A Phase 3, Randomized, Multicenter, Open-Label, Controlled Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Phase: PHASE3
Conditions: Paroxysmal Nocturnal Hemoglobinuria
Sponsor: Apellis Pharmaceuticals, Inc.

Apellis Pharmaceuticals, Inc
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PEGCETACOPLAN (APL-2) 
PROTOCOL APL2-308 
A PHASE 3, RANDOMIZED, MULTICENTER, 
OPEN-LABEL, CONTROLLED STUDY TO EVALUATE 
THE EFFICACY AND SAFETY OF PEGCETACOPLAN 
IN PATIENTS WITH PAROXYSMAL NOCTURNAL 
HEMOGLOBINURIA (PNH)
US IND No.: 123087 
EudraCT No.: 2018-004220-11 
Phase: 3  
Version: Amendment 3 
Date: 10 August 2020  
Confidentiality Statement
This document is confidential. It contains proprietary information of Apellis Pharmaceuticals, 
Inc. Any viewing or disclosure of such information that is not authorized in writing by Apellis 
Pharmaceuticals, Inc, is strictly prohibited. Such information may be used solely for the purpose 
of reviewing or performing this study. 

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INVESTIGATOR AGREEMENT 
Long Title:  
A Phase 3, Randomized, Multicenter, Open-Label, 
Controlled Study to Evaluate the Efficacy and 
Safety of Pegcetacoplan in Patients with 
Paroxysmal Nocturnal Hemoglobinuria (PNH) 
Short Title:  
PRINCE 
Protocol Number, Version, and Date: 
10 August 2020  
Study Phase: 
Phase 3  
Sponsor Name and Address:  
Apellis Pharmaceuticals, Inc 
 
100 5th Ave 
Waltham, MA 02451 
USA  
Investigational Test Article:  
Pegcetacoplan (APL- 2)
US IND Number: 
123087  
EudraCT Number: 
2018-004220-11  
Indication Studied: 
PNH  
Investigator Agreement: 
I have read the clinical study described herein, 
recognize its confidentiality, and agree to conduct 
the described trial in compliance with Good Clinical 
Practice (GCP), the ethical principles contained 
within the Declaration of Helsinki, this protocol, 
and all applicable regulatory requirements.  
 
 
Principal Investigator:  
 
Name: ____________________________________ 
 
 
Signature: _________________________________  
 
 
Date: ______/______/______ (DD/MMM/YYYY) 

PPD
PPD
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PROTOCOL AMENDMENT SUMMARY OF CHANGES
Amendment 3: Summary of Changes From the Previous Version
Amendment date: 10 August 2020 
Updates to the protocol implemented in this amendment are provided in the table below. 
Description of change 
Section(s) affected by 
change 
Nonsubstantial editorial and technical changes that did not impact content 
of the document have been made for grammar, clarity, and document 
usability. 
Entire document 
Removed language regarding an altitude correction factor for hemoglobin
because no subjects enrolled in the study live at altitudes 1000 meters 
above sea level. 
Synopsis, Section 4, Figure 2, 
Section 8, Section 9.1, 
Section 9.3, Section 10.2.3.3, 
Section 10.7, Section 11.1.1, 
formerly Appendix 5 
Added a section regarding the collection of COVID-19 test results. 
Section 12.8 
Updated the definition of an adverse event to be consistent with the new 
Apellis standard language. 
Section 13.1 
Updated the information regarding the recording of adverse events to be 
consistent with the new Apellis standard language. 
Section 13.2 
Removed Section 13.3 (Treatment and Follow-up of Adverse Events) 
because this information is now included in other updated sections. 
formerly Section 13.3 
Updated the information regarding the reporting of adverse events to be 
consistent with the new Apellis standard language and updated the section 
number from Section 13.4 to Section 13.3 given the removal of the 
original Section 13.3. 
Section 13.3 
Updated the information regarding serious adverse events to be consistent 
with the new Apellis standard language and updated the section number 
from Section 13.5 to Section 13.4. 
Section 13.4 
Removed Section 13.6 (Unexpected Adverse Events or Unexpected 
Suspected Adverse Reactions) because this information is now included in 
other updated sections. 
formerly Section 13.6 
Updated the information regarding pregnancy to be consistent with the 
new Apellis standard language and updated the section number from 
Section 13.7 to Section 13.5 
Section 13.5 
Added a new section, Section 13.6, regarding drug abuse, misuse, 
overdose, and medication error. 
Section 13.6 
Removed the reference related to the altitude correction factor. 
Section 16 

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Updated Appendix 4 (Amendment History) with the Amendment 2 
summary of changes. 
Appendix 4 
Removed Appendix 5 because it contained the altitude correction factor 
information that has been removed from the protocol. 
formerly Appendix 5 
The previously-labeled Appendix 6 (COVID-19 Changes) is now labeled 
Appendix 5 due to the removal of the previous Appendix 5. 
Appendix 5

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1.
TABLE OF CONTENTS 
INVESTIGATOR AGREEMENT...................................................................................................2
SPONSOR INFORMATION...........................................................................................................3
PROTOCOL AMENDMENT SUMMARY OF CHANGES ..........................................................4
1.
TABLE OF CONTENTS .............................................................................................6
LIST OF TABLES .........................................................................................................................11
LIST OF FIGURES .......................................................................................................................11
2.
SYNOPSIS .................................................................................................................12
3.
ABBREVIATIONS ....................................................................................................20
4.
SCHEDULE OF EVENTS .........................................................................................23
5.
INTRODUCTION ......................................................................................................29
5.1. 
Paroxysmal Nocturnal Hemoglobinuria .....................................................................29
5.2. 
Pegcetacoplan .............................................................................................................29
5.2.1.
Rationale for Treatment with Pegcetacoplan ......................................................30
5.2.2.
Summary of Clinical Experience .........................................................................30
6.
RATIONALE .............................................................................................................32
6.1. 
Purpose of the Study ...................................................................................................32
6.2. 
Dose Selection ............................................................................................................32
6.2.1.
Target Level of Pegcetacoplan Serum Concentration .........................................32
6.2.2.
Dosing Adjustment Option ..................................................................................33
6.3. 
Risk/Benefit ................................................................................................................33
7.
STUDY OBJECTIVES AND ENDPOINTS ..............................................................36
7.1. 
Primary Objective .......................................................................................................36
7.2. 
Secondary Objectives .................................................................................................36
7.3. 
Exploratory Objectives ...............................................................................................37
8.
STUDY DESIGN .......................................................................................................38
9.
SUBJECT SELECTION .............................................................................................41
9.1. 
Inclusion Criteria ........................................................................................................41
9.1.1.
Approved Methods of Contraception ..................................................................41
9.2. 
Exclusion Criteria .......................................................................................................42
9.3. 
Randomization Criteria ...............................................................................................43
10.
STUDY TREATMENTS ............................................................................................44

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10.1. 
Identity of Investigational Product .............................................................................44
10.1.1.
Blinding the Treatment Assignment ...............................................................44
10.2. 
Administration of Investigational Product ..................................................................44
10.2.1.
Interactive Response Technology (IRT) for Investigational Product 
Management ...................................................................................................44
10.2.2.
Allocation to Treatment ..................................................................................44
10.2.3.
Pegcetacoplan Dosing .....................................................................................44
10.2.3.1. Pegcetacoplan Administration ......................................................................45
10.2.3.2. Pegcetacoplan Dose Adjustments ................................................................45
10.2.3.3. Pegcetacoplan Escape Therapy ....................................................................46
10.3. 
Labeling, Packaging, Storage, and Handling ..............................................................46
10.3.1.
Labeling ..........................................................................................................46
10.3.2.
Packaging ........................................................................................................47
10.3.3.
Infusion Supplies ............................................................................................47
10.3.4.
Storage ............................................................................................................47
10.4. 
Investigational Product Accountability ......................................................................47
10.5. 
Subject Compliance ....................................................................................................47
10.6. 
Control:  Standard of Care (Excluding Complement Inhibitors) ................................48
10.7. 
Transfusions ................................................................................................................48
10.8. 
Prior and Concomitant Treatment ..............................................................................48
10.9. 
Vaccination .................................................................................................................49
10.10. Prophylactic Antibiotics .............................................................................................50
10.11. Rescue Antibiotics ......................................................................................................50
11.
STUDY PROCEDURES ............................................................................................51
11.1. 
Screening Period:  Visit 1 (up to Week –4 [Day –28]) ...............................................51
11.1.1.
Hemoglobin Stability:  Randomization Criteria .............................................52
11.2. 
Randomized Controlled Period:  Visit 2 (Week 0) to Visit 15 (Week 26) .................54
11.2.1.
Visit 2:  Day 1 .................................................................................................54
11.2.2.
Visit 3 to Visit 15 (Week 2 to Week 26) ........................................................55
11.2.2.1. Pegcetacoplan Administration Training .......................................................56
11.2.2.2. Vaccination and Prophylactic Antibiotic Procedures ...................................56
11.3. 
Pegcetacoplan Initiation Visit (for SOC [Excluding Complement Inhibitors] 
Treatment Arm Failures) ......................................................................................56

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11.4. 
Follow-up (if Required):  Visit 16 (Week 28), Visit 17 (Week 30), and 
Visit 18 (Week 34) ................................................................................................57
11.5. 
Unscheduled Visits .....................................................................................................57
11.5.1.
Data Monitoring Committee ...........................................................................58
11.6. 
Treatment Discontinuation and Study Withdrawal ....................................................58
11.6.1.
Discontinuation of Subjects ............................................................................58
11.6.2.
Reasons for Discontinuation ...........................................................................59
11.6.3.
Subjects “Lost to Follow-up” Prior to Last Scheduled Visit ..........................59
12.
ASSESSMENTS .........................................................................................................60
12.1. 
Assessments ................................................................................................................60
12.1.1.
Medical History ..............................................................................................60
12.1.2.
Thrombosis History ........................................................................................60
12.1.3.
Transfusion History ........................................................................................60
12.1.4.
Body Height and Weight ................................................................................60
12.1.5.
Subject Demographics ....................................................................................60
12.1.6.
Physical Examination .....................................................................................60
12.1.7.
Vital Signs ......................................................................................................61
12.1.8.
Electrocardiogram Monitoring .......................................................................61
12.1.9.
Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue 
Scale ................................................................................................................61
12.1.10.
Linear Analog Scale Assessment (LASA) for Quality of Life .......................62
12.1.11.
European Organisation for Research and Treatment of Cancer 
(EORTC) 30-Item Quality of Life Questionnaire ..........................................62
12.1.12.
Clinical Laboratory Tests ...............................................................................62
12.1.12.1.Hematology ..................................................................................................62
12.1.12.2.Coagulation ..................................................................................................62
12.1.12.3.Serum Chemistry .........................................................................................63
12.1.12.4.Urinalysis .....................................................................................................63
12.1.12.5.Other Panels .................................................................................................63
12.1.12.6.Human Chorionic Gonadotropin (Serum Pregnancy Test) and 
Follicle-Stimulating Hormone ..................................................................63
12.1.13.
Infusion Site and Pump-Safety Assessment ...................................................64
12.2. 
Pharmacokinetic Assessments ....................................................................................64
12.2.1.
Blood Sampling and Processing .....................................................................64

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12.2.2.
Analytical Method ..........................................................................................64
12.3. 
Flow Cytometry Assessments .....................................................................................64
12.4. 
Pharmacodynamic Assessments .................................................................................65
12.5. 
Antidrug Antibody Assessment ..................................................................................65
12.6. 
Blood Volume for Study Assessments .......................................................................65
12.7. 
Pregnancy Tests ..........................................................................................................66
12.8. 
COVID-19 Assessment ..............................................................................................66
13.
ADVERSE EVENTS ..................................................................................................67
13.1. 
Definition ....................................................................................................................67
13.2. 
Recording Adverse Events .........................................................................................67
13.3. 
Reporting Adverse Events ..........................................................................................68
13.3.1.
Relationship of Events to Study Treatment ....................................................68
13.3.2.
Severity of Events ...........................................................................................69
13.4. 
Serious Adverse Events ..............................................................................................69
13.5. 
Pregnancy ...................................................................................................................69
13.6. 
Drug Abuse, Misuse, Overdose, and Medication Error ..............................................70
14.
DATA MANAGEMENT AND STATISTICAL METHODS ...................................71
14.1. 
Data Collection ...........................................................................................................71
14.2. 
Clinical Data Management .........................................................................................71
14.3. 
Statistical Analysis Process ........................................................................................71
14.4. 
Planned Interim Analysis, Adaptive Design, and Data Monitoring 
Committee .............................................................................................................71
14.5. 
Sample Size Justification ............................................................................................71
14.6. 
Preservation of Type 1 Error ......................................................................................72
14.7. 
Statistical Analysis Methodology ...............................................................................72
14.7.1.
Analysis Sets ...................................................................................................72
14.7.1.1. Screened Set .................................................................................................72
14.7.1.2. Safety Set ......................................................................................................72
14.7.1.3. Intent-to-Treat (ITT) Set ..............................................................................72
14.7.1.4. Modified Intent-To-Treat (mITT) Set ..........................................................73
14.7.1.5. Per-Protocol Set ............................................................................................73
14.7.1.6. Pharmacokinetic (PK) Set ............................................................................73
14.7.1.7. Pharmacodynamic (PD) Set .........................................................................73

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14.7.1.8. Data Review for Analysis Sets .....................................................................73
14.7.2.
Efficacy Analyses ...........................................................................................73
14.7.2.1. Primary Endpoints ........................................................................................73
14.7.2.2. Secondary Endpoints ....................................................................................74
14.7.3.
Safety Analyses ..............................................................................................75
14.7.3.1. Adverse Events .............................................................................................75
14.7.3.2. Clinical Laboratory Tests .............................................................................75
14.7.3.3. Vital Signs and ECGs ...................................................................................76
14.7.4.
Pharmacokinetic Analyses ..............................................................................76
14.7.5.
Pharmacodynamic Analyses ...........................................................................76
14.7.6.
Other Data Analyses .......................................................................................76
14.8. 
Direct Access to Source Data/Documents ..................................................................77
14.9. 
Quality Control and Quality Assurance ......................................................................77
14.9.1.
Monitoring ......................................................................................................77
15.
ETHICS ......................................................................................................................78
15.1. 
Ethical Conduct of the Study ......................................................................................78
15.2. 
Institutional Review Board/Ethics Committee ...........................................................78
15.3. 
Subject Information and Consent ...............................................................................78
15.4. 
Confidentiality ............................................................................................................78
15.5. 
ClinicalTrials.gov .......................................................................................................78
15.6. 
Termination of Study ..................................................................................................78
15.7. 
Data Handling and Record Keeping ...........................................................................79
15.8. 
Protocol Amendments ................................................................................................79
15.9. 
Report Format .............................................................................................................79
15.10. Finance and Insurance ................................................................................................79
15.11. Publication Policy .......................................................................................................79
16.
REFERENCES ...........................................................................................................81
17.
APPENDICES ............................................................................................................82
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LIST OF TABLES 
Table 1:  Blood Volume During Study ..........................................................................................65
LIST OF FIGURES 
Figure 1: 
Predicted PK profile (green line) at the planned dose of 1080 mg biw, 
compared to the summary PK data at the NOAEL (13CATX-004 [black 
line]), ongoing PNH study APL-CP0514 270 mg/day cohort (blue line) and 
healthy volunteer study APL2-101 for both the 360 mg/day (brown line) and 
1300 mg biw cohorts (light blue line). ........................................................................33
Figure 2: 
APL2-308 Study Design .............................................................................................38
Figure 3: 
Screening Period Hemoglobin Requirements for Visit 2 Eligibility ..........................53
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2.
SYNOPSIS
Protocol Number: 
APL2-308 
Protocol Title: 
A Phase 3, Randomized, Multicenter, Open-Label, Controlled Study to Evaluate the Efficacy and 
Safety of Pegcetacoplan in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) 
Version Number:
Amendment 3 
Investigational Product, Dose, and Route of Administration: 
 Investigational Product: pegcetacoplan (also known as APL-2) 
 Doses: 
1080 mg twice weekly, or 
 1080 mg every 3 days (ie, a dose on every third day) 
 Route of Administration: Subcutaneous (SC) infusion 
Dose adjustment may be considered based on clinical response. 
Study Phase and Type: 
This is a multicenter, randomized, open-label, controlled, Phase 3 study.  
Number of Planned Subjects: 
54 randomized subjects: 
 pegcetacoplan:  36 subjects  
 standard of care (SOC), excluding complement inhibitors:  18 subjects 
Subjects must not have received treatment with a complement inhibitor for at least 3 months 
prior to screening.
Duration of Study Participation:  
The study consists of 3 periods. The maximum duration of subject participation will be 
approximately 38 weeks: 
 Screening Period:  up to 4 weeks 
 Randomized Controlled Period:  26 weeks 
 Safety Follow-up:  8 weeks 
Following the completion of the Randomized Controlled Period, subjects may be offered entry 
into an open-label extension study in order to continue to receive treatment with pegcetacoplan. 
These subjects will not complete the Safety Follow-up procedures for this study but will enter 
the extension study at the conclusion of the Randomized Controlled Period. 

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Rationale for the Study:
Phase 1 clinical experience has demonstrated that pegcetacoplan provides sustained inhibition of 
hemolytic activity in PNH patients who have never received treatment with a complement 
inhibitor (eg, eculizumab; Study APL2-CP-PNH-204 [Paddock]). To date, no safety signals have 
emerged from ongoing studies in PNH patients that preclude further development. Thus, this 
proposed Phase 3 study is to further evaluate treatment efficacy and safety of pegcetacoplan as 
monotherapy in patients with PNH. 
Study Objectives and Endpoints:  
Primary Objective 
The primary objective of this study is to evaluate the efficacy of pegcetacoplan, compared to 
SOC (excluding complement inhibitors), in patients with PNH, as assessed by:  
 Hemoglobin stabilization defined as avoidance of a >1-g/dL decrease in Hb levels 
from baseline in the absence of transfusion through Week 26 (Yes/No) 
AND 
 Reduction in lactate dehydrogenase (LDH) level from baseline to Week 26 
Secondary Objectives 
Secondary objectives of this study are:  
 To evaluate the efficacy of pegcetacoplan, compared to SOC (excluding complement 
inhibitors), as assessed by: 
Hemoglobin response (Yes/No) in the absence of transfusions (Hb response is 
-g/dL increase in Hb from baseline at Week 26) 
Change from baseline to Week 26 in absolute reticulocyte count (ARC)  
Change from baseline to Week 26 in Hb level  
 Number of packed red blood cell (PRBC) units transfused from baseline to 
Week 26 
 Change from baseline to Week 26 in Functional Assessment of Chronic Illness 
Therapy (FACIT)–Fatigue Scale score
 × the upper limit of normal [ULN]) 
from baseline to Week 26 in the absence of transfusions (Yes/No) 
 Normalization of LDH levels of 
× ULN from Week 4 to Week 26 (Yes/No) 
 Change from baseline to Week 26 in European Organization for Research and 
Treatment of Cancer (EORTC) 30-item Core Quality of Life Questionnaire 
(QLQ-C30) scores (version 3) 
Change from baseline to Week 26 in Linear Analog Assessment (LASA) scale 
scores

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Absolute reticulocyte count normalization (<1 × ULN) at Week 26 (Yes/No) 
 Time to failure of Hb stabilization  
Time to transfusion 
To evaluate the safety of pegcetacoplan as assessed by:
Incidence and severity of treatment-emergent adverse events (TEAEs)
Incidence of thromboembolic events 
Changes from baseline in laboratory parameters 
 Changes from baseline in electrocardiogram (ECG) parameters 
Incidence of anti-pegcetacoplan antibodies 
Exploratory Objectives
Exploratory objectives of the study are to evaluate: 
 
 
 Pegcetacoplan pharmacokinetic/pharmacodynamic (PK/PD), as assessed by:
Pegcetacoplan PK concentrations from baseline to Week 26 
Change from baseline to Week 26 in PNH clone distribution (red blood cells 
[RBCs] and white blood cells [WBCs]) 
Change from baseline to Week 26 in complement component 3 (C3) deposition in 
PNH Type II and III RBCs  
Complement levels from baseline to Week 26 (eg, total hemolytic complement 
activity assay [CH50], alternate complement pathway assay [AH50], and C3) 
Study Design: 
This is a prospective, randomized, multicenter, open-label, controlled study. Following 
screening, subjects will complete biweekly (biw) visits from Week 0 to Week 26. Subjects will 
be randomized either to pegcetacoplan or SOC (excluding complement inhibitors). Subjects 
randomized to the SOC (excluding complement inhibitors) treatment arm may receive 
2 g/dL below their baseline value.  
Inclusion Criteria 
At Visit 1 screening, subjects must fulfill all of the following inclusion criteria to be eligible for 
participation in the study: 
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1. Be at least 18 years old (inclusive).
2. 
× ULN at the screening visit.
3. Have PNH diagnosis, confirmed by high sensitivity flow cytometry (granulocyte or 
monocyte clone >10%). 
4. Have Hb less than the lower limit of normal (LLN) at the screening visit.  
5. Have ferritin greater than/equal to the LLN, or total iron binding capacity (TIBC) less 
than/equal to ULN at the screening visit, based on central laboratory reference ranges. If 
a subject is receiving iron supplements at screening, the investigator must ensure that the 
subject’s dose has been stable for 4 weeks prior to screening, and it must be maintained 
throughout the study. Subjects not receiving iron at screening must not start iron 
supplementation during the course of the study. 
6. Body mass index (BMI) 35 kg/m2 at the screening visit.
7. Have a platelet count of >50,000/mm3 at the screening visit. 
8. Have an absolute neutrophil count >500/mm3 at the screening visit. 
9. Women of childbearing potential (WOCBP) must have a negative pregnancy test at 
screening and must agree to use protocol-defined methods of contraception for the 
duration of the study and for 90 days after their last dose of study drug. 
10. Males must agree to use protocol-defined methods of contraception and agree to refrain 
from donating sperm for the duration of the study and for 90 days after their last dose of 
study drug. 
11. Have vaccination against Streptococcus pneumoniae, Neisseria meningitidis (types A, C, 
W, Y, and B), and Haemophilus influenzae (type B) either within 2 years prior to Day 1 
dosing, or agree to receive vaccination 14 days after starting treatment with 
pegcetacoplan (along with prophylactic antibiotic therapy for at least the 14 days between 
pegcetacoplan treatment initiation and vaccination and 14 days post vaccination).  
Vaccination is mandatory, unless documented evidence exists that subjects are 
nonresponders to vaccination (as evidenced by titers or display titer levels within 
acceptable local limits).  
12. Be willing and able to give informed consent. 
Exclusion Criteria
Subjects will be excluded from the study if there is evidence of any of the following criteria at 
screening:
1. Treatment with any complement inhibitor (eg, eculizumab) within 3 months prior to 
screening.  
2. Hereditary complement deficiency. 
3. History of bone marrow transplantation. 
4. Concomitant use of any of the following medications is prohibited if not on a stable 
regimen for the time period indicated below prior to screening: 

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 Erythropoietin or immunosuppressants for at least 8 weeks 
 Systemic corticosteroids for at least 4 weeks 
Vitamin K antagonists (eg, warfarin) with a stable international normalized ratio 
(INR) for at least 4 weeks 
 Iron supplements, vitamin B12 or folic acid for at least 4 weeks 
Low-molecular-weight heparin for at least 4 weeks 
5. History or presence of hypersensitivity or idiosyncratic reaction to compounds related to 
the investigational product or SC administration. 
6. Participation in any other investigational drug trial or exposure to other investigational 
agent, device, or procedure within 30 days or 5 half-lives, whichever is longer. 
7. Planning to become pregnant or currently a breastfeeding woman. 
8. History of meningococcal disease. 
9. Any comorbidity or condition (such as malignancy) that, in the opinion of the 
investigator, could put the subject at increased risk or potentially confound study data. 
Randomization Criteria 
At Visit 2 (Day 1), subjects must meet the following criteria in order to be randomized: 
10. 
9 g/dL, or Hb <9 g/
7 g/dL without signs or symptoms 
of sufficient severity to warrant a transfusion.
11. Negative urine pregnancy test for WOCBP. 
12. No active systemic bacterial, viral, or fungal infection within the 2-week period prior to 
receiving treatment with pegcetacoplan.
Sample Size Justification: 
A total of 48 randomized subjects (32 subjects to pegcetacoplan and 16 subjects to SOC) are 
required to achieve 90% power, at the 5% significance level (2-sided), using a 2-group Fisher's 
exact test with unequal allocation 2:1 to treatment groups (pegcetacoplan and SOC). Calculation 
assumes an increase of 45% in the proportion of subjects achieving Hb stabilization with 
pegcetacoplan compared to SOC (ie, a change from 5% [no treatment] to 50% [pegcetacoplan]). 
With the same number of subjects and an effect size of at least 1.2, the study will be at 96% for 
the LDH reduction endpoint. 
To account for loss of power due to discontinuations, the study will attempt to randomize 
54 subjects.
Statistical Methods:
Analysis Sets
Screened Set 
The screened set will include all subjects who signed the informed consent form (ICF). This set 
will be used only for the purpose of describing subject disposition.  

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Safety Set
The safety set will include all subjects who receive at least 1 dose of study medication 
(pegcetacoplan), or subjects who are randomized to SOC (excluding complement inhibitors). 
Subjects will be analyzed according to the treatment they received.  
Intent-to-Treat (ITT) Set 
The ITT set will include all randomized subjects. Subjects will be analyzed according to their 
assigned treatment, regardless of the treatment actually received. 
Modified Intent-To-Treat (mITT) Set 
The mITT will include all subjects in the ITT set who continue study treatment beyond Visit 4 
(Week 4). 
Per-Protocol (PP) Set
The per-protocol (PP) set will include all subjects in the ITT set who have not violated any 
inclusion or exclusion criteria and/or deviated from the protocol in a way that could influence 
their efficacy assessment. Decisions concerning the exclusion of subjects from the PP analysis 
set will be made and documented prior to database lock. 
Pharmacokinetic (PK) Set 
The PK population will include all subjects in the ITT Set who receive pegcetacoplan and have 
at least 1 evaluable postdose- PK measurement.
Pharmacodynamic (PD) Set
The PD population will include all subjects in the ITT set who have at least 1 evaluable 
postdose- PD measurement. 
Efficacy Analyses 
The efficacy endpoints will primarily be evaluated with the ITT set. All statistical testing will be 
at the 5% level of significance (2-sided) and all point estimates for the comparison between 
treatment groups will be accompanied by 2-sided 95% confidence intervals (CIs). 
All possible efforts will be made to ensure that subjects complete all the required assessments.  
Endpoints will be summarized and, where appropriate, plotted over time for each treatment 
group.  
Baseline assessments will be performed on Day 1 prior to the start of study treatment for subjects 
randomized to pegcetacoplan and at Day 1 for subjects randomized to SOC. 
Co-Primary Endpoints 
The co-primary efficacy endpoints will be analyzed, based on the ITT set.  

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The co-primary efficacy endpoints are:
1 g/dL in Hb levels from baseline 
to Week 26 in the absence of transfusions (Yes/No)
AND 
 Reduction in lactate dehydrogenase (LDH) level from baseline to Week 26   
For the first co-primary endpoint, the number and percentage of subjects who achieve Hb 
stabilization will be computed for treatment groups and compared between treatment groups 
using a stratified Cochran-Mantel-Haenszel (CMH) chi-square test. The treatment difference in 
percentages and 95% CI for the difference will be presented using the stratified Miettinen-
Nurminen method.  
Subjects who receive a transfusion through Week 26 or withdraw from the study before 
providing primary efficacy assessment will be categorized as failing to achieve Hb stabilization.
The second co-primary endpoint, change from baseline to Week 26 in LDH, will be analyzed 
using mixed model for repeated measures (MMRM) with:  the effects of treatment; stratification 
randomization; visit, visit-by-treatment interaction; baseline LDH level and baseline LDH level-
by-visit interaction using an unstructured covariance matrix.  The difference between treatment 
groups will be estimated, along with its 95% CI and p-value.  
All the subjects LDH levels prior to transfusion and/or switch to pegcetacoplan will be included 
in the model.
As missing data may potentially bias the outcome of the statistical analyses and the subsequent 
estimation of the magnitude of the treatment effect, the following sensitivity and supportive 
analyses will be performed to evaluate the robustness of the results from the primary analysis 
methods: 
 The first co-primary efficacy endpoint will also be analyzed using a logistic 
regression with the effects of treatment group and stratification factors included. The 
odds ratio of being an Hb stabilization achiever the pegcetacoplan versus SOC group 
and associated 95% CI will be estimated from the final model.
The second co-primary endpoint will be analyzed using an analysis of covariance 
(ANCOVA) model (ITT set) with a last observation carried forward (LOCF) 
approach for handling missing data. The ANCOVA model will include terms for 
treatment, stratification factors, and baseline LDH level.
The second co-primary endpoint will be analyzed using an ANCOVA model (ITT 
Set) with a best observation carried forward (BOCF) approach for handling missing 
data. The ANCOVA model will include terms for treatment, stratification factors, and 
baseline LDH level. 
 Analyses will be repeated using the mITT and PP sets. 
Secondary Endpoints 
The secondary endpoints will be analyzed using the ITT set and will be repeated using the PP 
set. 

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Summary statistics by randomization strata and by treatment groups will presented at each 
assessment visit during the 26-week randomized treatment period.  
Continuous endpoints will be analyzed using MMRM with the effects of:  treatment; 
stratification factors; visit, visit-by-treatment interaction; the relevant baseline level; and the 
Baseline level-by-visit interaction using an unstructured covariance matrix. The difference 
between treatment groups will be estimated, along with its 95% CI and p-value. If a subject 
receives a transfusion during his/her treatment period, the pre-transfusion Hb values, reticulocyte 
values, and FACIT-Fatigue Scale score will be used in the model.  
For categorical endpoints, the number and percentage of subjects will be tabulated by treatment 
group and compared between treatment groups using a stratified CMH chi-square test. 
Kaplan-Meier plots will be presented for time-to-event endpoints for each treatment group, and 
survival estimates will be provided. 
The number of units of PRBCs transfused will be compared between the treatment groups using 
a Wilcoxon rank-sum test. The difference between the medians will be estimated along with its 
95% CI (stratified). Subjects who withdraw before Week 26 will have the number of units 
estimated from the duration that they were in the study (ie, number per week × 12). This equates 
to an analysis of the frequency of transfusions.  
Safety Analyses
Safety analyses will be based on the safety set.
Safety measures assessed at study visits, including vital signs (temperature, systolic and diastolic 
blood pressures, pulse, and respiratory rate), clinical laboratory results, ECGs and 
anti-pegcetacoplan antibodies will be descriptively summarized by treatment group at baseline 
and for each postbaseline visit. Absolute values and changes from baseline will be summarized. 

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3.
ABBREVIATIONS
Term
Definition
51Cr 
chromium 51 
ADA 
antidrug antibodies 
ADR 
adverse drug reaction 
AE 
adverse event 
AH50 
alternate complement pathway assay 
AIV 
pegcetacoplan initiation visit 
ANCOVA 
analysis of covariance 
ARC 
absolute reticulocyte count 
biw 
twice weekly administration 
BMI 
body mass index 
BOCF 
best observation carried forward 
C3 
complement component 3 
CD71+ 
transferrin receptor 
CH50 
total hemolytic complement activity assay
CI 
confidence interval 
Cmax 
maximum drug plasma concentration 
CMH 
Cochran-Mantel-Haenszel (chi-square test) 
COVID-19 
coronavirus disease 2019 
CRF 
case report form 
DMC 
data monitoring committee 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EORTC 
European Organisation for Research and Treatment of Cancer 
EudraCT 
European Union Drug Regulating Authorities Clinical Trials (database) 
FACIT 
Functional Assessment of Chronic Illness Therapy 
FDA 
Food and Drug Administration 
FSH 
follicle-stimulating hormone 
GCP 
good clinical practice 
GLP 
good laboratory practice 
Hb 
hemoglobin 
Hib 
Haemophilus influenzae Type B (vaccine) 

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Term 
Definition 
HV
healthy volunteer
IB 
investigator’s brochure 
ICH 
International Council for Harmonisation 
ICF 
informed consent form 
IEC 
institutional ethics committee 
IND 
investigational new drug application 
INR 
international normalized ratio 
IRB 
institutional review board  
IRT 
interactive response technology 
ITT 
intent-to-treat (population) 
LASA 
Linear Analog Assessment Scale 
LDH 
lactate dehydrogenase 
LLN 
lower limit of normal 
LOCF 
last observation carried forward 
MAC 
membrane attack complex 
MAVE 
major adverse vascular event 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
modified intent-to-treat (population) 
MMRM 
mixed model repeated measures 
NOAEL 
no observed adverse effect level 
PCV13 
pneumococcal conjugate vaccine 
PD 
pharmacodynamic(s) 
PEG 
polyethylene glycol 
PI  
principal investigator  
PK 
pharmacokinetic(s) 
PNH 
paroxysmal nocturnal hemoglobinuria 
PP 
per-protocol (set) 
PPSV23 
pneumococcal polysaccharide vaccine 23  
PRBC 
packed red blood cells 
PT 
prothrombin time 
QLQ-C30 
30-item Core Quality of Life Questionnaire 
QoL 
quality of life 
QTc 
corrected QT interval 

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Term 
Definition 
QTcB
Bazett’s corrected QT interval
QTcF 
Fridericia’s corrected QT interval 
RBC 
red blood cell 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SC 
subcutaneous 
SOC 
standard of care 
SOP 
standard operating procedure 
TEAE 
treatment-emergent adverse event 
TIBC 
total iron binding capacity 
TMDD 
target-mediated drug disposition 
ULN 
upper limit of normal 
USA 
United States of America 
WBC 
white blood cell 
WHO 
World Health Organization 
WOCBP 
woman/women of childbearing potential 

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4. 
SCHEDULE OF EVENTS 
Study period
Screen
-ingA
Randomized controlled period 
Follow upB 
AIVC 
Study week 
Up to 
–4 
0 
2 
4 
6 
8 
10 
12 
14 
16 
18 
20 
22 
24 
26 
28 
30 
34 
-- 
Study day
Up to
–28
1 
15
29
43
57
71 
85 
99 
113
127 
141 
155 
169 
183 
197 
211 
239 
--
Study visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13
14 
15 
16 
17
18
-- 
Clinic visit window 
(±days) 
N/A
0 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
7 
7 
--
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
Height/weight 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Thrombosis history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Transfusion history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion
X 
Confirm Hb entry criteriaD
X 
Randomization 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vaccination 
 
 
XE 
E 
XE 
E 
 
 
Preventive antibioticsF 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
Physical examinationG
X 
X 
X 
X 
X 
X 
X 
CCI
C
C
I

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Study period 
Screen
-ingA 
Randomized controlled period 
Follow upB 
AIVC 
Study week
Up to
–4 
0 
2 
4 
6 
8 
10
12
14
16
18
20
22
24
26
28
30
34
--
Study day 
Up to 
–28 
1 
15 
29 
43 
57 
71 
85 
99 
113 
127 
141 
155 
169 
183 
197 
211 
239 
-- 
Study visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13
14 
15 
16 
17
18
-- 
Clinic visit window 
(±days) 
N/A 
0 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
7 
7 
-- 
12-lead electrocardiogramH 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
X 
X 
X 
X 
APL-2 administration trainingI 
 
X 
I 
 
 
 
X 
APL-2 administrationI 
 
 
X 
 
 
 
X 
Concomitant medications
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital sign measurementsJ
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis 
X 
X 
 
X 
 
X 
X 
X 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
BloodK 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PharmacokineticsL 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
X 
 
X 
 
X 
Anti-APL-2 Ab assay L 
 
X 
X 
 
 
X 
 
 
X 
 
 
 
X 
 
X 
 
Direct Antibody Test (Coombs)
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Lactate dehydrogenase
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology and chemistryS
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Absolute reticulocyte count
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Haptoglobin 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation profileM
X 
X 
X 
X 
X 
X
X 
X
X 

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APL2-308 Protocol Amendment 3 
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Confidential 
Study period 
Screen
-ingA 
Randomized controlled period 
Follow upB 
AIVC 
Study week
Up to
–4 
0 
2 
4 
6 
8 
10
12
14
16
18
20
22
24
26
28
30
34
--
Study day 
Up to 
–28 
1 
15 
29 
43 
57 
71 
85 
99 
113 
127 
141 
155 
169 
183 
197 
211 
239 
-- 
Study visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13
14 
15 
16 
17
18
-- 
Clinic visit window 
(±days) 
N/A 
0 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
7 
7 
-- 
Complement profile T 
(CH50, and AH50) 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
X 
 
X 
 
C3 Profile T 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Flow cytometry T 
X 
X 
X 
 
X 
 
 
X 
 
 
 
 
X 
X 
X 
X 
Plasma (free) Hb
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Ferritin 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy ( -HCG) or FSHN 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Genotyping for Gilbert’s 
SyndromeO 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine pregnancy testP 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
FACIT-Fatigue Scale 
 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
X 
LASA Scale
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
EORTC QLQ-C30 
Questionnaire 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse eventsQ
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dispense investigational 
productr, 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
X 

Pegcetacoplan
APL2-308 Protocol Amendment 3 
10 Aug 2020 
Apellis Pharmaceuticals, Inc 
Page 26 of 106 
Confidential 
Study period 
Screen
-ingA 
Randomized controlled period 
Follow upB 
AIVC 
Study week
Up to
–4 
0 
2 
4 
6 
8 
10
12
14
16
18
20
22
24
26
28
30
34
--
Study day 
Up to 
–28 
1 
15 
29 
43 
57 
71 
85 
99 
113 
127 
141 
155 
169 
183 
197 
211 
239 
-- 
Study visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13
14 
15 
16 
17
18
-- 
Clinic visit window 
(±days) 
N/A 
0 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
7 
7 
-- 
Return investigational product
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Abbreviations:  Ab = antibodies; AE = adverse event; AH50 = alternate complement pathway assay; AIV = APL-2 Initiation Visit; APL-2 = pegcetacoplan; -
HCG = beta-human chorionic gonadotropin; C3 = complement component 3; CH50 = total hemolytic complement activity assay; COVID-19 = coronavirus 
disease 2019; CRFs = case report forms; ECG = electrocardiogram; eCRF = electronic case report form; EORTC-QLQ-C30 = 30-item European Organization 
for Research and Treatment of Cancer Quality of Life Questionnaire; FACIT = Functional Assessment of Chronic Illness Therapy; FSH = follicle-stimulating 
hormone; Hb = hemoglobin; LASA = Linear Analog Assessment Scale; N/A = not applicable; PCV13 = pneumococcal conjugate vaccine (13-valent); PI = principal 
investigator; PK = pharmacokinetic(s); PPSV23 = pneumococcal polysaccharide vaccine (23-valent); PRBC = packed red blood cell; QTc = corrected QT 
interval; QTcF = Fridericia’s corrected QT interval; SC subcutaneous; SOC = standard of care; WOCBP = women of childbearing potential. 
A Within 5 days prior to Visit 2 (Week 0), each subject’s Hb must be evaluated by a local or central laboratory. If the subject meets the protocol-specified 
transfusion criteria, the subject must receive a PRBC transfusion so that the subject’s Hb levels no longer meets the protocol-specified requirements for PRBC 
transfusion. The posttransfusion Hb value should be confirmed by a local or central laboratory. Patients must not be randomized if they meet the protocol-
specified requirements for transfusion, and the Hb assessment to confirm eligibility should be scheduled so that the subject does not fall outside the screening 
window (up to Day –28). All Hb levels must be recorded in the eCRF.
B All subjects who complete Visit 15 (Week 26) and do not elect to participate in the open-label extension study will be asked to return to the investigator site for 
the Visit 16 (Week 28), Visit 17 (Week 30), and Visit 18 (Week 34) follow-up visits.  Subjects who discontinue treatment will be encouraged to continue to 
attend study visits to complete study assessments (except for treatment with pegcetacoplan) as detailed in the Schedule of Events. At minimum, subjects who 
discontinue dosing should complete follow-up procedures outlined in the Schedule of Events 2, 4, and 8 weeks after treatment discontinuation. If withdrawal of 
pegcetacoplan treatment is necessary, slow weaning should be considered and subjects should carefully be monitored for at least 8 weeks to detect serious 
hemolysis or other complications, as detailed in the investigator’s brochure. 
C Following Visit 2 (Week 0), subjects assigned to the SOC (excluding complement inhibitors) treatment arm who have a Hb level measured by the central  
laboratory (or local laboratory if necessary due to COVID-19) that is 2 g/dL below the baseline value will be switched to escape therapy with pegcetacoplan.  
These subjects will return to the site for a pegcetacoplan initiation visit. Following the pegcetacoplan initiation visit, subjects will maintain their regular visit 
schedule. 
D T
-Visit 2 Hb qualification assessment must be assessed to confirm subject eligibility at Visit 2 before the subject can be randomized into the 
study. 

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E In order to receive treatment with pegcetacoplan, subjects must have documented evidence of vaccination against the following within 2 years of screening: 
Neisseria meningitidis types A, C, W, Y, and B (administered as 2 separate vaccinations), Streptococcus pneumoniae (with a PCV13 or PPSV23 vaccine), and 
Haemophilus influenzae type B (Hib vaccine).  
Subjects randomized to pegcetacoplan: For subjects randomized to pegcetacoplan who do not have documented evidence of receiving any of the above 
vaccinations within 2 years prior to screening, the required missing vaccination(s) will be administered at Visit 3 (Week 2), prior to dosing with 
pegcetacoplan (along with boosters administered during the study at or after Visit 7 [Week 10], if required [see below]). Vaccination is mandatory, unless 
documented evidence exists that subjects are nonresponders to vaccination (as evidenced by titers or display titer levels within acceptable local limits). The PI 
will discuss with the sponsor regarding individual patient circumstances.  
If the subject requires vaccination against Neisseria meningitidis, a booster (for both vaccinations) should be administered after at least 8 weeks (Visit 7). If the 
subject requires vaccination against Streptococcus pneumoniae, PCV13 will be administered at Visit 3, and PPSV23 will be administered after at least 
8 weeks (Visit 7). 
Subjects randomized to SOC (excluding complement inhibitors): Subjects who are initially randomized to SOC (excluding complement inhibitors) who 
become eligible for pegcetacoplan escape therapy will receive any required vaccination(s) 2 weeks after initiation of treatment with pegcetacoplan. If 
required, as detailed above), the Neisseria meningitidis booster (for both vaccinations), and/or PPSV23 vaccination should be administered at least 8 weeks 
following the initial vaccination(s).      
F  In order to receive treatment with pegcetacoplan, subjects will require preventive antibiotics if they need to be vaccinated, as detailed in Footnote E above. In 
addition, subjects who do not require vaccination are recommended to receive preventive antibiotic therapy, as detailed below.  
Subjects randomized to pegcetacoplan: Subjects will be required to take ciprofloxacin 500 mg twice daily from Visit 2 (Day 1) to Visit 3 (Week 2) and 
continue to receive antibiotic prophylaxis until at least 14 days post vaccination. From that point forward, it is recommended that all subjects take penicillin V 
500 mg twice daily through the course of pegcetacoplan treatment.  
Subjects randomized to SOC (excluding complement inhibitors):  Subjects who are initially randomized to SOC (excluding complement inhibitors) do not 
need to initiate preventive antibiotic therapy at Day 1. If a subject becomes eligible for and initiates pegcetacoplan escape therapy, the subject should take 
ciprofloxacin 500 mg twice daily for 2 weeks, beginning on the first day of treatment with pegcetacoplan and continue to receive antibiotic prophylaxis until 
at least 14 days post vaccination. After 2 weeks of ciprofloxacin, it is recommended that subjects take penicillin V 500 mg twice daily through the course of 
pegcetacoplan treatment. 
G A full physical examination should be conducted, as indicated by the study schedule. A symptom-driven physical examination may be performed at other 
visits, at the PI’s discretion. 
H Triplicate 12-lead ECGs are to be performed within 1 hour predose at Visit 2 (Day 1).  Triplicate 12-lead ECGs will be performed prior to dosing at all other 
visits, if pegcetacoplan administration is occurring at the study site.  During the study, if the QTcF at any on-
 ms (mean of QTcF 
replicate values), the investigator should perform 3 additional ECGs over 20-60 minutes; if the mean QTcF of the 3 
 ms, the site should 
instruct the subject to return the following day to perform repeat triplicate ECGs.  An evaluation will be performed to look for other factors which may have 
contributed to QTc prolongation (eg, new concomitant medications, hypokalemia, etc.). 
I Subjects randomized to pegcetacoplan: For subjects randomized to the pegcetacoplan treatment arm, research nurses or other appropriately qualified 
research personnel will administer the first pegcetacoplan SC infusion at Visit 2 (Day 1) and will train subjects on how to self-administer. Following Visit 2, 
appropriately qualified research personnel will supervise self-administration of pegcetacoplan for at least the following 3 doses (which will be administered 
prior to Visit 3). Supervision of self-administration may be conducted at the subject’s home, at the study site, or at an off-site location convenient for the 
subject. Supervision of self-administration must continue until the subject is qualified to self-administer. 
Following self-administration qualification, subjects may self-administer pegcetacoplan SC infusions without supervision. Subjects may continue to self-
administer infusions at the study site on those days when a study visit occurs, but this is not required. Self-administration conducted at the study site will be 

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supervised to ensure that the subject continues to remain compliant with the administration guidelines. On all other days, subjects may self-administer at 
home, at the study site, or at an off-site location convenient to the subject. 
Subjects randomized to SOC (excluding complement inhibitors):  Subjects randomized to the SOC (excluding complement inhibitor) treatment arm that are 
assigned to pegcetacoplan escape therapy during the study will have research nurses or other appropriately qualified research personnel administer the first 
pegcetacoplan SC infusion and provide self-administration training at the study visit in which pegcetacoplan escape therapy is initiated.  Following this visit, 
appropriately qualified research personnel will supervise self-administration of pegcetacoplan for at least the following 3 doses at the subject’s home, the study 
site, or an off-site location convenient for the subject. Supervision of self-administration must continue until the subject is qualified to self-administer, and 
pegcetacoplan will be self-administered and supervised at the study site on days of study visits, if the subject elects to administer pegcetacoplan during the 
study visit. 
J Vital signs will be measured before venipuncture and ECG.  Monitoring of vital signs will occur at Visit 2 (Day 1) predose and 2 hours post dose 
(±30 minutes).  In addition, monitoring of vital signs will occur predose and 2 hours post dose (±30 minutes) during the pegcetacoplan Initiation Visit, if 
applicable.  At all other visits, if the subject elects to administer pegcetacoplan during the visit, vital signs should be measured predose. 
K If pegcetacoplan will be administered at the study visit, blood samples must be taken predose. The date and time of the last dose of pegcetacoplan should be 
recorded on the eCRF, as well as the date and time of the blood sample draw (to be used for PK analysis). 
L  Samples for PK and anti-pegcetacoplan assay assessments should not be collected for subjects randomized to the SOC (excluding complement inhibitors) 
treatment arm unless they become eligible for and elect to receive pegcetacoplan escape therapy. If a subject from the SOC (excluding complement inhibitors) 
treatment arm is to begin receiving pegcetacoplan escape therapy, a predose PK sample should be collected at the pegcetacoplan initiation visit and at each 
subsequent visit, as detailed in the Schedule of Events.  
M The use of silica reagents in coagulation panels should be avoided in subjects treated with pegcetacoplan. 
N -HCG for WOCBP; FSH for postmenopausal women. 
O Sample for genotyping to be obtained via buccal swab test completed at the Screening Visit.  
P  Urine pregnancy test should be completed for WOCBP prior to dosing on Day 1. 
Q On the days of clinic visits, an assessment of the pegcetacoplan infusion site will be made as a part of the AE assessment. If pegcetacoplan is administered at 
the visit, the site staff will observe the dosing and pump-use safety will be assessed and the infusion site will be checked again within 30 minutes after study 
drug administration. The infusion site assessments will be performed by an appropriately trained staff, as delegated by the investigator. The infusion site and 
surrounding area will be inspected for redness, swelling, induration, and bruising. The subject will be asked about the presence of pain and/or tenderness, and 
any issue related to pump use. The date, time, and outcome of the infusion-site assessment will be recorded on the source documents and CRFs. Subjects will 
be instructed to notify the PI or other study personnel in the event that an infusion site reaction occurs after self-administration of APL 2. All clinically relevant 
AEs, as determined by the investigator, from infusion site or related to pump use will be recorded as AEs. 
R Subjects randomized to pegcetacoplan treatment arm or receiving pegcetacoplan escape therapy only. Dispensation will depend on the subject’s dose regimen. 
Please consult the dispensation schedule. 
S  Hb, LDH, and reticulocyte count should be collected PRIOR to any transfusion. The assessment may be performed at a central or certified local laboratory. 
T Samples for PD assessments (Complement profile, C3 Profile, and Flow Cytometry) should be collected for subjects randomized both to the SOC (excluding   
complement inhibitors) and pegcetacoplan treatment arms.  

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5.
INTRODUCTION
This study is being conducted as part of a series of studies for the clinical development of 
pegcetacoplan. The study will be conducted in compliance with the protocol, Good Clinical 
Practice (GCP), and applicable regulatory requirements. The subject population will comprise 
adult male and female subjects with paroxysmal nocturnal hemoglobinuria (PNH). 
5.1.
Paroxysmal Nocturnal Hemoglobinuria
PNH is an acquired, rare, clonal, nonmalignant hematologic disease characterized by 
complement-mediated red blood cell (RBC) hemolysis, with or without hemoglobinuria, an 
increased susceptibility to thrombotic episodes, and/or some degree of bone marrow dysfunction. 
The onset of PNH is often insidious. Although there have been reports of spontaneous remission, 
the course of the disease is generally chronically progressive. 
It has been known for many years that PNH is caused by complement-mediated lysis of 
erythrocyte clones lacking functional CD55 and CD59 on their surface to protect them against 
this process. As such, these erythrocytes are particularly susceptible to the membrane attack 
complex (MAC) and have been shown to lyse readily in the presence of complement activation. 
Any therapy that effectively inhibits MAC formation is anticipated to be a plausible 
candidate-treatment for PNH. Eculizumab is a monoclonal anti-C5 antibody that inhibits the 
formation of the MAC, and eculizumab treatment has been approved for the treatment of this 
serious condition. However, inhibition of MAC formation does not appear to be sufficient to fully 
control the disease, as many PNH patients receiving eculizumab treatment still suffer from anemia, 
with only roughly 13% of patients being classified as complete responders (ie, achieving 
transfusion independence and normal hemoglobin [Hb] levels). Most of the patients (53%) were 
classified as partial responders with decreased transfusion needs and reduced lactate 
dehydrogenase (LDH), and 33% of patients were poor responders, with unchanged transfusion 
needs and persistent symptoms (DeZern et al. 2013).
Recent studies have suggested that significant opsonization of PNH erythrocytes by complement 
component 3 (C3) fragments is observed in patients receiving eculizumab treatment. This 
opsonization is believed to cause the removal of erythrocytes by the spleen and the liver, 
resulting in extravascular hemolysis. Extravascular hemolysis can be significant in a subset of 
eculizumab-treated PNH patients and is considered to be the principal contributor to the lack of 
complete eculizumab response in most patients.  
5.2. 
Pegcetacoplan 
Pegcetacoplan (also known as APL-2) is formed by a pentadecapeptide (combining a bioactive 
cyclic tridecapeptide C3-inhibiting moiety and a 2–amino acid linker) covalently coupled to each 
end of a linear 40-kDa polyethylene glycol (PEG) chain, so that there are 2 peptide moieties per 
molecule of pegcetacoplan. 
The peptide portion of the drug binds to complement C3 and is a broad inhibitor of the 
complement cascade, a biological process that is part of innate immunity and is involved in 

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multiple inflammatory processes. The PEGylation of the molecule imparts slower elimination 
from mammalian systems following administration.  
Pegcetacoplan infusion (drug product) is a solution of pegcetacoplan in 5% dextrose or a solution 
of pegcetacoplan in acetate-buffered mannitol or a solution of pegcetacoplan in acetate-buffered 
sorbitol for subcutaneous (SC) administration. Pegcetacoplan is being developed for the 
treatment of PNH. 
Further details can be found in the current version of the pegcetacoplan investigator’s brochure 
(IB). 
5.2.1. 
Rationale for Treatment with Pegcetacoplan 
Extravascular hemolysis, one of the parameters contributing to the ongoing need for RBC 
transfusions despite eculizumab therapy, is believed to be mediated by C3b opsonization rather 
than C5-dependent MAC-mediated intravascular hemolysis (Risitano et al. 2009).  While 
eculizumab is effective in addressing CD59 deficiency by preventing C5-dependent 
MAC-mediated hemolysis, PNH cells are also deficient in CD55, which normally accelerates the 
dissociation of C3-convertase enzymes, inhibiting the production of C3 fragments and 
subsequent opsonization. As a result, in the setting of eculizumab therapy, surviving PNH RBCs 
become opsonized with C3b, targeting them for clearance through extravascular hemolysis by 
macrophages bearing complement receptors in the liver and spleen.
Evidence for C3b-mediated extravascular hemolysis was observed in 3 patients exhibiting a 
“suboptimal hematologic response [to eculizumab] and massive C3 RBC binding” using 
chromium-51 (51Cr)–labeled RBCs. Although these subjects were still receiving eculizumab and 
had normal LDH levels, they demonstrated markedly reduced RBC half-lives (10, 11, and 
13 days, with a normal range of 25-35 days) and excess counts on images of the spleen and liver 
(Risitano et al.  2009). In contrast, C3b opsonization of RBCs is not observed in PNH patients 
who have not been treated with eculizumab, presumably because RBCs in these patients are 
rapidly lysed by MAC (Risitano et al. 2009).
In summary, while C5 inhibition has had a dramatic positive impact on the lives of many PNH 
patients, anti-C5 therapy has also led to the emergence of a subpopulation of PNH patients with 
persistent extravascular hemolysis and RBC transfusion requirements, despite continuous 
eculizumab therapy, that appear to result at least in part from C3b opsonization of RBCs.  It is 
reasonable, therefore, to expect that a treatment able to inhibit both MAC formation and C3 
opsonization will provide improved therapeutic benefit to PNH patients, compared to 
eculizumab.
5.2.2.
Summary of Clinical Experience
Clinical data from studies with pegcetacoplan in subjects with PNH indicates that pegcetacoplan
is effective in providing broad control of intravascular and extravascular hemolysis, as evidenced 
by increased and stable Hb levels, along with improvement in Functional Assessment of Chronic 
Illness Therapy- (FACIT-) Fatigue Scale score, normalization of LDH, normalization of absolute 
reticulocyte count (ARC), normalization of total bilirubin levels, along with reduction in C3 
fragment opsonization and increased numbers of PNH RBCs.  To date, pegcetacoplan at doses of 
270 mg/dL has been generally safe and well tolerated when administered via SC infusion. No 

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expected serious adverse drug reactions (ADRs) have been identified, and no deaths have 
occurred that are considered related to treatment with pegcetacoplan. 
Results from the Phase 3 APL2-302, a randomized, multicenter, open-label, active-comparator 
controlled study in adults with PNH, showed that pegcetacoplan at a dose of 1080 mg SC every 
2 weeks controlled the hematologic manifestations of PNH, with superiority for control of 
anemia, as compared with the C5 inhibitor, eculizumab. Pegcetacoplan was superior to 
eculizumab with regard to change from baseline (CFB) in Hb level. At Week 16, the 
pegcetacoplan group (n = 41) had an adjusted mean hemoglobin CFB of 2.4 g/dL from a baseline 
of 8.7 g/dL, compared to the eculizumab group (n = 39) who had a CFB of –1.5 g/dL from a 
baseline of 8.7 g/dL, resulting in a 3.8 g/dL difference between treatment groups (P<.0001).  
Additionally, pegcetacoplan met noninferiority on the key secondary endpoints of transfusion 
avoidance and absolute reticulocyte count (ARC). Transfusion avoidance was shown in 85% in 
the pegcetacoplan group, but only 15.4% in the eculizumab group. The adjusted mean CFB in 
absolute reticulocyte count was –136 x109/L, in the pegcetacoplan group vs 28 x109/L in the 
eculizumab group, resulting in a treatment difference of –164 x109/L. 
Pegcetacoplan did not demonstrate noninferiority to eculizumab in the change from baseline in 
LDH. However, the adjusted mean CFB were comparable at Week 16; –15 U/L in the 
pegcetacoplan group vs –10 U/L in the eculizumab group. Noninferiority for the FACIT-Fatigue 
score was not assessed due to the prespecified hierarchical testing; however, the adjusted mean 
CFB was 9.2 points in the pegcetacoplan group vs -2.7 points in the eculizumab group with a 
difference of 11.9 points between treatment groups. The magnitude of this treatment difference 
in FACIT-Fatigue score (a 3-point increase is generally accepted as clinically significant), as 
well as the consistency of results favoring pegcetacoplan across all primary and secondary 
endpoints, suggests that these improvements in fatigue are meaningful, even though the study 
was conducted in an open-label fashion. 
The safety of pegcetacoplan was comparable to eculizumab in this randomized controlled 
Phase 3 study, with a similar incidence of adverse events in each study group. The most common 
adverse events reported during the randomized controlled treatment period were injection site 
reactions (ISR), hemolysis, abdominal pain, and diarrhea. While some TEAEs occurred more 
frequently in the pegcetacoplan group (eg, ISRs and diarrhea), others occurred more frequently 
in the eculizumab group (eg, hemolysis and headache). TEAEs such as ISRs and diarrhea that 
occurred more frequently in the pegcetacoplan group did not limit overall tolerability, as none 
were serious, severe, or led to study drug discontinuation. The incidence of serious adverse 
events (SAEs) were comparable between the 2 treatment groups. There were 4 serious infections 
during the study, but none required study drug discontinuation, and none were cases of 
meningitis. Although there were 3 subjects who discontinued pegcetacoplan due to hemolysis 
(7.3% in the pegcetacoplan group vs. 0 in the eculizumab group), adverse events of hemolysis 
occurred less frequently in the pegcetacoplan group than in the eculizumab group (9.8% vs 
28.2%, respectively). Therefore, discontinuation of pegcetacoplan due to hemolysis does not 
reflect a safety concern, but rather a return to the currently approved PNH therapy, eculizumab. 
Overall, pegcetacoplan was generally well tolerated with an acceptable safety profile that can be 
managed effectively with monitoring.  
 

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6.
RATIONALE
Phase 1 clinical experience has demonstrated that pegcetacoplan provides sustained inhibition of 
hemolytic activity in PNH patients who have never received treatment with a complement 
inhibitor (eg, eculizumab; Study APL2-CP-PNH-204 [Paddock]). To date, no safety signals have 
emerged from ongoing studies of pegcetacoplan in PNH patients that would preclude further 
development. Thus, this proposed Phase 3 study is to further evaluate treatment efficacy and 
safety of pegcetacoplan as monotherapy in patients with PNH. 
6.1. 
Purpose of the Study 
This is a 2-arm, controlled study comparing pegcetacoplan administration against standard of 
care (SOC) for patients with PNH. 
The SOC arm will exclude any concurrent or recent (within 3 months) use of complement 
inhibitors. 
6.2. 
Dose Selection 
6.2.1. 
Target Level of Pegcetacoplan Serum Concentration 
The toxicological data accumulated from the animal studies were used to guide dose selection 
during the Phase 1 single ascending dose and multiple ascending dose studies in healthy 
volunteers (HVs) (Study
, Study 
, and Study 
). In 
particular, the highest doses were selected, based on exposure predicted by a PK model, and 
compared with the exposures observed at the no observed adverse effect level (NOAEL) in 
cynomolgus monkeys.   
The planned dose of pegcetacoplan is 1080 mg SC twice weekly, equivalent to 308 mg/day. 
Dose selection is based on past clinical experience with SC pegcetacoplan, coupled with 
nonclinical toxicological studies. Daily doses up to 360 mg/day have been tested in past and 
ongoing clinical trials and have been found to be well tolerated, with exposures that are well 
below the pegcetacoplan levels associated with the NOAEL in monkeys. While doses of 
180 mg/day and above have been shown to be pharmacologically active in both HVs and PNH 
patients, clinical and biomarker responses increased in a dose-dependent manner and with the 
maximum benefits being observed at doses of either 270 or 360 mg/day.    
Using a target-mediated drug disposition (TMDD) pharmacokinetic/pharmacodynamic (PK/PD) 
model (Mager and Jusko 2001), the relationship between dosing regimen and pegcetacoplan 
serum concentration is well-understood and well-predicted by the model.  Figure 1 is the 
predicted PK profile for the planned dose of 1080 mg twice weekly (green line), compared to the 
NOAEL PK data observed in the pivotal 9-month chronic toxicological study in monkeys (Study 
 [black line]). For comparison with previous human exposure, also included is the 
summary PK data from the ongoing PNH study, 
 (270 mg/day Cohort [blue line]), 
and healthy volunteer study, 
, at 360 mg/day (brown line) and 1300 mg biweekly 
(biw) (light blue line).  Both studies demonstrated pegcetacoplan to be safe and well tolerated. 
The figure illustrates that the PK exposure at the proposed Phase 3 dosing regimen should only 
derive a small increase in PK exposure previously observed in the PNH study 270 mg/day 
Cohort (Study APL-CP0514), a lower PK exposure (maximum concentration [Cmax]) than that 
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observed in Study 
 (higher dose, 1300 mg biw) and should be safely below that 
observed at the NOAEL.  
6.2.2. 
Dosing Adjustment Option
If a subject does not respond sufficiently to the planned dose of 1080 mg twice weekly, the 
dosing regimen may be changed to 1080 mg every 3 days upon agreement with the sponsor. The 
premise being that, to derive a sufficient response in some subjects, a higher level of 
pegcetacoplan serum concentrations may need to be targeted. The adjusted dosing regimen will 
result in a higher PK exposure than that originally planned (twice weekly versus once every 
3 days). As illustrated in Figure 1, the increase in PK exposure will be small, continue to be 
lower (Cmax) than that observed in study
 (higher dose, 1300 mg twice weekly) and 
safely below that observed at the NOAEL. 
Details on the criteria to be used to determine whether a subject should receive the dosing 
adjustment is provided in Section 10.2.3.2. 
Figure 1: Predicted PK profile (green line) at the planned dose of 1080 mg biw, compared 
to the summary PK data at the NOAEL (
 [black line]), ongoing PNH 
study APL-CP0514 270 mg/day cohort (blue line) and healthy volunteer study 
 for both the 360 mg/day (brown line) and 1300 mg biw cohorts (light 
blue line). 
 
 
6.3. 
Risk/Benefit 
There is an anticipated health benefit for study participants from receipt of study drug. At the 
proposed dose levels of pegcetacoplan, a significant decrease in complement-mediated hemolytic 
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activity was observed in all pegcetacoplan-treated subjects (both treatment-naive and those 
treated previously with eculizumab) in PNH Phase 1b studies. Pegcetacoplan is, therefore, 
expected to reduce complement-mediated hemolytic activity in PNH patients. In this context, a 
careful evaluation of the risk/benefit ratio should be made.  
A number of safety monitoring procedures are being monitored and assessed within this protocol 
(including, but not limited to:  physical examination, vital signs monitoring at specified intervals, 
12-lead electrocardiogram [ECG], hematology, serum chemistry, urinalysis, coagulation, and 
prompt reporting of predefined adverse events [AEs]) in order to ensure the subjects’ safety.
Infusion site and pump-use safety will be assessed during clinical visits, where pegcetacoplan is 
administered (see Section 12.1.13). 
The volume of blood planned for collection from each subject over the course of the study (see 
Section 12.6) will be kept to a minimum to limit the impact on the overall health of these anemic 
subjects. 
Systemic complement inhibition might predispose individuals to infections caused by 
encapsulated organisms, including Streptococcus pneumoniae, Neisseria meningitidis 
(serogroups A, C, W, Y, and B), and Haemophilus influenza type B. Subjects will be required to
have documented evidence of vaccination against these within 2 years of screening or will be 
required to receive vaccination upon initiation of pegcetacoplan therapy.  Section 10.9 provides 
the details of the vaccination requirements and procedures for this study.  
Prophylactic antibiotic therapy is required for any subject who necessitates vaccination(s) up 
until, and for 14 days after the required vaccination(s) has/have been administered. Following 
this, or for any subject who does not require vaccination, prophylactic antibiotic therapy is 
recommended. Section 10.10 provides the details of the prophylactic antibiotic therapy 
requirements and procedures for this study. Administration of prophylactic antibiotic therapy 
should be conducted, at the discretion of the treating investigator, in accordance with local 
treatment guidelines for patients with PNH who are receiving treatment with a complement 
inhibitor.  
Body temperature and vital signs will be monitored at all clinic visits, as well as relevant blood 
parameters throughout the study, to assess for signs of infection. Subjects will be provided with 
emergency study cards that include a list of symptoms associated with the aforementioned 
infections. This study card also guides subjects with instructions to contact their study physician 
or seek emergency medical care in the event they experience any of the listed symptoms. In the 
event of a suspected infection, the principal investigator (PI) should provide guidance on 
appropriate action to be taken, thereafter. 
The use of silica reagents in coagulation panels should be avoided. Apellis previously conducted 
an investigation into prolonged activated partial thromboplastin time (aPTTs) observed in 
subjects treated with pegcetacoplan. It was confirmed that false positive aPTT prolongation 
occurred when coagulation panels were performed using a Stago Analyzer and, specifically, 
silica reagents. It was determined that there was interference between the silica reagents and 
PEGylated pegcetacoplan, resulting in artificially prolonged aPTTs. 
Details regarding the dosing regimen and administration of pegcetacoplan are provided in 
Section 10. Subjects should be instructed to take their pegcetacoplan treatment as prescribed, and 

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to contact the investigator immediately for guidance in the event of any missed doses.
Discontinuation with pegcetacoplan or noncompliance with the prescribed dose regimen may 
lead to the potential for an increased risk for serious hemolysis. The sponsor’s medical monitor 
should be contacted before interrupting or discontinuing treatment with pegcetacoplan. 
Apellis is not currently aware of any evidence associating pegcetacoplan use with specific risks 
or complications of coronavirus disease 2019 (COVID-19)  Apellis recognizes the need to 
consider the public health risks of the COVID-19 pandemic within the context of conducting a 
geographic location, Apellis will continue to evaluate the risk/benefit around study conduct on an 
ongoing and patient-by-patient basis.

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7.
STUDY OBJECTIVES AND ENDPOINTS
7.1. 
Primary Objective 
The primary objective of this study is to evaluate the efficacy of pegcetacoplan, compared to 
SOC (excluding complement inhibitors), in patients with PNH, as assessed by:  
 Hemoglobin stabilization defined as avoidance of a >1 g/dl decrease in Hb levels 
from baseline in the absence of transfusion through Week 26 (Yes/No) 
AND 
 Reduction in lactate dehydrogenase (LDH) level from baseline to Week 26  
7.2. 
Secondary Objectives 
Secondary objectives of this study are:  
 To evaluate the efficacy of pegcetacoplan, compared to SOC (excluding complement 
inhibitors), as assessed by: 
 Hemoglobin response (Yes/No) in the absence of transfusions (Hb response is 
 g/dL increase in Hb from baseline at Week 26)
 Change from baseline to Week 26 in absolute reticulocyte count  
 Change from baseline to Week 26 in Hb level  
 Number of packed red blood cell (PRBC) units transfused from baseline to 
Week 26 
 Change from baseline to Week 26 in Functional Assessment of Chronic 
Illness Therapy- (FACIT-) Fatigue Scale score
 Normalization of Hb levels (defined as 1 × the upper limit of normal [ULN]) 
from baseline at Week 26 in the absence of transfusions (Yes/No) 
N
× ULN from Week 4 to Week 26 in the 
absence of transfusions (Yes/No) 
 Change from baseline to Week 26 in European Organization for Research and 
Treatment of Cancer (EORTC) 30-item Core Quality of Life Questionnaire 
(QLQ C30) scores (Version 3) 
 Change from baseline to Week 26 in Linear Analog Assessment (LASA) scale 
scores
 Absolute reticulocyte count normalization (<1 × ULN) at Week 26 (Yes/No) 
 Time of failure of Hb stabilization  
 Time to transfusion 
To evaluate the safety of pegcetacoplan as assessed by:
Incidence and severity of treatment-emergent adverse events (TEAEs) 

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 Incidence of thromboembolic events 
 Changes from baseline in laboratory parameters 
Changes from baseline in ECG parameters
Incidence of anti-APL2 antibodies 
7.3. 
Exploratory Objectives 
Exploratory objectives of the study are to evaluate: 
 
 
 
 Pegcetacoplan PK/PD, as assessed by: 
 Pegcetacoplan PK concentrations from baseline to Week 26 
 Change from baseline to Week 26 in PNH clone distribution (RBCs and white 
blood cells [WBCs]) 
 Change from baseline to Week 26 in C3 deposition in PNH Type II and III 
RBCs  
 Complement levels from baseline to Week 26 (eg, total hemolytic 
complement activity assay [CH50], alternate complement pathway assay 
[AH50], and complement component 3 [C3]) 
 
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8.
STUDY DESIGN
Figure 2 depicts the study design. This is a randomized, multicenter, open-label, controlled 
study. The study will consist of a screening period of up to 4-weeks, followed by a randomized 
controlled period of 26 weeks. A total of approximately 54 patients with PNH who meet all of 
the inclusion criteria and none of the exclusion criteria will be randomized (2:1 ratio) to receive 
either pegcetacoplan or to remain on their current SOC (excluding complement inhibitors) only 
from Visit 2 (Day 1) to Visit 15 (Week 26).  All patients who complete Visit 15 (Week 26) may 
roll over into a separate open-label, long-term extension study, or will complete the safety 
follow-up (Visit 16 [Week 28], Visit 17 [Week 30], and Visit 18 [Week 34]).  
Figure 2: 
APL2-308 Study Design 
 
 
Abbreviations:  APL-2 = pegcetacoplan; Tx = treatment; V = visit; W = week. 
a Screening may occur up to 4 weeks prior to Visit 2. Subjects may proceed from Visit 1 to Visit 2 once eligibility is 
confirmed (there is no required duration between screening at Visit 1 and Visit 2). Within 5 days prior to Visit 2, 
each subject’s Hb must be evaluated by a local or central laboratory. If the subject meets the protocol-specified 
transfusion guidelines (see Section 10.7), the subject must receive a PRBC transfusion so that the subject’s Hb level 
no longer meets the protocol-specified requirements for PRBC transfusion. The posttransfusion Hb value should be 
confirmed by a local or central laboratory. Patients must not be randomized if they meet the protocol-specified 
requirements for transfusion.
b Subjects randomized to pegcetacoplan will be assigned pegcetacoplan at a dose of 1080 mg twice weekly. The 
dose may be adjusted to pegcetacoplan at a dose of 1080 mg every 3 days (see Section 10.2.3.2).  
c Subjects assigned to the SOC (excluding complement inhibitors) treatment arm will commence escape 
pegcetacoplan therapy if they are classified as a failure for the first co-primary endpoint (see Section 10.2.3.3).   
d All subjects who complete Visit 15 (Week 26) and do not elect to participate in the open-label extension study will 
be asked to return to the investigator site for the Visit 16 (Week 28), Visit 17 (Week 30), and Visit 18 (Week 34) 
follow-up visits.  Subjects who discontinue treatment will be encouraged to continue to attend study visits to 
complete study assessments (except for treatment with pegcetacoplan), as detailed in the Schedule of Events. At a 
minimum, subjects who discontinue dosing should complete follow-up procedures outlined in the Schedule of 
Events 2, 4, and 8 weeks after treatment discontinuation. If withdrawal of pegcetacoplan treatment is necessary, 
slow weaning should be considered and subjects should carefully be monitored for at least 8 weeks to detect serious 
hemolysis or other complications, as detailed in the investigator’s brochure. 
APL-2 Treatment B
EscapeC
SCREENING A
Standard of Care 
(excluding complement inhibitors)
For all subjects not 
enrolling in 
extension trial
RANDOMIZED CONTROLLED PERIOD
FOLLOW-UP PERIOD D
All 
Subjects
V1
V2
V3
V4
V5
V6
V7
V8
V9
V10
V11
V12
V13
V14
V15
Up to 4 
Weeks
W0            W2         W4         W6         W8        W10      W12      W14      W16     W18      W20      W22       W24       W26              W28         W30             W34    
V16
V17
V18

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Randomization will be stratified by the number of PRBC transfusions within the 12 months prior 
to screening (<4; 
) (ie, number of transfusion events regardless of PRBC units transfused). 
The protocol-specified transfusion threshold is that a PRBC transfusion will be administered if 
Hb is <7 
and <9 g/dL with signs or symptoms of sufficient severity to warrant a 
transfusion. The corrected pretransfusion and posttransfusion Hb and number of units transfused 
must be documented in the case report form (CRF) (see Section 10.7).  
Within 5 days prior to Visit 2 (Week 0), each subject’s Hb must be evaluated by a local or 
central laboratory. If the subject meets the protocol-specified transfusion guidelines described 
above, the subject must receive a PRBC transfusion so that the subject’s Hb level no longer 
meets the protocol-specified requirements for PRBC transfusion. The post-transfusion Hb value 
should be confirmed by a local or central laboratory. Subjects must not be randomized if they 
meet the protocol-specified requirements for transfusion, and the Hb assessment to confirm 
eligibility should be scheduled so that the subject does not fall outside the screening window (up 
to Day –28). Screening-period Hb requirements to determine Hb eligibility are depicted in
Figure 3. 
On Day 1, subjects will be randomized to either pegcetacoplan or SOC (excluding complement 
inhibitors) using a 2:1 ratio. During the randomized controlled period, subjects will return to the 
clinical site every 2 weeks until Week 26 for efficacy and safety assessments. 
Subjects randomized to the SOC (excluding complement inhibitors) arm will continue to receive 
SOC treatment (with transfusions allowed per the instructions of the protocol), but will not be 
allowed to receive treatment with a complement inhibitor (eg, eculizumab) unless they qualify 
for pegcetacoplan escape therapy (see Section 10.2.3.3).  Similarly, subjects randomized to 
pegcetacoplan will not be allowed to receive treatment with other complement inhibitors. 
If, at any point during the study, any subject assigned to the SOC (excluding complement 
inhibitors) treatment arm that qualifies as a failure for the first co-primary endpoint will be 
offered early escape therapy with pegcetacoplan (see Section 10.2.3.3). 
Subjects who reach Visit 15 (Week 26) will be offered entry into an open-label extension study 
to continue treatment with pegcetacoplan. Visit 15 of Study APL2-308 will serve as the first visit 
for the open-label extension. These subjects will not complete the follow-up procedures detailed 
in this protocol.  
All subjects who complete Visit 15 (Week 26) and do not elect to participate in the open-label 
extension study will be asked to return to the investigator site for the Visit 16 (Week 28), 
Visit 17 (Week 30), and Visit 18 (Week 34) follow-up visits.  Subjects who discontinue 
treatment will be encouraged to continue to attend study visits to complete study assessments 
(except for treatment with pegcetacoplan), as detailed in the Schedule of Events (Section 4).  At 
minimum, subjects who discontinue dosing should complete follow-up procedures outlined in 
the Schedule of Events (Section 4) 2, 4, and 8 weeks after treatment discontinuation.  If 
withdrawal of pegcetacoplan treatment is necessary, slow weaning should be considered, and 
subjects should carefully be monitored for at least 8 weeks to detect serious hemolysis or other 
complications, as detailed in the IB. 
An external, independent data monitoring committee (DMC) will assess the safety/tolerability 
data of the study periodically. 

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Subjects who fail the screening procedures should not be rescreened for the study unless this is 
agreed upon in advance and documented in writing by the sponsor. 

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9.
SUBJECT SELECTION
The study is planned to randomize approximately 54 subjects with PNH. 
9.1.
Inclusion Criteria
At Visit 1 screening, subjects must fulfill all of the following inclusion criteria to be eligible for 
participation in the study: 
1. Be at least 18 years old (inclusive). 
2. Have LDH 1.5 × ULN at the screening visit. 
3. Have PNH diagnosis, confirmed by high sensitivity flow cytometry (granulocyte or 
monocyte clone >10%). 
4. Have Hb less than the lower limit of normal (LLN) at the screening visit.  
5. Have ferritin greater than/equal to the LLN, or total iron binding capacity (TIBC) less 
than/equal to ULN at the screening visit, based on central laboratory reference ranges. If 
a subject is receiving iron supplements at screening, the investigator must ensure that the 
subject’s dose has been stable for 4 weeks prior to screening, and it must be maintained 
throughout the study. Subjects not receiving iron at screening must not start iron 
supplementation during the course of the study. 
6. Body mass index (BMI) 35 kg/m2 at the screening visit.
7. Have a platelet count of >50,000/mm3 at the screening visit. 
8. Have an absolute neutrophil count >500/mm3 at the screening visit. 
9. Women of childbearing potential (WOCBP) must have a negative pregnancy test at 
screening and must agree to use protocol-defined methods of contraception for the 
duration of the study and for 90 days after their last dose of study drug. 
10. Males must agree to use protocol-defined methods of contraception and agree to refrain 
from donating sperm for the duration of the study and for 90 days after their last dose of 
study drug. 
11. Have vaccination against Streptococcus pneumoniae, Neisseria meningitidis (types A, C, 
W, Y, and B), and Haemophilus influenzae (type B) either within 2 years prior to Day 1 
dosing, or agree to receive vaccination 14 days after starting treatment with 
pegcetacoplan (along with prophylactic antibiotic therapy for at least the 14 days between 
pegcetacoplan treatment initiation and vaccination and for 14 days post vaccination).  
Vaccination is mandatory, unless documented evidence exists that subjects are 
nonresponders to vaccination (as evidenced by titers or display titer levels within 
acceptable local limits).  
12. Be willing and able to give informed consent. 
9.1.1. 
Approved Methods of Contraception 
Approved methods of contraception include:  oral contraceptives, intrauterine device, medically 
acceptable barrier methods (diaphragm or condom), implantable or injectable contraceptives (eg, 

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Depo-Provera) or removable birth control device (eg, NuvaRing or Ortho Evra patches); sexual 
abstinence (defined as refraining from heterosexual intercourse during the entire period of risk 
associated with the study treatments); and/or surgical sterilization (at least 6 months before 
dosing).  Sexual abstinence is only accepted when it is the preferred and usual lifestyle of the 
subject. Subjects not practicing abstinence as defined above and/or subjects practicing coitus 
interruptus (pull-out method) must agree to use an approved method of contraception during the 
study and 90 days after their last dose of study drug. 
9.2. 
Exclusion Criteria 
Subjects will be excluded from the study if there is evidence of any of the following criteria at 
screening: 
13. Treatment with any complement inhibitor (eg, eculizumab) within 3 months prior to 
screening.  
14. Hereditary complement deficiency. 
15. History of bone marrow transplantation. 
16. Concomitant use of any of the following medications is prohibited if not on a stable 
regimen for the time period indicated below prior to screening: 
 Erythropoietin or immunosuppressants for at least 8 weeks 
 Systemic corticosteroids for at least 4 weeks 
Vitamin K antagonists (eg, warfarin) with a stable international normalized 
ratio (INR) for at least 4 weeks 
 Iron supplements, vitamin B12, or folic acid for at least 4 weeks 
 Low-molecular-weight heparin for at least 4 weeks 
17. History or presence of hypersensitivity or idiosyncratic reaction to compounds related to 
the investigational product or SC administration. 
18. Participation in any other investigational drug trial or exposure to other investigational 
agent, device, or procedure within 30 days or 5 half-lives, whichever is longer. 
19. Planning to become pregnant or currently a breastfeeding woman. 
20. History of meningococcal disease. 
21. Any comorbidity or condition (such as malignancy) that, in the opinion of the 
investigator, could put the subject at increased risk or potentially confound study data. 

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9.3.
Randomization Criteria
At Visit 2 (Day 1), subjects must meet the following criteria in order to be randomized: 
1. Subjects must have Hb 
 g/dL, or Hb 7 g/dL and <9 g/dL without signs or symptoms 
of sufficient severity to warrant a transfusion.
2. Negative urine pregnancy test for WOCBP. 
3. No active systemic bacterial, viral, or fungal infection within the 2-week period prior to 
receiving treatment with pegcetacoplan. 

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10.
STUDY TREATMENTS
10.1. 
Identity of Investigational Product 
The test product is pegcetacoplan, which will be provided as a sterile solution of pegcetacoplan
(54 mg/mL) in acetate-buffered sorbitol, supplied in stoppered glass vials. Additional 
information regarding the investigational product is provided in the pegcetacoplan IB. 
10.1.1. 
Blinding the Treatment Assignment  
This is an open-label study. Treatment assignment will not be blinded.  
10.2.
Administration of Investigational Product
10.2.1. 
Interactive Response Technology (IRT) for Investigational Product Management 
A centralized IRT will be utilized for (but not limited to) the following investigational product 
management tasks:  randomization; investigational product supply management; inventory 
management and supply ordering; expiration tracking; and return of investigational product (if 
applicable). Please refer to the IRT Manual for further information. 
10.2.2. 
Allocation to Treatment 
Subjects who meet all the inclusion criteria and none of the exclusion criteria at screening 
(Visit 1), along with the randomization criteria at Visit 2 (Day 1), will be eligible to enter the 
study. Subjects will be randomly assigned at a 2:1 ratio to either the pegcetacoplan treatment arm 
or the SOC (excluding complement inhibitors) controlled treatment arm. 
Subject numbers are assigned to all subjects as they consent to take part in the study.  
The randomization number represents a unique number corresponding to the treatment arm 
allocated to the subject, once eligibility has been determined. 
The randomization will be stratified by the number of PRBC transfusions within the 12 months 
prior to Day –28 (<4
4) (ie, number of transfusion events regardless of PRBC units transfused). 
Individual subject treatment will be automatically assigned by the IRT. 
10.2.3. 
Pegcetacoplan Dosing 
Starting at Visit 2 (Day 1), subjects assigned to the pegcetacoplan treatment arm will receive SC 
infusions pegcetacoplan at a dosage of 1080 mg twice weekly. During the course of the study, 
subjects may be switched to an alternate dosing regimen of pegcetacoplan at 1080 mg every 
3 days, if warranted, based on clinical response and agreement from the sponsor (see 
Section 10.2.3.2). 
Dosing diaries will be utilized for pegcetacoplan and are to be completed for each dose 
administered at the study site or outside regular clinic visits. Subjects should not deviate from 
their pegcetacoplan dosing schedule:  Day 1 and Day 4 of each treatment week (eg, 
Monday/Thursday/Monday) or every 3 days (eg, Monday/Thursday/Sunday).  
Note:  Discontinuation with pegcetacoplan or noncompliance with the prescribed dose regimen 
may lead to the potential for an increased risk for serious hemolysis. Subjects should be 

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instructed to take their pegcetacoplan treatment as prescribed, and to contact the investigator 
immediately for guidance in the event of any missed doses. If withdrawal of pegcetacoplan 
treatment is necessary or a subject completes the trial and does not elect to participate in the 
extension study, slow weaning should be considered, and subjects should carefully be monitored 
for at least 8 weeks to detect serious hemolysis or other complications, as detailed in the IB. 
10.2.3.1. Pegcetacoplan Administration
Pegcetacoplan will be administered as a 20-mL SC infusion. The preferred site of infusion will 
be the abdomen; however, if a subject does not tolerate administration to the abdomen, 
alternative sites may be considered. 
For subjects randomized to the pegcetacoplan treatment arm, research nurses or other 
appropriately qualified research personnel will administer the first pegcetacoplan SC infusion at 
Visit 2 (Day 1) and will train subjects on how to self-administer.  Following Visit 2, 
appropriately qualified research personnel will supervise self-administration of pegcetacoplan for 
the following 3 doses (which will occur prior to Visit 3 [Week 4]). Supervision of self-
administration may be conducted at the subject’s home, at the study site, or at an off-site location 
convenient for the subject. Supervision of self-administration must continue until the subject is 
qualified to self-administer. 
Subjects randomized to the SOC (excluding complement inhibitors) treatment arm may qualify 
to receive pegcetacoplan escape therapy, as described in Section 10.2.3.3.  Subjects assigned to 
pegcetacoplan escape therapy will have research nurses or other appropriately qualified research 
personnel administer the first pegcetacoplan SC infusion and provide self-administration training 
at the study visit in which pegcetacoplan escape therapy is initiated, with the 3 doses following 
that visit supervised by appropriately qualified research personnel as detailed above. 
Following self-administration qualification, subjects may self-administer pegcetacoplan SC 
infusions without supervision at home, or at an off-site location convenient to the subject. 
Subjects may choose to continue to self-administer pegcetacoplan infusions at the study site on 
scheduled dosing days when a study visit coincides, although this is not required. 
Self-administration conducted at the study site will be supervised to ensure that the subject 
continues to remain compliant with the administration guidelines.
NOTE:  Self-administration may also be conducted by a member of the subject’s household or 
family member, etc. It is not intended to be restricted to the individual subject. Please refer to the 
Study Operations Manual for further details regarding the self-administration qualification. 
10.2.3.2. Pegcetacoplan Dose Adjustments 
Following commencement of monotherapy with pegcetacoplan, ie, at Day 1 (randomization; for 
subjects assigned to the pegcetacoplan treatment arm) or at any point following assignment to 
escape therapy with pegcetacoplan (see Section 10.2.3.3), LDH will be monitored as part of the 
scheduled assessments at the planned clinic visits. After Visit 4 (Week 4; after steady state has 
been achieved), for any subject receiving pegcetacoplan monotherapy, if LDH is >2 × ULN on 1 
occasion, a pegcetacoplan dose increase to 1080 mg every third day should be considered (see 
Section 6.2).  Any adjustment in dose will be discussed and confirmed, in writing, by Apellis. In 
the event of a dose increase, LDH will be monitored biweekly (unscheduled assessments, if 
applicable) for at least 4 weeks to assess the impact of the dose adjustment on LDH levels. 

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Decisions to escalate or de-escalate between the 2 pegcetacoplan dose regimens may be made by 
the sponsor.  
Doses above pegcetacoplan at 1080 mg every third day may be considered, if clinically 
indicated. Prior to implementation review by the DMC and institutional review board 
(IRB)/independent ethics committee (IEC) will occur and consist of examination of all 
cumulative safety, tolerability and efficacy data (eg, physical examinations, ECGs, vital signs, 
clinical laboratory tests, and AEs) and a thorough assessment of all safety data.  PK/PD data and 
predicted exposure for subsequent doses, based on emerging PK data, will also be reviewed prior 
to determining any proposed dose adjustment.  
10.2.3.3. Pegcetacoplan Escape Therapy  
Following Visit 2 (Week 0), subjects assigned to the SOC (excluding complement inhibitors) 
treatment arm who have an Hb level measured by the central laboratory that is 2 g/dL below the 
baseline value will be offered the opportunity to receive escape therapy with pegcetacoplan.  
In addition, if a subject presents with a thromboembolic event during this period, and the 
investigator excludes other possible causes of thrombosis and believes that the event was 
secondary to PNH, he/she may request a discussion with Apellis’ clinical team to evaluate 
whether the subject might be a candidate for escape therapy. Approval, if granted, will be 
documented in writing. 
Once it is confirmed that a subject randomized to the SOC (excluding complement inhibitors) 
treatment arm qualifies for and agrees to receive pegcetacoplan escape therapy, the subject 
should be encouraged to return to the site for an unscheduled visit to begin treatment with 
pegcetacoplan. Procedures for this visit are provided in Section 11.3. 
10.3. 
Labeling, Packaging, Storage, and Handling 
10.3.1. 
Labeling
Labels containing study information and pack identification are applied to the investigational 
product(s) container. 
All investigational product is labeled with a minimum of the following:  protocol number; 
dosage form (including product name and quantity in pack); route of administration; directions 
for use; storage conditions; batch number and/or packaging reference; the statements, “For 
clinical trial use only,” and/or “CAUTION: New Drug – Limited by Federal (or US) Law to 
Investigational Use,” and name/address of sponsor. 
Space is allocated on the label so that the site representative can record a unique subject 
identifier and date dispensed by the site to the subject. 
Additional labels may, on a case-by-case basis, be applied to the investigational product in order 
to satisfy national, local, or institutional requirements, but it must not: 
 Contradict the clinical study label 
 Obscure the clinical study label 
 Identify the study subject by name 

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Additional labels may not be added without the sponsor’s prior full agreement.
10.3.2.
Packaging
Investigational product is supplied in 20-cc glass vials. 
Changes to sponsor-supplied packaging prior to dosing may not occur without full agreement, in 
advance, by the sponsor. 
10.3.3. 
Infusion Supplies 
The sponsor will supply syringes, vial adapters, infusion sets, and ambulatory syringe infusion 
pumps, as required. Refer to the Study Operations Manual for further details. 
10.3.4. 
Storage 
The investigational product should be stored refrigerated at 2 to 8°C. 
The investigator has overall responsibility for ensuring that investigational product is stored in a 
secure, limited-access location. Limited responsibility may be delegated to the pharmacy or 
member of the study team, but this delegation must be documented. 
A pharmacist or appropriately qualified designated person will be responsible for storing the 
investigational product at the site appropriately and dispensing the vials of investigational 
product to the subject. The pharmacist/nominated team member will enter the unique subject 
identifier on the investigational product bottle/carton labels, as they are distributed. 
Temperature monitoring is required at the investigator site (or documented storage location) to 
ensure that the investigational product is maintained within an established temperature range. 
The investigator is responsible for ensuring that the temperature is monitored at the site 
throughout the duration of the study and that records are maintained. 
Subjects who are dispensed investigational product must be instructed on appropriate 
transportation requirements and storage conditions in their home environment. Subjects will not 
be required to log or record the temperature at which their investigational product is stored. 
10.4.
Investigational Product Accountability
Investigators will be provided with sufficient amounts of the investigational product to carry out 
this protocol for the agreed number of subjects. The investigator or designee will acknowledge 
receipt of the investigational product, documenting shipment content and condition. Accurate 
records must be maintained of all investigational product dispensed, used, returned, and/or 
destroyed. The investigator is responsible for ensuring the retrieval of all required study supplies 
from subjects. 
At the conclusion of the study, any unused investigational product will either be destroyed at the 
investigator site or be returned to the sponsor or designee for destruction, and destruction will be 
documented appropriately. If no supplies remain, this fact will be documented appropriately. 
10.5. 
Subject Compliance 
Subjects must be instructed to bring their empty/used investigational product packaging to every 
visit. The pharmacist/nominated person will record details on the drug accountability form. 

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Subjects will be instructed on the specific investigational product packaging that will be required 
to return to the site.
10.6. 
Control:  Standard of Care (Excluding Complement Inhibitors) 
Subjects randomized to SOC (excluding complement inhibitors) are eligible to receive any 
treatment considered to be local SOC except for complement inhibitors. Any transfusions 
received must be reported.   
Iron supplementation requirements are detailed in Section 10.8. 
10.7. 
Transfusions 
Transfusion history collected at the Screening Visit (Visit 1; up to Week –4) is described in 
Section 12.1.3. 
During the study treatment period (Visit 2 [Week 0] to Visit 15 [Week 26]), transfusions will be 
administered if subjects have either of the following:  
 Hb is <7 g/dL  
 
 g/dL - <9 g/dL with symptoms.  
In addition, Hb, LDH, and reticulocyte count should be collected PRIOR to any transfusion. The 
assessment may be performed at a central or certified local laboratory. 
If these criteria are not met and the PI believes that a transfusion is necessary, the PI should 
discuss with the sponsor before administering the transfusion. Transfusions that do not meet this 
criterion will be considered protocol deviations and may lead to data being excluded from the 
primary analysis. 
10.8. 
Prior and Concomitant Treatment 
Prior medications (including vitamins and herbal preparations), including those discussed in the 
exclusion criteria (Section 9.2), and procedures (any therapeutic intervention, such as 
surgery/biopsy or physical therapy) the subject takes or undergoes within 28 days (or 2 years for 
documentation of vaccination [see Section 11.2.2.2]) prior to the start of screening (Visit 1) until 
the first dose of study drug will be recorded on the subject’s CRF. 
Concomitant treatment refers to all treatment taken between the dates of the first dose of 
investigational product and the end of the follow-up period, inclusive. Concomitant treatment 
information must be recorded on the appropriate CRF page. Except for complement inhibitors 
(other than pegcetacoplan [eg, eculizumab]) and/or phlebotomy/venesection for iron overload, 
any concomitant medication deemed necessary for the subject’s SOC during the study, or for the 
treatment of any AE (along with the allowed medications described below) may be given at the 
discretion of the investigator.  It is the responsibility of the investigator to ensure that the details 
regarding all medications are recorded in full in the subject’s CRF. 
The following concomitant medications are allowed if the following conditions apply, and dose 
adjustments are not expected during the randomized controlled period (Visit 2 to Visit 15): 

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 Erythropoietin, if the subject has been receiving a stable dose for at least 8 weeks 
before screening. 
 Immunosuppressants, if the subject has been receiving a stable dose for at least 
8 weeks before screening. 
 Corticosteroids, if the subject has been receiving a stable dose for at least 4 weeks 
before screening. 
 Vitamin K antagonists (eg, warfarin) with a stable INR for at least 4 weeks before 
screening. 
 Iron supplements, vitamin B12, or folic acid, if the subject has been receiving a stable 
dose for at least 4 weeks before screening. If patients have previously received and 
tolerated iron chelation, this may be continued or reinitiated throughout the study if 
clinically indicated and upon discussion with the sponsor’s medical monitor. 
 Low-molecular-weight heparin, if the subject has been receiving a stable dose for at 
least 4 weeks before screening. 
If clinically indicated and deemed in the best interest of the subject, the frequency or dose level 
of any of the above may be adjusted by the investigator in consultation with the Apellis medical 
monitor. 
10.9. 
 Vaccination 
In order to receive treatment with pegcetacoplan, subjects must have documented evidence of 
vaccination against the following within 2 years of screening:  
 Neisseria meningitidis types A, C, W, Y, and B (administered as 2 separate 
vaccinations)  
 Streptococcus pneumoniae (with a PCV13 or PPSV23 vaccine)  
 Haemophilus influenzae type B (Hib vaccine).  
Subjects randomized to pegcetacoplan: For subjects randomized to pegcetacoplan who do not 
have documented evidence of receiving any of the above vaccinations within 2 years prior to 
screening, the required missing vaccination(s) will be administered at Visit 3 (Week 2), prior to 
dosing with pegcetacoplan (along with boosters administered during the study at or after Visit 7 
[Week 10], if required [see below]).  Vaccination is mandatory, unless documented evidence 
exists that subjects are nonresponders to vaccination (as evidenced by titers or display titer levels 
within acceptable local limits). The PI will discuss with the sponsor regarding individual patient 
circumstances.  
If the subject requires vaccination against Neisseria meningitidis, a booster (for both 
vaccinations) should be administered after at least 8 weeks (Visit 7).  
If the subject requires vaccination against Streptococcus pneumoniae, PCV13 will be 
administered at Visit 3, and PPSV23 will be administered after at least 8 weeks (Visit 7). 
Subjects randomized to SOC (excluding complement inhibitors):  Subjects who are initially 
randomized to SOC (excluding complement inhibitors) who become eligible for pegcetacoplan 

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escape therapy will receive any required vaccination(s) 2 weeks after initiation of treatment with 
pegcetacoplan. If required as detailed above, the Neisseria meningitidis booster (for both 
vaccinations), and/or PPSV23 vaccination should be administered at least 8 weeks following the 
initial vaccination(s). 
10.10. 
 Prophylactic Antibiotics 
In order to receive treatment with pegcetacoplan, subjects will require preventive antibiotics, as 
detailed below.  
Subjects randomized to pegcetacoplan:  Subjects will be required to take ciprofloxacin 500 mg 
twice daily from Visit 2 (Week 0) to Visit 3 (Week 2) and continue to receive antibiotic 
prophylaxis until 14 days post vaccination. From that point forward, it is recommended that 
subjects take penicillin V 500 mg twice daily through the course of pegcetacoplan treatment. 
Subjects randomized to SOC (excluding complement inhibitors):  Subjects who are initially 
randomized to SOC (excluding complement inhibitors) do not need to initiate preventive 
antibiotic therapy at Day 1. If a subject becomes eligible for and initiates pegcetacoplan escape 
therapy, the subject is required to take ciprofloxacin 500 mg twice daily for 2 weeks, beginning 
on the first day of treatment with pegcetacoplan and continue to receive antibiotic prophylaxis 
until 14 days post vaccination. After 2 weeks of ciprofloxacin, it is recommended that subjects 
take penicillin V 500 mg twice daily through the course of pegcetacoplan treatment.  
10.11. 
Rescue Antibiotics 
Body temperature, vital signs, and relevant blood parameters will be monitored regularly 
throughout the study to assess for signs of infection. Subjects will be provided with emergency 
study cards that include a list of symptoms associated with infections. This study card also 
guides subjects with instructions to contact their study physician or seek emergency medical care 
in the event they experience any of the listed symptoms. In the event of a suspected infection, the 
PI should provide guidance on appropriate action to be taken, thereafter. Action to be taken may 
include administration of a broad-spectrum antibiotic. 

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11.
STUDY PROCEDURES
Please see the Schedule of Events (Section 4) for a summary of the schedule of study 
participation and procedures.  The schedule of visit dates should be established, either prior to or 
at the time of screening, allowing subjects an opportunity to assess whether there are likely to be 
significant conflicts with other activities or planned absences. To the extent possible, subjects 
will be expected to adhere to the visit schedule and any re-scheduling of visits outside of the 
window specified in the Schedule of Events (Section 4) must be agreed upon, in advance, with 
the PI and sponsor.  
11.1.
Screening Period: Visit 1 (up to Week –4 [Day –28]) 
Screening procedures are listed in the Schedule of Events (Section 4). 
The subject will be screened to confirm that the subject-selection criteria for the study has been 
met. Informed consent will be obtained at screening prior to any study-related procedures being 
conducted (see Section 15.3).  
A screen failure is a subject who has given informed consent and failed to meet at least 1 of the 
inclusion criteria and/or met at least 1 of the exclusion criteria and has not been randomized or 
administered investigational product(s).  
Subjects should not be rescreened once they have been designated as a screen failure unless this 
is discussed in advance with the sponsor and documented in writing.  
Sufficient supplementation of iron, folic acid, and vitamin B12 must be confirmed prior the 
initiation of the Randomized Controlled Period.  Subjects taking supplements need to be on a 
stable dose 4 weeks prior to screening.   
The following assessments will be performed:
Informed consent 
 Demographics 
 Height/Weight 
 Medical history (including thrombosis history) 
Transfusion history
 Review of inclusion/exclusion criteria 
 Physical examination  
 Triplicate 12-lead ECG  
 Prior and concomitant medications 
 Vital sign measurements 
Urinalysis 
Blood tests (see Schedule of Events [Section 4] for details)
Buccal swab test (genotyping for Gilbert’s Syndrome) 

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 Adverse event assessment 
11.1.1. 
Hemoglobin Stability:  Randomization Criteria 
Within 5 days prior to Visit 2 (Week 0), each subject’s Hb must be evaluated by a local or 
central laboratory.  It is not required that the subject’s lab draw occur at the study site.  If the 
subject meets the protocol-specified transfusion guidelines described above, the subject must 
receive a PRBC transfusion so that the subject’s Hb level no longer meets the protocol-specified 
requirements for PRBC transfusion.  The posttransfusion Hb value should be confirmed by a 
local or central laboratory.  Subjects must not be randomized if they meet the protocol-specified 
requirements for transfusion as outlined in Section 10.7.  The blood draw to confirm Hb 
eligibility for study entry should be scheduled so that the subject is able to receive transfusion if 
necessary for study entry without falling out of the 28-day screening window. Figure 3 provides 
a graphic depiction of the Hb confirmation process for study entry between Visit 1 and Visit 2. 

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11.2.
Randomized Controlled Period: Visit 2 (Week 0) to Visit 15
(Week 26) 
11.2.1. 
Visit 2:  Day 1 
Following completion of the Screening Period, subjects will enter the Randomized Controlled 
Period and will be randomized to either the pegcetacoplan treatment arm or SOC (excluding 
complement inhibitors) treatment arm. Assessments will be performed as listed below and in the 
Schedule of Events (Section 4). 
Baseline values for subjects randomized to the pegcetacoplan treatment arm will be those
measurements taken prior to the start of study treatment. 
Prior to randomization and dosing: 
 
 
 Triplicate 12-lead ECG:  within 1 hour predose  
 Physical examination 
 Concomitant medications review
 Confirm inclusion/exclusion criteria
 Vital sign measurements 
 Urinalysis 
 Blood tests (see schedule of events [Section 4] for details) 
 Urine pregnancy test 
 FACIT-Fatigue scale
 LASA for Quality of Life 
 EORTC QLQ-C30 
 Randomization  
For subjects randomized to pegcetacoplan treatment arm only:
 Dispense investigational product and infusion materials 
 Train subject to perform home infusion  
 Pegcetacoplan infusion 
Assess infusion site
Vital sign measurements (2 hours post dose [±30 minutes])
Subjects will be required to have documented evidence of vaccination against Streptococcus 
pneumoniae, and Neisseria meningitidis (serogroups A, C, W, Y, and B), and Haemophilus 
influenza type B within 2 years of screening or will be required to receive vaccination upon 
initiation of pegcetacoplan therapy.  Section 10.9 provides the details of the vaccination 
requirements and procedures for this study.  
CCI

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Prophylactic antibiotic therapy is required for any subject taking pegcetacoplan. Section 10.10
provides the details of the prophylactic antibiotic therapy requirements and procedures for this 
study.  
11.2.2. 
Visit 3 to Visit 15 (Week 2 to Week 26) 
Through the Randomized Controlled Period, subjects randomized to the pegcetacoplan treatment 
arm will receive self-administered SC doses 1080 mg of pegcetacoplan twice weekly or every 
3 days, and subjects randomized to the SOC (excluding complement inhibitors) treatment arm 
will continue their SOC therapy. Subjects assigned to the SOC (excluding complement 
inhibitors) treatment arm may be assigned to pegcetacoplan escape therapy during the course of 
the Randomized Controlled Period if they meet the criteria to switch to escape therapy as 
detailed in Section 10.2.3.3. 
Study visits at the investigator site will be conducted biweekly from Visit 3 (Week 2) to Visit 15 
(Week 26). All visits will have a ±3-day visit window. 
Subjects may self-administer pegcetacoplan infusions at the study site but are not required to do 
so if the visit is not occurring on a scheduled dosing occasion.  Outside of study visit days, 
subjects will self-administer pegcetacoplan infusions at the subject’s home or at an off-site 
location convenient for the subject.  
Assessments will be performed as listed below and in the Schedule of Events (Section 4). 
 Vital sign measurements (performed prior to ECG and venipuncture)  
 Triplicate 12-lead ECG (prior to blood draw:  Weeks 4, 8, 12, 16, 20, and 26 only) 
 Concomitant medications review 
 Adverse event review 
 Urinalysis (Weeks 4, 8, 10, 12, 16, 18, 22, 24, and 26 only) 
 Blood tests (see Schedule of Events [Section 4] for details) 
 Urine pregnancy test  
 FACIT-Fatigue scale (Weeks 4, 8, 12, 16, 20, and 26 only) 
 LASA for Quality of Life (Weeks 4, 8, 12, 16, 20, and 26 only) 
 EORTC QLQ-C30 (Weeks 4, 8, 12, 16, 20, and 26 only) 
 Physical examination (Week 16 only) 
 Vaccination (Week 2 and Week 10 [if necessary], or following initiation of 
pegcetacoplan escape therapy; see Section 10.9) 
For subjects randomized to pegcetacoplan treatment arm or receiving pegcetacoplan 
escape therapy: 
 Dispense investigational product and infusion materials 
 Reconcile used investigation product returned by the patient 

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For subjects administering pegcetacoplan at the study visit:
Infuse pegcetacoplan
 Assess infusion site 
Subjects who reach Visit 15 (Week 26) of the Randomized Controlled Period will be offered 
entry into an open-label extension study, if eligible, per the extension study’s inclusion and 
exclusion criteria. For subjects who elect to enter the open-label extension study, Visit 15 will 
also serve as the first visit of the open-label extension study and follow-up procedures as detailed 
in this protocol will not be conducted. 
Subjects who do not enter the open-label extension study will complete the follow-up visits and 
will exit the study (see Section 11.4). 
11.2.2.1. Pegcetacoplan Administration Training 
Please see Section 10.2.3.1 for self-administration training requirements for subjects randomized 
to the pegcetacoplan treatment arm, or subjects who begin pegcetacoplan escape therapy during 
the course of the Randomized Controlled Period. 
11.2.2.2. Vaccination and Prophylactic Antibiotic Procedures 
Subjects will be required to have documented evidence of vaccination against Streptococcus 
pneumoniae, Neisseria meningitidis (serogroups A, C, W, Y, and B), and Haemophilus influenza 
type B within 2 years of screening or will be required to receive vaccination upon initiation of 
pegcetacoplan therapy.  Section 10.9 provides the details of the vaccination requirements and 
procedures for this study.  
Prophylactic antibiotic therapy is required for any subject that necessitates vaccination(s) until 
the required vaccination(s) has/have been administered and for 14 days post vaccination. 
Section 10.10 provides the details of the prophylactic antibiotic therapy requirements and 
procedures for this study.  
11.3. 
Pegcetacoplan Initiation Visit (for SOC [Excluding Complement 
Inhibitors] Treatment Arm Failures) 
Following Visit 2 (Week 0), subjects assigned to the SOC (excluding complement inhibitors) 
treatment arm who have a Hb level measured by the central laboratory that is 2 g/dL below the 
baseline value will be switched to escape therapy with pegcetacoplan. 
These subjects will return to the site for a pegcetacoplan initiation visit.  Assessments will be 
performed as listed below and in the Schedule of Events (Section 4). 
Prior to dosing: 
 Concomitant medications review
 Adverse event review
 Vital sign measurements 
 PK sample (see Schedule of Events [Section 4] for details) 

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 Dispense investigational product and infusion materials 
 Train subject to perform home infusion  
Pegcetacoplan infusion 
Assess infusion site
Vital sign measurements (2 hours post-dose [±30 minutes])
Following the pegcetacoplan initiation visit, subjects will maintain their regular visit schedule. 
11.4. 
Follow-up (if Required):  Visit 16 (Week 28), Visit 17 (Week 30), and 
Visit 18 (Week 34) 
All subjects who complete Visit 15 (Week 26) and do not elect to participate in the open-label 
extension study will be asked to return to the investigator site for the Visit 16 (Week 28), 
Visit 17 (Week 30), and Visit 18 (Week 34) follow-up visits.  
In addition, subjects who discontinue treatment and elect to withdraw prior to completing 
Visit 15 (Week 26) should complete the procedures outlined in this section 2, 4, and 8 weeks 
after treatment discontinuation. 
The Visit 16 (Week 28) follow-up visit has a visit window of ±3 days. The Visit 17 (Week 30) 
and Visit 18 (Week 34) follow-up visits have a visit window of ±7 days.  
Assessments listed below and outlined in the Schedule of Events (Section 4), will be performed: 
 Vital sign measurements (performed prior to ECG and venipuncture)  
 Triplicate 12-lead ECG 
 Concomitant medications 
Adverse event review
 Urinalysis  
Blood tests (see Schedule of Events [Section 4] for details)
 Urine pregnancy test  
 FACIT-Fatigue scale 
 LASA for Quality of Life 
 EORTC QLQ-C30  
 Physical examination  
 Reconcile used investigational product returned by the patient 
11.5. 
Unscheduled Visits 
Subjects may be asked to return to the clinical facility for additional visits if considered 
necessary by the PI or as relevant to subjects’ dosing regimens. 

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Unscheduled visits may include (but are not limited to) any of the procedures listed in the 
Schedule of Events (Section 4).  Examples of unscheduled visits include:
Initiation of pegcetacoplan escape therapy (see Section 11.3) 
Subjects return to the clinic to complete additional assessments and/or procedures, at 
the discretion of the investigator 
Subjects return to the clinic for pegcetacoplan dosing (based on patient’s dose, dosing 
schedule, ability to self-administer pegcetacoplan, and potential dose adjustments)
 LDH assessment in case of dose adjustment 
Safety monitoring
11.5.1.
Data Monitoring Committee
A DMC will review cumulative safety/tolerability data (eg, physical examinations, ECGs, vital 
signs, clinical laboratory tests, and AEs), efficacy (Hb and LDH levels, haptoglobin level, ARC, 
and RBC transfusions), and PK data. The DMC will have the responsibility to conduct a 
thorough safety assessment at regular predefined intervals during the Randomized Controlled 
Period of the study, as described in the DMC charter.  
In addition, an ad hoc data review may be recommended by the DMC or requested by the 
sponsor at any time during the study. 
The remit, roles, and responsibilities of the DMC will be specified in a separate DMC charter.
11.6. 
Treatment Discontinuation and Study Withdrawal 
11.6.1. 
Discontinuation of Subjects
A subject may withdraw from the study at any time for any reason without prejudice to his/her 
future medical care by the physician or at the institution. The investigator or sponsor may 
withdraw the subject at any time (eg, in the interest of subject safety). The investigator is 
encouraged to discuss withdrawal of a subject from investigational product with the medical 
monitor, when possible.  
Subjects who discontinue treatment will be encouraged to continue to attend study visits to 
complete study assessments (except for treatment with pegcetacoplan) as detailed in the 
Schedule of Events (Section 4).  At minimum, subjects who discontinue dosing should complete 
follow-up procedures outlined in the Schedule of Events (Section 4) 2, 4, and 8 weeks after 
treatment discontinuation (Follow-up Visits; see Section 11.3).  If withdrawal of pegcetacoplan
treatment is necessary, slow weaning should be considered, and subjects should carefully be 
monitored for at least 8 weeks to detect serious hemolysis or other complications, as detailed in 
the IB.  
Any subject withdrawn due to an AE (whether serious or nonserious) or clinically significant 
abnormal laboratory test values will be evaluated by the investigator and will be treated and/or 
followed up until the symptoms or values return to normal or acceptable levels, as judged by the 
PI.
Subjects who discontinue will not be replaced.  

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11.6.2. 
Reasons for Discontinuation 
The reason for withdrawal must be determined by the investigator and recorded in the subject’s 
medical record and on the CRF. If a subject is withdrawn for more than 1 reason, each reason 
should be documented in the source document and the most clinically relevant reason should be 
entered on the CRF.  
Reasons for discontinuation include, but are not limited to: 
 Adverse event which, in the opinion of the investigator, could jeopardize the safety of 
the subject. Any serious adverse event (SAE), clinically significant AE, severe 
laboratory abnormality, intercurrent illness, pregnancy, or other medical condition 
that indicates to the PI that continued participation is not in the best interest of the 
subject. 
 Withdrawal by subject. 
 Lost to follow-up. 
 Pregnancy.  
 Other (If “Other” is selected, the investigator must specify on the CRF). 
 Death. 
 Failure to meet randomization criteria. 
 Noncompliance with investigational product. 
 Noncompliance with protocol requirements or study-related procedures. 
 Physician decision. 
 Site terminated by sponsor. 
 Study terminated by sponsor, the Food and Drug Administration (FDA), or other 
regulatory authorities. 
 Withdrawal by parent/guardian. 
 Phlebotomy/venesection for iron overload. 
11.6.3. 
Subjects “Lost to Follow-up” Prior to Last Scheduled Visit 
A minimum of 3 documented attempts must be made to contact any subject lost to follow-up at 
any time point prior to the last scheduled contact (office visit or telephone contact). At least 1 of 
these documented attempts must include a written communication sent to the subject’s last 
known address via courier or mail (with an acknowledgement of receipt request) asking that 
he/she return to the site for final safety evaluations and to return any unused investigational 
product. 

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12.
ASSESSMENTS
12.1. 
Assessments 
Assessments to be performed during the study are described below. Every effort should be made 
to ensure that the protocol-required assessments are completed as described.
If deemed necessary, additional safety measurements may be performed, at the discretion of the 
PI. 
12.1.1. 
Medical History 
Medical history will be collected at the Screening Visit (Visit 1; up to Week –4). Medical history 
relating to Hb levels and pretransfusion Hb levels in the past year prior to study enrollment will 
be collected.  
12.1.2.
Thrombosis History
Thrombosis history will be collected at the Screening Visit (Visit 1; up to Week –4). 
12.1.3. 
Transfusion History 
At the Screening Visit, (Visit 1; up to Week –4), transfusion history from the previous 12 months 
must be obtained and recorded in the patient CRF. Historical information to be obtained will be: 
 Date of transfusion 
 Type of infusion (whole blood, PRBCs, or other) 
 Number of units transfused 
 Pretransfusion Hb value and associated date of sample (must be within 14 days prior 
to transfusion) 
12.1.4. 
Body Height and Weight 
Body height and body weight will be measured at the Screening Visit (Visit 1; up to Week –4). 
12.1.5. 
Subject Demographics
Subject demographics will be collected at the Screening Visit (Visit 1; up to Week –4). 
12.1.6. 
Physical Examination 
All physical examinations will include, at a minimum, assessment of the following:  general, 
head, ears, eyes, nose and throat, dentition, thyroid (endocrine), heart, chest, lungs, abdomen, 
skin, extremities, back/neck, musculoskeletal, and lymph nodes. 
The investigator (or designee) at the study site will examine each subject, as outlined in the 
Schedule of Events (Section 4). 
A symptom-driven physical examination may be performed at various unscheduled time points, 
if deemed necessary by the investigator. 

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12.1.7. 
Vital Signs 
Single measurements of body temperature, respiratory rate, blood pressure, and heart rate will be 
measured prior to dosing, as outlined in the Schedule of Events (Section 4).  
Vital signs may be taken at any other times, if deemed necessary. Blood pressure and heart rate 
measurements will be performed with subjects in a seated position after resting for 5 minutes, 
except when they are supine or semireclined because of study procedures and/or AEs (eg, nausea, 
dizziness) or if deemed necessary by the PI. 
Vital signs will be measured before venipuncture and ECG assessment, vital signs collected post 
dose will be timed from the completion of the study drug administration. 
Additional monitoring of vital signs will occur 2 hours post dose (±15 minutes) at Visit 2 
(Day 1) for subjects randomized to pegcetacoplan and at the pegcetacoplan Initiation Visit for 
subjects randomized to SOC who subsequently meet treatment failure criteria. 
12.1.8. 
Electrocardiogram Monitoring
Triplicate 12-lead ECGs will be measured at the time points outlined in the Schedule of Events 
(Section 4) with 3 readings taken 
 minute and 5 minutes apart.  Predose ECGs will be taken 
following resting in the supine position for 10 minutes in a quiet environment and prior to any 
blood sampling procedures. 
All ECGs will be recorded at the sites using the equipment provided by the vendor performing 
the centralized ECG analysis. 
The ECGs will be classified as normal, having a not clinically significant abnormality, or having 
a clinically significant abnormality. In addition, ECG parameters of ventricular rate, PR interval, 
QRS duration, and QT interval (uncorrected and corrected using both Bazett’s [QTcB] and 
Fridericia’s [QTcF] methods) will be reviewed for eligibility and ongoing safety. 
During the study, i
 ms (mean of QTcF replicate values), the investigator 
should perform 3 additional ECGs over 20-60 minutes; if the mean QTcF of the 3 repeat ECGs is 
 ms, the site should instruct the subject to return the following day to perform repeat 
triplicate ECGs.  An evaluation will be performed to look for other factors which may have 
contributed to QTc prolongation (eg, new concomitant medications, hypokalemia, etc.).
The full set of ECGs should be sent as soon as possible to the ECG central laboratory for 
verification; if the QTcF (mean of QTcF replicate values) has declined to below 500 ms and is 
returning towards baseline, dosing may continue. 
 ms, the 
investigator, medical monitor, and cardiology consultant will assess the timing of additional 
ECGs and possible discontinuation of pegcetacoplan dosing. Recommendation for 
discontinuation of pegcetacoplan will be made on an individualized management plan, based on 
the totality of the data. Because abrupt discontinuation of pegcetacoplan could result in rebound 
hemolysis and an associated risk of thrombosis, attention will be directed towards avoiding 
unnecessary dosing interruptions and all decisions regarding dosing will be clearly documented. 
12.1.9. 
Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Scale
The FACIT-Fatigue Scale is a 13-item Likert scaled instrument which is self-administered by the 
subjects during clinic visits, as outlined in the Schedule of Events (Section 4).  Subjects are

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presented with 13 statements and asked to indicate their responses as it applies to the past 7 days. 
The 5 possible responses are:  “Not at all” (0); “A little bit” (1); “Somewhat” (2); “Quite a 
bit” (3); and “Very much” (4). With 13 statements, the total score has a range of 0 to 52. Before 
calculating the total score, some responses are reversed to ensure that the higher score 
corresponds to a higher quality of life. The FACIT-Fatigue Scale and scoring guidelines are 
provided in Appendix 1.  
12.1.10. 
Linear Analog Scale Assessment (LASA) for Quality of Life 
The LASA consists of 3 items asking respondents to rate their perceived level of functioning. 
Specific domains include:  activity level, ability to carry out daily activities, and an item for 
overall QoL. A representation of the scale is presented in Appendix 2. Scores for the 3 individual 
components of the scale and the combined score will be included in the analysis; this will be 
described in the Statistical Analysis Plan (SAP). 
12.1.11. 
European Organisation for Research and Treatment of Cancer (EORTC) 
30-Item Quality of Life Questionnaire 
The EORTC QLQ-C30 (version 3.0) consists of 30 questions comprised of both multi-item 
scales and single-item measures to assess overall quality of life in subjects. Questions are 
designated by functional scales, symptom scales, and global patient QoL/overall perceived health 
status. Scoring guidelines from EORTC will be used to calculate patients’ scores. The QLQ-C30 
and scoring guidelines are provided in Appendix 3. 
12.1.12. 
Clinical Laboratory Tests 
All tests listed below will be performed as outlined in the Schedule of Events (Section 4).  In 
addition, laboratory safety tests may be performed at various unscheduled time points, if deemed 
necessary by the PI or recommended by the DMC. The clinical laboratory tests include (but are 
not limited to) the following (see Section 12.1.12.1, Section 12.1.12.2, Section 12.1.12.3, 
Section 12.1.12.4, Section 12.1.12.5, and Section 12.1.12.6):  
12.1.12.1. Hematology 
 Hb 
 Hematocrit 
 RBC count 
 Platelet count  
 WBC count with differential 
 Reticulocytes 
12.1.12.2. Coagulation 
 Prothrombin time (PT) 
 Fibrinogen 
 aPTT 
 D-Dimer 
NOTE:  The use of silica reagents in coagulation panels should be avoided in subjects treated 
with pegcetacoplan. 

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12.1.12.3. Serum Chemistry 
 Blood urea nitrogen (BUN) 
 Creatinine 
Estimated creatinine clearance 
(using Cockcroft-Gault formula) 
–screening only
 Bilirubin (total and direct)
 Albumin 
 Alkaline phosphatase (ALP) 
LDH 
Haptoglobin 
Gamma-glutamyl transferase 
(GGT) 
LDH isoenzymes
 Creatine kinase (CK) 
 Aspartate aminotransferase 
(AST) 
 Alanine aminotransferase 
(ALT)
 Uric acid 
 Glucose  
 Sodium 
 Potassium 
 Chloride 
 Ferritin 
 Erythropoietin (EPO) 
12.1.12.4. Urinalysis 
 pH 
 Specific gravity
 Protein 
 Glucose 
 Ketones 
 Bilirubin 
 Blood 
 Nitrite 
 Urobilinogen 
 Leukocyte esterase 
If an abnormality is noted for protein, blood, nitrite, and/or leukocyte esterase, a microscopic 
examination will be performed. 
12.1.12.5. Other Panels 
Plasma (free) Hb  
Direct Coombs 
Samples for genotyping (for Gilbert’s Syndrome) will be obtained via buccal swab tests done at 
the screening visit.
12.1.12.6. Human Chorionic Gonadotropin (Serum Pregnancy Test) and 
Follicle-Stimulating Hormone 
A serum pregnancy test will be performed for females only. Follicle-stimulating hormone (FSH) 
measurement will be performed for postmenopausal females at Visit 1 (up to Week –4) screening 
period only. 

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12.1.13. 
Infusion Site and Pump-Safety Assessment 
On the days of clinic visits, if pegcetacoplan is administered at the visit site, an assessment of the 
pegcetacoplan infusion site will be made as a part of the AE assessment. If pegcetacoplan is 
administered at the visit the site staff will observe the dosing and pump use safety will be 
assessed and the infusion site will be checked again within 30 minutes after study drug 
administration. The infusion site assessments will be performed by an appropriately trained staff, 
as delegated by the investigator. The infusion site and surrounding area will be inspected for 
redness, swelling, induration, and bruising. The subject will be asked about the presence of pain 
and/or tenderness, and any issue related to pump use. The date, time, and outcome of the infusion 
site assessment will be recorded on the source documents and CRFs. 
Subjects will be instructed to notify the PI or other study personnel in the event that an infusion 
site reaction occurs after self-administration of pegcetacoplan. All clinically relevant AEs, as 
determined by the investigator, from infusion site or related to pump use will be recorded as 
AEs. 
12.2. 
Pharmacokinetic Assessments 
12.2.1. 
Blood Sampling and Processing 
Blood samples for PK assessment of pegcetacoplan will be collected via direct venipuncture at 
all visits as detailed in the Schedule of Events (Section 4).  If pegcetacoplan is to be administered 
at the study site the blood sample must be taken predose.  
The date and time of the last dose of pegcetacoplan should be recorded in the eCRF, along with 
the date and time of the PK sample.  
Instructions for collection, handling, processing, storage, and shipping of samples will be 
provided in a separate sample handling manual prior to study initiation. 
Note:  Samples for PK assessment should not be collected for subjects randomized to the SOC 
(excluding complement inhibitors) treatment arm unless they become eligible for and elect to 
receive pegcetacoplan escape therapy. If a subject from the SOC (excluding complement 
inhibitors) treatment arm is to begin receiving pegcetacoplan escape therapy, a predose PK 
sample should be collected at the pegcetacoplan initiation visit and at each subsequent visit as 
detailed in the Schedule of Events (Section 4). 
12.2.2. 
Analytical Method 
Serum sample analysis will be performed using good laboratory practice- (GLP-) compliant 
validated procedures and methods. The methods used and the results obtained will be included in 
the final report as an appendix. 
12.3. 
Flow Cytometry Assessments 
Blood samples for flow cytometry assessment will be collected via direct venipuncture at the 
time points delineated in the Schedule of Events (Section 4).  Flow cytometry assessment will 
include, but not be limited to:  PNH clonal distribution of RBCs; PNH clonal distribution of 
immature reticulocytes (CD71+), monocytes, and granulocytes; and C3 deposition on RBCs.  

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Instructions for collection, handling, processing, storage, and shipping of samples will be 
provided in a separate sample handling manual prior to study initiation. 
12.4. 
Pharmacodynamic Assessments 
Blood samples will be collected via direct venipuncture at the time points delineated in the 
Schedule of Events (Section 4) for PD assessment of complement activation through the classical 
(ie, CH50) and alternative (ie, AP50) pathways.  Blood samples will also be collected to measure 
C3 levels. Other relevant PD markers may also be assessed.
Instructions for collection, handling, processing, storage, and shipping of samples will be 
provided in a separate Laboratory Reference Manual, prior to study initiation. 
12.5. 
Antidrug Antibody Assessment  
Subjects who test positive for anti–pegcetacoplan peptide antibodies or anti-PEG antibodies will 
be followed until the antibody levels revert to baseline and characterize their antibodies for titer, 
binding to the cyclic pentadecapeptide and PEG domains, and the neutralizing capacity. 
Subjects who discontinue dosing will need to have antidrug antibody (ADA) samples collected at 
the follow-up visits.  
Subjects who test positive for anti- pegcetacoplan peptide antibodies or anti-PEG antibodies at 
any time will be followed with ADA samples being collected every 6 months until the antibody 
levels revert to baseline. Samples that test positive will be characterized by an assay that will 
determine antibody titer, binding to the cyclic peptide or PEG domains, and measure neutralizing 
capacity. 
The proposed ADA sampling schedule was established to capture the ADA signal at baseline, 
along with any potential early onset and the dynamic profile (transient or persistent) of antibody 
formation while minimizing pegcetacoplan level in the sample. 
12.6. 
Blood Volume for Study Assessments 
Table 1:  Blood Volume During Study 
Assay
Number of 
time points 
Approximate 
volume per 
time point * 
(mL) 
Approximate 
sample 
volume over 
course of study 
(mL) 
Pharmacokinetics 
7 
5 
35 
Anti-pegcetacoplan peptide antibody and anti-
PEG antibody 
6 
5 
30 
Hematology 
17 
4 
68 
Chemistry (including pregnancy screening) 
17 
7.5 
127.5 
Coagulation profile 
8 
2.7 
21.6 
Complement profile (CH50, and AH50) 
7 
8 
56 

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Table 1:  Blood Volume During Study (Continued)
C3 Profile 
16 
8 
128 
Flow cytometry, PNH clones and C3 deposition 
8 
2 
16 
Plasma (free) Hb 
17 
6 
102 
Direct Coombs
12
3 
36
Total Approximate Blood Volume For Study: 
620.1* 
Abbreviations:  Ab = antibody; AH50 = alternate complement pathway assay; C3 = complement component 3; 
CH50 = total hemolytic complement activity assay; Hb = hemoglobin; PNH = paroxysmal nocturnal 
hemoglobinuria. 
*Represents the standard collection volume planned over the duration of the study; actual volume may vary. 
 
12.7.
Pregnancy Tests
For WOCBP, a serum pregnancy test will be performed at screening Visit 1 (up to Week –4), 
and subjects with a positive test will be excluded from the study. A follow-up urine pregnancy 
test will be performed at Visit 2 (Day 1) (a negative urine pregnancy test must be received before 
dosing with study drug). A urine pregnancy test will also be performed at each site visit, if 
applicable. A final urine pregnancy test will be performed at the follow-up Visit 16 (Week 32) or 
the Early Termination Visit. Male subjects will be counseled to avoid donating sperm during the 
time between the first dose at Visit 2 (Day 1) through 90 days after their last dose of study drug. 
12.8. 
COVID-19 Assessment 
If a subject has been tested for COVID-19, the results, if available, will be documented in the 
eCRF. 

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13.
ADVERSE EVENTS
13.1. 
Definition 
An adverse event (AE) is any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug related. An AE can, therefore, be any unfavorable and 
unintended sign, including a clinically significant abnormal laboratory finding, symptom, or 
disease temporally associated with the use of an investigational product, whether or not 
considered related to the investigational product. 
Adverse events can be spontaneously reported by the subject and/or in response to an open 
question from the study personnel or revealed by observation and will be recorded during the 
study at the investigational site. All identified AEs must be recorded and described on the 
appropriate AE or SAE page of the eCRF. 
Fluctuating or nonsignificant changes in laboratory values do not necessarily qualify for AE 
reporting. If these changes in laboratory values are assessed as clinically significant and/or lead 
to discontinuation of administration of investigational product, these should be reported as an 
AE. If these laboratory values are linked to a diagnosis, only the diagnosis should be reported as 
an AE.  
13.2. 
Recording Adverse Events 
Adverse events and SAEs will be collected from the signing of the informed consent form (ICF) 
until the completion of Visit 15 (for subjects who roll over into the open-label extension), or 
until the completion of follow-up (for subjects who do not roll over).   
Any events that occur prior to dosing will be categorized as pretreatment events; events 
occurring after dosing will be recorded as TEAEs (start date of dosing and, therefore, 
categorization of the event will be dependent on randomization assignment).  
For each AE, the investigator will evaluate and report the onset date (and time if applicable), 
resolution date (and time if applicable), intensity, causality, action taken, serious outcome, and 
whether or not it caused the subject to discontinue the study. 
If possible, the outcome of any AE that caused permanent discontinuation or was present at the 
end of the study should be reported, particularly if the AE was considered by the investigator to 
be related to the investigational product. Subjects experiencing AEs that cause interruption or 
discontinuation of investigational product, or those experiencing AEs that are present at the 
follow-up visit should receive follow-up as appropriate. 
All SAEs must be reported to the sponsor/Apellis Safety via eCRF within 24 hours of becoming 
aware of the event, whether or not the event is deemed treatment related. If the electronic data 
capture (EDC) system is not operational, the site must complete the paper SAE form and email 
to 
immediately and also within 24 hours of becoming aware of the event. 
The reported information submitted as a paper SAE must be entered into the EDC system once it 
becomes operational. 
Adverse events will be coded in accordance with the Medical Dictionary for Regulatory 
Activities (MedDRA). If known, the diagnosis of the underlying illness or disorder should be 
recorded, rather than its individual symptoms. 
CCI

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13.3.
Reporting Adverse Events
The sponsor has the responsibility to inform concerned health authorities, ethics committees, and 
investigators about Serious Unexpected Serious Adverse Reactions (SUSARs) in line with GCP 
guidance and applicable regulatory requirements. 
If required, specific SAEs should be reported to the concerned ethics committees in compliance 
with local requirements. 
13.3.1. 
Relationship of Events to Study Treatment 
All AEs that occur during this study will be recorded. The PI will review each event and assess 
its relationship to study drug treatment (definitely related, possibly related, unlikely related, not 
related). The date and time of onset, time relationship to drug dosing, duration, and outcome 
(recovered/resolved, recovered/resolved with sequelae, recovering/resolving, not recovered/not 
resolved, fatal or unknown [lost to follow-up]) of each event will be noted.  
The following definitions should be considered when evaluating the relationship of AEs and 
SAEs to the study treatment: 
Definitely 
Related 
Event or laboratory test abnormality, with plausible time relationship to drug intake 
Cannot be explained by disease or other drugs 
Response to withdrawal plausible (pharmacologically, pathologically) 
Event definitive pharmacologically or phenomenologically (ie, an objective and specific 
medical disorder or a recognized pharmacological phenomenon) 
Rechallenge satisfactory, if necessary 
Possibly 
Related 
Event or laboratory test abnormality, with reasonable time relationship to drug intake 
Could also be explained by disease or other drugs 
Information on drug withdrawal may be lacking or unclear
Unlikely 
Related 
Event or laboratory test abnormality, with a time to drug intake that makes a relationship 
improbable (but not impossible) 
Disease or other drugs provide plausible explanations 
Not Related
Event or laboratory test abnormality, is plausibly related to the participant’s clinical state, 
underlying disease, or the study procedure/conditions 
Time relationship to drug intake makes a relationship unreasonable 
Other obvious causes for event or laboratory test abnormality exist 

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13.3.2. 
Severity of Events 
The following definitions should be considered when evaluating the severity of AEs and SAEs: 
Mild 
Event results in mild or transient discomfort, not requiring intervention or treatment; 
does not limit or interfere with daily activities (eg, insomnia, mild headache). 
Moderate 
Event is sufficiently discomforting so as to limit or interfere with daily activities; may 
require interventional treatment (eg, febrile illness requiring oral medication). 
Severe 
Event results in significant symptoms that prevent normal daily activities; may require 
hospitalization or invasive intervention (eg, anemia resulting in blood transfusion). 
13.4. 
Serious Adverse Events 
An SAE is any AE or suspected adverse reaction that, in the view of either the investigator or 
sponsor, results in any of the following outcomes:  death; life-threatening; inpatient 
hospitalization or prolongation of existing hospitalization; a persistent or significant incapacity 
or substantial disruption of the ability to conduct normal life functions; or a congenital 
anomaly/birth defect.   
Important medical events that may not result in death, be life-threatening*, or require 
hospitalization may be considered serious when, based upon appropriate medical judgment, they 
may jeopardize the subject and may require medical/surgical intervention to prevent one of the 
outcomes listed in the above definition.   
Examples of important medical events include allergic bronchospasm requiring intensive 
treatment in an emergency room or at home; blood dyscrasias or convulsions that do not result in 
inpatient hospitalization; or the development of drug dependency or drug abuse. 
*Life-threatening is defined as an AE or suspected adverse reaction, which, in the view of either 
the investigator or sponsor, places the subject at immediate risk of death as it occurred. It does 
not include an AE or suspected adverse reaction that, had it occurred in a more severe form, 
might have caused death. 
Unexpected Adverse Event 
An AE is considered “unexpected” if it is not listed in the Reference Safety Information section 
of the investigator brochure (IB) in effect at the time of event onset. 
13.5. 
Pregnancy  
Although pregnancy is not an AE, all pregnancies and suspected pregnancies (including a 
positive pregnancy test regardless of age or disease state) occurring with a female subject or the 
female partner of a male subject, must be followed to conclusion to determine their outcome and 
are considered immediately reportable events. 
The pregnancy, suspected pregnancy, or positive pregnancy test must be reported to Apellis 
Safety within 24 hours of the investigator’s awareness using the paper Pregnancy Report form. 
The Pregnancy Report Form shall be signed and dated by the investigator and submitted via 
email to 
 
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The investigator must follow the subject until completion of the pregnancy and must report the 
outcome of the pregnancy (eg, delivery, termination, etc) and neonatal status up to 12 months 
postdelivery. An abnormal outcome is defined as any pregnancy that results in the birth of a 
child with persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions (formerly referred to as disabilities), congenital anomalies, or birth defects. 
In the event of an abnormal outcome, an SAE Report Form will be required. 
13.6.
Drug Abuse, Misuse, Overdose, and Medication Error
Occurrences of events of drug abuse, drug misuse, drug overdose, and medication error must be 
reported to Apellis Safety. 
Abuse of a medicinal product: persistent or sporadic, intentional excessive use of medicinal 
products, which is accompanied by harmful physical or psychological effects. 
Misuse: intentional and inappropriate use of a medicinal product not in accordance with the 
prescribed or authorized dose, route of administration and/or the indication(s) or not within the 
legal status of its supply. 
Overdose: administration of a quantity of study drug given per administration or per day, which 
is above the assigned dose. 
Medication Error: an error made in prescribing, dispensing, administration and/or use of the 
study drug. Medication errors are reportable to the sponsor as defined below: 
 The dispensing, administration, and/or use of the unassigned study drug. 
 The administration and/or use of an expired study drug. 
All AEs or SAEs associated with drug abuse, drug misuse, drug overdose, or medication error 
must be reported as appropriate. 
 

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14.
DATA MANAGEMENT AND STATISTICAL METHODS
14.1. 
Data Collection 
The investigators’ authorized site personnel must enter the information required by the protocol 
on the eCRF. A study monitor will visit each site in accordance with the monitoring plan and 
review the eCRF data against the source data for completeness and accuracy. 
Discrepancies between source data and data entered on the eCRF will be addressed by qualified 
site personnel. When a data discrepancy warrants correction, the correction will be made by 
authorized site personnel. Data collection procedures will be discussed with the site at the site 
initiation visit and/or at the investigator’s meeting. Once a subject is randomized, it is expected 
that site personnel will complete the eCRF entry within approximately 3 business days of the 
subject’s visit. 
14.2. 
Clinical Data Management 
Data are to be entered into a clinical database, as specified in the study-specific data management
plan. Quality control and data validation procedures are applied to ensure the validity and 
accuracy of the clinical database.
Data are to be reviewed and checked for omissions, errors, and values requiring further 
clarification using computerized and manual procedures. Data queries requiring clarification are 
to be communicated to the site for resolution. Only authorized personnel will make corrections to 
the clinical database, and all corrections are documented in an auditable manner. 
14.3. 
Statistical Analysis Process 
The study will be analyzed by the sponsor or its agent. All statistical analyses will be performed 
using SAS (SAS Institute, Cary, NC, USA), version 9.3 or higher. 
The SAP will provide the statistical methods and definitions for the analysis of the efficacy and 
safety data, as well as describe the approaches to be taken for summarizing other study 
information such as subject disposition, demographics and baseline characteristics, 
investigational product exposure, and prior and concomitant medications. The SAP will also 
include a description of how missing, unused, and spurious data will be addressed. 
The SAP for the final analysis will be finalized prior to final database lock and performing 
analyses to preserve the integrity of the statistical analysis and study conclusions. 
14.4. 
Planned Interim Analysis, Adaptive Design, and Data Monitoring 
Committee 
No interim analysis is planned. An external, independent data monitoring committee (DMC) will 
assess the safety/tolerability data of the study periodically. 
14.5. 
Sample Size Justification 
A total of 48 randomized subjects (32 subjects to pegcetacoplan and 16 subjects to SOC) are 
required to achieve 90% power, at the 5% significance level (2-sided), using a 2-group Fisher's 
exact test with unequal allocation 2:1 to treatment groups (pegcetacoplan and SOC). Calculation 

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assumes an increase of 45% in the proportion of subjects achieving Hb stabilization with 
pegcetacoplan, compared to SOC (ie, a change from 5% [no treatment] to 50% [pegcetacoplan]). 
With the same number of subjects and assuming an effect size of at least 1.2, the study will be at 
96% for the LDH reduction endpoint. 
To account for loss of power due to discontinuations, the study will attempt to randomize 
54 subjects.  
14.6.
Preservation of Type 1 Error
To preserve the Type 1 error, a fixed sequence testing strategy will be used; hence, statistical 
significance with the first secondary endpoint (Week 26 Hb response in the absence of 
transfusion [Yes/No]) will only be concluded if statistical significance is achieved with the 
primary analysis of the co-primary endpoints.  
The ordering of the secondary endpoints in this testing strategy will match the order in which 
they are presented in Secondary Efficacy Endpoints (see Section 7.2). 
14.7. 
Statistical Analysis Methodology  
A formal SAP will be developed and finalized prior to locking the database. The full details of 
data presentations and analyses will be provided in the SAP. Additional statistical analyses (other 
than those described in this section) may be performed, if deemed appropriate and included in 
the SAP. Any deviations from the final SAP or from what is outlined in the protocol will be 
discussed in the final study report.  
All endpoints will be summarized by treatment group and, where appropriate, by visit. 
Continuous data will be summarized using descriptive statistics (eg, mean and standard 
deviation), and categorical data will be summarized using frequency tables (counts and 
percentages). 
14.7.1. 
Analysis Sets  
14.7.1.1.
Screened Set
The screened set will include all subjects who signed the ICF. This set will be used only for the 
purpose of describing subject disposition.  
14.7.1.2.
Safety Set
The safety set will include all subjects who receive at least 1 dose of study medication 
(pegcetacoplan), and subjects who are randomized to SOC (excluding complement inhibitors). 
Subjects will be analyzed according to the treatment they received.  
14.7.1.3.
Intent-to-Treat (ITT) Set
The ITT set will include all randomized subjects. Subjects will be analyzed according to their 
assigned treatment, regardless of the treatment actually received. 

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14.7.1.4. Modified Intent-To-Treat (mITT) Set 
The mITT set will include all subjects in the ITT set who continue study treatment beyond 
Visit 4 (Week 4). 
14.7.1.5.
Per-Protocol Set 
The PP set will include all subjects in the ITT set who have not violated any inclusion or 
exclusion criteria and/or deviated from the protocol in a way that could influence their efficacy 
assessment. Decisions concerning the exclusion of subjects from the PP analysis set will be made 
and documented prior to database lock. 
14.7.1.6. Pharmacokinetic (PK) Set 
The PK population will include all subjects in the ITT set who receive pegcetacoplan and have at 
least 1 evaluable post-dose PK measurement. 
14.7.1.7. Pharmacodynamic (PD) Set 
The PD population will include all subjects in the ITT set who have at least 1 evaluable 
post-dose PD measurement. 
14.7.1.8. Data Review for Analysis Sets 
After all of the data have been verified/coded/entered into the database, a review will be 
performed. The purpose of this review will be to define the analysis sets. The review will also 
check the quality of the data, identifying outliers, and make decisions on how to deal with any 
data issues (eg, missing values, withdrawals, protocol deviations). After the preanalysis review, 
resolution of all issues, and documentation of all decisions, the database will be locked. 
14.7.2. 
Efficacy Analyses 
The efficacy endpoints will primarily be evaluated with the ITT set. All statistical testing will be 
at the 5% level of significance (2-sided) and all point estimates for the comparison between 
treatment groups will be accompanied by 2-sided 95% confidence intervals (CIs).  
All possible efforts will be made to ensure that subjects complete all the required assessments. 
As missing data may potentially bias the outcome of the statistical analyses and the subsequent 
estimation of the magnitude of the treatment effect, different strategies will be applied to provide 
a balanced assessment of treatment efficacy. 
Endpoints will be summarized and, where appropriate, plotted over time for each treatment 
group.  
Baseline will be taken at Day 1 prior to the start of study treatment for subjects randomized to 
pegcetacoplan and at Day 1 for subjects randomized to SOC. 
14.7.2.1. Primary Endpoints 
The co-primary efficacy endpoints will be analyzed, based on the ITT set.  
The co-primary efficacy endpoints are: 

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 Hemoglobin stabilization defined as avoidance of a > 1 g/dl decrease  in Hb levels 
from baseline in the absence of transfusion through Week 26 (Yes/No) 
AND 
 Reduction in lactate dehydrogenase (LDH) level from baseline to Week 26  
For the first co-primary endpoint, the number and percentage of subjects who achieve Hb 
stabilization will be computed for treatment groups and compared between treatment groups 
using a stratified Cochran-Mantel-Haenszel (CMH) chi-square test. The treatment difference in 
percentages and 95% CI for the difference will be presented using the stratified Miettinen-
Nurminen method.  
Subjects who receive a transfusion through Week 26 or withdraw from the study before 
providing primary efficacy assessment will be categorized as failing to achieve Hb stabilization.
The second co-primary endpoint, change from baseline to Week 26 in LDH, will be analyzed 
using mixed model for repeated measures (MMRM) with:  the effects of treatment; stratification 
randomization; visit, visit-by-treatment interaction; baseline LDH level; and baseline LDH level-
by-visit interaction using an unstructured covariance matrix.  The difference between treatment 
groups will be estimated, along with its 95% CI and p-value.  
All the subjects LDH levels prior to transfusion and/or switch to pegcetacoplan will included in 
the model. 
As missing data may potentially bias the outcome of the statistical analyses and the subsequent 
estimation of the magnitude of the treatment effect, the following sensitivity and supportive 
analyses will be performed to evaluate the robustness of the results from the primary analysis 
methods: 
 The first co-primary efficacy endpoint will also be analyzed using a logistic 
regression with the effects of treatment group and stratification factors included. The 
odds ratio of being an Hb stabilization achiever the pegcetacoplan versus SOC group 
and associated 95% CI will be estimated from the final model. 
 The second co-primary endpoint will be analyzed using an analysis of covariance 
(ANCOVA) model (ITT set) with a last observation carried forward (LOCF) 
approach for handling missing data. The ANCOVA model will include terms for 
treatment, stratification factors, and baseline LDH level. 
 The second co-primary endpoint will be analyzed using an ANCOVA model (ITT 
set) with a best observation carried forward (BOCF) approach for handling missing 
data. The ANCOVA model will include terms for treatment, stratification factors, and 
baseline LDH level. 
 Analyses will be repeated using the mITT and PP sets. 
14.7.2.2. Secondary Endpoints
The secondary endpoints will be analyzed using the ITT set and will be repeated using the PP 
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Summary statistics by randomization strata and by treatment groups will presented at each 
assessment visit during the 26-week randomized treatment period.  
Continuous endpoints will be analyzed using MMRM with the effects of:  treatment; 
stratification factors; visit; visit-by-treatment interaction; the relevant baseline level; and the 
baseline level-by-visit interaction using an unstructured covariance matrix. The difference 
between treatment groups will be estimated, along with its 95% CI and p-value. If a subject 
receives a transfusion during his/her treatment period, the pretransfusion Hb values, reticulocyte 
values, and FACIT-Fatigue Scale score will be used in the model.  
For categorical endpoints, the number and percentage of subjects will be tabulated by treatment 
group and compared between treatment groups using a stratified CMH chi-square test. 
Kaplan-Meier plots will be presented for time-to-event endpoints for each treatment group, and 
survival estimates will be provided. 
The number of units of PRBCs transfused will be compared between the treatment groups using 
a Wilcoxon rank-sum test. The difference between the medians will be estimated along with its 
95% CI (stratified). Subjects who withdraw before Week 26 will have the number of units 
estimated from the duration that they were in the study (ie, number per week × 12).  This equates 
to an analysis of the frequency of transfusions.  
14.7.3. 
Safety Analyses 
Safety analyses will be based on the safety set. 
Safety measures assessed at study visits, including vital signs (temperature, systolic and diastolic 
blood pressures, pulse, and respiratory rate), clinical laboratory results, ECGs and 
anti-pegcetacoplan antibodies will be descriptively summarized by treatment group at baseline 
and for each postbaseline visit. Absolute values and changes from baseline will be summarized. 
14.7.3.1. Adverse Events 
Treatment-emergent adverse events are defined as those AEs that develop or worsen after the 
first dose of study medication and for up to 30 days beyond the last dose of study medication. 
The current version of MedDRA will be used to classify all AEs.  
Treatment-emergent adverse events will be summarized by System Organ Class and Preferred 
Term, in accordance with MedDRA. The number of subjects reporting each AE preferred term 
will be tabulated for all TEAEs and separately for those considered as possibly related to study 
treatment by the investigator. The number of subjects reporting SAEs will also be tabulated. 
Adverse-event summaries will be presented for each period of the study (randomized treatment 
and after early escape) separately, within each treatment group. 
The number of subjects reporting thromboembolic events will be tabulated for each period of the 
study, separately, within each treatment group.  
14.7.3.2. Clinical Laboratory Tests 
Changes from baseline in laboratory will be summarized using descriptive statistics by treatment, 
visit, and nominal time post dose. Baseline will be taken as the last measurement prior to the first 
dose of pegcetacoplan.  

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Out-of-range values will be flagged in the data listings.
14.7.3.3.
Vital Signs and ECGs
Changes from baseline in vital signs and ECG parameters will be summarized using descriptive 
statistics by treatment, visit, and nominal time post dose. Baseline will be taken as the last 
measurement prior to the first dose of pegcetacoplan.  
Values of potential clinical significance (eg, 
 ms from baseline) will be 
flagged in listings and summarized by treatment. 
Electrocardiogram parameters will be analyzed using concentration effect models. 
14.7.4. 
Pharmacokinetic Analyses  
The PK concentrations will be evaluated using the PK set. 
Concentrations will be summarized using descriptive statistics over time for the run-in period (all 
subjects) and the randomized treatment period (pegcetacoplan group).  
Individual subject concentration-time data will be plotted against actual sampling time. Median 
profiles of the concentration-time data, using nominal sampling times, will also be presented. 
Both linear-linear and linear-log plots will be presented.  
Population PK and exposure-response modeling of the safety and efficacy data will be described 
in a pegcetacoplan Population PK/PD Analysis Plan.  The methods will be based on the FDA 
Guidances for both Exposure-Response and Population Pharmacokinetics (FDA 1999; FDA 
2003). 
14.7.5. 
Pharmacodynamic Analyses 
The PD endpoints will be evaluated using the PD set. 
Absolute values, changes from baseline, and percent changes from baseline will be summarized 
using descriptive statistics over time for the run-in period (all subjects) and the randomized 
treatment period by treatment group.  
Individual subject-time profiles will be plotted against actual sampling time. Median profiles 
over time, using nominal sampling time, will also be presented.  
The PD endpoints will be compared between treatment groups using mixed effect repeated 
measures analyses.  
14.7.6. 
Other Data Analyses 
Demographic data, baseline characteristics, physical examination, concomitant medication, 
medical history data, and study medication exposure will be summarized by treatment group. 
World Health Organization (WHO) and MedDRA coding dictionaries will be used for the 
concomitant medications and medical histories, respectively. 

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14.8.
Direct Access to Source Data/Documents
The PI must maintain, at all times, the primary records (ie, source documents) of each subject’s 
data for data verification. Examples of source documents are:  medical records, laboratory 
reports, study drug records, and eCRFs that are used as the source. 
The PI will permit study-related monitoring, audits, and inspections by the sponsor and/or its 
designee, IRB/IEC, and the regulatory agencies at any time during the study. The PI will ensure 
that the auditor is allowed direct access to the source data, medical records, eCRFs, and the 
Site’s regulatory file for the study and any other pertinent information.  
14.9.
Quality Control and Quality Assurance
This study is to be performed in full compliance with the protocol, GCP, and applicable 
regulatory requirements. The PI, sponsor, and/or designee(s) are responsible for ensuring that the 
study staff receive appropriate training on the protocol, study procedures, and any other relevant 
information.  
Quality assurance and quality control systems are implemented and maintained using written 
Investigative site, sponsor and/or designee standard operating procedures (SOPs) to ensure that 
the study is conducted and data are generated, documented (recorded), and reported in 
compliance with the protocol, GCP, applicable regulatory requirement(s), and national and local 
laws, rules, and regulations. 
Quality control checks will be applied at each stage of data handling (eg, edit checks) to ensure 
that all data are reliable and have been processed correctly.  
14.9.1. 
Monitoring 
On-site monitoring will be performed by the sponsor’s designee for the duration of the study. 
The monitor will ensure that the study is conducted, recorded, and reported in accordance with 
the protocol, SOPs, GCP, and applicable regulatory requirements. The monitor will verify the 
accuracy and completeness of the eCRF entries, source documents, and other study-related 
records against each other. The PI will provide direct access to source data/documents for study-
related monitoring. It is important that the PI and the staff are available at these visits. The 
monitor will record the date of each visit together with a summary of the status and progress of 
the study. Proposed actions will be documented in writing to the PI. 

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15.
ETHICS
15.1. 
Ethical Conduct of the Study 
This research will be carried out in accordance with the protocol, applicable regulations, the 
ethical principles set forth in the Declaration of Helsinki, and the International Council for 
Harmonisation (ICH) Harmonised Tripartite Guideline (Guideline for Good Clinical Practice), 
E6, R2 (ICH GCP). 
15.2.
Institutional Review Board/Ethics Committee
The study protocol, any amendments to the protocol, the ICF, the IB, and other study-specific 
information will be reviewed and approved by the IRB/IEC. The study will not be initiated until 
the IRB/IEC has approved the protocol or a modification, thereof. All records pertaining to 
IRB/IEC submission and approval should be kept in the site’s regulatory files and the sponsor’s 
trial master file. 
The IRB/IEC must be constituted and operate in accordance with the all applicable regulatory 
requirements. 
15.3. 
Subject Information and Consent 
The PI or appropriate designee is responsible for obtaining an informed consent. A written 
informed consent, in compliance with ICH Guideline E6, must be obtained from each subject 
prior to screening and enrollment or performing any study-related procedures.
The purpose of the study, the procedures to be carried out, and the potential hazards will be 
described to the subjects in nontechnical terms. The subject will be given sufficient time to 
consider the study’s implications before deciding to participate in the study. The subject and/or 
legal guardian will be required to sign and date an ICF and will be assured that they may 
withdraw from the study at any time without jeopardizing their medical care. The PI shall retain 
the original, signed informed consent for study participation in the subject’s medical record and 
shall provide the subject and/or legal guardian with a copy of the signed consent.
If there are any changes/amendments to the approved protocol that may directly affect the 
subject’s decision to continue participation in the study, the ICF shall be amended to incorporate 
the changes to the protocol and the subject must re-sign the IRB-/IEC-approved, amended ICF. 
15.4. 
Confidentiality 
Confidentiality of subject’s information must be maintained in accordance with national and 
local privacy laws. 
15.5. 
ClinicalTrials.gov 
This study has been listed with ClinicalTrials.gov, as required. 
15.6. 
Termination of Study 
The sponsor reserves the right to suspend or discontinue this study for administrative and/or 
safety reasons, at any time. The PI reserves the right to discontinue dosing subjects, at any time, 

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for safety reasons, but should contact the sponsor prior to discontinuing a subject from 
pegcetacoplan. 
15.7. 
Data Handling and Record Keeping 
The PI must maintain all documentation related to this study. All essential documents (as defined 
in the ICH Guideline E6) and the data generated in connection with this study, together with the 
original copy of the final report, will be retained for at least 5 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 at least 5 years have elapsed since the formal 
discontinuation of clinical development of the investigational product.  These documents should 
be retained for a longer period if required by the applicable regulatory requirements or by an 
agreement with the sponsor.  
It is the responsibility of the sponsor to inform the PI/Institution as to when these documents no 
longer need to be retained. 
15.8. 
Protocol Amendments 
Any amendments to the study protocol deemed necessary as the study progresses will be 
discussed between sponsor and the PI. The PI will not implement any changes to the protocol 
without an agreement by the sponsor and prior review and documented approval from the 
IRB/IEC of an amendment, except where necessary to eliminate immediate hazards to study 
subject or when the changes involve only logistical or administrative aspects of the study (eg, 
change in staff, telephone numbers). 
Amendment(s) will be approved and signed off in the same way as the protocol.  
15.9. 
Report Format 
According to the ICH Harmonised Tripartite Guideline (Organization of the Common Technical 
Document for the Registration of Pharmaceuticals for Human Use M4 and the ICH M2 Expert 
Working Group), the final report will be written according to the ICH E3 Guideline (Structure 
and Content of Clinical Study Reports). 
15.10. 
 
Finance and Insurance 
Finance and insurance will be addressed in a Clinical Trial Agreement between the PI/Institution
and the sponsor. 
15.11. 
 
Publication Policy 
The data generated for this study are considered confidential information and are the property of 
the sponsor. All study information provided to the PI and site personnel by the sponsor shall not 
be published or disclosed to a third party without the prior written consent of the sponsor.  
Apellis will endeavor to publish the results of all qualifying, applicable, and covered studies 
according to external guidelines in a timely manner, regardless of whether the outcomes are 
perceived as positive, neutral, or negative. Additionally, Apellis adheres to external guidelines 
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done for large, multicenter Phase 2-4 and certain other studies, as determined by Apellis. The 
purpose of the publication steering committee is to act as a noncommercial body that advises or 
decides on dissemination of scientific study data in accordance with the scope of this policy. 
All publications relating to Apellis products or projects must undergo appropriate technical and 
intellectual property review, with Apellis agreement to publish prior to release of information. 
The review is aimed at protecting the sponsor’s proprietary information existing either at the 
commencement of the study or generated during the study. To the extent permitted by the 
publisher and copyright law, the PI will own (or share with other authors) the copyright on 
his/her publications. To the extent that the PI has such sole, joint, or shared rights, the PI grants 
the sponsor a perpetual, irrevocable, royalty-free license to make and distribute copies of such 
publications. 
The term “publication” refers to any public disclosure, including:  original research articles, 
review articles, oral presentations, abstracts and posters at medical congresses, journal 
supplements, letters to the editor, invited lectures, opinion pieces, book chapters, electronic 
postings on medical/scientific websites, or other disclosure of the study results, in printed, 
electronic, oral, or other form. 
Subject to the terms of the paragraph below, the investigator shall have the right to publish the 
study results, and any background information provided by the sponsor that is necessary to 
include in any publication of study results, or necessary for other scholars to verify such study 
results.  Notwithstanding the foregoing, no publication that incorporates the sponsor’s 
confidential information shall be submitted for publication without the sponsor’s prior written 
agreement to publish and shall be given to the sponsor for review at least 60 days prior to 
submission for publication. If requested in writing by Apellis, the institution and PI shall 
withhold submission of such publication for up to an additional 60 days to allow for filing of a 
patent application. 
If the study is part of a multicenter study, the first publication of the study results shall be made 
by the sponsor in conjunction with the sponsor’s presentation of a joint, multicenter publication 
of the compiled and analyzed study results. If such a multicenter publication is not submitted to a 
journal for publication by the sponsor within an 18-month period after conclusion, abandonment, 
or termination of the study at all sites, or after the sponsor confirms there shall be no multicenter 
study publication of the study results, an investigator may individually publish the study results 
from the specific site in accordance with this section.  The investigator must, however, 
acknowledge in the publication the limitations of the single-site data being presented. 
Unless otherwise required by the journal in which the publication appears, or the forum in which 
it is made, authorship will comply with the International Committee of Medical Journal Editors 
(ICMJE) current standards. Participation as an investigator does not confer any rights to 
authorship of publications. 
 

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16.
 
REFERENCES
DeZern AE, Dorr D, Brodsky RA. Predictors of hemoglobin response to eculizumab therapy in 
paroxysmal nocturnal hemoglobinuria. Eur J Haematol. 2013;90(1):16–24. 
[FDA] Food and Drug Administration. Guidance for industry: population pharmacokinetics. 
Available at: https://www.fda.gov/downloads/drugs/guidances/UCM072137.pdf. 1999. Accessed 
20 September 2018. 
[FDA] Food and Drug Administration. Guidance for industry: exposure-response relationships – 
study design, data analysis, and regulatory applications. Available at: 
https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm
072109.pdf. 2003. Accessed: 20 September 2018. 
[FDA] Food and Drug Administration. Guidance for Industry and Investigators: Safety 
Reporting Requirements for INDs and BA/BE Studies. Available at: 
https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-
gen/documents/document/ucm227351.pdf. 2012. Accessed: 09 November 2018. 
Mager DE, Jusko WJ. General pharmacokinetic model for drugs exhibiting target-mediated drug 
disposition. J Pharmacokinet Pharmacodyn. 2001;28(6):507-532. 
Risitano AM, Notaro R, Marando L, et al. Complement fraction 3 binding on erythrocytes as 
additional mechanism of disease in paroxysmal nocturnal hemoglobinuria patients treated by 
eculizumab. Blood. 2009;113(17):4094-4100.  
 
 
 
 

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17.
 
APPENDICES

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