investigator’s determination of 
resolution of symptoms, subjects should resume the 900 mg dose within the 
recommended dosing schedule, ie, every 14 ± 2 days.  If a subject requires extended 
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dose adjustments of IP indicating that the subject is no longer adequately responding 
to the treatment regimen, the subject will be discontinued from the study.  
If any scheduled dose of IP is delayed from the scheduled visit date (by more than 
2 days), then the dose will be administered as soon as possible, and subsequent 
doses will be adjusted accordingly to remain every 14 days (± 2 days) from the 
adjusted dose date.
Administration of IP (ABP 959 or eculizumab) will be withheld for any subject who 
experiences a Grade 3 or 4 adverse event per the National Cancer Institute (NCI; 
US) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0,
reported by the investigator as related to IP. Re-exposure to IP may occur only when 
the event resolves to ≤Grade 1 or the subject’s baseline and if the investigator and 
Amgen, or its designee, agree that subject safety will not be compromised.
Subjects are to be discontinued from the study and treated per standard of care if 
they develop a meningococcal infection or become pregnant.
8.5.7
Prior and Concomitant Therapy
Any experimental (biological or non-biological) therapy (within or outside a clinical 
study) is prohibited at any time during the study.
Excessive vitamin C intake, ie, more than 2000 mg a day, and intravenous 
immunoglobulin treatment are prohibited at any time during the study.
Subjects taking erythropoietin and/or immunosuppressants, corticosteroids, low 
molecular weight heparin, iron supplements, and/or folic acid must be on a stable 
dose, and the dose must be expected to remain stable during the treatment periods.
Subjects taking anticoagulants must be at a stable international normalized ratio
(INR) level and are expected to maintain a stable INR level during the treatment
periods.
Any non-experimental, prescribed therapy, including prophylactic antibiotics, that 
is considered necessary for the subject’s welfare may be given at the discretion of 
the investigator.
All subjects who prematurely discontinue treatment with the IP should be offered 
alternative treatment if applicable.  Treatment should be given according to normal 
clinical practice, after EOS assessments have been performed.
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8.5.8
Treatment Compliance
IP will be administered by site staff and recorded in the eCRF and subject records.  
No other measures of compliance are required.  Records of IP used and intervals 
between visits will be kept during the study.  Drug accountability will be noted by the 
study monitor during study center visits and at the completion of the study.  An up-to-
date treatment inventory/dispensing record must be maintained.
8.5.9
Assignment to Treatment
When subjects enter the screening period for the study, the investigator (or designee) 
will contact the IXRS and receive a unique 11-digit subject identification number 
before any study procedures are performed.  This number will be used to identify the 
subject throughout the clinical study and must be used on all study documentation 
related to that subject.  Unique 11-digit subject identification numbers will be 
assigned in sequential order for each site in the format 168XXXXX###, where 
“168XXXXX” refers to the site number, and “###” refers to the sequential subject 
ordering as each subject at a site is entered into the IXRS (eg, 16812345001).  
Signing of the ICF establishes entry into the screening period.
The subject identification number must remain constant throughout the entire clinical 
study; it must not be changed at the time of rescreening, enrollment, or 
randomization. This number will not necessarily be the same as the randomization 
number assigned for the study.
Upon completion of screening and confirmation of eligibility, the investigator (or 
designee) will contact the IXRS to randomize the subject centrally to 1 of the 
2 treatment sequences (Figure 1).  Randomization will occur within 8 days before the 
first dose of IP administration and will be stratified by RBC transfusion received within 
the last 12 months before randomization (yes vs no).
8.5.10
Unblinding Procedures
A subject’s treatment assignment should only be unblinded when knowledge of the 
treatment is essential for the further management of the subject.  Unblinding at the 
study site for any other reason will be considered a protocol deviation.  The 
investigator is strongly encouraged to contact the PRA or Amgen Medical Monitor (or 
designee) before unblinding any subject’s treatment assignment but must do so 
within 1 working day after the event.
The identity of IP assigned to subject numbers or to individual boxes of IP will be 
available for emergency situations through the IXRS. Authorized site staff will be 
provided with a unique Personal Identification Number (PIN) to access the IXRS to 
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obtain unblinding information. This PIN is unique to the individual and must not be 
shared. 
8.6
Efficacy and Safety Variables
8.6.1
Efficacy and Safety Measurements Assessed
Schedules of assessments and procedures are provided in Table 1 and Table 2 for 
Period 1, and Table 3 for Period 2.
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Table 1. Schedule of Assessments and Procedures – Screening to Period 1 Week 25
Screen Baseline
Period 1 Treatment Phase a
(≤ 28 
days)
Visit 1
Week 1
Visit 2
Wk 3
Visit 3
Wk 5
Visit 4
Wk 7
Visit 5
Wk 9
Visit 6
Wk 11
Visit 7
Wk 13
Visit 7a
Wk 14
Visit 8
Wk 15
Visit 9
Wk 17
Visit 10
Wk 19
Visit 11
Wk 21
Visit 12
Wk 23
Visit 13
Wk 25
General Assessments
Informed consent
X
Medical and medication 
history
X
Physical examination
  X b
Vital signs c
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medication
  X d
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse event recording
  X e
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood transfusion data 
collection
X
X
X
X
X
X
X
X
X
X
X
X
X
Treatments
ABP 959/eculizumab dose f
X
X
X
X
X
X
X
X
X
X
X
X
X
Laboratory Assessments
Serum chemistry g, h
X
X i
X
X
X
X
X
X
Hematology g, j
X
X i
X
X
X
X
X
X
Hemolysis-related tests k
X i
X
X
X
Coagulation g,l
X
C-reactive protein p
Xp
(X)p
(X)p
(X)p
(X)p
(X)p
(X)p
(X)p
(X)p
(X)p
(X)p
(X)p
(X)p
(X)p
Hemoglobinuria m
X i
X
X
X
X
X
Total complement (CH50)
X i
X
X
X
X
X
Pregnancy n
X
Liver Doppler ultrasound
X
Pharmacokinetic sampling o
X
X
X
X, X o
Xo
X
X
X
Anti-drug antibodies o
X
X
X
X
X
X
BUN = blood urea nitrogen; IP = investigational product; Wk = week.
a
All visits can be conducted in a ± 2-day window.
b
Physical examination includes height and weight at screening.
c
Vital signs include pulse, respiratory rate, temperature, and blood pressure (BP).  Systolic and diastolic BP will be measured on the same arm (preferentially the left arm) after the 
subject has been in a supine/sitting position for 5 minutes.
d
At the screening assessment, all concomitant medications from 3 months before the planned start of study treatment will be recorded.
e
Only serious adverse events that occur from the time of signed informed consent until day 1 will be reported.
 
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f
ABP 959/eculizumab dose to be administered after all assessments are completed for each visit.  If a dose is delayed from the scheduled visit date (by > 2 days), the dose will be 
administered as soon as possible, and subsequent doses will be adjusted accordingly to remain every 14 ± 2 days from the adjusted dose date.
g
Clinical laboratory and pregnancy tests will be performed at local laboratories for screening.  Clinical laboratory tests will be performed at central laboratories for all visits after 
screening, including additional and repeat laboratory safety testing that may be performed at the discretion of the investigator.
h
Serum chemistry will include sodium, potassium, BUN/urea, creatinine, total protein, albumin, total and direct bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline 
phosphatase, lactate dehydrogenase, non-fasting glucose, and uric acid. Haptoglobin will also be assessed.
I
Serum chemistry, hematology, hemolysis-related tests, hemoglobinuria, and total complement for the baseline visit can be performed up to 3 days prior to the baseline visit (visit 1, 
week 1).
j
Hematology assessment will include complete blood count, which will include hemoglobin, packed cell volume, red blood cell count, white blood cell count, absolute neutrophil count, 
and platelet count.
k
Hemolysis-related laboratory tests will include type III cells (erythrocytes, monocytes, and granulocytes), and serum-free hemoglobin.
l
Coagulation assessment will include prothrombin time and international normalized ratio.
m
Urine samples will be tested for the presence of hemoglobin. Subjects will be requested to collect the first urine void on the morning of each visit.
n
Serum or urine pregnancy tests will be conducted only for women of childbearing potential and will be performed at local laboratories.
o
Pharmacokinetic (PK) and anti-drug antibody (ADA) samples will be shipped to a central laboratory.  Both samples should be taken immediately prior to administration of IP.  Details will 
be provided in a laboratory manual.  Subjects with positive ADA results will be assessed for neutralizing antibodies.  At visit 7 (week 13) a postinfusion- PK serum sample will be
collected immediately after the end of infusion, as indicated by the X.  A PK serum sample will also be collected 7 days (± 2 days) following the visit 7 (week 13) dosing and is noted 
above as visit 7a (week 14).
p
Collection of C-reactive protein will be completed at visit 1 and during each breakthrough event as indicated by the (X).
 
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Table 2. Schedule of Assessments and Procedures – Period 1 Week 27 to Week 53
Period 1 Treatment Phase a
Visit 14
Wk 27
Visit 15
Wk 29
Visit 16
Wk 31
Visit 17
Wk 33
Visit 18
Wk 35
Visit 19
Wk 37
Visit 20
Wk 39
Visit 21
Wk 41
Visit 22
Wk 43
Visit 23
Wk 45
Visit 24
Wk 47
Visit 25
Wk 49
Visit 26
Wk 51
Visit 27
Wk 53
General Assessments
Physical examination
X
X
Vital signs b
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medication
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse event recording
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood transfusion data collection
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Treatments
ABP 959/eculizumab dose c
X
X
X
X
X
X
X
X
X
X
X
X
X
Laboratory Assessments
Serum chemistry d, e 
X
X
X
X
X
X
X
X
X
X
X
Hematology d, f
X
X
X
X
X
X
X
X
X
X
X
Hemolysis-related tests g
X
X
X
C-reactive protein j
(X)j
(X)j
(X)j
(X)j
(X)j
(X)j
(X)j
(X)j
(X)j
(X)j
(X)j
(X)j
(X)j
(X)j
Hemoglobinuria h
X
X
X
X
X
X
Total complement (CH50)
X
X
X
X
X
X
Pharmacokinetic sampling i
X
X
X
X
X
X
Anti-drug antibodies i
X
X
X
X
X
X
BUN = blood urea nitrogen; IP = investigational product; Wk = week.
a
All visits can be conducted in a ± 2-day window.
b
Vital signs include pulse, respiratory rate, temperature, and blood pressure (BP).  Systolic and diastolic BP will be measured on the same arm (preferentially the left arm) after the 
subject has been in a supine/sitting position for 5 minutes.
c
ABP 959/eculizumab dose to be administered after all assessments are completed for each visit.  If any scheduled dose is delayed from the scheduled visit date (by more than 2 days), 
the dose will be administered as soon as possible, and subsequent doses will be adjusted accordingly to remain every 14 ± 2 days from the adjusted dose date.
d
Clinical laboratory tests will be performed at central laboratories, including additional and repeat laboratory safety testing that may be performed at the discretion of the investigator.
e
Serum chemistry will include sodium, potassium, BUN/urea, creatinine, total protein, albumin, total and direct bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline 
phosphatase, lactate dehydrogenase, non-fasting glucose, and uric acid. Haptoglobin will also be assessed.
f
Hematology assessment will include complete blood count, which will include hemoglobin, packed cell volume, red blood cell count, white blood cell count, absolute neutrophil count, 
and platelet count.
g
Hemolysis-related laboratory tests will include type III cells (erythrocytes, monocytes, and granulocytes) and serum-free hemoglobin.
h
Urine samples will be tested for the presence of hemoglobin. Subjects will be requested to collect the first urine void on the morning of each visit.
i
Pharmacokinetic and anti-drug antibody (ADA) samples will be shipped to a central laboratory.  Both samples should be taken immediately prior to administration of IP.  Details will be 
provided in a laboratory manual.  Subjects with positive ADA results will be assessed for neutralizing antibodies.
j
Collection of C-reactive protein is to be completed during each breakthrough event as indicated by the (X).
 
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Table 3. Schedule of Assessments and Procedures – Period 2 Week 53 to End of Study Visit (Week 79)
Period 2 Treatment Phase a
EOSl
Visit 27
Wk 53
Visit 28
Wk 55
Visit 29
Wk 57
Visit 30
Wk 59
Visit 31
Wk 61
Visit 32
Wk 63
Visit 33
Wk 65
Visit 34
Wk 67
Visit 35
Wk 69
Visit 36
Wk 71
Visit 37
Wk 73
Visit 38
Wk 75
Visit 39
Wk 77
Visit 40
Wk 79
General Assessments
Physical examination
X
Vital signs b
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medication
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse event recording
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood transfusion data 
collection
X
X
X
X
X
X
X
X
X
X
X
X
X
Treatments
ABP 959/eculizumab dosec
X
X
X
X
X
X
X
X
X
X
X
X
X
Laboratory Assessments
Serum chemistry d, e 
X
X
X
X
X
X
X
X
X
X
Hematology d, f
X
X
X
X
X
X
X
X
X
X
Hemolysis-related tests g
X
X
X
X
C-reactive protein k
(X)k
(X)k
(X)k
(X)k
(X)k
(X)k
(X)k
(X)k
(X)k
(X)k
(X)k
(X)k
(X)k
Hemoglobinuria h
X
X
X
X
X
X
Pregnancy j
X
Total complement (CH50)
X
X
X
X
X
X
Pharmacokinetic samplingi
X
X
X
X
X
X
Anti-drug antibodies i
X
X
X
X
X
X
BUN = blood urea nitrogen; EOS = end of study; IP = investigational product; Wk = week.
a
All visits can be conducted in a ± 2-days window.
b
Vital signs will include pulse, respiratory rate, temperature, and blood pressure (BP).  Systolic and diastolic BP will be measured on the same arm (preferentially the left arm) after the 
subject has been in a supine/sitting position for 5 minutes.
c
ABP 959/eculizumab dosing to be administered after all assessments are completed for each visit.  If any scheduled dose of IP is delayed from the scheduled visit date (by more than 2 
days), then the dose will be administered as soon as possible, and subsequent doses will be adjusted accordingly to remain every 14 ± 2 days from the adjusted dose date.
d
Clinical laboratory tests will be performed at central laboratories, including additional and repeat laboratory safety testing that may be performed at the discretion of the investigator.
e
Serum chemistry will include sodium, potassium, BUN/urea, creatinine, total protein, albumin, total and direct bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline 
phosphatase, lactate dehydrogenase, non-fasting glucose, and uric acid. Haptoglobin will also be assessed.
f
Hematology assessment will include complete blood count, which will include hemoglobin, packed cell volume, red blood cell count, white blood cell count, absolute neutrophil count, 
and platelet count.
g
Hemolysis-related laboratory tests will include type III cells (erythrocytes, monocytes, and granulocytes) and serum-free hemoglobin.
h
Urine samples will be tested for the presence of hemoglobin. Subjects will be requested to collect the first urine void on the morning of each visit.
i
Pharmacokinetic and anti-drug antibody (ADA) samples will be shipped to a central laboratory.  Both samples should be taken immediately prior to administration of IP.  Details will be 
provided in a laboratory manual.  Subjects with positive ADA results will be assessed for neutralizing antibodies.
 
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j
Serum or urine pregnancy tests will be conducted only for women of childbearing potential and will be performed at local laboratories.
k
Collection of C-reactive protein is to be completed during each breakthrough event as indicated by the (X).
l
If a subject discontinues IP and will not receive commercial eculizumab, or another PNH treatment after EOS, the subject will be monitored for at least 8 weeks to detect serious 
hemolysis and other reactions as detailed in Section 9.4.2.
 
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8.6.1.1
Efficacy Measurements
The primary efficacy endpoint for the parallel comparison is hemolysis as measured by 
LDH at week 27.
The primary efficacy endpoint for the crossover comparison is hemolysis, as measured 
by the time-adjusted AUEC of LDH from week 13 to week 27, from week 39 to week 
53, and from week 65 to week 79.
The secondary efficacy endpoints are:

Total complement, total hemoglobin, serum-free hemoglobin, haptoglobin, 
bilirubin, degree of hemoglobinuria, and type III erythrocytes at week 27, week 
39, week 53, and post-crossover week 65 and week 79

Crossover comparison of hemolysis as measured by LDH at week 53 and 
week 79

Lactate dehydrogenase-time profile

Red blood cell transfusion

Pharmacokinetic area under the curve (AUC) of ABP 959 and eculizumab from 
week 13 to week 15, and trough PK
8.6.1.2
Safety Measurements
Safety endpoints include:

Treatment-emergent adverse events

Treatment-emergent serious adverse events

Treatment-emergent events of interest (EOIs) 

Incidence of anti-drug antibodies (ADAs)
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9
STUDY EVALUATIONS BY VISIT
After the screening visit, there will be 40 additional visits: 26 visits in Period 1 and 
14 visits in Period 2.
9.1
Screening (28 Days Before Randomization)
Unless otherwise stated, screening assessments/procedures will be performed within 
28 days before randomization. Randomization will occur within 8 days before the first 
dose of IP administration and will be stratified by RBC transfusion received within the 
last 12 months before randomization (yes vs no).
Assessments/procedures performed as routine standard of care, prior to the subject 
signing informed consent, and according to the criteria outlined in Section 10, can be 
used for screening purposes as long as the assessments/procedures were performed 
within 28 days before randomization.
The following screening assessments/procedures will be performed:

Informed consent

Medical history (including history of PNH) and medication history
•
All concomitant medications from 3 months before the planned start of 
study treatment will be recorded.  

Physical examination, including evaluation of body systems, height, and weight

Vital signs (systolic and diastolic blood pressure [BP], pulse, respiratory rate, 
and temperature)

Concomitant medications

Adverse event recording (only serious adverse events will be reported between 
the signing of the ICF and day 1). 
•
Any adverse events occurring during the screening period will be 
recorded as medical history; any serious adverse events will be recorded 
and reported as outlined in Section 11.2.2.

Clinical laboratory testing, including serum chemistry, hematology, and 
coagulation

Serum or urine pregnancy test for women of childbearing potential

Liver Doppler ultrasound
9.1.1
Screen Failures
If a subject has not met all eligibility criteria at the end of the screening period, the 
subject will be registered as a screen fail. Laboratory assessments used to determine 
subject eligibility may be repeated during the screening period before the subject is 
considered a screen failure.  Screen-failed subjects may be eligible for rescreening up to 
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2 times at the investigator’s discretion (ie, a total of 3 screens including initial screening).  
Rescreen subjects must first be registered as screen failures in IXRS and subsequently 
registered as rescreens. Once the subject is registered as rescreened, a new 28-day
screening window will begin. Subjects will retain the same subject identification number 
assigned at the original screening. If the rescreening period begins more than 30 days 
after the original signing of the ICF, all screening procedures, including informed 
consent, must be repeated.
9.2
Treatment Period 1
9.2.1
Period 1 Visits
The following assessments/procedures will be performed before study treatment is 
administered per the schedule of assessments in Table 1 and Table 2 for Period 1 visits 
(± 2 days for each visit):

Vital signs (systolic and diastolic BP, pulse, respiratory rate, and temperature)

Any changes in concomitant medications since the last assessment

All adverse events, including increases in severity or frequency of pre-existing 
conditions, will be recorded.  Serious adverse events will be reported as outlined 
in Section 11.2.2.

Blood transfusion data collection

Clinical laboratory testing, including serum chemistry and hematology

Hemolysis-related tests 

Collection of C-reactive protein to be completed at visit 1 and during each 
breakthrough event

Total complement CH50

Pretreatment PK samples

At visit 7 (week 13), a post-infusion PK serum sample will be collected 
immediately after the end of infusion.  A PK serum sample will also be collected 
7 days (± 2 days) following the visit 7 (week 13) dosing, noted in Table 1 as
visit 7a (week 14).

Pretreatment ADA samples 
•
Subjects with positive ADA results will be assessed for neutralizing 
antibodies.  

Urine testing for hemoglobinuria

At visit 14 (week 27) study assessments will also include physical examination.
Serum chemistry, hematology, hemoglobinuria, and total complement (CH50) for the 
baseline visit can be performed up to 3 days prior to the baseline visit (visit 1, week 1).
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At each visit, after completion of pretreatment procedures, ABP 959 or eculizumab will 
be administered as an IV infusion in a double-blinded fashion.
9.3
Visit 27 (Week 53)/Crossover
For subjects who do not complete Period 1, the EOS visit will be 2 weeks (± 2 days) 
after the last dose of IP.
At the week 53 visit the following assessments will be performed at the study center:

Physical examination, including evaluation of body systems

Vital signs (systolic and diastolic BP, pulse, respiratory rate, and temperature)

Concomitant medications since the last assessment 

Adverse events, including increases in severity or frequency of pre-existing 
conditions 
•
For subjects who discontinue the study, any serious adverse events
ongoing at the EOS visit will be followed until they resolve or are 
considered chronic or stable.

Blood transfusion data collection

Dosing with ABP 959 or eculizumab

Clinical laboratory testing, including serum chemistry, hematology, 
hemolysis-related tests, and total complement (CH50)

Urine testing for hemoglobinuria

Pretreatment PK samples

Pretreatment ADA samples 
•
Subjects with positive ADA results will be assessed for neutralizing 
antibodies.  
9.4
Treatment Period 2
9.4.1
Period 2 Visits
The following assessments/procedures will be performed prior to administration of study 
treatment per the schedule of assessments in Table 3 for Period 2 visits (± 2 days for 
each visit):

Vital signs (systolic and diastolic BP, pulse, respiratory rate, and temperature)

Concomitant medications since the last assessment 

Adverse events, including increases in severity or frequency of pre-existing 
conditions

Blood transfusion data collection

Clinical laboratory testing, including serum chemistry and hematology

Hemolysis-related tests
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
Single collection of C-reactive protein to be completed during each breakthrough 
event

Total complement (CH50)

Pretreatment PK samples

Pretreatment ADA samples
•
Subjects with positive ADA results will be assessed for neutralizing 
antibodies.  

Urine testing for hemoglobinuria
After completion of pretreatment procedures, ABP 959 or eculizumab will be 
administered as an IV infusion in a double-blinded fashion.
9.4.2
Visit 40 (Week 79)/End of Study
For subjects completing Period 2, the EOS visit will be at week 79.  For subjects who do 
not complete Period 2, the EOS visit will be 2 weeks (± 2 days) after the last dose of IP.
At the week 79 visit or at the time of early discontinuation, the following assessments will 
be performed at the study site:

Physical examination, including evaluation of body systems

Vital signs (systolic and diastolic BP, pulse, respiratory rate, and temperature)

Concomitant medications  

Adverse events, including increases in severity or frequency of pre-existing 
conditions 
•
Any serious adverse events ongoing at week 79 will be followed until 
they resolve or are considered chronic or stable.

Blood transfusion data collection

Clinical laboratory testing, including serum chemistry, hematology, and
hemolysis-related tests

Urine testing for hemoglobinuria

Serum or urine pregnancy test for WOCBP
Samples will also be collected for analyses of:

Total complement (CH50)

Pharmacokinetics

Anti-drug antibodies
If a subject will not receive commercial eculizumab or another PNH treatment after EOS, 
the subject will enter a follow-up period to be monitored for detection of serious
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hemolysis and other reactions 8 weeks after last dose of IP.  Adverse events and 
related treatments (eg, blood transfusion data, concomitant medications, procedures) 
will be recorded in the eCRF during the follow-up period.
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10
METHODS OF ASSESSMENT
10.1
Physical Examination 
Physical examinations will be performed by a physician and will include examination of 
the following: general appearance, head, ears, eyes, nose, throat, neck, skin, 
cardiovascular system, respiratory system, abdominal system, and nervous system.  
Clinically significant findings will be recorded in the eCRF. Clinically significant changes 
from baseline will be reported as adverse events.
10.2
Vital Signs and Weight
Systolic BP and diastolic BP will be measured on the same arm (preferentially on the left 
arm) after the subject has been in a supine or sitting position for 5 minutes.  Pulse may
be recorded simultaneously with BP measurements.  Respiratory rate and temperature 
will also be recorded.
Body weight (kg) will be measured without shoes or jacket.  Height and weight will be 
determined at screening.
During the study, the measurement of vital signs may be repeated at the discretion of 
the investigator for safety reasons.  Clinically significant abnormal findings will be 
reported as adverse events.
10.3
Medical History
The subject’s medical history will be obtained prior to randomization and recorded on the 
eCRF. A detailed history of PNH will be obtained.
10.4
Adverse Event Assessments
The investigator is responsible for ensuring that all adverse events observed by the 
investigator or reported by the subject that occur from the day of randomization through 
the EOS visit or for 8 weeks after the last dose of IP for subjects that will not receive 
commercial eculizumab or another PNH treatment after EOS are reported using the 
applicable eCRF (eg, Medical History or Adverse Event Summary CRF).  All serious 
adverse events should be followed until they resolve or are considered chronic or stable.
10.5
Concomitant Medication Assessments
Information regarding the type, date(s) taken, and dose of concomitant medications and
treatments will be collected.
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10.6
Blood Transfusion Data Collection
Detailed information regarding the date, reason for blood transfusion, type, and amount 
transfused will be collected for each subject.
10.7
Pregnancy Test
Pregnancy will be determined by evaluation of -human chorionic gonadotropin in serum 
or urine via local laboratories. Subjects who are pregnant are excluded from the study.
Any pregnancies occurring on study will be reported as indicated in Section 11.4.
10.8
Clinical Laboratory Testing
Venous blood samples will be taken for clinical laboratory tests at the time points 
indicated in Table 1, Table 2, and Table 3.  Screening assessments will be performed 
locally, and all other clinical laboratory tests will be performed at the central laboratory.
The following parameters will be determined:
Hematology:  Complete blood count (including hemoglobin, packed cell volume, RBC
count, white blood cell count, ANC, and platelet count).
Clinical chemistry:  Sodium, potassium, BUN/urea, creatinine, total protein, albumin, 
total and direct bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline 
phosphatase, LDH, non-fasting glucose, uric acid, and haptoglobin.
Hemolysis-related laboratory tests:  Type III cells (erythrocytes, monocytes, and 
granulocytes) and serum-free hemoglobin.
Coagulation: Prothrombin time and INR.
C-reactive protein: Collection of C-reactive protein is to be completed at Visit 1 and 
during each breakthrough event.
Urine test for hemoglobinuria:  A sample of urine will be tested for hemoglobinuria at 
the time points indicated in Table 1, Table 2, and Table 3.  Subjects will be requested to 
collect the first urine void on the morning of each visit for shipment to the central 
laboratory.
Total complement (CH50) (central laboratory):  Blood samples for total complement 
(CH50) will be collected at the time points indicated in Table 1, Table 2, and Table 3.
and analyzed via the CH50 total complement assay.
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Immunology (central laboratory): Blood samples for ADA assessments will be collected 
at the time points indicated in Table 1, Table 2, and Table 3.
Further details of the procedures to be followed for sample collection, storage, and 
shipment will be documented in a laboratory manual.
Samples testing positive for binding antibodies will also be tested for neutralizing 
antibodies and may be further characterized. Additional blood samples may be obtained 
to rule out ADAs.
Sites will be notified if any subject tests positive for neutralizing antibodies to ABP 959 or 
eculizumab at the final scheduled study visit.  If results are not provided to the sites, no 
neutralizing antibodies have been detected.  Subjects who test positive for neutralizing 
antibodies to ABP 959 or eculizumab at the final scheduled study visit may be asked to 
return for additional follow-up testing. This testing may occur approximately every 
3 months starting from when the site has been notified of the positive result, until:

Neutralizing antibodies are no longer detectable.
OR

The subject has been followed for a period of at least 1 year (± 4 weeks) 
post-administration of ABP 959 or eculizumab.
All follow-up results, both positive and negative, will be communicated to the sites.  More 
frequent testing (eg, every month) or testing for a longer period of time may be 
requested in the event of safety-related concerns. 
Subjects who test positive for binding, non-neutralizing antibodies and have clinical 
sequelae that are considered potentially related to ABP 959 or eculizumab antibody 
response may also be asked to return for additional follow-up testing.
10.9
Blood Samples for Pharmacokinetic Analysis
During treatment, a series of predose serum samples (trough) will be taken according to
the schedules in Table 1, Table 2, and Table 3.  Serum concentrations of ABP 959 and 
eculizumab will be determined by a central PK laboratory. The exact times of blood 
sampling will be recorded.
Subjects will also have a post-infusion PK serum sample collected immediately after the 
end of infusion at visit 7 (week 13) and an additional PK serum sample collected 7 days 
(± 2 days) following the visit 7 (week 13) dosing, noted in Table 1 as visit 7a (week 
14).
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Details of the procedures to be followed for sample collection, storage, and shipment will 
be documented in the laboratory manual.
10.10 Liver Doppler Ultrasound
To assess for evidence of acute thrombosis, liver Doppler ultrasonography will be 
conducted according to the schedule in Table 1.
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11 SAFETY DATA COLLECTION, RECORDING, AND REPORTING
11.1
Adverse Events
11.1.1
Definition of Adverse Events
An adverse event is defined as any untoward medical occurrence in a clinical trial 
subject.  The event does not necessarily have a causal relationship with study treatment.  
The investigator is responsible for ensuring that any adverse events observed by the 
investigator or reported by the subject is recorded in the subject’s medical record as well 
as in the eCRF.
The definition of adverse events includes worsening of a pre-existing medical condition.  
Worsening indicates that the pre-existing medical condition (eg, diabetes, migraine 
headaches, gout) has increased in severity, frequency, and/or duration, and/or has an 
association with a significantly worse outcome.  In the case of worsening of a 
pre-existing condition, the start date of the event is the date when the first signs of 
worsening were observed.  A pre-existing condition that has not worsened during the 
study or involves an intervention, such as elective cosmetic surgery or a medical 
procedure while on study, is not considered an adverse event.
11.1.2
Reporting Procedures for Adverse Events
The investigator is responsible for ensuring that all adverse events observed by the 
investigator or reported by the subject that occur from day 1 through the EOS visit or for 
8 weeks after last dose of IP for subjects that will not receive commercial eculizumab or 
another PNH treatment after EOS are reported using the applicable eCRF Adverse 
Event Summary page. Adverse events observed by the investigator or reported by the 
subject that occur after signing of informed consent but before day 1 will be recorded as 
medical history, unless the adverse event is serious.
The investigator must assign the following adverse event attributes:

Adverse event diagnosis or syndrome(s), if known (if not known, signs or
symptoms)

Dates of onset and resolution

Severity

Assessment of relatedness to IP

Action taken
Adverse events must be graded for severity according to the NCI-CTCAE (US), version 
5.0 (http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm).
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The investigator must assess whether the adverse event is possibly related to IP.  This 
relationship is indicated by a “yes” or “no” response to the question: “Is there a 
reasonable possibility that the event may have been caused by the IP?”
Worsening of PNH should not be reported as an adverse event.  However, any specific 
symptoms or sequelae of the disease progression or recurrence (eg, organ failure, 
respiratory distress) will be considered adverse events and will be captured on the 
eCRF.
The investigator is responsible for reviewing laboratory test results and determining 
whether an abnormal value for any individual study subject represents a clinically 
significant change from the subject’s baseline values.  In general, abnormal laboratory 
findings without clinical significance (based on the investigator’s judgment) are not to be 
recorded as adverse events.  However, laboratory value changes that require treatment 
or adjustment in current therapy are considered adverse events.  Where applicable, 
clinical sequelae (not the laboratory abnormality) are to be recorded as the adverse 
events.
The investigator’s clinical judgment is used to determine whether a subject is to be 
removed from treatment due to an adverse event.  A subject, or subject’s legal guardian, 
can also voluntarily withdraw from treatment due to an adverse event.  If the subject 
withdraws consent, the subject is encouraged to undergo, at a minimum, an EOS
assessment.
11.2
Serious Adverse Events
11.2.1
Definition of Serious Adverse Events
A serious adverse event is defined as an adverse event that meets at least 1 of the 
following serious criteria:

Fatal

Life-threatening (places the subject at immediate risk of death)

Requires inpatient hospitalization or prolongation of existing hospitalization

Results in persistent or significant disability/incapacity

Congenital anomaly/birth defect

Other medically important serious event
An adverse event would meet the criterion of “requires hospitalization” if the event 
necessitated an admission to a health care facility (eg, overnight stay).
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If an investigator considers an event to be clinically important, but it does not meet any 
of the serious criteria, the event could be classified as a serious adverse event under the 
criterion of “other medically important serious event.”  Examples of such events could 
include allergic bronchospasm, convulsions, blood dyscrasias, drug-induced liver injury, 
or events that necessitate an emergency room visit, outpatient surgery, or urgent 
intervention.
11.2.2
Reporting Procedures for Serious Adverse Events
The investigator is responsible for ensuring that all serious adverse events observed by 
the investigator or reported by the subject that occur after signing of the ICF through the 
EOS visit or for 8 weeks after last dose of IP for subjects that will not receive commercial 
eculizumab or another PNH treatment after EOS are recorded in the subject’s medical 
record and are submitted to Amgen.  
The serious adverse event must be submitted to Amgen, or its designee, within 24 hours 
following the investigator’s knowledge of the event via the applicable eCRF.
If the electronic data capture (EDC) system is not functional, the serious adverse event
can be reported by faxing a completed paper Serious Adverse Event Fax Cover Sheet 
and Serious Adverse Event report form or by direct telephone communication with PRA 
Safety Risk Management at the numbers provided below. The event must be updated 
electronically in the EDC by the clinical site once the EDC function resumes.
Contact information to Safety Risk Management/PRA, to the attention of: 
PRA Drug Safety Center
For North America and South America Clinical Sites:
Fax:
+1 888-772-6919 or
+1 434-951-3482
Phone:
+1 800-772-2215 or
+1 434-951-3489
CHOSafety@prahs.com/SAOSafety@prahs.com
For Europe, Asia, and Pacific Region Clinical Sites:
Fax:
+44 179-252-5720
Phone:
+49 621-878-2154
MHGSafety@prahs.com
New information relating to a previously reported serious adverse event must be 
submitted to Amgen, or its designee.  All new information for serious adverse events
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must be sent to Amgen, or its designee, within 24 hours following knowledge of the new 
information.  The investigator may be asked to provide additional follow-up information, 
which may include a discharge summary or extracts from the medical record.  
Information provided about the serious adverse event must be consistent with that 
recorded on the applicable eCRF (eg, Adverse Event Summary eCRF).
Elective hospitalizations are not considered serious adverse events. If a subject is 
permanently withdrawn from protocol-required therapies because of a serious adverse 
event, this information must be submitted to Amgen, or its designee.
To comply with worldwide reporting regulations for serious adverse events, the treatment 
assignment of subjects who develop serious, unexpected, and related adverse events
may be unblinded by Amgen, or its designee, before submission to regulatory 
authorities.  Investigators will receive notification of related serious adverse event reports 
sent to regulatory authorities in accordance with local requirements.
Determination of expectedness for Amgen products will be based on the contents of the 
Investigator’s Brochure/Development Core Safety Information for IP and the regional 
prescribing information for products being studied for an approved use.  Expectedness 
assessments are to be made for all IPs (Amgen and non-Amgen) using the appropriate 
reference safety information per local regulatory reporting requirements.  Suspected 
unexpected serious adverse reactions (SUSARs) reported for subjects receiving a 
non-Amgen IP are to be expedited according to local requirements.
Amgen, or its designee, will report serious adverse events and/or SUSARs as required 
to regulatory authorities, investigators/institutions, and IRBs/IECs in compliance with all 
reporting requirements according to local regulations and GCPs. 
The investigator is to notify the appropriate IRB/IEC of serious adverse events occurring 
at the site and of other adverse event reports received from Amgen, in accordance with 
local procedures and statutes.
After the protocol-required reporting period defined above, the investigator does not 
need to actively monitor subjects for serious adverse events.  However, if the 
investigator becomes aware of a serious adverse event after this protocol-required 
reporting period, the investigator will report the event to Amgen within 24 hours following 
the investigator’s knowledge of the event.  Serious adverse events reported outside of 
the protocol-required reporting period will be captured within the safety database as 
clinical trial cases for the purposes of expedited reporting.
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11.3
Events of Interest
Events of Interest for ABP 959/eculizumab will be defined in the Statistical Analysis Plan 
(SAP) and analyzed from the clinical database.  There are no expedited reporting 
requirements for EOIs (other than those that meet other reporting requirements).
11.4
Pregnancy Reporting
Female Subjects Who Become Pregnant

Investigator will collect pregnancy information on any female subject who 
becomes pregnant while taking protocol-required therapies through end of 
study.

Information will be recorded on the Pregnancy Notification Worksheet.  The 
worksheet must be submitted to Amgen Global Patient Safety within 24 hours of 
learning of a subject’s pregnancy.  (Note: Sites are not required to provide any 
information on the Pregnancy Notification Worksheet that violates the country or 
regions local privacy laws).

After obtaining the female subject’s signed authorization for release of 
pregnancy and infant health information, the investigator will collect pregnancy 
and infant health information and complete the pregnancy questionnaire for any 
female subject who becomes pregnant while taking protocol-required therapies 
through end of study.  This information will be forwarded to Amgen Global 
Patient Safety.  Generally, infant follow-up will be conducted up to 12 months 
after the birth of the child (if applicable).

Any termination of pregnancy will be reported to Amgen Global Patient Safety, 
regardless of fetal status (presence or absence of anomalies) or indication for 
procedure. 

While pregnancy itself is not considered to be an adverse event or serious 
adverse event, any pregnancy complication or report of a congenital anomaly or 
developmental delay, fetal death, or suspected adverse reactions in the neonate 
will be reported as an adverse event or serious adverse event.  Note that an 
elective termination with no information on a fetal congenital malformation or 
maternal complication is generally not considered an adverse event, but still 
must be reported to Amgen as a pregnancy exposure case.

If the outcome of the pregnancy meets a criterion for immediate classification as 
a serious adverse event (eg, female subject experiences a spontaneous 
abortion, stillbirth, or neonatal death or there is a fetal or neonatal congenital 
anomaly) the investigator will report the event as a serious adverse event.

Any serious adverse event occurring as a result of a post-study pregnancy 
which is considered reasonably related to the study treatment by the 
investigator, will be reported to Amgen Global Patient Safety.  While the 
investigator is not obligated to actively seek this information in former study 
subjects, he or she may learn of a serious adverse event through spontaneous 
reporting. 

Any female subject will be discontinued from the study and treated per standard 
of care if they become pregnant.
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Male Subjects With Partners Who Become Pregnant 
In the event a male subject fathers a child during study treatment, the information will be 
recorded on the Pregnancy Notification Worksheet.  The worksheet must be submitted 
to Amgen Global Patient Safety within 24 hours of the site’s awareness of the 
pregnancy.  (Note: Sites are not required to provide any information on the Pregnancy 
Notification Worksheet that violates the country or regions local privacy laws).

The investigator will attempt to obtain a signed authorization for release of 
pregnancy and infant health information directly from the pregnant female 
partner to obtain additional pregnancy information.

After obtaining the female partner’s signed authorization for release of 
pregnancy and infant health information, the investigator will collect pregnancy 
outcome and infant health information on the pregnant partner and her baby and 
complete the pregnancy questionnaires.  This information will be forwarded to 
Amgen Global Patient Safety.

Generally, infant follow-up will be conducted up to 12 months after the birth of 
the child (if applicable). 

Any termination of the pregnancy will be reported to Amgen Global Patient 
Safety regardless of fetal status (presence or absence of anomalies) or 
indication for procedure.
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12
DATA MANAGEMENT AND STATISTICAL ANALYSIS
The data management and statistical analysis of this study will be performed by PRA, an 
external clinical research organization (CRO).
12.1
Data Management
Previous and concomitant medications will be coded using the latest available World 
Health Organization (WHO) Drug Reference Dictionary. Coexistent diseases and 
adverse events will be coded using the latest available Medical Dictionary for Regulatory 
Activities (MedDRA).
When the database has been declared to be complete and accurate, the database will 
be locked.
12.2
Sample Size Estimation
Approximately 40 subjects will be randomized 1:1 to 1 of the 2 treatment sequences (TR 
or RT [Section 8.1]). 
The sample size of 40 was chosen to provide approximately 87% power to demonstrate 
non-inferiority (NI) at a 1-sided significance level of 0.025 on the primary endpoint 
(Section 8.6.1.1) of week 27 LDH for the parallel comparison, assuming an inter-subject 
coefficient of variation (CV) of 130% for ABP 959 and eculizumab, a true geometric 
mean ratio (GMR) of 1 between ABP 959 and eculizumab, an NI margin of 2.873, and a 
10% dropout rate. The 2.873 margin is considered appropriate to rule out a potential 
clinically relevant difference, as it essentially equates to a mean LDH in the ABP 959 
arm of less than 1.5-fold of the mean LDH in the eculizumab arm.
The sample size of 40 will also provide greater than 95% power to demonstrate 
similarity at a 2-sided significance level of 0.05 on the primary endpoint of time-adjusted 
AUEC of LDH from week 13 to week 27, from week 39 to week 53, and from week 
65 to week 79 for the crossover comparison, assuming an intra-subject CV of 34%, a 
true GMR of 1 between ABP 959 and eculizumab, a similarity margin of (0.77, 1.30), and 
a 10% dropout rate.
Blinded assessments of the inter-subject CV of LDH and the intra-subject CV of 
time-adjusted AUEC of LDH will be performed.  If the aggregated intra-subject CV of 
AUEC is greater than 44%, additional subjects will be enrolled if feasible. If the 
aggregated inter-subject CV of LDH is greater than 130%, the primary endpoint of 
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parallel comparison of LDH at week 27 will be replaced by crossover comparison of LDH 
at week 53 and week 79.
12.3
Statistical Analysis Plan
An SAP will be written and finalized prior to unblinding for the primary analysis of the 
week 27 LDH. The SAP will provide a detailed description of the statistical methods and 
expand on the details provided in the protocol. Additional analyses may be added. 
Table, listing, and figure shells will also be included.
12.4
Randomization
Subjects will be randomized 1:1 to receive ABP 959 and eculizumab in 1 of 2 treatment 
sequences in a 2-period crossover design. Randomization will be performed using an 
IXRS.  Randomization will occur within 8 days before the first dose of IP administration
and will be stratified by RBC transfusion received within the last 12 months before 
randomization (yes vs no).  The randomization schedule will be prepared by a 
statistician not otherwise involved in the conduct of the study.
12.5
Analysis Sets
The primary analysis for the parallel comparison of week 27 LDH will be performed using 
the Full Analysis Set (FAS) based on the treatment as randomized in Period 1. The 
primary analysis for the crossover comparison of time-adjusted AUEC of LDH will be 
performed using the Modified Full Analysis Set (mFAS) according to treatment per the 
randomized sequence.  The per-protocol analysis sets will be used for sensitivity 
analyses of the primary efficacy endpoints based on actual treatment received.
Analysis of safety endpoints will be performed using the Safety Analysis Set according to 
the actual treatment received.  The PK Concentration Analysis Set and PK Parameter 
Analysis Set will be used to analyze PK concentration data and parameters, 
respectively, based on the actual treatment received.
12.5.1
Full Analysis Set
The FAS will consist of all randomized subjects, with treatment as randomized in Period 
1 regardless of treatment actually received. 
12.5.2
Modified Full Analysis Set
The mFAS will consist of all randomized subjects who have an LDH-time profile 
evaluable for the time-adjusted AUEC within at least one of the following 14-week 
assessment periods: week 13 to week 27, week 39 to week 53, and week 65 to week
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79, according to treatment per the randomized sequence regardless of treatment 
actually received.
12.5.3
Per-protocol Analysis Sets
12.5.3.1
Per-protocol Analysis Set for the Primary Endpoint of Lactate 
Dehydrogenase at Week 27 for the Parallel Comparison
The per-protocol analysis set for the primary endpoint of LDH at week 27 for the parallel 
comparison (PPP) is a subset of the FAS, which includes subjects who did not 
experience an important protocol deviation between week 13 and week 27 that affects 
their primary efficacy evaluation for the parallel comparison. The protocol deviations that 
affect primary efficacy evaluation will be determined based on a blinded data review 
prior to database snapshot for the primary analysis of week 27 LDH for the parallel 
comparison. Analyses for the PPP analysis set will be based on actual treatment 
received. 
12.5.3.2
Per-protocol Analysis Set for the Primary Endpoint of AUEC for the 
Crossover Comparison  
The per-protocol analysis set for the primary endpoint of time-adjusted AUEC for the 
crossover comparison (PPC) is a subset of the mFAS, which includes subjects who did 
not experience an important protocol deviation during week 13 to week 27, week 39 to 
week 53, and week 65 to week 79 that affects their primary efficacy evaluation for the 
crossover comparison.  The protocol deviations that affect primary efficacy evaluation
will be determined based on a blinded data review prior to database lock for the 
crossover comparison.  Analyses for the PPC analysis set will be based on actual 
treatment received.
12.5.4
Safety Analysis Set
The Safety Analysis Set will consist of all treated subjects with treatment assignment 
based on actual treatment received.
12.5.4.1
Pharmacokinetic Concentration Analysis Set
The Pharmacokinetics Concentration Analysis Set will be defined as the subset of 
subjects in the Safety Analysis Set who have at least 1 serum concentration of ABP 959 
or eculizumab.  
12.5.4.2
Pharmacokinetics Parameter Analysis Set
The Pharmacokinetics Parameter Analysis Set will be defined as a subset of subjects in 
the Safety Analysis Set who have an evaluable ABP 959 or eculizumab serum
concentration time profile from week 13 to week 15.
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12.6
Statistical Methods
Categorical variables will be summarized using the number and percentage of subjects 
falling into each category.  Continuous variables will be summarized using mean, 
standard error or standard deviation, median, minimum, maximum, and number of 
subjects with observations.
12.6.1
Missing Data
Missing LDH values will not be imputed.
12.6.2
Demographic and Baseline Data
The following demographic and baseline characteristics will be summarized for each 
analysis set: age (in years, at time of signing informed consent), race, sex, ethnicity, 
height, and weight.  Disease history and baseline disease characteristics will also be 
summarized.
12.6.3
Subject Disposition
The following information will be summarized for subject disposition and accountability:

Number of subjects randomized will be tabulated by country and site

Subject disposition (including number of subjects who were screened, 
randomized, treated with ABP 959/eculizumab, completed study, and 
discontinued study early with reason for discontinuation)

Summaries of analysis populations with reason for exclusion

Important protocol deviations

Number and percentage of subjects on study at each visit

Randomization list of subjects and their actual versus randomized treatment 
sequence
12.6.4
Primary Endpoints
12.6.4.1
Parallel Comparison
The primary endpoint for the parallel comparison is hemolysis, as measured by LDH at 
week 27.  It will be analyzed when all subjects have completed or have had the chance 
to complete their week 53 visits.
The primary analysis of the primary endpoint of week 27 LDH for the parallel comparison 
will be conducted on the FAS. The analysis will be repeated in the PPP analysis set as 
a sensitivity analysis.  
The clinical similarity of the week 27 LDH between treatments will be assessed by 
comparing the 1-sided 97.5% upper confidence interval (CI) limit for the GMR of the LDH 
at week 27 between ABP 959 and eculizumab treatment with a NI margin of 2.873. The 
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point estimate of the mean difference in the log-transformed LDH and the corresponding
1-sided 97.5% upper CI limit will be estimated from a linear mixed effects model with 
treatment, stratification factor, week 1 LDH value, time (as a continuous variable), and 
treatment by time interaction term as fixed effects, and subject as a random effect.
Lactate dehydrogenase values from all assessed time points from week 13 to week 27 
will be included in the mixed model.  The point estimate and the upper CI limit for the 
GMR will then be calculated by transforming back to the original scale. 
LDH values impacted by confounding events (eg, acute infection, or trauma including 
surgery), unrelated to efficacy of IP that trigger dose adjustment, will be excluded from 
the primary comparison of LDH.  The details will be described in the SAP.
12.6.4.2
Crossover Comparison
The primary endpoint for the crossover comparison is hemolysis, as measured by the 
time-adjusted AUEC of LDH from week 13 to week 27, from week 39 to week 53, and 
from week 65 to week 79.
The primary analysis of the primary endpoint of time-adjusted AUEC of LDH for the 
crossover comparison will be conducted on the mFAS.  The analysis will be repeated in 
the PPC analysis set, as a sensitivity analysis.
The linear trapezoidal rule will be used to derive the AUEC of LDH from week 13 to 
week 27, from week 39 to week 53, and from week 65 to week 79 for each subject.  The 
time-adjusted AUEC will be calculated by dividing the AUEC by the total duration of 
observed LDH data (in weeks) of each individual subject within each 14-week 
assessment period. An LDH-time profile will be considered evaluable for AUEC if it 
contains at least 3 LDH measurements within the 14-week assessment period.  LDH 
values impacted by confounding events (ie, acute infection, or trauma including surgery), 
unrelated to efficacy of IP that trigger dose adjustment, will be excluded from the 
calculation of AUEC.  The details will be described in the SAP.
The clinical similarity of the AUEC between treatments will be assessed by comparing 
the 2-sided 90% CI for the GMR of the time-adjusted AUEC of LDH (week 13 to week
27, week 39 to week 53, and week 65 to week 79) between ABP 959 and eculizumab 
treatment with a similarity margin of (0.77, 1.30).  The point estimate of the mean 
difference in the log-transformed time-adjusted AUEC and the corresponding 2-sided 
90% CI will be calculated from a linear mixed effects model with treatment, stratification 
factor, assessment period, and sequence as fixed effects, and subject as a random 
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effect.  The point estimate and CI for the GMR will then be calculated by transforming 
back to original scale.
12.6.5
Secondary Endpoints
The secondary endpoints of total complement, total hemoglobin, serum-free hemoglobin, 
haptoglobin, bilirubin, degree of hemoglobinuria, and type III erythrocytes (%) at 
week 27, week 39, week 53, week 65, and week 79 will be summarized descriptively by 
randomized treatment (ABP 959 vs eculizumab) using the FAS.
The secondary endpoint of crossover comparison of LDH at week 53 and week 79 will 
be evaluated descriptively. The point estimate of the mean difference in the 
log-transformed LDH between treatments and the corresponding 1-sided 97.5% upper
CI limit will be calculated from a linear mixed effects model with treatment, stratification 
factor, period, and sequence as fixed effects and subject as a random effect. The point 
estimate and 1-sided 97.5% upper CI limit for the GMR will then be calculated by 
transforming back to original scale. LDH values impacted by confounding events (ie,
acute infection, or trauma including surgery), unrelated to efficacy of IP that trigger dose 
adjustment, will be excluded from the crossover comparison of LDH.  The details will be 
described in the SAP.
For the secondary endpoint of RBC transfusions, summary statistics for the number of 
packed red cells transfused per month after week 13 will be presented. A descriptive 
summary of LDH at each time point through the EOS visit will be presented. Individual 
and mean LDH-time profile through the EOS visit will also be presented graphically.
The pharmacokinetic AUC from week 13 to week 15 will be analyzed on the PK 
Parameter Analysis Set according to the actual treatment received with GMR and the 
90% CI provided descriptively. Serum ABP 959 and eculizumab trough concentrations 
will be summarized descriptively on the PK Concentration Analysis Set for the study 
through the EOS visit by actual treatment (ABP 959 or eculizumab) and by visit within 
each period.
12.6.6
Safety Endpoints
The safety endpoints of the study are:

Treatment-emergent adverse events

Treatment-emergent serious adverse events

Treatment-emergent EOIs

Incidence of ADAs
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Safety will be assessed for the study through the EOS visit in the Safety Analysis Set.  
Safety endpoints will be summarized descriptively.  
12.6.6.1
Adverse Events
Only treatment-emergent adverse events will be summarized.  Treatment-emergent 
events are those that begin or increase in severity or frequency at or after the time of 
first treatment up to the EOS visit.  
All reported adverse events will be assigned the system organ class (SOC) and 
preferred term according to the current version of MedDRA and graded by NCI-CTCAE, 
version 5.0.  The number and percentage of subjects reporting adverse events (all, 
serious, and fatal) and EOIs will be tabulated by treatment (ABP 959 vs eculizumab) for 
the study through the EOS visit, for each study period, and for each 14-week 
assessment period (ie, week 13 to week 27, week 39 to week 53, and week 65 to 
week 79).  
All treatment-emergent adverse events will be summarized by treatment arm and 
according to the current version of MedDRA SOC and preferred term.  Summaries will 
be provided for the incidences of all treatment-emergent adverse events by severity.  
Additional summaries will be presented for serious adverse events, adverse events 
leading to discontinuation from the study, and EOIs.  All adverse event data will be listed 
by subject, and a separate listing will include all serious adverse events, including any 
deaths on study.
12.6.6.2
Immunogenicity
The number and percentage of subjects developing ADAs will be tabulated by visit and
treatment (ABP 959 vs eculizumab) for Period 1 and by treatment sequence for the 
study through the EOS visit using the Safety Analysis Set.  
12.6.6.3
Investigational Product Administration
Summary statistics will be provided for the total number of doses and cumulative dose of 
ABP 959 and eculizumab for Period 1, Period 2, and overall for the study.
12.6.6.4
Concomitant Medications
Concomitant medications will be coded by the latest available WHO Drug Reference 
Dictionary and will be summarized using the number and percentage of subjects 
receiving each category of medication for Period 1, Period 2, and overall for the study.
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12.6.6.5
Clinical Laboratory Tests
Laboratory data will be summarized by visit and treatment.
12.6.6.6
Vital Signs and Physical Examinations
Vital signs will be summarized by visit and treatment.
Abnormal findings from physical examinations will be listed by subject and assessed for 
clinical significance and included in the adverse event listings and summaries.
12.6.7
Interim Analyses
Blinded assessments of the inter-subject CV of LDH and the intra-subject CV of 
time-adjusted AUEC of LDH will be performed. 
The first blinded interim check of CV will take place prior to the end of enrollment. If 
the aggregated intra-subject CV of AUEC is greater than 44%, additional subjects will be 
enrolled if feasible. The second blinded interim check of CV will take place when 
approximately all subjects complete their week 27 visit. If the aggregated inter-subject 
CV of LDH at week 27 is greater than 130%, the primary endpoint of parallel 
comparison of LDH at week 27 will be replaced by crossover comparison of LDH at 
week 53 and week 79.
Details of the interim analyses will be provided in the SAP.  
12.6.8
Data Monitoring Committee
A DMC external to Amgen and PRA will be formed with members consisting of 
individuals chosen for their expertise in PNH.  Members of the DMC will include, at a 
minimum, physicians external to Amgen and PRA and appropriate statistical 
representation external to Amgen and PRA.  The primary role of this independent DMC 
will be to monitor safety data. Details regarding the DMC will be provided in the DMC 
Charter.
Independent safety reviews of unblinded safety data will be performed by the DMC 
approximately every 6 months (or as determined by the DMC) throughout the study, as 
outlined in the DMC Charter, and the DMC will communicate any major safety concerns 
and recommendations regarding study modification or termination to Amgen 
management at any time during the conduct of the study. 
Records of all meetings will be archived.  Selected Amgen staff, or its designee, may 
serve as liaisons to the external DMC but will not be voting members and will not be 
unblinded to the results.  
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Blinded study data will also be monitored on an ongoing basis by the clinical study team. 
Approved 
 
 


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13
MONITORING PROCEDURES (QUALITY ASSURANCE)
Amgen has ethical, legal, and scientific obligations to conduct this study in accordance 
with established research principles and ICH GCP guidelines. As such, to fulfill these 
obligations and to maintain a current understanding of study progress, Amgen monitors
(or designees) will visit the investigative sites during study conduct in addition to 
maintaining telephone and written communication. On-site visits, telephone calls, and 
regular inspection of the eCRFs will be conducted to assess subject enrollment, 
compliance with protocol procedures, completeness and accuracy of data entered on the 
eCRFs, verification of eCRF data against original source documents, and occurrence of 
adverse events. The investigator must provide the monitor with full access to all source 
and study documents.
13.1
Routine Monitoring
Monitors assigned by Amgen, or its designee, will conduct regular site visits to the 
investigational facilities for the purpose of monitoring various aspects of the study. The 
investigator must agree to personnel authorized by Amgen, or its designee, having direct 
access to the clinical (or associated) files and clinical study supplies (dispensing and 
storage areas) for all study subjects considered for study entry for the purpose of 
verifying entries made in the eCRF and must assist with their activities, if requested. 
Adequate time and space for monitoring visits should be made available by the 
investigator.
The site must complete the eCRFs in a timely manner and on an ongoing basis to allow 
regular review by the study monitor.
Whenever a subject name is revealed on a document that is to be collected for the 
sponsor, the name must be blacked out permanently by the site personnel, leaving the 
initials visible, and must be annotated with the subject number as identification.
13.2
Inspections and Auditing Procedures
Amgen, or its designee, may conduct audits at the investigative sites including, but not 
limited to, drug supply, presence of required documents, the informed consent process, 
and comparison of eCRFs with source documents. All medical records (progress notes) 
must be available for audit. The investigator agrees to participate with audits conducted 
at a convenient time in a reasonable manner.
Government regulatory authorities may also inspect the investigation site during or after 
the study. The investigator or designee should contact Amgen, or its designee, 
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immediately if this occurs. He/she must cooperate fully with regulatory authorities or 
other audits conducted at a convenient time in a reasonable manner.
The purpose of an audit is to assess whether ethics, regulatory, and quality 
requirements are fulfilled.
Approved 
 
 


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14
STUDY MANAGEMENT AND MATERIALS
14.1
Electronic Case Report Forms
An eCRF will be used to store and transmit subject information. The file structure and 
format for the eCRF will be provided by the sponsor or their representative and should 
be handled in accordance with the instructions provided.
The eCRF must be reviewed and electronically signed and dated by the investigator.
Access to the eCRF will be strictly password protected and limited to personnel directly 
participating in the study. Complete data should be entered into the eCRF by examining 
personnel or the appropriate site staff. The eCRF must be completed as soon as 
possible after any subject evaluation or communication. If data are to be changed due 
to erroneous input or other reason, an electronic audit trail will track these changes. The 
eCRFs and computers that store them must be accessible to study monitors and other 
regulatory auditors.
14.2
Data Collection
During each study visit, a physician participating in the study will maintain progress 
notes in the subject’s medical records to document all significant observations. At a
minimum, these notes will contain:

The date of the visit and the corresponding day or visit in the study schedule 
(eg, screening, day 1, week 2, etc.)

General condition and status remarks by the subject, including any significant 
medical findings; the severity, frequency, duration, and resolution of any 
reported adverse event, and the investigator’s assessment as to whether or not 
the reported adverse event is study drug-related

Changes in concomitant medications or dosages

A general reference to the procedures completed

The signature or initials of all physicians making an entry in the medical record 
(progress notes)
In addition, any contact with the subject via telephone or other means that provides 
significant clinical information will also be documented in the medical record (progress 
notes), as described above. 
Information from the medical records (progress notes) and other source documents will 
be promptly transcribed to the appropriate section of the eCRF.
Changes to information in the medical record (progress notes), eCRF, and other source 
documents will be initialed and dated on the day the change is made by the investigator
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or designee. If the reason for the change is not apparent, a brief explanation for the 
change will be written adjacent to the change.
14.3
Source Documents Maintenance
Source documents contain the results of original observations and activities of a clinical 
investigation. Source documents include, but are not limited to, medical records 
(progress notes), computer printouts, screening logs, and recorded data from automated 
instruments. 
All source documents from this study will be maintained by the investigator and made 
available for inspection by authorized persons. The original signed ICF for each subject
shall be filed with records kept by the investigator and a copy shall be given to the 
subject.
14.4
Record Maintenance
All data derived from the study will remain the property of Amgen Inc.
Records must be retained in accordance with the current ICH Guidelines on GCP. All 
essential study documents including records of subjects, source documents, eCRFs and 
study drug inventory must be kept on file.
Essential documents should be retained until at least 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region, or until at least 2 years have elapsed since the 
formal discontinuation of clinical development of the IPs. However, essential documents 
may be retained for a longer period if required by the applicable regulatory requirements 
or by agreement with the sponsor.
The investigator will not dispose of any records relevant to this study without written 
permission from the sponsor and will give the sponsor the opportunity to collect such 
records. The investigator shall take responsibility for maintaining adequate and accurate 
hard copy source documents of all observations and data generated during this study. 
Such documentation is subject to inspection by the sponsor, its representatives, and 
regulatory authorities.
If an investigator moves, withdraws from an investigation, or retires, the responsibility for 
maintaining the records may be transferred to another person who will accept 
responsibility. Notice of transfer must be given to and agreed to by the sponsor.
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14.5
Confidentiality
All information obtained during the conduct of the study with respect to the subject’s 
state of health will be regarded as confidential. For disclosure of any such information, 
an agreement will be obtained in writing. 
The investigator must ensure that each subject’s anonymity is maintained. On eCRFs 
and other documents submitted to the sponsor or the CRO, subjects must not be 
identified by name. Instead, subjects will only be known by the unique subject number 
allocated to them to ensure confidentiality on all study documentation. Subjects will 
retain this unique number throughout the study. The investigator will keep a separate 
log of these codes.
To comply with government regulatory guidelines and to ensure subject safety, it may be 
necessary for the sponsor and its representative, the CRO personnel, the local research 
review board, or regulatory authorities, such as the US FDA  or the European Medicines 
Agency (EMA), to review subjects’ medical records as they relate to this study. Only the 
subject’s unique number on the eCRFs will identify him/her, but his/her full name may be 
made known to a drug regulatory authority or other authorized government or health 
care officials, if necessary, and to personnel designated by the sponsor.
Documents that are not for submission to the sponsor or the CRO (eg, consent forms) 
will be maintained by the investigator in strict confidence, except to the extent necessary 
to allow monitoring by the sponsor and the CRO, and auditing by regulatory authorities. 
No documents identifying subjects by name will leave the investigative site, and subject
identity will remain confidential in all publications related to the study.
Approved 
 
 


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15
ADMINISTRATION PROCEDURES
15.1
Regulatory Approval
Amgen Inc., or their appointed agents, will be responsible for ensuring that appropriate 
regulatory authority approvals are obtained, according to local country requirements.
No subject may enter the study until this approval has been obtained. A copy of the 
approval (where one is provided as requested, according to local country requirements) 
will be provided to the investigator and to the IRB/IEC.
15.2
Protocol Amendments
In accordance with ICH Topic E6 (R1) Guideline for GCP, the investigator should not 
implement any deviation from or changes to the protocol without agreement by the 
sponsor and documented approval from the IRB/IEC of a protocol amendment, except 
where necessary to eliminate an immediate hazard(s) to study subjects, or when the 
change(s) involves only logistical or administrative aspects of the study (eg, change in 
monitor[s], change of telephone number[s]).
Any change to the protocol must be handled as a protocol amendment. Any potential 
amendment must be approved by the sponsor. A written amendment must be submitted 
to the appropriate regulatory authorities and to the IRB/IEC assuming this responsibility. 
The investigator must await IRB/IEC approval of protocol amendments before 
implementing the changes, except where necessary to eliminate apparent immediate 
hazard to subjects. In these cases, the IRB/IEC must be notified within 5 days of the 
change.
All amendments to the protocol must be approved in writing by both the appropriate 
regulatory authorities and the IRB/IEC, except for administrative amendments, which 
require notification but not written approval. Once approved, the protocol amendment 
will be distributed to all recipients of the original protocol, with instructions to append the 
amendment to the protocol.
If, in the judgment of the local IRB/IEC or the investigator and/or sponsor, the protocol
amendment alters the study design or procedures and/or increases the potential risk to 
the subject, the currently approved written ICF will require modification. The modified 
ICF must also be reviewed and approved by the sponsor, appropriate regulatory 
authorities, and the IRB/IEC. In such cases, repeat informed consent must be obtained 
from subjects enrolled in the study before participation continues.
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15.3
Protocol Adherence and Deviations
The protocol must be read thoroughly, and the instructions must be followed. However, 
exceptions will be made in emergency situations when the protection, safety, and 
well-being of the subject(s) requires immediate intervention based on the judgment of 
the investigator or a responsible, appropriately trained and credentialed professional(s) 
designated by the investigator as a subinvestigator.
In the event of a significant protocol deviation due to an emergency, accident, or error, 
the investigator or designee must contact the Medical Monitor at the earliest possible 
time by telephone. This allows for an early joint decision to be made as to whether or 
not the subject should continue in the study. The investigator, the sponsor, and the 
Medical Monitor will document this decision.
15.4
Publication Policy
Authorship of any publications resulting from this study will be determined on the basis 
of the Uniform Requirement for Manuscripts Submitted to Biomedical Journals 
(International Committee of Medical Journal Editors), which states:

Authorship credit is to be based on (1) substantial contributions to conception 
and design, acquisition of data, or analysis and interpretation of data; (2) drafting 
the article or revising it critically for important intellectual content; (3) final 
approval of the version to be published; 4) agreement to be accountable for all 
aspects of the work in ensuring that questions related to the accuracy or integrity 
of any part of the work are appropriately investigated and resolved. Authors are 
to meet conditions 1, 2, 3, and 4.

When a large, multicenter group has conducted the work, the group is to identify 
the individuals who accept direct responsibility for the manuscript.  These 
individuals are to fully meet the criteria for authorship defined above.

Acquisition of funding, collection of data, or general supervision of the research 
group, alone, does not justify authorship.

All persons designated as authors are to qualify for authorship, and all those 
who qualify are to be listed.

Each author is to have participated sufficiently in the work to take public 
responsibility for appropriate portions of the content.
All publications (eg, manuscripts, abstracts, oral/slide presentations, book chapters) 
based on this study must be submitted to Amgen for review.  The Clinical Trial 
Agreement between the institution, investigator, and Amgen will detail the procedures 
for, and timing of, Amgen’s review of publications.
Approved 
 
 


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15.5
Clinical Study Report
A final clinical study report (CSR) will be prepared according to the ICH guideline on 
Structure and Contents of Clinical Study Reports. A final CSR will be prepared 
regardless of whether the study is completed or prematurely terminated. 
15.6
Contractual and Financial Details
The investigator (and/or, as appropriate, the hospital administrative representative) and 
Amgen, or its designee, will sign a clinical study agreement prior to the start of the study, 
outlining overall Amgen, or its designee, and investigator responsibilities in relation to 
the study. Financial disclosure statements will be completed only as required by local 
regulations.
15.7
Compensation
Any arrangements for compensation to subjects for injuries or illnesses that arise in the 
study are described in the Compensation for Injury section of the ICF that is available as 
a separate document.
15.8
Discontinuation of the Study
This study may be terminated by Amgen at any time. In terminating the study, Amgen, 
the CRO (PRA), and the investigator will ensure that adequate consideration is given to 
the protection of the subjects’ interests.  Amgen will not provide ABP 959 or eculizumab
for subjects after termination of the trial or upon a subject’s discontinuation from the 
study.
Possible reasons for early termination of the study include the following:

New or emerging safety information that negatively affects the benefit/risk 
assessment of the product or trial as a whole

Insufficient patient recruitment

Lack of efficacy

Administrative reasons

Sponsor decision
15.9
Study Center File Management
The investigator is responsible for assuring that the Study Center File is maintained. 
The Study Center File will contain, but will not be limited to, the information listed below:
1. Investigator’s brochure
2. Current, signed version of the protocol and any previous versions of the protocol
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3. Protocol amendments (if applicable)
4. Operations manual (if applicable)
5. Current ICF (blank) and any previous versions of the ICF
6. Curricula vitae of investigator(s) and subinvestigator(s) and photocopy of their 
respective license(s) where required by law; Original US FDA Form 1572 (for all 
studies conducted under US Investigational New Drug [IND] regulations), or 
equivalent, signed by all principal investigators. The names of any subinvestigators 
must appear on this form. Investigators must also complete all regulatory 
documentation as required the ICH GCP and by local or national regulations.
7. Documentation of IRB/IEC approval of the protocol, the ICF, any protocol 
amendments, and any ICF revisions
8. All correspondence between the investigator, IRB/IEC, and the sponsor/CRO relating 
to study conduct
9. Lab certification(s)
10. Monitoring log
11. Study drug invoices
12. Signature list of all staff completing eCRFs
13. Signature list of all staff completing drug accountability summaries
Approved 
 
 


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16
REFERENCE LIST
European Medicines Evaluation Agency (EMEA), Committee for Medicinal Products for 
Human Use (CHMP).  Guideline on similar biological medicinal products. CHMP/437/04  
Rev 1(draft).
European Medicines Evaluation Agency (EMEA), Committee for Medicinal Products for 
Human Use (CHMP).  Guideline on similar biological medicinal products containing 
biotechnology-derived proteins as active substance: quality issues.
EMEA/CHMP/BWP/247713/2012, (Rev1) (draft).
European Medicines Evaluation Agency (EMEA), Committee for Medicinal Products for 
Human Use (CHMP).  Guideline on similar biological medicinal products containing 
monoclonal antibodies: nonclinical and clinical issues. 
EMEA/CHMP/BMWP/403543/2010, (Rev1) (draft).
European Medicines Evaluation Agency (EMEA), Committee for Medicinal Products for 
Human Use (CHMP). Guideline on similar biological medicinal products containing 
biotechnology-derived proteins as active substance:  Non-clinical and clinical issues.
EMEA/CHMP/BMWP/42832/2005, Rev.1.(draft).
Hill A, Richards SJ, Hillmen P. Recent developments in the understanding and 
management of paroxysmal nocturnal haemoglobinuria. Br J Haematol. 2007;137:181-
192. 
Hillmen P, Young NS, Schubert J, et al. The complement inhibitor eculizumab in 
paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2006;355:1233-1243.
Kelly R, Richards S, Hillmen P, Hill A. The pathophysiology of paroxysmal nocturnal 
hemoglobinuria and treatment with eculizumab. Ther Clin Risk Manag. 2009;5:911-921. 
Rother RP, Bell L, Hillmen P, et al. The clinical sequelae of intravascular hemolysis and 
extracellular plasma hemoglobin: a novel mechanism of human disease. JAMA. 
2005;293:1653-1662.
Soliris® (eculizumab) – Summary of Product Characteristics. http://www.ema.europa.eu;
2018.
United States Food and Drug Administration.  Guidance for Industry: Scientific 
considerations in demonstrating biosimilarity to a reference product.  February 2012a, 
US FDA (draft).
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United States Food and Drug Administration.  Guidance for Industry: Quality 
considerations in demonstrating biosimilarity to a reference protein product.  February 
2012b, US FDA (draft).
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17 APPENDICES
17.1
Appendix 1: Elements of Informed Consent
ELEMENTS OF INFORMED CONSENT
Both the informed consent discussion and the written ICF and any other written 
information to be provided to subjects should include explanations of the following:

That the study involves research.

The purpose of the study.

The study treatment(s) and the probability for random assignment to each 
treatment.

The study procedures to be followed, including all invasive procedures.

The subject’s responsibilities.

Those aspects of the study that are experimental.

The reasonably foreseeable risks or inconveniences to the subject and, when 
applicable, to an embryo, fetus, or nursing infant.

The reasonably expected benefits.  When there is no intended clinical benefit to 
the subject, the subject should be made aware of this.

The alternative procedure(s) or course(s) of treatment that may be available to 
the subject and their important potential benefits and risks.

The compensation and/or treatment available to the subject in the event of 
study-related injury.

The anticipated prorated payment, if any, to the subject for participating in the 
study.

The anticipated expenses, if any, to the subject for participating in the study.

That the subject’s participation in the study is voluntary and that the subject may 
refuse to participate or withdraw from the study, at any time, without penalty or 
loss of benefits to which the subject is otherwise entitled.
•
That the monitor(s), the auditor(s), the IRB/IEC, and the regulatory 
authority(ies) will be granted direct access to the subject’s original 
medical records for verification of clinical study procedures and/or data, 
without violating the confidentiality of the subject, to the extent permitted 
by the applicable laws and regulations and that, by signing a written ICF, 
the subject or the subject’s legally acceptable representative is 
authorizing such access.

That records identifying the subject will be kept confidential and, to the extent 
permitted by the applicable laws and/or regulations, will not be made publicly 
available. If the results of the study are published, the subject’s identity will 
remain confidential.

That the subject or the subject’s legally acceptable representative will be 
informed in a timely manner if information becomes available that may be 
relevant to the subject’s willingness to continue participation in the study.

The person(s) to contact for further information regarding the study and the 
rights of study subjects, and who to contact in the event of study-related injury.

The foreseeable circumstances and/or reasons under which the subject’s 
participation in the study may be terminated.

The expected duration of the subject’s participation in the study.

The approximate number of subjects involved in the study.
Approved 
 
 


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Page 1 of 14
Summary of Changes: Version 4.0
A RANDOMIZED, DOUBLE-BLIND, ACTIVE-CONTROLLED PHASE 3 STUDY 
EVALUATING THE EFFICACY AND SAFETY OF ABP 959 COMPARED WITH 
ECULIZUMAB IN ADULT SUBJECTS WITH PAROXYSMAL NOCTURNAL 
HEMOGLOBINURIA (PNH)
Test Drug:
ABP 959
Protocol Number:
20150168
EudraCT number:
2017-001418-27
Study Phase:
3
Date and Version:
05 March 2020; Version 4.0
Key Contacts:
Amgen Inc.:
 
Senior Manager
Global Study Management 
Amgen Inc. 
One Amgen Center Drive 
Thousand Oaks, CA USA 
91320 
Phone:
Email: 
Clinical Research Organization (CRO):
Project Director
PRA Health Sciences
995 
Research 
Park 
Blvd. 
Suite 
300Charlottesville, VA  USA
22911
Phone:
Email: 
This study will be conducted in compliance with the protocol, Good Clinical Practice (GCP) 
as set forth in the International Conference for Harmonisation (ICH) guidelines on GCP (ICH 
E6), and applicable local regulatory requirements.
CONFIDENTIAL
This document is a confidential communication of Amgen Inc. Acceptance of this document constitutes 
agreement by the recipient that no unpublished information contained herein shall be published or disclosed 
without prior written approval, except that this document may be disclosed to the appropriate Institutional 
Review Board(s)/Independent Ethics Committee(s) under the condition that they keep it confidential.
Approved 
 
 


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Page 2 of 14
Rationale:
This amendment is issued to make the following changes:

To update the planned number of sites from 25 to 45.

To update the threshold of the aggregated intra-subject CV from the first blinded
interim analysis from 42% to 44% according to the modified statistical analysis after
adding week 13 to week 27 data.

To update the primary endpoint for crossover comparison to include an additional
assessment period from week 13 to week 27. Appropriate statistical sections were
updated as well.

To add the End of Study definition as last subject, last visit in Section 8.3.1 (End of
Study Definition).

To amend text in Section 8.5.7 (Prior and Concomitant Therapy) to clarify that
concomitant therapy may include prophylactic antibiotics.

To update timing of the first blinded interim check of CV to take place prior to the end
of enrollment rather than when approximately 20 subjects complete their week 27
visit.

To clarify the criteria for discontinuation of the trial in Section 15.8 (Discontinuation of
the Study).

To make minor administrative updates and non-substantive grammatical and
typographic corrections (changes not detailed in this summary).
Approved 
 
 


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Summary of Changes:
Any changes in the synopsis that also appear in the body of the protocol will appear only 
once in this summary of changes document, under the section number.
Section:  Cover Page, page 1
Replace:
Clinical Research Organization (CRO):
Project Manager
PRA Health Sciences
731 Arbor Way, Suite 100
Blue Bell, PA USA
19422
Phone:
Mobile:
Email:  
With:
Clinical Research Organization (CRO):
Project Director
PRA Health Sciences
995 Research Park Blvd. Suite 300Charlottesville, VA  
USA
22911
Phone:
Email:  
Section:  Synopsis, Study Centers, page 4
Section: 8.1 Overall Study Design and Plan, page 19
Replace:  
Approximately 25 sites 
With:
Approximately 45 sites
Approved 
 
 


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Section:  Synopsis, Planned Study Dates, page 4
Section:  8.3 Study Duration, page 20
Replace:  
The planned duration of the clinical study is approximately 27 months (approximately 9 
months for enrollment and approximately 18 months for treatment), from approximately Q1 
2019 to Q2 2021. 
With:
The planned duration of the clinical study is approximately 30 months (approximately 12
months for enrollment and approximately 18 months for treatment), from approximately Q1 
2019 to Q3 2021.
Section:  Synopsis, Number of Subjects, page 6
Section:  12.2 Sample Size Estimation, page 51-52
Replace:
The sample size of 40 was chosen to provide approximately 87% power to demonstrate 
non-inferiority (NI) at a 1-sided significance level of 0.025 on the primary endpoint of week 
27 LDH for the parallel comparison, assuming an inter-subject coefficient of variation (CV) of 
130% for ABP 959 and eculizumab, a true geometric mean ratio (GMR) of 1 between ABP 
959 and eculizumab, a NI margin of 2.873, and a 10% dropout rate.  The 2.873 margin is 
considered appropriate to rule out a potential clinically relevant difference, as it essentially 
equates to a mean LDH in the ABP 959 arm of less than 1.5-fold of the mean LDH in the 
eculizumab arm.  The sample size of 40 will also provide 90% power to demonstrate 
similarity at a 2--sided significance level of 0.05 on the primary endpoint of time-adjusted 
area under the effect curve (AUEC) of LDH for the crossover comparison, assuming an 
intra-subject CV of 34%, a true GMR of 1 between ABP 959 and eculizumab, a similarity 
margin of (0.77, 1.30), and a 10% dropout rate.  Blinded assessments of the inter-subject 
CV of LDH and the intra-subject CV of time-adjusted AUEC of LDH will be performed.  If the 
aggregated intra-subject CV of AUEC is greater than 42%, additional subjects may be 
enrolled. If the aggregated inter-subject CV of LDH is larger than 130%, the primary 
endpoint of parallel comparison of LDH at week 27 will be replaced by crossover 
comparison of LDH at week 53 and week 79.
With: 
The sample size of 40 was chosen to provide approximately 87% power to demonstrate 
non-inferiority (NI) at a 1-sided significance level of 0.025 on the primary endpoint of week 
27 LDH for the parallel comparison, assuming an inter-subject coefficient of variation (CV) of 
130% for ABP 959 and eculizumab, a true geometric mean ratio (GMR) of 1 between ABP 
959 and eculizumab, an NI margin of 2.873, and a 10% dropout rate.  The 2.873 margin is 
considered appropriate to rule out a potential clinically relevant difference, as it essentially 
equates to a mean LDH in the ABP 959 arm of less than 1.5-fold of the mean LDH in the 
eculizumab arm.  The sample size of 40 will also provide greater than 95% power to 
demonstrate similarity at a 2--sided significance level of 0.05 on the primary endpoint of 
time-adjusted area under the effect curve (AUEC) of LDH from week 13 to week 27, from 
week 39 to week 53, and from week 65 to week 79 for the crossover comparison, 
assuming an intra-subject CV of 34%, a true GMR of 1 between ABP 959 and eculizumab, a 
Approved 
 
 


Product:  ABP 959
Protocol Number: 20150168
05 March 2020
Page 5 of 14
similarity margin of (0.77, 1.30), and a 10% dropout rate.  Blinded assessments of the inter-
subject CV of LDH and the intra-subject CV of time-adjusted AUEC of LDH will be 
performed.  If the aggregated intra-subject CV of AUEC is greater than 44%, additional 
subjects will be enrolled if feasible. If the aggregated inter-subject CV of LDH is greater
than 130%, the primary endpoint of parallel comparison of LDH at week 27 will be replaced 
by crossover comparison of LDH at week 53 and week 79.
Section:  Synopsis, Duration of Treatment, page 6
Replace:  
Study participation consists of a screening period of up to 4 weeks, followed by Period 1 
(treatment every 14 ± 2 days for a total of 52 weeks), followed by Period 2 (treatment every 
14 ± 2 days for a total of 26 weeks), and an end of study visit 2 weeks (± 2 days) after the 
last dose of IP.  The total duration of study treatment is up to 78 weeks. 
With:
Study participation consists of a screening period of up to 4 weeks, followed by Period 1 
(treatment every 14 ± 2 days for a total of 52 weeks), followed by Period 2 (treatment every 
14 ± 2 days for a total of 26 weeks), and an end of study (EOS) visit 2 weeks (± 2 days) after 
the last dose of IP.  The total duration of study treatment is up to 78 weeks.
Section:  Synopsis, Study Evaluations, page 6
Replace:
Primary Endpoint for Crossover Comparison: 
•
Hemolysis, as measured by the time-adjusted AUEC of LDH from week 39 to 53 
and from week 65 to 79
With:
Primary Endpoint for Crossover Comparison: 
•
Hemolysis, as measured by the time-adjusted AUEC of LDH from week 13 to 
week 27, from week 39 to week 53, and from week 65 to week 79
Section:  Synopsis, Study Evaluations, page 6
Replace:
Secondary Endpoints: 
•
Pharmacokinetic area under the curve (AUC) of ABP 959 and eculizumab from 
week 13 to 15, and trough PK
With: 
Secondary Endpoints: 
•
Pharmacokinetic area under the curve (AUC) of ABP 959 and eculizumab from 
week 13 to week 15, and trough PK
Approved 
 
 


Product:  ABP 959
Protocol Number: 20150168
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Page 6 of 14
Section:  Synopsis, Statistical Methods, page 7
Replace:  
The primary analysis of the primary endpoint of time-adjusted AUEC of LDH for the 
crossover comparison will be conducted on the Modified Full Analysis Set (mFAS), 
consisting of all randomized subjects who have an LDH-time profile evaluable for the time-
adjusted AUEC within week 39 to 53 and/or within week 65 to 79, according to treatment per 
the randomized sequence regardless of treatment actually received.  
With:
The primary analysis of the primary endpoint of time-adjusted AUEC of LDH for the 
crossover comparison will be conducted on the Modified Full Analysis Set (mFAS), 
consisting of all randomized subjects who have an LDH-time profile evaluable for the time-
adjusted AUEC within at least one of the following 14-week assessment periods: week 
13 to week 27, week 39 to week 53, and week 65 to week 79, according to treatment per 
the randomized sequence regardless of treatment actually received.  
Section:  Synopsis, Statistical Methods, page 7
Section:  12.6.4.2 Crossover Comparison, page 55
Replace:  
The linear trapezoidal rule will be used to derive the AUEC of LDH from week 39 to 53 and 
from week 65 to 79 for each subject.  
With:
The linear trapezoidal rule will be used to derive the AUEC of LDH from week 13 to week 
27, from week 39 to week 53, and from week 65 to week 79 for each subject.  
Section:  Synopsis, Statistical Methods, page 7
Section:  12.6.4.2 Crossover Comparison, page 55-56
Replace:  
The clinical similarity of the AUEC between treatments will be assessed by comparing the 2-
sided 90% CI for the GMR of the time-adjusted AUEC of LDH (within weeks 39 to 53 and 
within weeks 65 to 79) between ABP 959 and eculizumab treatment with a similarity margin 
of (0.77, 1.30). The point estimate of the mean difference in the log-transformed time-
adjusted AUEC and the corresponding 2- sided 90% CI will be calculated from a linear 
mixed effects model with treatment, stratification factor, period, and sequence as fixed 
effects, and subject as a random effect.  
With:
The clinical similarity of the AUEC between treatments will be assessed by comparing the 2-
sided 90% CI for the GMR of the time-adjusted AUEC of LDH (week 13 to week 27, week 
39 to week 53, and week 65 to week 79) between ABP 959 and eculizumab treatment with 
a similarity margin of (0.77, 1.30). The point estimate of the mean difference in the log-
transformed time-adjusted AUEC and the corresponding 2--sided 90% CI will be calculated 
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Product:  ABP 959
Protocol Number: 20150168
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Page 7 of 14
from a linear mixed effects model with treatment, stratification factor, assessment period, 
and sequence as fixed effects, and subject as a random effect.  
Section:  Synopsis, Statistical Methods, page 7
Replace:  
The analysis of secondary endpoints (except for PK) will be conducted on the FAS. Total 
complement, total hemoglobin, serum-free hemoglobin, haptoglobin, bilirubin, degree of 
hemoglobinuria, and type III erythrocytes (%) at weeks 27, 39, 53, 65, and 79 will be 
summarized descriptively. For the endpoint of RBC transfusions, summary statistics for the 
number of packed red cells transfused per month after week 13 will be presented. A 
descriptive summary of LDH at each time point through the end of study (EOS) visit will be 
presented. Individual and mean LDH  time profile through EOS visit will also be presented 
graphically.
With:
The analysis of secondary endpoints (except for PK) will be conducted on the Full Analysis 
Set (FAS). Total complement, total hemoglobin, serum-free hemoglobin, haptoglobin, 
bilirubin, degree of hemoglobinuria, and type III erythrocytes (%) at weeks 27, 39, 53, 65, 
and 79 will be summarized descriptively. For the endpoint of RBC transfusions, summary 
statistics for the number of packed red cells transfused per month after week 13 will be 
presented. A descriptive summary of LDH at each time point through the EOSvisit will be 
presented. Individual and mean LDH  time profiles through the EOS visit will also be 
presented graphically.
Section:  Synopsis, Statistical Methods, page 7
Replace:  
The PK Parameter Analysis Set will be defined as the subset of subjects in the Safety 
Analysis Set who have an evaluable ABP 959 or eculizumab serum concentration time 
profile from weeks 13 to 15.  Pharmacokinetic AUC from week 13 to 15 will be analyzed on 
the PK Parameter Analysis Set according to the actual treatment received with GMR and 
90% CI provided descriptively. 
With:
The PK Parameter Analysis Set will be defined as the subset of subjects in the Safety 
Analysis Set who have an evaluable ABP 959 or eculizumab serum concentration-time 
profile from week13 to week 15.  Pharmacokinetic AUC from week 13 to week 15 will be 
analyzed on the PK Parameter Analysis Set according to the actual treatment received with 
GMR and 90% CI provided descriptively.
Section:  Synopsis, Statistical Methods, page 8
Section: 12.6.6.1 Adverse Events, page 57
Replace:  
The number and percentage of subjects reporting adverse events (all, serious, and fatal) 
and EOIs will be tabulated by treatment (ABP 959 vs eculizumab) for the study through the 
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Product:  ABP 959
Protocol Number: 20150168
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Page 8 of 14
EOS visit, for each study period, and for the final 14 weeks of each period (ie, weeks 39 to 
53 and weeks 65 to 79).  
With:
The number and percentage of subjects reporting adverse events (all, serious, and fatal) 
and EOIs will be tabulated by treatment (ABP 959 vs eculizumab) for the study through the 
EOS visit, for each study period, and for each 14-week assessment period (ie, week 13 to 
week 27, week 39 to week 53, and week 65 to week 79).  
Section:  4 List of Abbreviations and Definition of Terms, page 12-13
Add:
BUN
blood urea nitrogen
PIN
Personal Identification Number
Section:  8.1 Overall Study Design and Plan, page 19
Replace:
Randomization will occur within 8 days before the first dose of IP administration and will be 
stratified by red blood cell (RBC) transfusion received within the last 12 months before 
randomization (yes vs no).
With: 
Randomization will occur within 8 days before the first dose of IP administration (defined as 
day 1) and will be stratified by red blood cell (RBC) transfusion received within the last 12 
months before randomization (yes vs no).
Section:  8.2 Discussion of Study Design and Plan, page 20
Replace:
The assessment of the primary endpoint for the parallel comparison of the study will be 
based on LDH at week 27, and the assessment of the primary endpoint for the crossover 
comparison will be based on time-adjusted AUEC of LDH from week 39 to 53 and from 
week 65 to 79.  
With: 
The assessment of the primary endpoint for the parallel comparison of the study will be 
based on LDH at week 27, and the assessment of the primary endpoint for the crossover 
comparison will be based on the time-adjusted area under the effect curve (AUEC) of LDH 
from week 13 to week 27, from week 39 to week 53, and from week 65 to week 79.  
New section, page 21
Add:
Section: 8.3.1 End of Study Definition 
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Product:  ABP 959
Protocol Number: 20150168
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Page 9 of 14
The end of the study will be defined as the date the last subject completes the week 
79 visit or the date of the last subject’s last completed scheduled procedure.
Section:  8.5.7 Prior and Concomitant Therapy, page 27
Replace:
Any non-experimental, prescribed therapy that is considered necessary for the subject’s 
welfare may be given at the discretion of the investigator.
With:
Any non-experimental, prescribed therapy, including prophylactic antibiotics, that is 
considered necessary for the subject’s welfare may be given at the discretion of the 
investigator.
Section: 8.6.1 Table 1. Schedule of Assessments and Procedures – Screening to Period 1 
Week 25, page 30-31
Add:
To row “Coagulationg” add footnote designation “l”
Replace:
o
Pharmacokinetic (PK) and anti-drug antibody (ADA) samples will be shipped to a central 
laboratory. Both samples should be taken immediately prior to administration of IP.  
Details will be provided in a laboratory manual.  Subjects with positive ADA results will 
be assessed for neutralizing antibodies.  At visit 7 (week 13) a postinfusion  PK serum 
sample will be collected immediately after the end of infusion, as indicated by the X.  A 
PK serum sample will also be collected 7 days (± 2 days) after dosing on visit 7a (week 
14).
With:
o
Pharmacokinetic (PK) and anti-drug antibody (ADA) samples will be shipped to a 
central laboratory.  Both samples should be taken immediately prior to administration of 
IP.  Details will be provided in a laboratory manual.  Subjects with positive ADA results 
will be assessed for neutralizing antibodies.  At visit 7 (week 13) a postinfusion  PK 
serum sample will be collected immediately after the end of infusion, as indicated by the 
X.  A PK serum sample will also be collected 7 days (± 2 days) following the visit 7 
(week 13) dosing and is noted above as visit 7a (week 14).
Section: 8.6.1 Table 3. Schedule of Assessments and Procedures – Period 2 Week 53 to 
End of Study Visit (Week 79), page 33
Add:
To table abbreviations: IP = investigational product;
Replace:
c
ABP 959/eculizumab dosing to be administered after all assessments are completed for 
each visit.  If any scheduled dose of investigational product is delayed from the 
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Protocol Number: 20150168
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scheduled visit date (by more than 2 days), then the dose will be administered as soon 
as possible, and subsequent doses will be adjusted accordingly to remain every 14 ± 2 
days from the adjusted dose date.
i
Pharmacokinetic and anti-drug antibody (ADA) samples will be shipped to a central 
laboratory.  Both samples should be taken immediately prior to administration of 
investigational product.  Details will be provided in a laboratory manual.  Subjects with 
positive ADA results will be assessed for neutralizing antibodies
With:
c
ABP 959/eculizumab dosing to be administered after all assessments are completed for 
each visit.  If any scheduled dose of IP is delayed from the scheduled visit date (by more 
than 2 days), then the dose will be administered as soon as possible, and subsequent 
doses will be adjusted accordingly to remain every 14 ± 2 days from the adjusted dose 
date
i
Pharmacokinetic and anti-drug antibody (ADA) samples will be shipped to a central 
laboratory.  Both samples should be taken immediately prior to administration of IP.  
Details will be provided in a laboratory manual.  Subjects with positive ADA results will 
be assessed for neutralizing antibodies
Section:  8.6.1.1 Efficacy Measurements, page 35
Replace:
The primary efficacy endpoint for the crossover comparison is hemolysis, as measured by 
the time-adjusted area under the effect curve (AUEC) of LDH from week 39 to week 53, and 
from week 65 to week 79. 
With: 
The primary efficacy endpoint for the crossover comparison is hemolysis, as measured by 
the time-adjusted AUEC of LDH from week 13 to week 27, from week 39 to week 53, and 
from week 65 to week 79.
Section:  9.2.1 Period 1 Visits, page 37
Replace:
•
At visit 7 (week 13), a post-infusion PK serum sample will be collected immediately 
after the end of infusion.  A PK serum sample will also be collected 7 days (± 2 days) 
after dosing on visit 7a (week 14)
•
Pretreatment ADAs 
With: 
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Product:  ABP 959
Protocol Number: 20150168
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•
At visit 7 (week 13), a post-infusion PK serum sample will be collected immediately 
after the end of infusion.  A PK serum sample will also be collected 7 days (± 2 days) 
following the visit 7 (week 13) dosing, noted in Table 1 as visit 7a (week 14).
•
Pretreatment ADA samples
Section:  9.3 Visit 27 (Week 53)/Crossover, page 38
Replace:
•
Samples for ADAs 
With: 
•
Pretreatment ADA samples
•
Subjects with positive ADA results will be assessed for neutralizing 
antibodies.  
Section:  9.4.1 Period 2 Visits, page 39
Replace:
•
Pretreatment ADAs 
With: 
•
Pretreatment ADA samples
•
Subjects with positive ADA results will be assessed for neutralizing 
antibodies.  
Section:  9.4.2 Visit 40 (Week 79)/End of Study, page 40
Replace:
AEs and related treatments (eg, blood transfusion data, concomitant medications, 
procedures) will be recorded in the eCRF during the follow-up period.
With: 
Adverse events and related treatments (eg, blood transfusion data, concomitant 
medications, procedures) will be recorded in the eCRF during the follow-up period.
Section:  10.9 Blood Samples for Pharmacokinetic Analysis, page 43
Replace:
Subjects will also have a post-infusion PK serum sample collected immediately after the end 
of infusion at visit 7 (week 13) and an additional PK serum sample collected 7 days (± 2 
days) after dosing on visit 7a (week 14).
With: 
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Product:  ABP 959
Protocol Number: 20150168
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Page 12 of 14
Subjects will also have a post-infusion PK serum sample collected immediately after the end 
of infusion at visit 7 (week 13) and an additional PK serum sample collected 7 days (± 2 
days) following the visit 7 (week 13) dosing, noted in Table 1 as visit 7a (week 14).
Section:  11.2.2 Reporting Procedures for Serious Adverse Events, page 48
Replace:
Elective hospitalizations are not considered SAEs.  
With: 
Elective hospitalizations are not considered serious adverse events.  
Section:  12.5.2 Modified Full Analysis Set, page 52-53
Replace:  
The mFAS will consist of all randomized subjects who have an LDH-time profile evaluable 
for the time-adjusted AUEC within weeks 39 to 53 and/or within weeks 65 to 79, according 
to treatment per the randomized sequence regardless of treatment actually received.  
With:
The mFAS will consist of all randomized subjects who have an LDH-time profile evaluable 
for the time-adjusted AUEC within at least one of the following 14-week assessment 
periods: week 13 to week 27, week 39 to week 53, and week 65 to week 79, according to 
treatment per the randomized sequence regardless of treatment actually received.  
Section:  12.5.3.2 Per-protocol Analysis Set for the Primary Endpoint of AUEC for the 
Crossover Comparison, page 53
Replace:
The per-protocol analysis set for the primary endpoint of time-adjusted AUEC for the 
crossover comparison (PPC) is a subset of the mFAS, subjects who did not experience an 
important protocol deviation during weeks 39 to 53 and weeks 65 to 79 that affects their 
primary efficacy evaluation for the crossover comparison.  
With: 
The per-protocol analysis set for the primary endpoint of time-adjusted AUEC for the 
crossover comparison (PPC) is a subset of the mFAS, which includes subjects who did not 
experience an important protocol deviation during week 13 to week 27, week 39 to week
53, and week 65 to week 79 that affects their primary efficacy evaluation for the crossover 
comparison.  
Section:  12.5.4.2 Pharmacokinetics Parameter Analysis Set, page 53
Replace:
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The Pharmacokinetics Parameter Analysis Set will be defined as a subset of subjects in the 
Safety Analysis Set who have an evaluable ABP 959 or eculizumab serum concentration 
time profile from weeks 13 to 15.
With: 
The Pharmacokinetics Parameter Analysis Set will be defined as a subset of subjects in the 
Safety Analysis Set who have an evaluable ABP 959 or eculizumab serum concentration 
time profile from week 13 to week 15.
Section:  12.6.4.2 Crossover Comparison, page 55
Replace:
The primary endpoint for the crossover comparison is hemolysis, as measured by the time-
adjusted AUEC of LDH from week 39 to week 53, and from week 65 to week 79.
With:
The primary endpoint for the crossover comparison is hemolysis, as measured by the time-
adjusted AUEC of LDH from week 13 to week 27, from week 39 to week 53, and from 
week 65 to week 79.
Section:  12.6.7 Interim Analyses, page 58
Replace:  
The first blinded interim check of CV will take place when approximately 20 subjects 
complete their week 27 visit.  If the aggregated intra-subject CV of AUEC is greater than 
42%, additional subjects will be enrolled if feasible.  The second blinded interim check of CV 
will take place when all subjects complete their week 27 visit.  If the aggregated inter-subject 
CV of LDH at week 27 is larger than 130%, the primary endpoint of parallel comparison of 
LDH at week 27 will be replaced by crossover comparison of LDH at week 53 and week 79.
With:
The first blinded interim check of CV will take place prior to the end of enrollment.  If the 
aggregated intra-subject CV of AUEC is greater than 44%, additional subjects will be 
enrolled if feasible. The second blinded interim check of CV will take place when 
approximately all subjects complete their week 27 visit.  If the aggregated inter-subject CV 
of LDH is greater than 130%, the primary endpoint of parallel comparison of LDH at week 
27 will be replaced by crossover comparison of LDH at week 53 and week 79.
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Product:  ABP 959
Protocol Number: 20150168
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Page 14 of 14
Section: 15.8 Discontinuation of Study, page 67
Replace:
Amgen will not provide ABP 959 or eculizumab for subjects after termination of the trial or 
upon discontinuation of the study.
With:
Amgen will not provide ABP 959 or eculizumab for subjects after termination of the trial or 
upon a subject’s discontinuation from the study.
Possible reasons for early termination of the study include the following:

New or emerging safety information that negatively affects the benefit/risk 
assessment of the product or trial as a whole

Insufficient patient recruitment

Lack of efficacy

Administrative reasons

Sponsor decision
Approved