A Phase 3, Multi-Center, Randomized, Double-Masked, Sham-Controlled Study to Compare the Efficacy and Safety of Intravitreal Pegcetacoplan Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (AMD)
Phase: PHASE3
Conditions: Geographic Atrophy
Sponsor: Apellis Pharmaceuticals, Inc.

 
 
PEGCETACOPLAN (APL-2) 
PROTOCOL APL2-304 
A PHASE 3, MULTICENTER, RANDOMIZED, 
DOUBLE-MASKED, SHAM-CONTROLLED STUDY TO 
COMPARE THE EFFICACY AND SAFETY OF 
INTRAVITREAL PEGCETACOPLAN THERAPY WITH 
SHAM INJECTIONS IN PATIENTS WITH 
GEOGRAPHIC ATROPHY (GA) SECONDARY TO 
AGE-RELATED MACULAR DEGENERATION (AMD) 
 
US IND No.: 124784 
EudraCT No.: 2018-001435-52 
Phase: 3 
Version: Amendment 5 
Date: 12 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. 
Apellis Pharmaceuticals, Inc
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Pegcetacoplan 
APL2-304 Protocol Amendment 5 
12 August 2020 
INVESTIGATOR AGREEMENT 
Long Title:  
A Phase 3, Multi-Center, Randomized, Double-
Masked, Sham-Controlled Study to Compare the 
Efficacy and Safety of Intravitreal Pegcetacoplan 
Therapy with Sham Injections in Patients with 
Geographic Atrophy (GA) Secondary to Age-
Related Macular Degeneration (AMD) 
Short Title:  
Oaks 
Protocol Number, Version, and Date: 
APL2-304 / Amendment 5 / 12 August 2020  
Study Phase:  
Phase 3  
Sponsor Name and Address:  
Apellis Pharmaceuticals, Inc 
 
100 5th Ave 
 
Waltham, MA 02451 
 
USA  
Investigational Test Article:  
Pegcetacoplan intravitreal injection (also known as 
APL-2) 
US IND Number: 
124784 
EudraCT Number: 
2018-001435-52 
Indication Studied: 
Geographic atrophy secondary to age-related 
macular degeneration 
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) 
 
Apellis Pharmaceuticals, Inc
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Pegcetacoplan 
APL2-304 Protocol Amendment 5 
12 August 2020 
PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Amendment 5: Summary of Changes From the Previous Version  
Amendment Date: 12 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 changes that did not impact content of the document have 
been made for clarity. 
Entire document 
Updated company address 
Investigator Agreement and Sponsor 
Information 
Changed APL-2 to International Nonproprietary Name: pegcetacoplan, 
updated related abbreviations and protocol title 
Entire document 
Added the descriptor “maximum” when referencing reading speed 
Synopsis, Section 5.1.2, 
Section 5.1.5, Section 12.7.2, 
Section 12.7.3 
Removed the 6-month follow-up period and updated the study length 
from 30 months to 24 months and made it a 30- or 60-day follow-up 
period based on treatment group because that length of time is deemed 
sufficient to evaluate the safety of pegcetacoplan based on its half-life in 
the vitreous. Additionally, there is an option for subjects to enroll in a 
separate extension study (Study APL2-GA-305) during which longer-
term safety and efficacy will be collected. 
Synopsis, Section 8, 
Section 8.1.3.2.1, Section 11.8 
Inclusion criterion 6c was updated from “Reliability test ratio must be 
≤20%” to “Fixation losses must be ≤20%” on the basis of regulatory 
feedback provided to the microperimetry device manufacturer 
Synopsis, Section 6.1.1 
Updated the text regarding the sample size to both simplify and reduce 
redundancies 
Synopsis, Section 12.5 
Previous Section 4.1.3.1, Pharmacokinetics, moved to Section 4.1.3.2 to 
follow Section 4.1.3.1, Toxicology 
Section 4.1.3.1, Section 4.1.3.2 
Updated the formulation information 
Section 4.1.2, Section 7.3.3.1 
Revised number of injections for each treatment arm because the 
injections at Month 24 will no longer be administered 
Section 7.3.1 (Table 1), Section 8 
Updated the text regarding endophthalmitis for clarity 
Section 7.5.3 
Updated Study Schema 
Section 8 
Revised Study Procedures based on the removal of the Month 24 
injection and the 6-month follow-up period 
Section 8 
Revised the language regarding genotyping samples to indicate that these 
samples will be collected only for subjects who consent to the analysis 
Section 9.7 
Updated the language within the Adverse Events definition section to be 
consistent with the new Apellis standard language 
Section 11.1 
Updated the language within the Recording Adverse Events section to be 
consistent with the new Apellis standard language 
Section 11.2 
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Pegcetacoplan 
APL2-304 Protocol Amendment 5 
12 August 2020 
Removed the section on Treatment and Follow-up of Adverse Events 
because the information contained within it is now included in other 
revised sections to align with new Apellis standard language 
Section 11.3 
Updated the language within the Reporting Adverse Events section to be 
consistent with the new Apellis standard language 
Section 11.3 
Updated the language within the Serious Adverse Events section to be 
consistent with the new Apellis standard language 
Section 11.4 
Removed the section on Unexpected Adverse Events or Unexpected 
Suspected Adverse Reactions because the information contained within it 
is now included in other revised sections to align with new Apellis 
standard language 
previously Section 11.6 
Updated the language within the Pregnancy section to be consistent with 
the new Apellis standard language 
Section 11.6 
Removed APL-2 investigator’s brochure from references 
Section 15 
Updated Footnote G and M 
Appendix A, Appendix B, 
Appendix C, Appendix D, and 
Appendix K 
Deleted follow-up visits from Schedules of Activities 
Appendix B and Appendix D, and 
Table B and Table D of Appendix K 
Deleted pegcetacoplan and sham administration and postinjection 
assessment from Visit 20 of the Schedule of Activities for monthly and 
every-other-month treatment groups Month 13 to Month 24 
Appendix B and Appendix D and 
Tables B and D of Appendix K 
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Pegcetacoplan 
APL2-304 Protocol Amendment 5 
12 August 2020 
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. 
INTRODUCTION ......................................................................................................23 
4.1. 
Background .................................................................................................................23 
4.1.1. 
Age-Related Macular Degeneration .....................................................................23 
4.1.2. 
Pegcetacoplan .......................................................................................................23 
4.1.3. 
Nonclinical Data ...................................................................................................24 
 
 
 
 
4.1.4. 
Clinical Data .........................................................................................................27 
4.1.5. 
Rationale ...............................................................................................................28 
4.1.5.1. 
Rationale for Pegcetacoplan for Treatment of Geographic 
Atrophy .....................................................................................................28 
4.1.6. 
Dose Selection ......................................................................................................28 
4.2. 
Risk/Benefit ................................................................................................................28 
5. 
STUDY OBJECTIVES ..............................................................................................30 
5.1.1. 
Primary Objective .................................................................................................30 
5.1.2. 
Key Secondary Objectives ....................................................................................30 
5.1.3. 
Secondary Objectives ...........................................................................................30 
5.1.4. 
Safety Objectives ..................................................................................................30 
5.1.5. 
Exploratory Objectives .........................................................................................31 
6. 
PATIENT POPULATION ..........................................................................................32 
6.1.1. 
Inclusion Criteria ..................................................................................................32 
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12 August 2020 
6.1.2. 
Exclusion Criteria .................................................................................................33 
6.2. 
Women of Childbearing Potential ..............................................................................34 
6.3. 
Women of Nonchildbearing Potential ........................................................................34 
6.4. 
Approved Methods of Contraception .........................................................................34 
6.5. 
Discontinuation of Subjects ........................................................................................35 
7. 
TREATMENT OF SUBJECTS ..................................................................................36 
7.1. 
Allocation to Treatment ..............................................................................................36 
7.2. 
Masking and Minimization of Bias ............................................................................36 
7.2.1. 
Unmasking ............................................................................................................37 
7.3. 
Dosage and Administration ........................................................................................37 
7.3.1. 
Dose Levels and Treatment Arms ........................................................................37 
7.3.2. 
Treatment Administration .....................................................................................37 
7.3.3. 
Drug Supplies .......................................................................................................38 
7.3.3.1. 
Identity of Investigational Product ...........................................................38 
7.3.3.2. 
Storage ......................................................................................................38 
7.3.3.3. 
Accountability ...........................................................................................38 
7.3.4. 
Intravitreal Pegcetacoplan Administration ...........................................................39 
7.4. 
Sham Injection Administration ...................................................................................39 
7.5. 
Concomitant Therapies ...............................................................................................39 
7.5.1. 
Treatment of New Exudation Related to Active Choroidal 
Neovascularization in the Study Eye and/or Fellow Eye ...............................39 
7.5.2. 
Prohibited Therapies .............................................................................................40 
7.5.3. 
Endophthalmitis Treatment ..................................................................................40 
8. 
STUDY PROCEDURES ............................................................................................42 
8.1. 
Study Visit Schedule ...................................................................................................43 
8.1.1. 
Screening Period—Within 28 Days Prior to Randomization/ Treatment 
(Day –28 to –1) ...............................................................................................43 
8.1.1.1. 
Visit 1—All Subjects ................................................................................43 
8.1.2. 
Randomization/ Initial Treatment—Day 1—Within 28 Days of 
Screening ........................................................................................................44 
8.1.2.1. 
Visit 2—All Groups ..................................................................................44 
8.1.3. 
Treatment Phase—24 Months ..............................................................................44 
8.1.3.1. 
Months 1-12 ..............................................................................................44 
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8.1.3.2. 
Months 13-24 ............................................................................................45 
8.1.4. 
Early Termination Visit ........................................................................................46 
8.1.5. 
Unscheduled Visits ...............................................................................................46 
9. 
ASSESSMENTS.........................................................................................................47 
9.1. 
Informed Consent .......................................................................................................47 
9.2. 
Demographic Information/ Medical/ Surgical History ...............................................47 
9.3. 
Ocular History/ Ocular Procedures .............................................................................47 
9.4. 
Vital Signs ..................................................................................................................47 
9.5. 
Physical Examination .................................................................................................47 
9.6. 
Laboratory Analysis of Blood and Urine ....................................................................47 
9.7. 
Genotyping Samples ...................................................................................................48 
9.8. 
Urine Pregnancy Test .................................................................................................48 
9.9. 
Patient-Reported Outcomes ........................................................................................49 
9.9.1. 
The National Eye Institute Visual Functioning Questionnaire 25-Item 
Version (NEI-VFQ) ........................................................................................49 
9.9.2. 
The Functional Reading Independence (FRI) Index ............................................49 
9.10. 
Best Corrected Visual Acuity and Low Luminance Best Corrected Visual 
Acuity ...................................................................................................................49 
9.11. 
Minnesota Low-Vision Reading (MNREAD) Test or Radner Reading Charts 
(in select countries) ...............................................................................................50 
9.12. 
Home-Based Functional Digital Applications (optional, select sites) ........................50 
9.13. 
Complete Ophthalmic Exam .......................................................................................50 
9.14. 
Ocular Imaging and Microperimetry ..........................................................................50 
9.15. 
Postinjection Assessment............................................................................................51 
9.16. 
Blood Volume for Study Assessments .......................................................................52 
9.17. 
Samples for Clinical Repository (Optional, Select Sites) ...........................................52 
9.17.1. 
Approval by the Institutional Review Board or Ethics Committee ................53 
9.17.2. 
Sample Collection ...........................................................................................53 
9.17.3. 
Confidentiality and Data Ownership ..............................................................53 
9.17.4. 
Consent to Participate in the Clinical Repository ...........................................54 
9.17.5. 
Withdrawal From the Clinical Repository ......................................................54 
9.17.6. 
Monitoring and Oversight...............................................................................54 
10. 
SAFETY EVALUATIONS ........................................................................................55 
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10.1. 
Data Monitoring Committee .......................................................................................55 
11. 
ADVERSE EVENTS..................................................................................................56 
11.1. 
Definition ....................................................................................................................56 
11.2. 
Recording Adverse Events .........................................................................................56 
11.3. 
Reporting Adverse Events ..........................................................................................57 
11.3.1. 
Relationship of Events to Study Treatment ....................................................57 
11.3.2. 
Severity of Events ...........................................................................................57 
11.4. 
Serious Adverse Events ..............................................................................................58 
11.5. 
Treatment and Follow-up of Adverse Events .............................................................58 
11.6. 
Pregnancy ...................................................................................................................59 
11.7. 
Disease Progression ....................................................................................................59 
11.8. 
Withdrawal .................................................................................................................59 
12. 
DATA MANAGEMENT AND STATISTICAL CONSIDERATIONS ....................60 
12.1. 
Data Collection ...........................................................................................................60 
12.2. 
Clinical Data Management .........................................................................................60 
12.3. 
Statistical Analysis Process ........................................................................................60 
12.4. 
Planned Interim Analysis and Data Safety Monitoring Committee ...........................60 
12.5. 
Sample Size Calculation and Power Considerations ..................................................61 
12.6. 
Statistical Analysis Sets ..............................................................................................61 
12.7. 
Efficacy Analyses .......................................................................................................62 
12.7.1. 
Primary Efficacy Analysis ..............................................................................62 
12.7.2. 
Secondary Efficacy Analysis ..........................................................................63 
12.7.3. 
Exploratory Efficacy Analysis ........................................................................64 
12.8. 
Safety Analyses ..........................................................................................................64 
12.8.1. 
Anti-Therapeutic Antibodies ..........................................................................65 
12.8.2. 
Death ...............................................................................................................65 
12.8.3. 
Ocular Assessments ........................................................................................65 
12.9. 
Handling of Missing Data ...........................................................................................65 
12.10. Visit Windows ............................................................................................................65 
13. 
ETHICS ......................................................................................................................66 
13.1. 
Ethical Conduct of the Study ......................................................................................66 
13.2. 
Institutional Review Board/Ethic Committee .............................................................66 
13.3. 
Subject Information and Consent ...............................................................................66 
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12 August 2020 
14. 
ADMINISTRATIVE CONSIDERATIONS ..............................................................67 
14.1. 
Direct Access to Source Data/Documents ..................................................................67 
14.2. 
Quality Control and Quality Assurance ......................................................................67 
14.3. 
Monitoring ..................................................................................................................67 
14.4. 
Data Handling and Record Keeping ...........................................................................67 
14.5. 
Protocol Amendments ................................................................................................68 
14.6. 
Report Format .............................................................................................................68 
14.7. 
Finance and Insurance ................................................................................................68 
14.8. 
Publication Policy .......................................................................................................68 
14.9. 
ClinicalTrials.gov .......................................................................................................69 
14.10. Termination of Study ..................................................................................................69 
15. 
REFERENCES ...........................................................................................................70 
16. 
APPENDICES ............................................................................................................72 
APPENDIX A: VISIT SCHEDULE—Monthly Group—Screening, Day 1 through 
Month 12 ...............................................................................................................72 
APPENDIX B: VISIT SCHEDULE—Monthly Group—Month 13 to Month 24 ..................75 
APPENDIX C: VISIT SCHEDULE—Every-Other-Month Group—Screening, Day 1 
Through Month 12 ................................................................................................78 
APPENDIX D: VISIT SCHEDULE—Every-Other-Month Group—Month 13 to 
Month 24 ...............................................................................................................81 
APPENDIX E: NATIONAL EYE INSTITUTE VISUAL FUNCTIONING 
QUESTIONNAIRE 25-ITEM VERSION ............................................................84 
APPENDIX F: FUNCTIONAL READING INDEPENDENCE INDEX (FRI) ...................101 
APPENDIX G: MINNESOTA LOW-VISION READING TEST (MNREAD) AND 
RADNER READING CARDS...........................................................................102 
APPENDIX H: GRADING SCALE FOR ASSESSMENT OF ANTERIOR 
CHAMBER FLARE OR CELLS .......................................................................103 
APPENDIX I: GRADING SCALE FOR ASSESSMENT OF VITREOUS CELLS ............105 
APPENDIX J: AMENDMENT HISTORY ...........................................................................106 
APPENDIX K: PROTOCOL CHANGES TO BE FOLLOWED DURING COVID-
19 RESTRICTIONS ...........................................................................................118 
 
 
 
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APL2-304 Protocol Amendment 5 
12 August 2020 
 
LIST OF TABLES 
Table 1:  Treatment Arms with Approximate Number of Subjects ...............................................37 
Table 2:  Laboratory Sampling and Analysis ................................................................................48 
Table 3:  Total Study Blood Volume .............................................................................................52 
Table 4:  Power to Detect a Difference Among 3 Groups With an Equal Size of 
200 Subjects ................................................................................................................61 
 
LIST OF FIGURES 
Figure 1:  Study Schema ................................................................................................................42 
 
 
 
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12 August 2020 
2. 
SYNOPSIS 
Study Title 
A Phase 3, Multicenter, Randomized, Double-Masked, Sham-Controlled Study to Compare the Efficacy and Safety 
of Intravitreal Pegcetacoplan Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary 
to Age-Related Macular Degeneration (AMD) 
Protocol Number, Version, and Date 
APL2-304/ Amendment 5/ 12 August 2020 
Investigational Product, Dose, and Route of Administration 
• 
Pegcetacoplan (also known as APL-2) 
• 
15 mg/0.1 mL 
• 
Intravitreal (IVT) Injection 
Study Arms 
Arm 
Abbreviation 
Randomization 
Pegcetacoplan 15 mg/0.1 mL monthly for 24 months 
PM 
2 
Pegcetacoplan 15 mg/0.1 mL every other month for 24 months 
PEOM 
2 
Sham monthly for 24 months 
SM 
1 
Sham every other month for 24 months 
SEOM 
1 
Study Phase and Type 
Phase 3, multicenter, randomized, double-masked, sham-injection controlled 
Number of Subjects and Sites 
• 
Approximately 600 subjects 
• 
Approximately 100 sites 
Objectives  
Primary   
To evaluate the efficacy of pegcetacoplan compared to sham injection in patients with GA secondary to AMD 
assessed by change in the total area of GA lesions from baseline as measured by FAF. 
Key Secondary 
To evaluate the efficacy of pegcetacoplan compared to sham injection in patients with GA secondary to AMD with 
respect to: 
• 
Monocular maximum reading speed (study eye), as assessed by Minnesota Low-Vision Reading Test 
(MNREAD) or Radner Reading Charts (in select countries) 
• 
Functional Reading Independence (FRI) index score 
• 
Normal luminance best corrected visual acuity score (NL-BCVA) in the study eye  
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Secondary: 
• 
To evaluate the efficacy of pegcetacoplan compared to sham injection in patients with GA secondary 
to AMD with respect to: 
o 
Low luminance best corrected visual acuity score (LL-BCVA) in the study eye  
o 
Low luminance deficit (LLD) in the study eye 
o 
Total area of GA lesion(s) in the study eye 
o 
Monocular critical print size (study eye), as assessed by MNREAD or Radner Reading Charts 
(in select countries)  
o 
National Eye Institute Visual Functioning Questionnaire 25 Item Version (NEI VFQ-25) 
distance activity subscale score (in select countries) 
o 
Macular functional response as assessed by mesopic microperimetry  
Safety: 
• 
To evaluate the safety and tolerability of pegcetacoplan compared to sham injection in patients with 
GA secondary to AMD as indicated by: 
o 
Incidence and severity of ocular and systemic treatment-emergent adverse events 
o 
Incidence of anti-therapeutic antibodies directed against pegcetacoplan 
o 
Incidence of new active CNV in the study eye 
Exploratory 
• 
To evaluate the efficacy of pegcetacoplan compared to sham injection in patients with GA secondary 
to AMD as indicated by: 
o 
NEI VFQ-25 composite score  
o 
NEI VFQ-25 near activity subscale score (in select countries) 
o 
Comparison between study eye and fellow eye in change in GA lesion size  
o 
To evaluate the binocular maximum reading speed as assessed by MNREAD or Radner 
Reading Charts (in select countries) 
o 
To evaluate the binocular critical print size as assessed by MNREAD or Radner Reading 
Charts (in select countries) 
• 
To evaluate the relationship between genetic polymorphisms associated with AMD with GA 
progression and response to pegcetacoplan 
• 
To evaluate the incidence of new onset of subclinical CNV in the study eye  
• 
To assess sensitivity and specificity of a digital reading speed application to detect disease progression 
/ regression (optional, select sites) 
• 
To assess sensitivity and specificity of a digital visual function application to detect disease 
progression / regression (optional, select sites) 
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Inclusion Criteria 
The study eye must meet all inclusion criteria. If both eyes meet the inclusion criteria, the eye with the worst visual 
acuity at the screening visit will be designated as the study eye. If both eyes have the same visual acuity, the right 
eye will be selected as the study eye. 
Ocular-specific inclusion criteria apply to the study eye only, unless otherwise specified. 
1. Age ≥60 years. 
2. Normal Luminance best corrected visual acuity of 24 letters or better using Early Treatment Diabetic 
Retinopathy Study (ETDRS) charts (approximately 20/320 Snellen equivalent). 
3. Clinical diagnosis of GA of the macula secondary to AMD as determined by the investigator and confirmed 
by the reading center. 
4. The GA lesion must meet the following criteria as determined by the central reading center’s assessment of 
fundus autofluorescence (FAF) imaging at screening: 
a. 
Total GA area must be ≥2.5 and ≤17.5 mm2 (1 and 7 disk areas [DA] respectively) 
b. If GA is multifocal, at least 1 focal lesion must be ≥1.25 mm2 (0.5 DA), with the overall aggregate area 
of GA as specified above in 4a. 
c. 
The entire GA lesion must be completely visualized on the macula centered image and must be able to 
be imaged in its entirety and not contiguous with any areas of peripapillary atrophy. 
d. Presence of any pattern of hyperautofluorescence in the junctional zone of GA. Absence of 
hyperautofluorescence (ie, pattern = none) is exclusionary.1 
5. Adequate clarity of ocular media, adequate pupillary dilation, and fixation to permit the collection of good 
quality images as determined by the investigator.  
6. Meets the following criteria related to microperimetry:  
a. 
Able to detect fixation target. 
b. Total elapsed time to complete the 10-2 68-point exam is ≤30 minutes in duration.  
c. 
Fixation losses must be ≤20%.  
d. Subject is willing and able to undertake microperimetry assessment in the opinion of the investigator.  
7. Female subjects must be: 
a. 
Women of non–childbearing potential (WONCBP), or 
b. Women of childbearing potential (WOCBP) with a negative serum pregnancy test at screening and 
must agree to use protocol defined methods of contraception for the duration of the study and refrain 
from breastfeeding for the duration of the study. 
8. Males with female partners of childbearing potential must agree to use protocol defined methods of 
contraception and agree to refrain from donating sperm for the duration of the study. 
9. Willing and able to give informed consent and to comply with the study procedures and assessments.  
Exclusion Criteria 
Ocular specific exclusion criteria apply to the study eye only, unless otherwise specified. 
1. GA secondary to a condition other than AMD such as Stargardt disease, cone rod dystrophy, or toxic 
maculopathies like plaquenil maculopathy in either eye. 
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2. Spherical equivalent of the refractive error demonstrating > 6 diopters of myopia or an axial length 
>26 mm. 
3. Any history or active choroidal neovascularization (CNV), associated with AMD or any other cause, 
including any evidence of retinal pigment epithelium rips or evidence of neovascularization anywhere 
based on SD-OCT imaging and/or fluorescein angiography as assessed by the reading center. 
4. Presence of an active ocular disease that in the opinion of the investigator compromises or confounds visual 
function, including but not limited to, uveitis, other macular diseases (eg, clinically significant epiretinal 
membrane [ERM], full thickness macular hole or uncontrolled glaucoma/ocular hypertension). Benign 
conditions in the opinion of the investigator such as peripheral retina dystrophy are not exclusionary. 
5. Intraocular surgery (including lens replacement surgery) within 3 months prior to randomization.  
6. History of laser therapy in the macular region. 
7. Aphakia or absence of the posterior capsule. Note: YAG laser posterior capsulotomy for posterior capsule 
opacification done at least 60 days prior to screening is not exclusionary. 
8. Any ocular condition other than GA secondary to AMD that may require surgery or medical intervention 
during the study period or, in the opinion of the investigator, could compromise visual function during the 
study period.  
9. Any contraindication to IVT injection including current ocular or periocular infection.  
10. History of prior intravitreal injection. 
11. Unable to perform microperimetry reliably in the opinion of the investigator. 
12. Prior participation in another interventional clinical study for intravitreal therapies in either eye (including 
subjects receiving sham).  
13. Prior participation in another interventional clinical study for geographic atrophy in either eye including 
investigational oral medication and placebo. 
14. Participation in any systemic experimental treatment or any other systemic investigational new drug within 
6 weeks or 5 half-lives of the active ingredient (whichever is longer) prior to the start of study treatment. 
Note: clinical trials solely involving observation, over-the-counter vitamins, supplements, or diets are not 
exclusionary.  
15. Medical or psychiatric conditions that, in the opinion of the investigator, make consistent follow-up over 
the 24-month treatment period unlikely, or would make the subject an unsafe study candidate. 
16. Any screening laboratory value (hematology, serum chemistry or urinalysis) that in the opinion of the 
investigator is clinically significant and not suitable for study participation. 
17. Known hypersensitivity to fluorescein sodium for injection or hypersensitivity to pegcetacoplan or any of 
the excipients in pegcetacoplan solution.  
Study Design 
This is a 24-month, Phase 3, multicenter, randomized, double-masked, sham-injection controlled study to assess the 
efficacy and safety of multiple IVT injections of pegcetacoplan in subjects with GA secondary to AMD. 
The study will randomize approximately 600 subjects across approximately 100 multinational sites. Subjects will be 
screened within 28 days before receiving pegcetacoplan or sham injection. Upon entry into the study, subjects will 
be assigned a screening number. Subjects who meet all inclusion and none of the exclusion criteria will return to the 
clinic for randomization and treatment on Visit 2 (Day 1). At this visit, subjects will be randomized 2:2:1:1 to 
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receive pegcetacoplan monthly, pegcetacoplan every other month, sham injection monthly, or sham injection every 
other month, respectively. Randomization will be stratified according to GA lesion area at screening (< 7.5 mm2; ≥ 
7.5 mm2), and presence of CNV in the fellow eye. 
All subjects will be assessed monthly during the first 12 months regardless of treatment regimen. From Month 12 to 
Month 24, subjects will follow the outlined visit schedule (Appendix A to Appendix D) based on treatment 
assignment (ie, subjects in the monthly groups will be assessed monthly while subjects in the every-other-month 
[EOM] groups will be assessed every other month). The last visit in the study will be at Month 24, approximately 30 
days (monthly treatment group) or 60 days (EOM treatment group) after the last visit at which investigational 
product is administered.  At the end of the 24-month study period, subjects will have the option to enroll into a 
separate open-label study.  
Subjects who discontinue study treatment can continue participation in the study and should be encouraged to return 
to the clinical site for as many follow-up visits as they can (with the exception of pegcetacoplan/sham 
administration). Subjects who wish to fully withdraw from the study before Month 24, should be encouraged to 
complete the early termination visit. 
Endpoints and statistical analysis: 
Endpoints 
Primary Efficacy Endpoint 
• 
Change from baseline to Month 12 in total area of GA lesion(s) in the study eye (in mm2) based on 
fundus autofluorescence (FAF).  
Key Secondary Efficacy Endpoints 
• 
Change from baseline in monocular maximum reading speed (study eye), as assessed by MNREAD or 
Radner Reading Charts at Month 24 (in select countries) 
• 
Change from baseline in Functional Reading Independence (FRI) index score, at Month 24. 
• 
Change from baseline in normal luminance best corrected visual acuity score (NL-BCVA) at Month 24 
as assessed by ETDRS chart.  
Secondary Efficacy Endpoints 
• 
Change from baseline in low luminance best corrected visual acuity score (LL-BCVA) at Month 12 
and Month 24 as assessed by ETDRS chart.  
• 
Change from baseline in low luminance deficit (LLD) at Month 12 and Month 24. 
• 
Change from baseline at each planned assessment in the total area of GA lesion(s) in the study eye (in 
mm2) as assessed by FAF. 
• 
Change from baseline in monocular critical print size (study eye), as assessed by MNREAD or Radner 
Reading Charts, at Month 12 and Month 24 (in select countries).  
• 
Change from baseline in the National Eye Institute Visual Functioning Questionnaire 25-Item Version 
(NEI VFQ-25) distance activity subscale score at Month 12 and Month 24 (in select sites).  
• 
Number of scotomatous points assessed by mesopic microperimetry for the evaluation of the macular 
functional response.  
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• 
Change in macular sensitivity as assessed by mesopic microperimetry for the evaluation of the macular 
functional response. 
Exploratory Endpoints   
• 
Change from baseline in NEI VFQ-25 composite score at Month 12 and Month 24.  
• 
Change from baseline in NEI VFQ-25 near activity subscale score at Month 12 and Month 24 (in 
select countries). 
• 
Comparison between study eye and fellow eye in change in GA lesion size from baseline to Month 12 
and Month 24.  
• 
Binocular maximum reading speed as assessed by MNREAD or Radner Reading Charts over time (in 
select countries).  
• 
Binocular critical print size as assessed by MNREAD or Radner Reading Charts over time (in select 
countries). 
• 
Relationship between genetic polymorphisms associated with AMD with GA progression and response 
to pegcetacoplan. 
• 
Incidence of new onset of subclinical CNV in the study eye.  
• 
Assess sensitivity and specificity of a digital reading speed application to detect disease progression / 
regression (optional, select sites). 
• 
Assess sensitivity and specificity of a digital visual function application to detect disease progression / 
regression (optional, select sites). 
Safety Endpoints 
• 
Incidence and severity of ocular and systemic treatment-emergent adverse events.  
• 
Incidence of anti-therapeutic antibodies directed against pegcetacoplan. 
• 
Incidence of new active CNV in the study eye. 
Analysis of Primary Efficacy Endpoint 
The primary efficacy endpoint is the change from baseline to Month 12 in the total area of GA lesion(s) in eyes 
injected with pegcetacoplan, either monthly (PM) or every-other month (PEOM), or sham injections. GA lesion area 
(mm2) as measured by a quantified central reading center based on FAF images. The primary analysis will be the 
comparison of pegcetacoplan, either monthly (PM) or every-other month (PEOM) versus the combined 2 sham arms 
(the 2 sham arms will be combined into a single ‘control’ group). 
The null and alternative hypotheses for the primary efficacy analysis are: 
H0: µS = µPM   vs  
HA:  µS ≠ µPM , and 
H0: µS = µPEOM  vs  
HA:  µS ≠ µPEOM  
Note: here µ indicates each group’s respective mean change from baseline to Month 12 in GA lesion area for the 
comparison of the primary endpoint. 
A mixed effect model for longitudinal data will be used to analyze the change from baseline in GA lesion area. The 
model will include treatment, and presence of CNV in the fellow eye as fixed effects; baseline GA lesion area (at 
screening), time (in months) as a factor; as well as the time × treatment interaction term. All available data up to 12 
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months will be included in the model for the primary analysis. The mean change from baseline to 12 months will be 
estimated from the model (ie, least square [LS] mean) and compared between each of the pegcetacoplan arms to the 
sham control. For other time point of interest, LS mean change from baseline will be estimated and compared 
between treatments. Unstructured variance covariance will be used, 
For the analysis of final study data, a similar model including data up to 24 months will be used and LS means at 
time points of interest will be estimated and compared between treatment. 
This study is expected to have an approximately 5 DMC data reviews. Allocating an alpha level of 0.0001 for each 
DMC data review, the alpha level remains for the efficacy analysis at 0.0495 to maintain an overall study alpha of 
0.05. 
The hypothesis testing strategy for the primary and secondary efficacy endpoints will be based on the Gate-keeping 
multiple testing procedures controlling for the study wide type I error strongly at 2-sided 0.0495 as follows:  
Step 1. The mean GA lesion growth at 12 months will be compared between the PM group and the Control at 
the α level of 0.0495. If the null hypotheses of no difference between groups in this step is rejected, the testing 
proceeds to Step 2 and Step 3. If it’s not rejected, the testing procedure stops at this step.  
Step 2. The mean GA lesion growth at 12 months will be compared between the PEOM group and the Control 
at the α1 level. If the null hypotheses of no difference between groups in this step is rejected, the α1 level will 
be passed down to Step 3. The actual value of α1 will be specified in the SAP and it will be defined to ensure 
an adequate power of at least 80% for the comparison in this step. 
Step 3. The mean GA lesion growth at 24 months will be compared between the PM group and the Control at 
the α level of 0.0495 if the null hypotheses are rejected at both Step 1 and Step 2; or at the α level of (0.0495 – 
α1) if Step 2 testing does not reject the null hypothesis. If the null hypothesis at this step is rejected, the α level 
used at this step will be passed down to the next step of testing. If it’s not rejected, the testing procedure stops at 
this step.  
Step 4. The prioritization and alpha allocation for the remaining secondary endpoints will be specified in the 
SAP. 
The following sensitivity and supportive analyses will be performed to evaluate the robustness of the results from 
the primary analysis method: 
• 
Analyses will be repeated using the mITT and per-protocol sets 
• 
Primary and secondary endpoints will also be summarized with no pooling of the 2 sham arms. The 
comparison for pegcetacoplan and sham injection within each dose regimen (ie, PM vs SM and PEOM 
vs SEOM) will be conducted 
• 
Multiple imputation (MI) methods and other sensitivity analyses will be explored, and details will be 
provided in the SAP 
Analysis for Key Secondary and Secondary Endpoint(s) 
The key secondary and secondary endpoints will be analyzed in the same fashion as the primary endpoint using 
mixed effect model. The binary secondary endpoints will be analyzed using Cochran-Mantel-Haenszel test stratified 
by the randomization stratification factors. Hypothesis testing for 3 key secondary endpoints will be performed in 
the order specified. The SAP will provide more details on multiplicity adjustment and the approach for alpha 
spending among the endpoints.  
Sample Size Justification 
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Subjects will be randomized in a 2:2:1:1 ratio to receive treatment with pegcetacoplan monthly, pegcetacoplan every 
other month, sham monthly, or sham every other month. The annual growth rate in GA lesion area is expected to 
have a mean of 1.47, 1.70 and 2.13 mm2/year for pegcetacoplan monthly, pegcetacoplan every-other-month, and 
sham-pooled groups, respectively, as estimated from the results of a Phase 2 trial for pegcetacoplan. The standard 
deviation of the lesion growth is estimated to be 1.50 mm2 based on the same Phase 2 trial data or 1.25 mm2 based 
on natural history data.27 ie, With a sample size of 200 subjects in each group (ie, a total enrollment of 600 subjects) 
and the observed annual growth rate in GA lesion area from Phase 2 trial for pegcetacoplan, the study will have 
99.2% power to show the difference between PM and sham group and 81.5% power to show the difference between 
PEOM and sham group using the common standard deviation of 1.5 mm2 and 2-sided alpha of 0.05. The 
approximation is calculated using PROC POWER one-way analysis of variance, SAS 9.4. The study power is likely 
larger when utilizing the longitudinal data to model the primary endpoint. The actual study power may also vary 
based on the distribution of the stratification factors (ie, lesion area at screening, presence of CNV in fellow eye), 
and site enrollment. 
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3. 
ABBREVIATIONS 
Abbreviation
Term
AE 
adverse event 
AMD 
age-related macular degeneration 
ATA 
anti-therapeutic antibodies 
BCVA 
best corrected visual acuity 
CH50 
classical pathway of complement functional test 
CNV 
choroidal neovascularization 
CRF (eCRF) 
case report form (electronic CRF) (used interchangeably) 
DA 
disk area 
DCFP 
digital color fundus photography 
DMC 
data monitoring committee 
EDC 
electronic data capture 
EOM 
every other month 
ERG 
electroretinography 
ERM 
epiretinal membrane 
ETDRS 
Early Treatment Diabetic Retinopathy Study 
FAF 
fundus autofluorescence 
FFA/FA 
fundus fluorescein angiography or fluorescein angiography 
FRI 
functional reading independence index 
FSH 
follicle-stimulating hormone 
GA 
geographic atrophy 
GCP 
Good Clinical Practice 
HCG 
human chorionic gonadotropin 
IB 
investigator’s brochure 
ICF 
informed consent form  
 form 
ICH 
International Council for Harmonisation 
IEC 
independent ethics committee 
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Abbreviation
Term
IOP 
intraocular pressure 
IRB 
institutional review board 
ITT 
intent-to-treat 
IV 
intravenous 
IVT 
intravitreal 
IWR 
interactive web response 
LH 
luteinizing hormone 
LL-BCVA 
low luminance best corrected visual acuity 
LLD 
low luminance deficit 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
modified intention to treat 
MNREAD 
Minnesota Low-Vision Reading Test 
MOP 
manual of procedures 
NEI VFQ-25 
National Eye Institute Visual Functioning Questionnaire 25-Item Version 
NIR 
near infrared reflectance 
NOEL 
no observable effect level 
NL-BCVA 
normal luminance best corrected visual acuity 
OCT 
optical coherence tomography 
OCT-A 
optical coherence tomography angiography 
PEG 
polyethylene glycol 
PEG40 
polyethylene glycol (40-kDa nominal molecular weight) 
PEOM 
pegcetacoplan every-other-month 
PI 
principal investigator 
PK 
pharmacokinetics 
PM 
pegcetacoplan monthly 
PP 
per protocol 
RPE 
retinal pigment epithelium 
SAE 
serious adverse event 
SC 
subcutaneous 
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Abbreviation
Term
SC5b-9 
soluble terminal complement complex 
SD-OCT 
spectral domain optical coherence tomography 
SEOM 
sham every-other-month 
SM 
sham monthly 
SOP 
standard operating procedures 
TEAE 
treatment-emergent adverse event 
t1/2 
terminal elimination half-life 
VA 
visual acuity 
VEGF 
vascular endothelial growth factor 
WOCBP 
women of childbearing potential 
WONCBP 
women of nonchildbearing potential 
 
 
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4. 
INTRODUCTION 
4.1. 
Background 
This study is being conducted as part of a series of studies for the clinical development of 
pegcetacoplan for advanced Age-related Macular Degeneration (AMD) (neovascular AMD and 
geographic atrophy [GA]). The trial will be conducted in compliance with this protocol, Good 
Clinical Practice (GCP), and applicable regulatory requirements. The subject population will 
comprise adult male and female subjects with GA secondary to AMD. 
4.1.1. 
Age-Related Macular Degeneration 
Age-related macular degeneration is the leading cause of severe vision loss in people over the age 
of 65 in the United States and other Western countries.2 In the United States, about 1.75 million 
people have the advanced forms of AMD.3 The early signs of AMD (drusen and pigmentary 
changes) are common in individuals over age 65 and precede the late stage forms, which are 
visually devastating. The late stage forms of AMD are classified into either macular 
neovascularization (neovascular, wet, or exudative AMD) or GA. 
Geographic Atrophy is a disease characterized by thinning and loss of the retinal pigment 
epithelium (RPE) and concurrent atrophy of photoreceptors and choriocapillaris.4,5,6  Clinically, 
GA is characterized by gradually expanding atrophy leaving islands of dead retinal cells in the 
back of the eye. Although GA can result in significant visual function deficits in reading, night 
vision, and dark adaptation, and produce dense, irreversible scotomas in the visual field, the 
initial decline in visual acuity may be relatively limited if the fovea is spared. When the fovea is 
involved, GA quickly causes blindness.  
Genetic susceptibility has become increasingly recognized as a risk factor and important 
contributor to AMD. More than 19 genetic polymorphisms have been demonstrated to influence 
AMD risk, with as many as 5 of these encoded by genes that modulate the complement system. 
Inflammatory processes, especially those mediated by complement are thought to play a key role 
in AMD.5 It is thought that these may contribute to loss of choriocapillaris, photoreceptors, and 
RPE cells.  
GA is responsible for approximately 20% of all cases of legal blindness in North America (ie, 
BCVA 20/200 or worse) with increasing incidence and prevalence owing to a higher life 
expectancy.4  While there is treatment for exudative AMD with anti-VEGF therapies, no 
approved therapy exists for GA which is usually bilateral and relentlessly progressive. It 
represents a significant unmet need as it leads to significant visual impairment and affects more 
than 5 million people worldwide.13 
An overview of available information regarding pegcetacoplan follows below. Further details 
can be found in the pegcetacoplan investigator’s brochure (IB).26 
4.1.2. 
Pegcetacoplan 
Pegcetacoplan is a PEGylated cyclic peptide inhibitor of complement C3. Pegcetacoplan is 
formed by 2 identical pentadecapeptides (combining a bioactive cyclic tridecapeptide C3-
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inhibiting moiety and a 2-amino acid linker) covalently coupled to each end of a linear 40 kDa 
polyethylene glycol (PEG) chain. 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 
multiple inflammatory processes. The PEGylation of the molecule imparts slower clearance from 
the vitreous humor following administration.  
Pegcetacoplan Intravitreal Injection 15 mg/0.1 mL will be provided as a 150 mg/ mL sterile 
solution of pegcetacoplan in stoppered glass vials. Pegcetacoplan is a sterile, isotonic solution in 
acetate-buffer, pH 5.0, containing trehalose. The drug product is packaged in 2R clear Type I 
glass vials with 13 mm FluroTec-coated chlorobutyl grey stoppers and sealed with 13 mm 
aluminum/polypropylene flip-off type seals.  
4.1.3. 
Nonclinical Data 
This section is intended to briefly summarize information on the safety, tolerability, and PK of 
intravitreal (IVT), intravenous (IV) and subcutaneous (SC) injections of pegcetacoplan. For 
complete and detailed information, refer to the IB. 
As pegcetacoplan is only pharmacologically active in primates, the pivotal IVT toxicological 
studies have been conducted in cynomolgus monkeys. The safety and tolerability of 
IVT-administered pegcetacoplan has been assessed in a Good Laboratory Practice 
(GLP)-compliant pivotal chronic (9-month) repeat-dose study in cynomolgus monkeys. In 
addition, 2 GLP-compliant 2-month ocular bridging studies (the first comparing drug substance 
from 2 different CMOs, the second assessing the safety and tolerability profiles of 3 different 
formulations to support the Phase 3 clinical study) have been conducted in cynomolgus monkeys 
as well. . Pegcetacoplan was observed to be minimally immunogenic in the 9-month study as 
evidenced by a lack of circulating antibodies in the majority of monkeys studied. The NOEL for 
chronic (9-month) IVT dosing was concluded to be >24.8 mg/eye. The results of this 9-month 
chronic study in cynomolgus monkeys support the safety of chronic IVT injections of 
pegcetacoplan at monthly or bimonthly intervals in humans. 
PK assessments included in the chronic (9-month) study revealed serum concentrations of 
pegcetacoplan that were approximately dose-proportional 24 hours after the first IVT dose. The 
serum t1/2 of IVT-administered pegcetacoplan, determined in a separate PK assessing a 
10 mg/eye dose (in 50 µL), was 10.4 days although the pegcetacoplan levels measured in the 
serum following infrequent IVT administration are orders of magnitude lower than 
pharmacological serum levels achieved with SC or IV administration. 
Additional nonclinical studies in monkeys and rabbits, including assessments of other routes of 
administration (SC and IV), have further defined pegcetacoplan’s safety profile. . Pegcetacoplan 
has been shown to be generally tolerated through all 3 routes of administration assessed (IVT, 
SC, and IV), with no adverse effects observed in safety pharmacology studies (in vivo 
cardiopulmonary telemetry and in vitro hERG inhibition assay) and genotoxicity studies (Ames, 
in vitro aneugenicity and clastogenicity in TK6 cells, and in vivo clastogenicity in mouse 
micronuclei).  
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4.1.4. 
Clinical Data 
The initial safety and tolerability of pegcetacoplan following IVT administration in humans was 
tested in an open-label, single dose escalation, Phase I clinical study in patients with wet age-
related macular degeneration under protocol POT-CP043014 (NCT02461771). The study was 
conducted in multiple ophthalmology clinical sites in the US and Australia. A single dose of 
pegcetacoplan was administered on Day 1 to patients suffering from wet AMD currently 
receiving anti-VEGF standard of care. Three escalating doses of pegcetacoplan administered IVT 
were studied. Three subjects received 4 mg; 3 subjects received 10 mg, and 7 subjects received 
20 mg. No serious adverse events (SAEs) or drug-related adverse events (AEs) of concern were 
observed. It was concluded that administration of a single dose of pegcetacoplan IVT up to 
20 mg is safe and well tolerated.  
A Phase 2 study (Protocol POT-CP121614; NCT02503332) to assess the safety, tolerability, and 
evidence of activity of multiple intravitreal injections of pegcetacoplan in subjects with 
geographic atrophy secondary to AMD has been completed. The study was conducted at multiple 
ophthalmology clinical sites in the US, Australia, and New Zealand. Subjects were randomized 
in a 2:1:2:1 manner to either receive pegcetacoplan IVT 15 mg monthly for 12 months; sham 
IVT monthly for 12 months; pegcetacoplan IVT 15 mg every other month for 12 months; or 
sham IVT every other month for 12 months.  
This study demonstrated a statistically significant slowing of disease progression at Month 12 at 
the prespecified alpha of 0.1. Pegcetacoplan administered monthly showed a 29% (P=.008) 
reduction in the rate of GA lesion growth compared to sham and pegcetacoplan administered 
every other month showed a 20% (P=.067) reduction. Pegcetacoplan has been generally well 
tolerated. The most frequently reported AEs have been related to the injection procedure 
(intravitreal injection), which are commonly found in this type of study. An imbalance in new 
active choroidal neovascularization (CNV) in subjects treated with pegcetacoplan was observed 
and the risk of developing new exudation may be increased in subjects with a prior history of 
neovascular AMD in the fellow eye. One subject in the sham arm, 1/81 (1%) was observed to 
have developed new active study eye exudation compared with 25/165 (15%) subjects that 
received pegcetacoplan IVT injections, 26 subjects in total. Of the 25 pegcetacoplan treated 
subjects with new active CNV, 18 subjects received PM treatment and 7 subjects received 
PEOM treatment. 
Seventeen of the 25 (68%) subjects that developed new active study eye CNV had a prior history 
of neovascular AMD in the nonstudy fellow eye. No significant imbalance in history of 
neovascular AMD in the fellow eye was observed among the 3 arms to explain the imbalance in 
new exudation observed in study eyes. Visual acuity data did not demonstrate clear differences 
between subjects developing new study eye exudation compared with those that did not. 
A Phase 1b study (Protocol APL2-103; NCT 03777332) to assess the safety of pegcetacoplan in 
subjects with GA secondary to AMD and low vision is currently ongoing. This study is being 
conducted at multiple ophthalmology clinical sites across the US. Subjects receive monthly 
treatment with intravitreal pegcetacoplan for 24 months. 
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4.1.5. 
Rationale 
4.1.5.1. 
Rationale for Pegcetacoplan for Treatment of Geographic Atrophy 
The rationale for the use of a complement inhibitor in patients with AMD is based on evidence 
from both human and animal studies. Human biochemical, genetic, and clinical lines of evidence 
indicate that the complement system plays a role in the etiology of AMD. Complement 
components including C3, the membrane attack complex, and complement factor H, are present 
in drusen and basal laminar deposits in eyes from patients with AMD.7,8,9,10  Genetic variants of 
complement factor H,8,11,12,13,14 C3,15,16 complement factor I17 and other complement 
components18,19,20 have been associated with altered risks for the development of both the 
neovascular and atrophic forms of AMD. Patients with AMD also have signs of systemic 
complement activation, exhibiting higher serum levels of Complement Factor B, C3a, C5a, 
SC5b-9 (soluble terminal complement complex), C3d, and Ba compared to age-matched 
controls.21,22,23,24  
4.1.6. 
Dose Selection 
A single dose of 15 mg/0.1 mL injection administered monthly or EOM for 24 months will be 
tested in this study (see Section 7.3.1). Pegcetacoplan was well tolerated in a panel of animal 
toxicology studies. A 9-month, repeat-dose GLP study in cynomolgus monkeys was conducted 
to evaluate the safety of IVT injections of pegcetacoplan at doses up to 24.8 mg/eye at a 
frequency of 1 injection every 4 weeks. 
In this pivotal chronic toxicological study conducted in monkeys, the NOEL was established as 
>24.8 mg of pegcetacoplan delivered intravitreally every 4 weeks for 9 months using a 100 µL 
injection. The volume of the human vitreous is approximately 4 mL, which is approximately  
2.7-fold larger than the mean vitreous volume of cynomolgus monkeys, 1.5 mL.25 Based on the 
difference in vitreous volume between man and cynomolgus and the NOEL defined in 
nonhuman primates, the human equivalent dose was determined to be 67 mg/eye every 4 weeks. 
The dose (15 mg/injection) of pegcetacoplan that will be evaluated in this clinical study is 
expected to result in drug concentrations approximately 4.5-fold lower that the NOEL observed 
in cynomolgus monkeys.  
To support appropriate assessments of dose response to pegcetacoplan, pegcetacoplan is 
administered in 2 different frequencies in the study: monthly and every other month.  
Physician feedback injecting a 200 mg/mL solution in the Phase 1 (Study POT-CP043014; 
NCT02461771) trial confirmed that 150 mg/mL is the highest practical concentration that can be 
routinely administered, which set the dose of the Phase 2 trial to 15 mg (ie, 0.1 mL of a 
150 mg/mL solution). The 15-mg dose given monthly was found to be the most efficacious in the 
Phase 2 trial. The 15 mg dose given every other month demonstrated slightly less efficacy but 
offers a reduced treatment burden for patients and physicians.  
4.2. 
Risk/Benefit 
The Phase 1 (Study POT-CP043014; NCT02461771) and Phase 2 (Study POT-CP121614; 
NCT02503332) studies provide supporting evidence of a positive benefit-risk profile for the use 
of pegcetacoplan in treating patients with AMD, specifically patients with GA. These 
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preliminary results of an up to 28% reduction of GA progression rate support the evaluation of 
pegcetacoplan in a Phase 3 study.  
The reported safety data from these studies demonstrated an acceptable safety and tolerability 
profile with no clinically significant safety concerns observed. A total of 178 patients have 
received at least 1 dose (15 mg/injection) of pegcetacoplan as part of these studies. In the Phase 2 
study in patients with GA an imbalance in new exudation in subjects treated with pegcetacoplan 
was observed. Section 4.1.4 provides a summary of the study design and key results from both 
studies. 
The safety monitoring practices employed by this protocol (complete ophthalmologic exam, IOP 
monitoring, OCT, fluorescein angiography, vital signs, hematology, serum chemistry, urinalysis, 
physical exam, vital signs, and AE questioning) are adequate to protect the subjects’ safety. 
There are also risks associated with the ophthalmic procedures required for participants in this 
study. However, these are all standard procedures that are widely performed in ophthalmology. 
In the days following any IVT injection, patients are at risk of developing sterile or infectious 
intraocular inflammation (eg, endophthalmitis). In recent studies conducted with pegcetacoplan 
IVT from a single manufacturer, events of transient moderate and severe intraocular 
inflammation have been observed. Other risks of IVT injection include traumatic cataract, retinal 
detachment, increased IOP, and hemorrhage.  
The amount of blood (See Section 9.16) planned for collection from each subject over the 
24 months of the study does not pose an undue risk in this patient population. 
There is a potential health benefit for trial participants from receipt of study drug. If efficacious, 
pegcetacoplan is expected to alter the course of GA and slow its rate of progression. 
 
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5. 
STUDY OBJECTIVES  
5.1.1. 
Primary Objective 
To evaluate the efficacy of pegcetacoplan compared to sham injection in patients with GA 
secondary to AMD assessed by change in the total area of GA lesions from baseline as measured 
by fundus autofluorescence (FAF). 
5.1.2. 
Key Secondary Objectives 
To evaluate the efficacy of pegcetacoplan compared to sham injection in patients with GA 
secondary to AMD with respect to: 
• Monocular maximum reading speed (study eye), as assessed by Minnesota Low-
Vision Reading Test (MNREAD) or Radner Reading Charts (in select countries) 
• Functional Reading Independence (FRI) index score 
• Normal luminance best corrected visual acuity score (NL-BCVA) in the study eye  
5.1.3. 
Secondary Objectives  
• To evaluate the efficacy of pegcetacoplan compared to sham injection in patients with 
GA secondary to AMD with respect to: 
o Low luminance best corrected visual acuity score (LL-BCVA) in the study 
eye  
o Low luminance deficit (LLD) in the study eye 
o Total area of GA lesion(s) in the study eye 
o Monocular critical print size (study eye), as assessed by MNREAD or Radner 
Reading Charts (in select countries)  
o National Eye Institute Visual Functioning Questionnaire 25-Item Version 
(NEI VFQ-25) distance activity subscale score (in select countries) 
o Macular functional response as assessed by mesopic microperimetry  
5.1.4. 
Safety Objectives 
• To evaluate the safety and tolerability of pegcetacoplan compared to sham injection 
in patients with GA secondary to AMD as indicated by: 
o Incidence and severity of ocular and systemic treatment-emergent adverse 
events 
o Incidence of anti-therapeutic antibodies directed against pegcetacoplan 
o Incidence of new active CNV in the study eye 
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5.1.5. 
Exploratory Objectives 
• To evaluate the efficacy of pegcetacoplan compared to sham injection in patients with 
GA secondary to AMD as indicated by: 
o NEI VFQ-25 composite score  
o NEI VFQ-25 near activity subscale score (in select countries) 
o Comparison between study eye and fellow eye in change in GA lesion size  
o To evaluate the binocular maximum reading speed as assessed by MNREAD 
or Radner Reading Charts (in select countries) 
o To evaluate the binocular critical print size as assessed by MNREAD or 
Radner Reading Charts (in select countries) 
• To evaluate the relationship between genetic polymorphisms associated with AMD 
with GA progression and response to pegcetacoplan 
• To evaluate the incidence of new onset of subclinical CNV in the study eye 
• To assess sensitivity and specificity of a digital reading speed application to detect 
disease progression / regression (optional, select sites) 
• To assess sensitivity and specificity of a digital visual function application to detect 
disease progression / regression (optional, select sites) 
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6. 
PATIENT POPULATION 
The study population includes approximately 600 subjects to be randomized at approximately 
100 multinational sites. To participate in the study, subjects must be diagnosed with GA of the 
macula secondary to AMD in the study eye.  
6.1.1. 
Inclusion Criteria  
The study eye must meet all inclusion criteria. If both eyes meet the inclusion criteria, the eye 
with the worst normal luminance visual acuity at the screening visit will be designated as the 
study eye. If both eyes have the same visual acuity, the right eye will be selected as the study 
eye.  
Ocular-specific inclusion criteria apply to the study eye only, unless otherwise specified. 
1. Age ≥60 years. 
2. Normal Luminance best corrected visual acuity of 24 letters or better using Early 
Treatment Diabetic Retinopathy Study (ETDRS) charts (approximately 20/320 Snellen 
equivalent). 
3. Clinical diagnosis of GA of the macula secondary to AMD as determined by the 
investigator and confirmed by the reading center. 
4. The GA lesion must meet the following criteria as determined by the central reading 
center’s assessment of FAF imaging at screening: 
a. 
Total GA area must be ≥2.5 and ≤17.5 mm2 (1 and 7 disk areas [DA] respectively). 
b. If GA is multifocal, at least 1 focal lesion must be ≥1.25 mm2 (0.5 DA), with the overall aggregate 
area of GA as specified above in 4a. 
c. 
The entire GA lesion must be completely visualized on the macula centered image and must be able to 
be imaged in its entirety and not contiguous with any areas of peripapillary atrophy. 
d. Presence of any pattern of hyperautofluorescence in the junctional zone of GA. Absence of 
hyperautofluorescence (ie, pattern = none) is exclusionary.1 
5. Adequate clarity of ocular media, adequate pupillary dilation, and fixation to permit the 
collection of good quality images as determined by the investigator.  
6. Meets the following criteria related to microperimetry:  
a. 
Able to detect fixation target. 
b. Total elapsed time to complete the 10-2 68-point exam is ≤30 minutes in duration.  
c. 
Fixation losses must be ≤20%.  
d. Subject is willing and able to undertake microperimetry assessment in the opinion of the investigator. 
7. Female subjects must be: 
a. 
Women of non–childbearing potential (WONCBP), or 
b. Women of childbearing potential (WOCBP) with a negative serum pregnancy test at screening and 
must agree to use protocol defined methods of contraception for the duration of the study and refrain 
from breastfeeding for the duration of the study. 
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8. Males with female partners of childbearing potential must agree to use protocol defined 
methods of contraception and agree to refrain from donating sperm for the duration of the 
study. 
9. Willing and able to give informed consent and to comply with the study procedures and 
assessments.  
6.1.2. 
Exclusion Criteria  
Ocular specific exclusion criteria apply to the study eye only, unless otherwise specified. 
1. GA secondary to a condition other than AMD such as Stargardt disease, cone rod 
dystrophy, or toxic maculopathies like plaquenil maculopathy in either eye. 
2. Spherical equivalent of the refractive error demonstrating > 6 diopters of myopia or an 
axial length >26 mm. 
3. Any history or active CNV, associated with AMD or any other cause, including any 
evidence of retinal pigment epithelium rips or evidence of neovascularization anywhere 
based on SD-OCT imaging and/or fluorescein angiography as assessed by the reading 
center. 
4. Presence of an active ocular disease that in the opinion of the investigator compromises 
or confounds visual function, including but not limited to, uveitis, other macular diseases 
(eg, clinically significant epiretinal membrane [ERM], full thickness macular hole) or 
uncontrolled glaucoma/ocular hypertension). Benign conditions in the opinion of the 
investigator such as peripheral retina dystrophy are not exclusionary. 
5. Intraocular surgery (including lens replacement surgery) within 3 months prior to 
randomization.  
6. History of laser therapy in the macular region. 
7. Aphakia or absence of the posterior capsule. Note: YAG laser posterior capsulotomy for 
posterior capsule opacification done at least 60 days prior to screening is not 
exclusionary. 
8. Any ocular condition other than GA secondary to AMD that may require surgery or 
medical intervention during the study period or, in the opinion of the investigator, could 
compromise visual function during the study period.  
9. Any contraindication to IVT injection including current ocular or periocular infection.  
10. History of prior intravitreal injection.  
11. Unable to perform microperimetry reliably in the opinion of the investigator. 
12. Prior participation in another interventional clinical study for intravitreal therapies in 
either eye (including subjects receiving sham). 
13. Prior participation in another interventional clinical study for geographic atrophy in either 
eye including investigational oral medication and placebo. 
14. Participation in any systemic experimental treatment or any other systemic 
investigational new drug including within 6 weeks or 5 half-lives of the active ingredient 
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(whichever is longer) prior to the start of study treatment. Note: clinical trials solely 
involving observation, over-the-counter vitamins, supplements, or diets are not 
exclusionary.  
15. Medical or psychiatric conditions that, in the opinion of the investigator, make consistent 
follow-up over the 24-month treatment period unlikely, or would make the subject an 
unsafe study candidate. 
16. Any screening laboratory value (hematology, serum chemistry or urinalysis) that in the 
opinion of the investigator is clinically significant and not suitable for study participation. 
17. Known hypersensitivity to fluorescein sodium for injection or hypersensitivity to 
pegcetacoplan or any of the excipients in pegcetacoplan solution.  
6.2. 
Women of Childbearing Potential 
WOCBP are defined as premenopausal women physiologically capable of becoming pregnant. 
6.3. 
Women of Nonchildbearing Potential 
WONCBP are defined as women meeting any of the following criteria: 
• Older than 45 years with amenorrhea for > 2 years or older than 60 years with 
amenorrhea for > 1 year. Both confirmed by follicle-stimulating hormone (FSH) and 
LH levels. 
• Has undergone hysterectomy, 
• Has undergone bilateral oophorectomy, 
• Has undergone bilateral salpingectomy. 
6.4. 
Approved Methods of Contraception 
Approved methods of contraception include:  
• Combined (estrogen-and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation: 
o Oral 
o Intravaginal 
o Transdermal 
• Progestogen-only hormonal contraception associated with inhibition of ovulation: 
o Oral 
o Injectable 
o Implantable 
• Intrauterine device  
• Intrauterine hormone-releasing system  
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• Bilateral tubal occlusion 
• Vasectomized partner (provided that partner is the sole sexual partner of the WOCBP 
trial participant and that the vasectomized partner has received medical assessment 
of the surgical success) 
• Sexual abstinence (defined as refraining from heterosexual intercourse during the 
entire period of risk associated with the study treatments). Sexual abstinence is only 
accepted when it is the preferred and usual lifestyle of the subject. 
Subjects must agree to use an approved method of contraception during the study and 90 days 
after their last dose of study drug. 
6.5. 
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 treatment with the investigational product 
(IP) with the medical monitor, when possible. 
Subjects who discontinue treatment with the IP can continue participation in the study and 
should be encouraged to return to the clinical site for as many follow-up visits as they can. In the 
event that a subject terminates early from the study, all early termination procedures should be 
performed even if they are outside the allowed study window.  
The reason for termination, date of stopping treatment with IP, all follow-up information and the 
total amount of IP administered must be recorded in the case report form (CRF) and source 
documents. 
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7. 
TREATMENT OF SUBJECTS 
7.1. 
Allocation to Treatment 
Each subject will be assigned a unique screening number after signing the informed consent. 
Subjects who complete the study screening assessments and meet all the eligibility criteria will 
be scheduled to enter the study and randomized on Day 1. As part of the screening process, the 
reading center will evaluate FAF, OCT, Digital Color Fundus Photograph (DCFP), Near Infrared 
Reflectance (NIR), and fluorescein angiography (FA) to provide an objective assessment of 
subject eligibility. Subjects will be randomized 2:2:1:1 to receive treatment with PM, PEOM, 
sham injection monthly (SM) or sham injection every other month (SEOM), respectively. 
Table 1 presents the treatment arms along with the approximate number of subjects and 
injections per arm. 
The randomization scheme will be generated and maintained by the sponsor, or designee. 
Subject randomization will be stratified by GA lesion area at screening (< 7.5 mm2; ≥ 7.5 mm2) 
and presence of CNV in the fellow eye (yes; no). Further details on the randomization 
procedures will be described in the statistical analysis plan.  
7.2. 
Masking and Minimization of Bias 
The intent of masking is to limit the occurrence of conscious and unconscious bias in the conduct 
and interpretation of the clinical study. Bias could arise from the influence that the knowledge of 
a specific treatment assignment may have on the recruitment and allocation of subjects, their 
subsequent care, the assessment of endpoints, the handling of withdrawals, and so on. The 
essential aim of masking, therefore, is to prevent identification of the treatments by the subject 
and the masked assessors associated with the conduct of the study until all such opportunities for 
bias have passed. 
This is a double-masked study. Designated masked study site staff (eg, assistant(s), visual acuity 
technicians, OCT technicians, photographers, technicians administering questionnaires, subjects, 
reading center personnel, the assigned evaluating physician(s), and the sponsor) will be masked 
to treatment assignment. However, the treating physician and any associated support staff 
involved in performing the intravitreal or sham injections will be unmasked to study treatment. 
These individuals are not allowed to discuss treatment and/or patient outcome with masked study 
staff, including the evaluating physician. The principal investigator must be masked to subjects’ 
treatment assignment. To prevent bias in treatment assignment, eligible subjects will be 
randomized using a web-based randomization system. Documentation will be put in place to 
avoid unintentional unmasking during the study. All study roles will be clearly documented on 
the site delegation of authority log and once the roles have been designated and executed, these 
roles should not be switched during the conduct of the study. In unforeseen circumstances, a site 
can contact the sponsor to switch a study staff member from the masked role to the unmasked 
role but not vice versa. 
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7.2.1. 
Unmasking  
In the event of a medical emergency where the knowledge of subject treatment by masked 
individuals (eg, the subject or his/her physician) is required, an individual investigator (or 
designee) will have the ability to unmask the treatment assignment for a specific subject and 
share that information with the appropriate parties. All documentation indicating unmasking 
must be retained with the subject’s source documentation in a secure manner. A DMC will be 
set-up to monitor patient safety and review data. The DMC will be provided unmasked safety 
data but will be masked to efficacy data unless this data is deemed medically necessary. 
Procedures for DMC unmasking will be documented in a DMC Charter.  
For regulatory reporting and if required by local regulations, the sponsor will unmask study 
treatment for all serious, unexpected adverse reactions that are considered to be related to study 
drug. Subjects who have had their treatment assignment unmasked secondary to a serious or 
unexpected AE or medical emergency will no longer receive study treatment. However, they 
should continue to complete as many of the follow-up visits as possible. 
The study unmasking for the primary analysis at 12 months will be limited to the analysis team 
and personnel only on an as-needed basis. All other personnel in the “masked” role will remain 
masked until the end of study. A document listing out the roles and responsibilities of the 
individuals participating in the unmasking analysis will be provided prior to the unmasking.  
7.3. 
Dosage and Administration 
7.3.1. 
Dose Levels and Treatment Arms 
After randomization and during the treatment phase beginning at Day 1, all subjects will receive 
a single dose of 15 mg pegcetacoplan/0.1 mL or sham injection intravitreally either monthly or 
every other month depending on treatment designation as presented in Table 1 below.  
Table 1:  Treatment Arms with Approximate Number of Subjects 
Treatment Arms 
Pegcetacoplan 15 mg/0.1 mL monthly for 24 months (n= approximately 200 subjects; 24 pegcetacoplan 
injections) 
Pegcetacoplan 15 mg/0.1 mL EOM for 24 months (n= approximately 200 subjects; 12 pegcetacoplan 
injections) 
Sham monthly for 24 months (n= approximately 100 subjects; 24 sham injections) 
Sham EOM for 24 months (n= approximately 100 subjects; 12 sham injections) 
7.3.2. 
Treatment Administration  
Only qualified study staff and those delegated the responsibility of study drug administration on 
the delegation of authority log should perform this procedure. All staff should be appropriately 
trained on all procedures prior to performing the procedures. Sites should follow the Visit 
Schedule for order of procedures and assessments.  
Administration of study treatment (pegcetacoplan or sham) can be done on a separate day from 
the assessment visit if both days fall within the visit window. If this occurs on the randomization 
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visit, then the administration of pegcetacoplan or sham should be done within 3 days of 
randomization and after approval from the medical monitor. When study treatment 
administration is on a day other than a study visit, then the only assessment that must be done on 
the day of study treatment administration is the IOP preinjection. 
If a subject falls outside the visit window for a dosing visit, the dose should be skipped and the 
subject should be scheduled on time for the next dosing visit. 
7.3.3. 
Drug Supplies 
7.3.3.1. 
Identity of Investigational Product 
Pegcetacoplan will be supplied as a liquid solution in stoppered glass vials and should be stored 
according to the label. Specific instructions for preparing pegcetacoplan for the IVT injection 
procedure will be provided in the manual of procedures. Pegcetacoplan Intravitreal Injection 
15 mg/0.1 mL (150 mg/mL) is a sterile, isotonic solution of pegcetacoplan in acetate-buffer, pH 
5.0, containing trehalose. The drug product is packaged in 2R clear Type I glass vials with 
13 mm FluroTec-coated chlorobutyl grey stoppers and sealed with 13-mm 
aluminum/polypropylene flip-off type seals.  
Sham will be provided as empty stoppered glass vials and should be stored according to the 
label.  
7.3.3.2. 
Storage  
Vials should be automatically stored as per the instructions until ready for use. Each vial should 
only be used once. Vials should not be shaken and should be protected from sunlight.  
7.3.3.3. 
Accountability 
Pegcetacoplan drug product and sham vials will be provided to a designee at the study site and 
must be stored in a pharmacy or otherwise locked and secured, at the temperature specified on 
the label. The drug product supply is accessible only to those individuals authorized by the PI. 
The sponsor will supply sufficient quantities of pegcetacoplan drug product and sham to allow 
completion of this study. The site should only use the investigational medicinal product provided 
by the sponsor for use in the study. 
Designated unmasked study staff will provide the study treatments to the subjects in accordance 
with their assigned subject numbers and the randomization schedule. During the study, the 
receipt of the drugs supplied at the clinical site and of study treatment dispensation for each 
subject will be documented in drug accountability records. These drug accountability records are 
to be kept separate from the patient medical records and other source documents. 
All used vials should be retained by the clinical site until drug accountability monitoring is 
performed and then returned to the sponsor or designee or destroyed per sponsor instructions. At 
the conclusion of the study, any unused IP returned to the sponsor or designee, or destroyed per 
sponsor instructions, and this will be documented in the drug accountability records. 
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7.3.4. 
Intravitreal Pegcetacoplan Administration 
Subjects receiving active treatment will be administered 0.1 mL IVT injection of pegcetacoplan 
according to their treatment designation using a thin wall needle. Detailed instructions on drug 
preparation, preinjection procedures, administration of pegcetacoplan, and postinjection 
procedures will be provided in the manual of procedures. 
Clinic staff involved in the injection tray assembly, anesthetic preparation, and study drug 
preparation and administration will follow appropriate aseptic techniques to minimize the risk of 
potential AEs associated with IVT injections. 
Administration of pegcetacoplan is only allowed if preinjection IOP ≤21 mm Hg. If necessary, 
antiglaucomatous medication can be given to lower the IOP. To minimize transient IOP 
elevation after IVT injection of pegcetacoplan, decompression of the eye must be performed 
before all pegcetacoplan injections. This is done by applying moderate pressure to the globe with 
cotton swabs for 30-60 seconds during anesthetic preparation.  
In addition to the procedures outlined in the protocol and manual of procedures (MOP), 
adherence to specific institutional policies associated with IVT injections will be observed. 
7.4. 
Sham Injection Administration  
The procedure for sham injection will be the same as that used for IVT injection until the actual 
injection but no actual injection will occur. The injecting physician will only touch the study eye 
with the blunt end of the syringe. No needle or medication will be injected inside the eye. 
Detailed instructions on sham injection procedures and postinjection procedures will be provided 
in the manual of procedures.  
Subjects randomized to the monthly or every-other-month sham-injection groups will receive 
sham injection monthly or every other month, respectively. The same assessments will be 
performed as for the subjects in the pegcetacoplan groups.  
7.5. 
Concomitant Therapies 
Any concomitant medications a participant is receiving at the start of the study, within 30 days 
prior to screening, or that are given for any reason during the study (except for routine 
medications given for ocular procedures required by the protocol, such as topical anesthetic) 
must be recorded in the source documents and CRF including start and stop date and time, dose, 
route, and indication. In addition, all invasive intraocular procedures from the previous 5 years 
must also be recorded in the source documents and CRF including start and stop dates. Surgical 
anesthetics, paramedical or alternative therapies (eg, acupuncture, herbal supplements) should 
also be recorded in the source documents and CRF within 30 days prior to screening. 
Metoclopramide or other agents to prevent nausea induced by fluorescein injection may be 
administered at the discretion of the PI. 
7.5.1. 
Treatment of New Exudation Related to Active Choroidal Neovascularization in 
the Study Eye and/or Fellow Eye 
The suspected onset or presence of new exudation related to active CNV secondary to AMD in 
the study eye and/or fellow eye must be documented in the source documents and CRF. If the 
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investigator suspects new exudation related to active CNV in the study eye based on fundus 
examination and/or OCT findings (eg, subretinal fluid, intraretinal fluid, cystoid macular edema, 
serous pigment epithelial detachment), a fluorescein angiography and Optical Coherence 
Tomography Angiography (OCT-A; select sites only) must also be captured following the 
imaging protocol procedure. All images, as outlined above, must be sent to the reading center. 
The reading center will provide a report indicating whether or not evidence of active, exudative 
AMD is present or absent, based on the images sent for assessment. 
The determination about initiation of anti-VEGF treatment for the exudation related to active 
CNV is the sole responsibility of the investigator. Treatment with anti-VEGF should start after 
the report is received by the site from the reading center, with the exception of cases with clear 
evidence of disease activity (eg,; subretinal hemorrhage, extensive subretinal fluid and/or edema, 
and/or presence of subretinal hyperreflective material) that, in the opinion of the investigator, 
may have a detrimental visual impact if not treated immediately.  
If it is determined that the subject requires anti-VEGF therapy, ranibizumab or aflibercept should 
be selected and administered by the injecting (unmasked) physician. Ranibizumab should be 
given monthly and aflibercept every other month after 3 monthly loading doses. The frequency 
of aflibercept can be changed to monthly if deemed necessary by the investigator, however the 
physician should refrain from using as-needed treatment (PRN) or treat and extend protocols. 
Every effort should be made to use the same anti-VEGF therapy for a subject during the course 
of the study and all treatments should be documented in the CRF. 
If anti-VEGF therapy is administered in the study eye on the same day as an pegcetacoplan (or 
sham) injection, the anti-VEGF therapy shall be administered first and the pegcetacoplan or 
sham injection shall occur at least 30 minutes after the anti-VEGF injection and only if the IOP 
is ≤21 mm Hg. Anti-glaucomatous medication can be given to lower the IOP to the appropriate 
range to allow for the pegcetacoplan injection.  
In order to avoid potential unmasking, if anti-VEGF and pegcetacoplan are given at the same 
visit, the unmasked physician must perform both procedures. If the anti-VEGF therapy is given 
on a separate day from the pegcetacoplan administration, either the masked or the unmasked 
physician may perform this injection.  
Treatment with anti-VEGF is allowed in the fellow eye. The treatments for the fellow eye can be 
administered according to the site’s standard protocol for CNV treatment. Any treatments or 
therapies administered to the fellow eye within 5 years of screening and while on study should be 
recorded as a concomitant medication. 
7.5.2. 
Prohibited Therapies  
The PI should make a determination regarding patient continuation of therapies used to treat 
concomitant medical conditions. Therapies as noted in the inclusion/exclusion criteria are 
prohibited as specified. 
7.5.3. 
Endophthalmitis Treatment 
Endophthalmitis cases must be reported as SAEs. The decision to treat a participant for 
endophthalmitis or suspected endophthalmitis will be guided by the clinical judgment of the 
investigator and in accordance with local guidelines (as applicable). A culture sample should be 
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performed prior to making a decision on treatment. The treatment method (pars plana vitrectomy 
vs intravitreal injection of antibiotics) and choice of antimicrobial agents are also at the 
discretion of the physician and should follow current standard practice patterns. The decision to 
use IVT steroids (eg, dexamethasone) for the treatment of endophthalmitis is also at the 
discretion of the physician. 
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The planned length of participation in the study for each subject is approximately 25 months 
(from the beginning of the screening period through completion of the Month 24 visit). After 
completion of the 24-month treatment period, subjects will be offered entry into a separate open-
label study. 
8.1. 
Study Visit Schedule 
Below is a condensed description of the study visits and the procedures and examinations that 
will be performed. Please refer to the Visit Schedule in Appendix A to Appendix D for a detailed 
schedule of procedures/assessments for the monthly and EOM visit schedules. Additional safety 
assessments not listed in this section or the flow chart may be performed if considered necessary 
at the discretion of the investigator. 
8.1.1. 
Screening Period—Within 28 Days Prior to Randomization/ Treatment (Day –28 
to –1) 
8.1.1.1. 
Visit 1—All Subjects  
Note: All ophthalmic procedures (including imaging) are to be performed on both eyes, except 
where specified.  
Before any study-specific procedures are performed, the purpose and nature of the study should 
be explained and the patient should read, sign, and date the Institutional Review 
Board/Independent Ethics Committee (IRB/IEC)-approved Informed Consent Form (ICF). The 
individual obtaining consent from the patient and a witness, if applicable, should also sign and 
date the ICF. Once the patient has signed the ICF, a screening number should be assigned to the 
patient. Demographic information, significant medical/surgical history within the previous 
5 years, invasive ocular procedures within the previous 5 years, and concomitant medications 
used within 30 days prior to screening should be collected (including vitamins and all over-the-
counter as well as prescription medications). Complete smoking/ tobacco history should also be 
collected. 
Subject eligibility should then be determined by reviewing the inclusion/exclusion criteria and 
the study eye should be selected. Prior to the administration of fluorescein, blood and urine 
should be collected for safety labs (including blood for human chorionic 
gonadotropin/follicle-stimulating hormone/luteinizing hormone [HCG/FSH/LH], if applicable) 
and vital signs along with a physical examination including weight and height should be 
performed. 
A complete ophthalmic exam including slitlamp exam of the cornea, iris, anterior chamber, 
aqueous reaction (cells and flare), dilated fundus exam of the vitreous and retina, and intraocular 
pressure (IOP) measurement. Normal luminance BCVA should be performed prior to dilating the 
eyes. Images should be captured as outlined in the Visit Schedule (FAF, NIR, DCFP, FFA) and 
forwarded to the reading center for determination of eligibility if applicable.  
Mesopic microperimetry should be performed on both eyes post dilation of the eyes and 
forwarded to the reading center. 
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8.1.2. 
Randomization/ Initial Treatment—Day 1—Within 28 Days of Screening 
8.1.2.1. 
Visit 2—All Groups 
At this visit, all inclusion/exclusion criteria should be reviewed prior to randomization and 
dosing, including the determination of eligibility by the reading center. Subjects will be 
randomized using the Interactive Web Response (IWR) System. A complete ophthalmic exam 
including slitlamp exam of the cornea, iris, anterior chamber, lens, and aqueous reaction (cells 
and flare), dilated fundus exam of the vitreous and retina, and IOP measurement will be 
performed and imaging collected as per the Visit Schedule. 
All assessments should be performed on the same day. All study visits should be scheduled and 
projected based on the Day 1 visit date. 
Blood should be drawn for anti-pegcetacoplan antibodies.  
Prior to dilating the eyes, all functional tests should be performed (NL-BCVA, LL-BCVA, and 
MNREAD or Radner Reading Charts [in select countries]). Subjects at select sites will be trained 
on how to use the home-based digital applications for visual function and reading speed if the 
subject decides to participate in this portion. This training must occur after completion of all 
functional tests (NL-BCVA, LL-BCVA). Tests completed using the digital application at select 
sites (optional) should be completed prior to dilating the eyes but after completion of all 
functional tests and quality of life measures (NL-BCVA, LL-BCVA, MNREAD or Radner 
Reading Charts [in select countries], NEI VFQ-25, and FRI). The subject should be instructed to 
take the electronic device home and to complete the digital application weekly on the same day 
each week, if possible. The quality of life measures (NEI VFQ-25 and FRI) should be 
administered by the masked site staff.  
Imaging should be performed including FAF, SD-OCT, OCT-A (select sites), endothelial cell 
count (select sites) and NIR and sent to the reading center for evaluation.  
Study drug or sham injection should be performed by the unmasked physician as described in the 
manual of procedures and the study eye should be monitored post injection as outlined in 
Section 9.16. A follow-up phone call should be scheduled with the subject 4 ± 2 days after 
randomization Day 1 to assess for any AEs.  
8.1.3. 
Treatment Phase—24 Months  
8.1.3.1. 
 Months 1-12 
8.1.3.1.1. Visits 3-14 (Monthly and Every-Other Month Group)  
During this phase, there will be clinic visits every month. Dosing and assessments will occur 
monthly in the monthly pegcetacoplan and sham injection treatment arms. Dosing will occur 
every other month in the EOM pegcetacoplan and sham injection treatment arms, however, the 
subjects will return monthly for assessments (with no dose given).  
A complete ophthalmic exam including slitlamp exam of the cornea, iris, anterior chamber, lens, 
and aqueous reaction (cells and flare), dilated fundus exam of the vitreous and retina, and IOP 
measurement will be performed and imaging collected as per the Visit Schedule. 
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Blood will be drawn for safety labs, anti-pegcetacoplan antibodies, and genotyping (Month 2 
only) prior to the administration of fluorescein as per the Visit Schedule. Samples will be 
collected for the clinical repository for those subjects that consent to this portion.  
Prior to dilating the eyes, all functional tests will be performed (NL-BCVA, LL-BCVA, and 
MNREAD or Radner Reading Charts [in select countries]). Tests completed using the digital 
application at select sites (optional) will be completed prior to dilating the eyes but after 
completion of all functional tests and quality of life measures (NL-BCVA, LL-BCVA, 
MNREAD or Radner Reading Charts [in select countries], NEI VFQ-25, and FRI). At select 
sites the subject should be instructed to take the electronic device home and to complete the 
digital application weekly on the same day each week, if possible. The subject will be instructed 
to bring back the electronic device for the visits specified in the schedule of events. The quality 
of life measures (NEI VFQ-25 and FRI) will be administered by the masked site staff.  
Mesopic microperimetry should be performed on both eyes (where specified) post dilation of the 
eyes and forwarded to the reading center. 
Imaging will be performed including FAF, FFA, SD-OCT, OCT-A (select sites), endothelial cell 
count (select sites) and NIR and sent to the reading center for evaluation per the visit schedule.  
Study drug or sham injection should be performed by the unmasked physician as described in the 
manual of procedures and the study eye should be monitored post injection as outlined in 
Section 9.16. A follow-up phone call should be scheduled with the subject as outlined in the 
schedule of events.  
In the event that a subject is early terminated from the study, all early termination procedures 
should be performed even if they are outside the allowed study window.  
If the subject would like to discontinue dosing but is amenable to continuing in the study, the site 
should make every effort to have the subject complete as many follow-up visits as possible.  
8.1.3.2. 
Months 13-24  
8.1.3.2.1. Visits 15-26 (Monthly Group) and 15-20 (Every-Other-Month Group) 
During this phase, clinic visits will follow treatment designation (ie, the monthly subjects will 
return monthly for dosing and assessments and the EOM group will return EOM for dosing and 
assessments). At select sites, subjects will complete the home-based digital assessments weekly 
during this period.  
A complete ophthalmic exam including slitlamp exam of the cornea, iris, anterior chamber, lens, 
and aqueous reaction (cells and flare), dilated fundus exam of the vitreous and retina, and IOP 
measurement will be performed and imaging collected as per the Visit Schedule. 
Blood should be drawn for safety labs, genotyping, and anti-pegcetacoplan antibodies prior to 
the administration of fluorescein as per the Visit Schedule. Samples will be collected for the 
clinical repository for those subjects that consented to this portion.  
Prior to dilating the eyes, all functional tests should be performed (NL-BCVA, LL-BCVA, and 
MNREAD or Radner Reading Charts [in select countries]). The quality of life measures (NEI 
VFQ-25 and FRI) should be administered by the masked site staff.  
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Mesopic microperimetry should be performed on both eyes (where specified) post dilation of the 
eyes and forwarded to the reading center. 
Imaging should be performed including FAF, FFA, SD-OCT, OCT-A (select sites), endothelial 
cell count (select sites) and NIR and sent to the reading center for evaluation per the visit 
schedule.  
IVT (or sham) injection should be performed by the unmasked physician as described in the 
manual of procedures and the study eye should be monitored post injection as outlined in 
Section 9.16. 
In the event that a subject is early terminated from the study, all early termination procedures 
should be performed even if they are outside the allowed study window.  
If the subject would like to discontinue dosing but is amenable to continuing in the study, the site 
should make every effort to have the subject complete as many follow-up visits as possible.  
The completion of the 24-month study period occurs approximately 30 days (monthly treatment 
group) and approximately 60 days (EOM treatment group) after the last visit at which 
investigational product (IP) is administered. The period following last dose of IP is sufficient to 
evaluate the safety of pegcetacoplan based on its half-life in the vitreous; further details can be 
found in the pegcetacoplan IB. At the end of the 24-month study period, subjects will have the 
option to enroll in a separate open-label study. 
8.1.4. 
Early Termination Visit 
A list of all assessments to be performed at the early termination visit can be found on the Visit 
Schedule. All subjects who end the study early for any reason must complete the early 
termination visit, however all efforts should be made to have the subject return for as many 
follow-up visits as possible even if dosing does not occur. All ophthalmic procedures are to be 
performed on BOTH EYES. 
8.1.5. 
Unscheduled Visits 
If a subject returns to the clinical site before their next scheduled visit for an assessment of an 
AE or at the request of the physician, all safety assessments should be performed and any 
additional assessments as deemed medically necessary by the physician.   
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9. 
ASSESSMENTS 
The following evaluations will be performed during the study as outlined in the Visit Schedule in  
Appendix A to Appendix D. Refer to the MOP for detailed descriptions of study-related 
procedures. 
9.1. 
Informed Consent  
Written informed consent for participation must be obtained before performing any study-
specific assessments. Informed consent for all subjects should be maintained within the subject 
source documentation.  
9.2. 
Demographic Information/ Medical/ Surgical History  
Demographic information will be collected from all subjects including but not limited to date of 
birth, race/ ethnicity (where locally permitted). All significant medical conditions and surgeries 
within the past 5 years should be captured for the subject including chronic and ongoing 
conditions. Any history or current use of tobacco is to be collected. 
9.3. 
Ocular History/ Ocular Procedures  
Ocular history within the previous 5 years should be collected and recorded for all subjects. The  
history should include any significant previous ocular surgeries, procedures and/ or medications 
or treatments used for these conditions.  
9.4. 
Vital Signs 
Vital signs consist of body temperature, respiratory rate, blood pressure (systolic and diastolic), 
and heart rate measurements.  
On injection visits, vital signs will be measured prior to dosing. Vital signs should be taken with 
the patient in a seated position after resting for 5 minutes. Vital signs will be measured before 
venipuncture. 
9.5. 
Physical Examination  
A physical exam will be performed and should include but should not be limited to an evaluation 
of the eyes, ears, nose, throat, lymph nodes, head, and neurological function. A patient’s height 
and weight should also be measured at screening. If any abnormalities are noted at screening, the 
PI, or designee, should determine the clinical significance of the finding and whether this will 
pose any safety risk to the subject. Any changes from baseline should be noted and the clinical 
significance assessed. Any new, clinically significant, findings should be documented as AEs.  
9.6. 
Laboratory Analysis of Blood and Urine 
Collection of blood and urine will occur at the study site and the samples will be shipped to a 
central laboratory for analysis. All samples (including urine) should be collected prior to 
treatment and FFA/OCT-A assessments (if applicable). Procedures for the collection and 
processing of blood and urine are provided in the laboratory manual.  
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Table 2 presents the laboratory and urine analysis that will be performed.  
Table 2:  Laboratory Sampling and Analysis 
Hematology 
Chemistry 
Urinalysis 
Other 
Hemoglobin  
Hematocrit  
Red blood cell count   
White blood cell count 
with differential  
Platelet count 
Blood urea nitrogen  
Creatinine  
Bilirubin (total, direct 
and indirect)  
Albumin  
Alkaline phosphatase  
Aspartate 
aminotransferase  
Alanine 
aminotransferase  
Creatine kinase  
Glucose 
Electrolytes (sodium, 
potassium, chloride, 
bicarbonate) 
pH 
Specific gravity 
Protein 
Glucose 
Ketones 
Bilirubin 
Blood 
Nitrite  
Urobilinogen 
Leukocyte esterase 
Genotyping  
Anti-pegcetacoplan Ab  
Human chorionic 
gonadotropina  
Follicle-stimulating 
hormoneb  
Luteinizing hormoneb  
 
 
a Serum Pregnancy Test (ie, HCG) will be performed for females of childbearing potential at screening only.  
b FSH and LH will be performed for postmenopausal females at screening only. 
The principal investigator, or designee, must review the results of the screening visit clinical 
laboratory tests (including any retest results) and confirm that these results do not show evidence 
of any medical condition that would make study participation inappropriate. The principal 
investigator, or designee, should also assess any changes from baseline at the follow-up visits 
and the final visit. Clinically significant laboratory values are to be recorded as AEs. 
9.7. 
Genotyping Samples 
The genetic marker sample will be used to evaluate the relationship between genetic 
polymorphisms associated with AMD with disease progression and response to pegcetacoplan. 
A whole-blood sample will be collected for genetic marker analysis. These samples will be 
collected only for those subjects who consent to this analysis.  
These samples will be stored as per the clinical repository guidelines outlined in Section 9.17 if 
the subject consents to this portion of the study. These samples will be stored up to 15 years after 
the date of the final closure of the associated clinical database if the patient consented to the 
clinical repository.  
9.8. 
Urine Pregnancy Test 
Urine pregnancy test will be performed in WOCBP only as outlined in the Visit Schedule in 
Appendix A to Appendix D. 
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9.9. 
Patient-Reported Outcomes 
Data will be collected via interview-administered questionnaires to assess patient-reported 
outcomes during scheduled visits as outlined in the Visit Schedule. The questionnaire should be 
administered by the masked site staff and should be performed prior to any other assessments 
being performed that day.  
Questionnaire data will be used to assess subject-reported efficacy of pegcetacoplan and changes 
in quality of life over time. Questionnaires will be translated into the appropriate language for 
each country or region. 
9.9.1. 
The National Eye Institute Visual Functioning Questionnaire 25-Item Version 
(NEI-VFQ) 
The NEI-VFQ is an interviewer-administered questionnaire designed to assess patient-reported 
visual function (Appendix E). The NEI-VFQ is to be administered by the masked staff. It is a 25-
item questionnaire with a composite score and covers 12 domains of functional health status and 
well-being (general health, general vision, ocular pain, near activities (select countries), distance 
activities (select countries), social functioning, mental health, role difficulties, dependency, 
driving, color vision, and peripheral vision). Scoring yields 12 subscales based on the 12 
domains covered in the questionnaire. These scales are scored from 0 to 100 with higher scores 
indicating better visual function. The recall period is not specified; however, it is important that 
the patient uses the same recall period each time the questionnaire is administered throughout 
their participation in the study.  
9.9.2. 
The Functional Reading Independence (FRI) Index 
The FRI will be interviewer-administered and is an individualized assessment of functional 
reading independence (Appendix F). The questionnaire has 7 items with 1 total index score. 
Higher levels on the scale represent higher functional reading independence. The recall period is 
7 days. 
9.10. 
Best Corrected Visual Acuity and Low Luminance Best Corrected 
Visual Acuity 
Best corrected visual acuity (including best corrected visual acuity under low luminance 
[LL-BCVA]) will be measured at each visit as per the visit schedule by certified study staff. The 
study staff performing visual acuity should be masked to the treatment assignment. Best 
corrected visual acuity testing will be assessed on ETDRS chart starting at a distance of 4 m, 
performed by a certified VA examiner, and should precede any examination requiring 
administration of eye drops to dilate the eye or any examination requiring contact with the eye.  
The LL-BCVA acuity will be measured by placing a neutral density trial lens causing a reduction 
of 2.0 log units in luminance. The same requirements apply to measurement of low luminance 
visual acuity as described above for best corrected visual acuity. Low luminance deficit will be 
auto-calculated.  
A Visual Acuity Specifications procedure manual and training materials will be provided to all 
sites. All examiners will require certification prior to performing this assessment as part of the 
study.  
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9.11. 
Minnesota Low-Vision Reading (MNREAD) Test or Radner Reading 
Charts (in select countries)  
MNREAD Test or Radner Reading Charts (Appendix G) should be administered first 
monocularly for both eyes and then binocularly. The Manual of Operations should be referenced 
for a list of versions that should be administered based on country. These tests should be 
administered prior to dilating the eyes. 
9.12. 
Home-Based Functional Digital Applications (optional, select sites) 
In addition to in-clinic assessments, visual function and reading speed will also be evaluated 
using applications on an electronic device. Subjects who decide to participate in this portion will 
be trained on how to use the digital applications during the Day 1 visit and will complete the 
assessments using the digital application in the clinic at Day 1, Months 1-3, Month 6, 12, 18, 
and 24. In-clinic assessments on the digital application should be completed after completion of 
all functional tests and quality of life measures prior to dilating the eyes (NL-BCVA, LL-BCVA, 
MNREAD or Radner Reading Charts [in select countries], NEI VFQ 25, and FRI). 
Subjects will also take home the electronic device to complete visual function and reading speed 
assessments weekly beginning at Day 1. Subjects should be instructed to complete the 
assessments on the same day each week and at approximately the same time of day each week, if 
possible. 
9.13. 
Complete Ophthalmic Exam 
The complete ophthalmic exam will consist of the following: 
• External examination of the eye and adnexa. 
• Routine screening for eyelids/pupil responsiveness (including ptosis, abnormal pupil 
shape, unequal pupils, abnormal reaction to light, and afferent pupillary defect). 
• Slitlamp examination (cornea, anterior chamber, iris, lens, aqueous reaction [cells and 
flare]). Please see Appendix H for grading scales.  
• Dilated fundus exam including evaluation of retina and vitreous (ie, posterior segment 
abnormalities, retinal hemorrhage/detachment, and vitreal hemorrhage density and 
vitreous cells). Vitreal hemorrhage density and vitreous cells grading scales are 
outlined in Appendix I.  
• IOP measurement—A measurement of intraocular pressure will be conducted using 
either Tono-Pen or Goldmann applanation tonometer as outlined in the MOP. This 
should be performed prior to dilating the eyes and the same method should be used 
for all measurements in the same subject throughout the study. 
9.14. 
Ocular Imaging and Microperimetry  
The following ocular images will be obtained and sent to the reading center as outlined in the 
visit schedule. A reading center manual along with training materials will be provided to all sites 
which will provide information on standardized procedures for the collection, storage, and 
transmission of all images. Prior to any images being taken at the site, site personnel must be 
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properly trained and certified and test images and systems and software must be certified and 
validated by the reading center. Only trained and certified site staff delegated the responsibility 
of image collection should perform this task. Ocular images obtained as part of this study are: 
• Digital Color Fundus Photographs  
• Fluorescein Angiography  
• Spectral Domain Optical Coherence Tomography imaging  
• Fundus Autofluorescence (Heidelberg Spectralis Instrument)  
• Near Infrared Reflectance  
• Endothelial Cell Count (Specular Microscopy): Select sites only 
• Mesopic Microperimetry of the study eye only (at screening, performed on both eyes)  
o To account for the learning curve of this test, the patient is allowed up to 3 
attempts to meet the criteria for this portion  
• Optical Coherence Tomography Angiography (OCT-A): Select sites only  
If a patient misses a visit during which ocular images should have been taken, the images should 
be collected at the next scheduled study visit. 
In the event that a subject is suspected to have new active CNV in the study eye and/or the 
fellow eye, an SD-OCT and FFA using the protocol specified procedures should be performed 
and sent to the reading center to confirm the diagnosis (Section 7.5.1). In addition, in select sites, 
OCT-A should also be captured according to the study imaging protocol and sent to the reading 
center.  
9.15. 
Postinjection Assessment 
The study eye will be assessed after the intravitreal injection of pegcetacoplan or sham to ensure 
that the injection procedure and/or the study medication have not endangered the health of the 
eye. The initial postinjection assessments should be done within 5 minutes post injection and 
include a gross assessment of vision (light perception, hand motion). If the subject passes the 
gross vision test, he/she can be released from the clinic. If the subject does not pass the gross 
vision test, IOP must be measured at that time. Additional IOP measurement must be taken 
approximately every 30 minutes thereafter until IOP ≤30 mm Hg and the subject is able to be 
released from the clinic.  
All subjects receiving an anti-VEGF (ranibizumab or aflibercept) and pegcetacoplan/sham 
injection on the same day, should have the IOP measured prior to and after the anti-VEGF 
(prepegcetacoplan). The second injection (pegcetacoplan/sham) can only be given if the  
IOP ≤21 mm Hg. Antiglaucomatous medication can be given to lower the IOP. The subject can 
only be released from the clinic if the IOP is ≤30 mm Hg. 
Any subject who develops a significant and sustained raise in IOP (>30 mm Hg) after any 
injection, should be monitored according to the investigator’s clinical judgment and may 
undergo additional procedures and measurements of IOP beyond those specified in the protocol 
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as well as IOP lowering procedures. If any concern or immediate toxicity is noted, the subject 
will remain at the site and will be treated according to the physician’s clinical judgment. 
9.16. 
Blood Volume for Study Assessments 
Table 3:  Total Study Blood Volume 
Assay 
Number of time 
points 
Approximate 
volume per time 
point * (mL) 
Approximate 
sample volume 
over course of 
study (mL)—all 
groups 
Anti-pegcetacoplan antibodies 
9 
2 
18 
*Hematology 
8 
4 
32 
**Chemistry (incl. HCG/LH) 
8 
5 
40 
FSH/LH (postmenopausal women 
only) 
- 
5 
- 
Genotyping samplea 
1 
8 
8 
Clinical repository (select sites and 
only subjects that consent to clinical 
repository) 
5 
14 
70 
Total blood volume 
 
 
168 a 
Abbreviations: HCG=human chorionic gonadotropin; FSH=follicle-stimulating hormone ; LH=luteinizing hormone 
a Represents the standard collection volume planned over the duration of the study, actual volume may vary by 
group and across sites. 
* Volume will vary slightly between regions and analyzing labs based on the standard methodology. 
** In some regions, may be included in the chemistry sample based on local methodology. 
 
9.17. 
Samples for Clinical Repository (Optional, Select Sites) 
Apellis intends to apply genomic research across the pegcetacoplan development program to 
explore how genomic variations may affect the clinical parameters associated with and response 
to pegcetacoplan. Select sites will be asked to collect additional whole-blood samples and 
derivatives thereof in a centrally administered facility for the long-term storage of human 
biologic specimens. The collection and analysis of these specimens will facilitate the rational 
design of new pharmaceutical agents and the development of diagnostic tests, which may allow 
for individualized drug therapy for subjects in the future. Specimens for the Genetic 
Biorepository will be collected from subjects who give specific consent to participate in this 
optional research only and this will only be done at a select group of sites.  
Specimens will be used to achieve the following objectives: 
• To study the association of biomarkers with efficacy, AEs, or disease progression 
• To increase knowledge and understanding of disease biology 
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• To study drug response, including drug effects and the processes of drug absorption 
and disposition  
• To develop biomarker or diagnostic assays and establish the performance 
characteristics of these assays  
Future research may suggest other genes, gene categories, proteins, etc. as candidates for 
influencing not only response to pegcetacoplan but also susceptibility to AMD for which 
pegcetacoplan may be evaluated. Thus, this additional genomic research may involve the future 
study of additional unnamed genes or gene categories, but only as they relate to AMD disease 
susceptibility and drug action.  
9.17.1. 
Approval by the Institutional Review Board or Ethics Committee 
Collection and submission of biological samples to the clinical repository is contingent upon the 
review and approval of the exploratory research and the clinical repository portion of the N by 
each site’s IRB or IEC and, if applicable, an appropriate regulatory body. If a site has not been 
granted approval for clinical repository sampling, this section of the protocol (Section 9.17) will 
not be applicable at that site. 
9.17.2. 
Sample Collection 
The following samples will be collected for research purposes, including but not limited to research on 
dynamic (noninherited) biomarkers related to AMD and related diseases, pegcetacoplan, and signaling 
pathways related to AMD and the complement pathway: 
• Residual whole-blood clinical genotyping sample 
• 14-mL whole-blood sample collected at the specified time points 
For all samples, dates of consent and specimen collection should be recorded on the associated 
clinical repository page of the eCRF. For sampling procedures, storage conditions, and shipment 
instructions, see the laboratory manual. 
All collected specimens will be destroyed no later than 15 years after the date of final closure of 
the clinical database. The clinical repository storage period will be in accordance with the 
IRB/EC-approved ICF and applicable laws (eg, health authority requirements). 
9.17.3. 
Confidentiality and Data Ownership 
Patient medical information associated with clinical repository specimens is confidential and 
may only be disclosed to third parties as permitted by the ICF (or separate authorization for use 
and disclosure of personal health information) signed by the patient, unless required by law. 
Data derived from clinical repository specimen analysis on individual subjects will generally not 
be provided to the subjects or to study investigators unless required by law. The aggregate results 
of any research conducted using clinical repository specimens will be available in accordance 
with the effective Apellis policy on study data publication. 
Any inventions and resulting patents, improvements, and/or know-how originating from the use 
of the clinical repository data will become and remain the exclusive and unburdened property of 
Apellis, including the right to sell, license, or assign the invention to another entity.  
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9.17.4. 
Consent to Participate in the Clinical Repository 
The ICF will contain a separate section or separate ICF that will address participation in the 
clinical repository. The investigator or authorized designee will explain to each patient the 
objectives, methods, and potential hazards of participation in the clinical repository. Subjects 
will be told that they are free to refuse to participate and may withdraw their specimens at any 
time and for any reason during the storage period. Subjects who decline to participate in the 
clinical repository can still participate in this clinical study. The investigator should document 
whether the patient has given consent to participate by completing the clinical repository 
Research Sample Informed Consent eCRF. In the event of a clinical repository participant’s 
death or loss of competence, the participant’s specimens and data will continue to be used as part 
of the clinical repository research. 
9.17.5. 
Withdrawal From the Clinical Repository 
Subjects who give consent to provide clinical repository specimens have the right to withdraw 
their specimens from the clinical repository at any time for any reason. If a patient wishes to 
withdraw consent to the testing of his or her specimens, the investigator must inform the sponsor 
in writing of the patient’s wishes using the clinical repository Patient Withdrawal Form and, if 
the study is ongoing, must enter the date of withdrawal on the Clinical Repository Research 
Sample Withdrawal of Informed Consent eCRF. The patient will be provided with instructions 
on how to withdraw consent after the study is closed. A patient’s withdrawal from this study 
does not, by itself, constitute withdrawal of specimens from the clinical repository. Likewise, a 
patient’s withdrawal from the clinical repository does not constitute withdrawal from this portion 
of the study. 
9.17.6. 
Monitoring and Oversight 
Clinical Repository specimens will be tracked in a manner consistent with GCP by a 
quality-controlled, auditable, and appropriately validated laboratory information management 
system to ensure compliance with data confidentiality as well as adherence to authorized use of 
specimens as specified in this protocol and in the ICF. Apellis monitors and auditors will have 
direct access to appropriate parts of records relating to patient participation in the clinical 
repository for the purposes of verifying the data provided to Apellis. The site will permit 
monitoring, audits, IRB/EC review, and health authority inspections by providing direct access 
to source data and documents related to the clinical repository samples. 
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10. 
SAFETY EVALUATIONS  
Any clinically significant abnormalities persisting at the end of the study/ early withdrawal or 
end of the posttreatment phase will be followed by the investigator until resolution or until a 
clinically stable endpoint is reached. The study includes a number of evaluations to monitor 
safety including monitoring of AEs, postinjection monitoring, laboratory and urine sampling, 
physical examination, and vital signs.  
10.1. 
Data Monitoring Committee 
An external, independent data monitoring committee (DMC) will be formed with the purpose of 
reviewing all data across the conduct of the study on an ongoing basis. The DMC will follow a 
charter that will outline the frequency of meetings and the roles and responsibilities of all 
members. The DMC will meet at the beginning of the study and approximately every 6 months 
thereafter and will perform a masked review of all relevant events on an ongoing basis. An ad 
hoc meeting of the DMC may be convened by the sponsor or the DMC chairperson at any time 
between the regularly scheduled DMC meetings and data reviews, if warranted by new safety 
information or for any other reason. The DMC will communicate their recommendations to the 
sponsor who will notify the appropriate health authorities according to local regulatory 
requirements.  
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11. 
ADVERSE EVENTS 
11.1. 
Definition 
An AE is any untoward medical occurrence associated with the use of a drug in humans, whether 
or not it is 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 IP, whether or not considered related to the IP. 
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 
recording but are still collected and recorded via the appropriate eCRF form, if applicable. If 
these changes in laboratory values are linked to a diagnosis, this diagnosis should be reported as 
an AE, especially if the diagnosis constitutes an SAE or leads to discontinuation of 
administration of IP. 
11.2. 
Recording Adverse Events 
Adverse events and SAEs will be collected from the signing of the consent form until the last 
visit or early termination visit, 30 days after the last IP administration for the monthly treatment 
groups and 60 days after the last IP administration for the EOM treatment groups. 
Any events that occur prior to dosing will be categorized as pretreatment events; events 
occurring after dosing will be recorded as treatment-emergent adverse events (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 IP. Subjects experiencing AEs that cause interruption or discontinuation of IP, 
or those experiencing AEs that are present at the last visit or early termination 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 (or for paper-based study[ies]), 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. 
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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. 
11.3. 
Reporting Adverse Events 
The sponsor has the responsibility to inform concerned health authorities, ethic committees, and 
investigators about suspected unexpected serious adverse reactions in line with GCP guidance 
and applicable regulatory requirements. 
If required, specific SAEs should be reported to the concerned ethic committees in compliance 
with local requirements  
11.3.1. 
Relationship of Events to Study Treatment 
All AEs that occur during this study will be recorded. The investigator will review each event 
and assess its relationship to study treatment (definitely related, possibly related, unlikely related, 
not related, unknown). 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) 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) 
Re-challenge 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 
Unknown 
Report suggests an adverse event, however, cannot be judged at this time because 
information is insufficient or contradictory 
More data for proper assessment is needed, or additional data is under examination 
11.3.2. 
Severity of Events 
The following definitions should be considered when evaluating the severity of AEs and SAEs: 
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Mild 
Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention 
not indicated. 
Moderate 
Minimal, local or noninvasive intervention indicated; limiting age-appropriate 
instrumental ADL a. 
Severe 
Medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care ADLb. 
Note: An experience may be severe but may not be serious, eg, severe headache). 
Abbreviation: ADL=activities of daily living 
A semicolon indicates ‘or’ within the description of the grade. 
a Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing 
money, etc. 
b Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not 
bedridden. 
11.4. 
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 or surgical intervention to prevent one of the 
outcomes listed in the above definition.  
Examples of such 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 IB. 
11.5. 
Treatment and Follow-up of Adverse Events 
AEs (whether serious or nonserious), including clinically significant abnormal laboratory test 
values, will be evaluated by the investigator and treated and/or followed up until the symptoms 
or value(s) return to baseline or are clinically stable. Treatment of AEs will be performed by 
appropriately trained medical personnel, either at the clinical site or at a nearby hospital 
emergency room. When appropriate, medical tests and/or examinations will be performed to 
document resolution of the event(s).  
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AEs continuing after completion of the study will be followed up by telephone or with visits per 
the discretion of the investigator. If possible, the outcome of any AE that caused discontinuation 
from the study 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 study drug. 
11.6. 
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 
. 
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. 
11.7. 
Disease Progression 
Normal progression or worsening of the medical condition under study (eg, vision loss due to the 
progression of GA in either eye), by itself, does not necessarily constitute an AE unless the 
change can be reasonably attributed to an action of the test article and not only to its lack of 
efficacy. Disease progression that requires an intervention (eg, administration of IVT anti-VEGF 
agents for neovascular AMD) should be recorded as an AE in the eCRF.  
11.8. 
Withdrawal 
Participants may choose to discontinue from treatment or to completely withdraw from this study 
for any reason at any time without penalty or prohibition from enrolling in other clinical 
protocols. 
Participants wishing to withdraw from the study completely will be offered an early termination 
visit. This early termination visit will include the examinations outlined in Section 8.1.5. 
Participants wishing to discontinue treatment but willing to continue with other study 
procedures, will return to the clinical site for follow-up visits, as per protocol, until Month 24. 
Additional information on subject discontinuation is provided in Section 6.5. 
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12. 
DATA MANAGEMENT AND STATISTICAL CONSIDERATIONS 
12.1. 
Data Collection 
The investigators’ authorized site personnel must enter the information required by the protocol 
on the CRF. A study monitor will visit each site in accordance with the monitoring plan and 
review the CRF data against the source data for completeness and accuracy. Discrepancies 
between source data and data entered on the CRF 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.  
12.2. 
Clinical Data Management 
Data are to be entered into a clinical database as specified in the contract research organization’s 
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. 
12.3. 
Statistical Analysis Process 
The study will be analyzed by the sponsor or its agent.  
The statistical analysis plan (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, IP exposure, and prior and concomitant medications. The SAP will also include a 
description of how missing, unused, and spurious data will be addressed.  
To preserve the integrity of the statistical analysis and study conclusions, the SAP will be 
finalized prior to database lock. All statistical analyses will be performed using SAS (SAS 
Institute, Cary, NC 27513). 
12.4. 
Planned Interim Analysis and Data Safety Monitoring Committee  
No interim analysis is planned for this study. During the study, patient safety will be monitored 
on a continuous basis by the medical monitor until the last patient completes his or her last 
scheduled study assessment. 
An independent DMC will also be established to provide an ongoing, independent review and 
assessment of the safety data, and to safeguard the interests and 
safety of the participating patients in the study. The ongoing review of SAEs and other 
responsibilities of the DMC will be described in the DMC Charter. 
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The overall Type I (alpha) error rate for the study will be 0.05. To accommodate DMC data 
reviews, the alpha available for efficacy hypothesis testing will be reduced by 0.0001 for each 
DMC review. The study is expected to have 3-4 DMC data reviews prior to the primary analysis 
of 12-month data and 1 review afterward.  
12.5. 
Sample Size Calculation and Power Considerations  
Subjects will be randomized in a 2:2:1:1 ratio to receive treatment with pegcetacoplan monthly, 
pegcetacoplan every other month, sham monthly, or sham every other month. The annual growth 
rate in GA lesion area is expected to have a mean of 1.47, 1.70 and 2.13 mm2/year for 
pegcetacoplan monthly, pegcetacoplan every-other-month, and sham-pooled groups, 
respectively, as estimated from the results of a Phase 2 trial for pegcetacoplan. The standard 
deviation of the lesion growth is estimated to be 1.50 mm2 based on the same Phase 2 trial data 
or 1.25 mm2 based on natural history data.27 The following table provides an approximation of 
the study power for a sample size of 200 subjects in each group (ie, a total enrollment of 
600 subjects) under different alpha values and standard deviations. The approximation is 
calculated using PROC POWER one-way analysis of variance, SAS 9.4. The study power is 
likely larger when utilizing the longitudinal data to model the primary endpoint. The actual study 
power may also vary based on the distribution of the stratification factors (ie, lesion area at 
screening, presence of CNV in fellow eye), and site enrollment.   
Table 4:  Power to Detect a Difference Among 3 Groups With an Equal Size of 
200 Subjects  
Common 
standard 
deviation (mm2) 
Alpha 
(2-sided) 
Power for a true mean of 1.47, 1.70, and 2.13 mm2/year for 
PM, PEOM, and sham, respectively 
PM vs sham 
PEOM vs sham 
Overall  
(among 3 groups) 
1.25 
0.0495 
> 99.9% 
92.9% 
99.9% 
1.25 
0.0248 
99.9% 
88.2% 
99.7% 
1.40 
0.0495 
99.7% 
86.5% 
99.3% 
1.40 
0.0248 
99.3% 
79.4% 
98.6% 
1.50 
0.0495 
99.2% 
81.5% 
98.4% 
1.50 
0.0248 
98.4% 
73.1% 
97.0% 
Abbreviations: PM = pegcetacoplan monthly; PEOM = pegcetacoplan every other month. 
12.6. 
Statistical Analysis Sets  
The safety set will consist of all subjects who receive any amount of IP. 
The intent-to-treat (ITT) set will include all randomized subjects. Subjects will be analyzed in 
the treatment arm assigned at randomization with the 2 sham treatment arms being combined 
into a single ‘control’ group.  
The modified ITT (mITT) set will include all randomized subjects who receive at least 1 
injection of pegcetacoplan or sham and have baseline and at least 1 postbaseline value of GA 
lesion in the study eye as assessed by FAF. 
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The per-protocol (PP) set will include all ITT subjects who follow the protocol without any 
major deviation(s) that could impact the integrity of the data. A detailed description of the 
reasons for exclusion from the PP population will be included in the statistical analysis plan 
(SAP). 
12.7. 
Efficacy Analyses 
The primary, secondary, and exploratory efficacy analyses will be performed using the ITT set 
and presented by treatment group. 
12.7.1. 
Primary Efficacy Analysis 
The primary efficacy endpoint is the change from baseline to Month 12 in the total area of GA 
lesion(s) in eyes injected with pegcetacoplan, either monthly (PM) or every-other month 
(PEOM), or sham injections. GA lesion area (mm2) as measured by a quantified central reading 
center based on FAF images. The primary analysis will be the comparison of pegcetacoplan, 
either monthly (PM) or every-other month (PEOM) versus the combined 2 sham arms (the 2 
sham arms will be combined into a single ‘control’ group). 
The null and alternative hypotheses for the primary efficacy analysis are: 
H0: µS = µPM   vs  HA:  µS ≠ µ PM, and 
H0: µS = µPEOM vs  HA:  µS ≠ µPEOM  
Note: here µ indicates each group’s respective mean change from baseline to Month 12 in GA 
lesion area for the comparison of the primary endpoint. 
A mixed effect model for longitudinal data will be used to analyze the change from baseline in 
GA lesion area. The model will include treatment and presence of CNV in the fellow eye as 
fixed effects; baseline GA lesion area (at screening), time (in months) as a factor; as well as the 
time × treatment interaction term. All available data up to 12 months will be included in the 
model for the primary analysis. The mean change from baseline to 12 months will be estimated 
from the model (ie, least square [LS] mean) and compared between each of the pegcetacoplan 
arms to the sham control. For other time point of interest, LS mean change from baseline will be 
estimated and compared between treatments. Unstructured variance covariance will be used. 
For the analysis of final study data, a similar model including data up to 24 months will be used 
and LS means at time points of interest will be estimated and compared between treatment. 
As indicated in an earlier section, the study is expected to have an approximately 5 DMC data 
reviews. Allocating an alpha level of 0.0001 for each DMC data review, the alpha level remains 
for the efficacy analysis at 0.0495 to maintain an overall study alpha of 0.05. 
The hypothesis testing strategy for the primary and secondary efficacy endpoints will be based 
on the Gate-keeping multiple testing procedures controlling for the study wide type I error 
strongly at 2-sided 0.0495 as follows:  
Step 1. The mean GA lesion growth at 12 months will be compared between the PM group 
and the Control at the α level of 0.0495. If the null hypotheses of no difference between 
groups in this step is rejected, the testing proceeds to Step 2 and Step 3. If it’s not rejected, 
the testing procedure stops at this step.  
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Step 2. The mean GA lesion growth at 12 months will be compared between the PEOM 
group and the Control at the α1 level. If the null hypotheses of no difference between groups 
in this step is rejected, the α1 level will be passed down to Step 3. The actual value of α1 will 
be specified in the SAP and it will be defined to ensure an adequate power of at least 80% for 
the comparison in this step. 
Step 3. The mean GA lesion growth at 24 months will be compared between the PM group 
and the Control at the α level of 0.0495 if the null hypotheses are rejected at both Step 1 and 
Step 2; or at the α level of (0.0495 – α1) if Step 2 testing does not reject the null hypothesis. 
If the null hypothesis at this step is rejected, the α level used at this step will be passed down 
to the next step of testing. If it’s not rejected, the testing procedure stops at this step.  
Step 4. The prioritization and alpha allocation for the remaining secondary endpoints will be 
specified in the SAP. 
The following sensitivity and supportive analyses will be performed to evaluate the robustness of 
the results from the primary analysis method: 
• Analyses will be repeated using the mITT and PP sets 
• Primary and secondary endpoints will also be summarized with no pooling of the 2 
sham arms. The comparison for pegcetacoplan and sham injection within each dose 
regimen (ie, PM vs SM and PEOM vs SEOM) will be conducted 
• Multiple imputation methods and other sensitivity analyses will be explored, and 
details will be provided in the SAP 
12.7.2. 
Secondary Efficacy Analysis 
The key secondary and secondary endpoints will be analyzed in the same fashion as the primary 
endpoint using mixed effect model. The binary secondary endpoints will be analyzed using 
Cochran-Mantel-Haenszel test stratified by the randomization stratification factors. Hypothesis 
testing for 3 key secondary endpoints will be performed in the order specified. The SAP will 
provide more details on multiplicity adjustment and the approach for alpha spending among the 
endpoints.  
Key Secondary Efficacy Endpoints 
• Change from baseline in maximum monocular reading speed (study eye), as assessed 
by MNREAD or Radner Reading Charts at Month 24 (in select countries) 
• Change from baseline in FRI index score, at Month 24. 
• Change from baseline in NL-BCVA at Month 24 as assessed by ETDRS chart.  
Secondary Efficacy Endpoints 
• Change from baseline in LL-BCVA at Month 12 and Month 24 as assessed by 
ETDRS chart.  
• Change from baseline in LLD at Month 12 and Month 24. 
• Change from baseline at each planned assessment in the total area of GA lesion(s) in 
the study eye (in mm2) as assessed by FAF. 
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• Change from baseline in monocular critical print size (study eye), as assessed by 
MNREAD or Radner Reading Charts, at Month 12 and Month 24 (in select 
countries).  
• Change from baseline in the NEI VFQ-25 distance activity subscale score at Month 
12 and Month 24 (in select countries).  
• Number of scotomatous points assessed by mesopic microperimetry for the 
evaluation of the macular functional response.  
• Change in macular sensitivity as assessed by mesopic microperimetry for the 
evaluation of the macular functional response. 
12.7.3. 
Exploratory Efficacy Analysis 
Summary statistics will be provided for the following exploratory endpoints: 
• Change from baseline in NEI VFQ-25 composite score at Month 12 and Month 24.  
• Change from baseline in NEI VFQ-25 near activity subscale score at Month 12 and 
Month 24 (in select countries). 
• Comparison between study eye and fellow eye in change in GA lesion size from 
baseline to Month 12 and Month 24.  
• Binocular maximum reading speed as assessed by MNREAD or Radner Reading 
Charts over time (in select countries).  
• Binocular critical print size as assessed by MNREAD or Radner Reading Charts over 
time (in select countries). 
• Relationship between genetic polymorphisms associated with AMD with GA 
progression and response to pegcetacoplan. 
• Incidence of new onset of subclinical CNV in the study eye.  
• Assess sensitivity and specificity of a digital reading speed application to detect 
disease progression / regression (optional, select sites). 
• Assess sensitivity and specificity of a digital visual function application to detect 
disease progression / regression (optional, select sites). 
12.8. 
Safety Analyses 
Adverse events will be collected from the time of the first study drug administration until a 
subject completes the study or discontinues prematurely. Treatment-emergent adverse events are 
defined as those AEs that develop or worsen after the first dose of study medication and 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 the MedDRA coding dictionary. The number of 
subjects reporting each AE Preferred Term will be tabulated for all TEAEs and separately for 
those considered as related to study treatment by the investigator or designee. Number of 
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subjects reporting SAEs will also be tabulated. Adverse event summaries will be presented for 
each treatment group separately.  
Adverse events will be summarized by MedDRA coding terms, and separate tabulations also will 
be produced for related AEs (those considered by the investigator as definitively drug related), 
SAEs, and discontinuations due to AEs. Vital signs data and findings from physical and 
ophthalmologic examinations will be tabulated for changes over time on study. Laboratory 
parameters will be summarized for changes across study by using descriptive statistics. Separate 
summaries will be prepared for systemic (nonocular) and ocular AEs, with events in the study 
eye and nonstudy eye summarized separately 
12.8.1. 
Anti-Therapeutic Antibodies   
Data on anti-therapeutic antibodies (ATAs) directed against pegcetacoplan will be summarized 
by the number and percentage of subjects with confirmed positive ATAs.  
12.8.2. 
Death  
Patient deaths and primary cause of death will be summarized.  
12.8.3. 
Ocular Assessments  
Descriptive summaries will be generated for ocular assessments, such as VA and IOP. 
12.9. 
Handling of Missing Data 
All efforts will be made to minimize missing data. A full description of the imputation methods 
will be provided in the SAP.  
12.10. 
Visit Windows 
Analysis visits will be derived with windows for the monthly visits to assess the primary 
endpoint. Baseline is defined as the date of randomization. If 2 or more treatment visits occur 
within a window, the closest visit to the target day will be used as that analysis visit; if 2 visits 
are equidistant from the scheduled analysis visit day, the later analysis visit will be used. 
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13. 
ETHICS 
13.1. 
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 ICH Harmonized Tripartite 
Guidance for Good Clinical Practice, E6, R1 (ICH GCP). 
13.2. 
Institutional Review Board/Ethic Committee 
The study protocol, any amendments to the protocol, 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 sponsor’s Trial 
Master File. 
The IRB/IEC must be constituted and operate in accordance with the principles and requirements 
described in ICH Guidance E6 and national and local regulations as deemed appropriate. 
13.3. 
Subject Information and Consent 
The principal investigator, or designee, is responsible for obtaining an informed consent. A 
written informed consent, in compliance with ICH Guidance E6, must be obtained from each 
subject at the screening visit, prior to 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, which 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. 
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14. 
ADMINISTRATIVE CONSIDERATIONS 
14.1. 
Direct Access to Source Data/Documents 
The principal investigator, or designee, 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 printed CRF pages that are used 
as the source. 
The investigator will permit trial-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 
investigator 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.  
14.2. 
Quality Control and Quality Assurance 
This study is to be performed in full compliance with the protocol, GCP, and applicable 
regulatory requirements. The principal investigator, sponsor, and/or its designee 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, and the applicable regulatory requirement(s) and local laws, 
rules, 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. 
14.3. 
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 the 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 investigator, or designee, will provide direct access to source 
data/documents for study-related monitoring. It is important that the investigator and the 
investigator site 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 investigator. 
14.4. 
Data Handling and Record Keeping 
The investigator must maintain all documentation related to this study. All essential documents 
(as defined in the ICH Guideline E6 and applicable local regulations) and the data generated in 
connection with this study, together with the original copy of the final report, will be retained for 
at least 2 years after the last approval of a marketing application in an ICH region and until there 
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are no pending or contemplated marketing applications in an ICH region or at least 2 years have 
elapsed since the formal discontinuation of clinical development of the IP. 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 investigator/institution as to when these 
documents no longer need to be retained. 
14.5. 
Protocol Amendments 
Any amendments to the study protocol deemed necessary as the study progresses will be 
discussed between sponsor and the investigator. The investigator will not implement any changes 
to the protocol without an agreement by the sponsor and prior review and documented 
approval/favorable opinion 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). 
Changes resulting in amendments will be made jointly between the sponsor and the investigator 
and must be confirmed in writing. Amendment(s) will be approved and signed off in the same 
way as the protocol.  
14.6. 
Report Format 
According to the ICH Harmonized 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). 
14.7. 
Finance and Insurance 
Finance and insurance will be addressed in a Clinical Trial Agreement between the sponsor and 
the investigator/institution. 
14.8. 
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 
(eg, Good Publication Practices 2) when forming a publication steering committee, which is 
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 
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commencement of the study or generated during the study. To the extent permitted by the 
publisher and copyright law, the investigator will own (or share with other authors) the copyright 
on his/her publications. To the extent that the investigator has such sole, joint, or shared rights, 
the investigator 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 investigator 
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 
current standards. Participation as an investigator does not confer any rights to authorship of 
publications. 
14.9. 
ClinicalTrials.gov  
This study will be listed with ClinicalTrials.gov. 
14.10. 
Termination of Study 
The sponsor reserves the right to suspend or discontinue this study for administrative and/or 
safety reasons at any time. The investigator reserves the right to discontinue dosing subjects at 
any time for safety reasons.  
 
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15. 
REFERENCES 
1. Holz FG, Bindewald-Wittich A, Fleckenstein M, et al. Progression of geographic atrophy and 
impact of fundus autofluorescence patterns in age-related macular degeneration. American 
journal of ophthalmology. 2007;143(3):463-472. 
2. Rein DB, Wittenborn JS, Zhang X, et al. Forecasting age-related macular degeneration through 
the year 2050: the potential impact of new treatments. Archives of ophthalmology. 
2009;127(4):533-540. 
3. Friedman DS, O'Colmain BJ, Munoz B, et al. Prevalence of age-related macular degeneration in 
the United States. Archives of ophthalmology. 2004;122(4):564-572. 
4. Holz FG, Strauss EC, Schmitz-Valckenberg S, van Lookeren Campagne M. Geographic atrophy: 
clinical features and potential therapeutic approaches. Ophthalmology. 2014;121(5):1079-1091. 
5. Sunness JS, Bressler NM, Tian Y, Alexander J, Applegate CA. Measuring geographic atrophy in 
advanced age-related macular degeneration. Investigative ophthalmology & visual science. 
1999;40(8):1761-1769. 
6. Sunness JS, Gonzalez-Baron J, Applegate CA, et al. Enlargement of atrophy and visual acuity 
loss in the geographic atrophy form of age-related macular degeneration. Ophthalmology. 
1999;106(9):1768-1779. 
7. Crabb JW, Miyagi M, Gu X, et al. Drusen proteome analysis: an approach to the etiology of age-
related macular degeneration. Proceedings of the National Academy of Sciences of the United 
States of America. 2002;99(23):14682-14687. 
8. Hageman GS, Anderson DH, Johnson LV, et al. A common haplotype in the complement 
regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. 
Proceedings of the National Academy of Sciences of the United States of America. 
2005;102(20):7227-7232. 
9. Lommatzsch A, Hermans P, Muller KD, Bornfeld N, Bird AC, Pauleikhoff D. Are low 
inflammatory reactions involved in exudative age-related macular degeneration? Morphological 
and immunhistochemical analysis of AMD associated with basal deposits. Graefe's archive for 
clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und 
experimentelle Ophthalmologie. 2008;246(6):803-810. 
10. Mullins RF, Russell SR, Anderson DH, Hageman GS. Drusen associated with aging and age-
related macular degeneration contain proteins common to extracellular deposits associated with 
atherosclerosis, elastosis, amyloidosis, and dense deposit disease. FASEB journal : official 
publication of the Federation of American Societies for Experimental Biology. 2000;14(7):835-
846. 
11. Edwards AO, Ritter R, 3rd, Abel KJ, Manning A, Panhuysen C, Farrer LA. Complement factor H 
polymorphism and age-related macular degeneration. Science. 2005;308(5720):421-424. 
12. Haines JL, Hauser MA, Schmidt S, et al. Complement factor H variant increases the risk of age-
related macular degeneration. Science. 2005;308(5720):419-421. 
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13. Klein RJ, Zeiss C, Chew EY, et al. Complement factor H polymorphism in age-related macular 
degeneration. Science. 2005;308(5720):385-389. 
14. Maller J, George S, Purcell S, et al. Common variation in three genes, including a noncoding 
variant in CFH, strongly influences risk of age-related macular degeneration. Nature genetics. 
2006;38(9):1055-1059. 
15. Seddon JM, Yu Y, Miller EC, et al. Rare variants in CFI, C3 and C9 are associated with high risk 
of advanced age-related macular degeneration. Nature genetics. 2013;45(11):1366-1370. 
16. Yates JR, Sepp T, Matharu BK, et al. Complement C3 variant and the risk of age-related macular 
degeneration. The New England journal of medicine. 2007;357(6):553-561. 
17. van de Ven JP, Nilsson SC, Tan PL, et al. A functional variant in the CFI gene confers a high risk 
of age-related macular degeneration. Nature genetics. 2013;45(7):813-817. 
18. Fritsche LG, Chen W, Schu M, et al. Seven new loci associated with age-related macular 
degeneration. Nature genetics. 2013;45(4):433-439, 439e431-432. 
19. Gold B, Merriam JE, Zernant J, et al. Variation in factor B (BF) and complement component 2 
(C2) genes is associated with age-related macular degeneration. Nature genetics. 2006;38(4):458-
462. 
20. Horie-Inoue K, Inoue S. Genomic aspects of age-related macular degeneration. Biochemical and 
biophysical research communications. 2014;452(2):263-275. 
21. Hecker LA, Edwards AO. Genetic control of complement activation in humans and age related 
macular degeneration. Advances in experimental medicine and biology. 2010;703:49-62. 
22. Hecker LA, Edwards AO, Ryu E, et al. Genetic control of the alternative pathway of complement 
in humans and age-related macular degeneration. Human molecular genetics. 2010;19(1):209-
215. 
23. Machalinska A, Dziedziejko V, Mozolewska-Piotrowska K, Karczewicz D, Wiszniewska B, 
Machalinski B. Elevated plasma levels of C3a complement compound in the exudative form of 
age-related macular degeneration. Ophthalmic research. 2009;42(1):54-59. 
24. Scholl HP, Charbel Issa P, Walier M, et al. Systemic complement activation in age-related 
macular degeneration. PloS one. 2008;3(7):e2593. 
25. Leeds JM, Henry SP, Bistner S, Scherrill S, Williams K, Levin AA. Pharmacokinetics of an 
antisense oligonucleotide injected intravitreally in monkeys. Drug metabolism and disposition: 
the biological fate of chemicals. 1998;26(7):670-675. 
26. Fleckenstein M, Mitchell P, Freund KB, et al. The Progression of Geographic Atrophy Secondary 
to Age-Related Macular Degeneration. Ophthalmology. 2018; 125(3):369-390. 
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G. Only subjects that sign the separate consent for the clinical repository and genotyping will have these samples collected. A 14-mL whole-blood sample will be collected at each 
of the specified visits. 
H. Blood pressure, respiratory rate, heart rate, and temperature. On dosing days, vital signs should be taken predose. 
I. Height and weight should be collected at screening. 
J. Perform assessments prior to dilating the eyes. 
K. In select countries, the MNREAD or Radner Reading Charts should be done during the study visit, prior to dilating the eyes. It should be performed monocularly first, then 
binocularly. 
L. Microperimetry assessments will be performed post dilation. Data will be forwarded to the reading center. 
M. To be administered by the masked site staff prior to any other assessments performed on that day. In-clinic assessments on the digital application should be completed after 
completion of all functional tests and quality of life measures prior to dilating the eyes. 
N. At select sites, and for those subjects who decide to participate, the digital applications will be completed on an electronic device and will consist of assessments for visual 
function and reading speed. Subjects will receive training at Day 1 on the use of the digital applications and the electronic device and will perform the tests using the application 
in the clinic at Month 1, Month 2, Month 3, Month 6, Month 12, Month 18, and Month 24. Beginning at Day 1, subjects will complete the functional assessments weekly at 
home. Subjects should be instructed to complete the assessments on the same day each week and at approximately the same time of day each week, if possible.  
O. FAF and SD-OCT images, near infrared reflectance, fluorescein angiograms, and fundus photographs will be performed for the study eye only on days where 'SE' is specified 
and for both eyes at all other visits as specified in the above schedule and will be sent to the reading center for evaluation (consult the reading center manual for specifics on 
image capture, processing, and transmission). Images should be captured prior to dosing on dosing days. If a subject misses a study visit or images cannot be obtained at a 
specific visit, study staff should make every effort to obtain images at the next scheduled visit. If new active CNV is suspected, SD-OCT, FFA and OCT-A (select sites) images 
must be collected and sent to the reading center for analysis. 
P. Postinjection assessments should be performed within 5 minutes after dosing by the unmasked physician or study staff and should include a gross assessment of vision (finger-
counting, hand-motion, then light perception when applicable). If subject passes gross vision test, the subject may leave the site. If subject fails gross vision test, the tonometry 
should be performed. IOP should be ≤30 mm Hg  in order for the subject to leave the site. If necessary, antiglaucomatous medication can be given to lower the IOP. If IOP is 
>30 mm Hg, assessments will continue every approximately 30 minutes from the previous measurement until the subject passes gross vision test and IOP is ≤30 mm Hg. Note: if 
the study eye is treated with a ranibizumab or aflibercept injection during the same visit as the study treatment (pegcetacoplan or sham), the treatment with ranibizumab or 
aflibercept must be performed first. The pre- and  post- anti-VEGF IOP values must be measured and recorded on the eCRF. 
Q. Starting at Day 1, study subjects will be contacted by study site staff within 4 ± 2 days after each study treatment visit (through Month 3) to collect any information on any 
safety concerns, decrease in vision, eye pain, unusual ocular events, or any new ocular symptoms in the study eye. If the physician determines that there are any safety concerns, 
a follow-up visit should be scheduled as soon as possible. 
R. Record concomitant medications (ie, prescription and over-the-counter medications) used by the patient within 30 days of screening and throughout the subject's participation in 
the study. 
S. In addition to the time points indicated on the study schedule, OCT-A should be performed at the time of any suspected new active CNV. If new active CNV is confirmed in the 
study eye, OCT-A should be repeated every 2 months for the study eye. 
T. Administration of pegcetacoplan or sham can be done on separate days from the assessment visit if both days fall within the visit window. Administration of study treatment 
(pegcetacoplan or sham) can be done on a separate day from the assessment visit if both days fall within the visit window. If this occurs on the randomization visit, then the 
administration of pegcetacoplan or sham should be done within 3 days of randomization and after approval from the medical monitor. When study treatment administration is on 
a day other than  a study visit, then the only assessment that must be done on the day of study treatment administration is preinjection IOP. 
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I. Height and weight should be measured at screening. 
J. Perform assessments prior to dilating the eyes. 
K. In select countries, the MNREAD or Radner Reading Charts should be done during the study visit, prior to dilating the eyes. It should be performed monocularly first, then 
binocularly. 
L. Microperimetry assessments will be performed post dilation. Data will be forwarded to the reading center. 
M. To be administered by the masked site staff prior to any other assessments performed on that day. In-clinic assessments on the digital application should be completed after 
completion of all functional tests and quality of life measures prior to dilating the eyes. 
N. At select sites, and for those subjects who decide to participate, the digital applications will be completed on an electronic device and will consist of assessments for visual 
function and reading speed. Subjects will receive training at Day1 on the use of the digital applications and the electronic device and will perform the tests using the application 
in the clinic at Month 1, Month 2, Month 3, Month 6, Month 12, Month 18, and Month 24. Beginning at Day 1, subjects will complete the functional assessments weekly at 
home. Subjects should be instructed to complete the assessments on the same day each week and at approximately the same time of day each week, if possible.  
O. FAF and SD-OCT images, near infrared reflectance, fluorescein angiograms, and fundus photographs will be performed for the study eye only on days where 'SE' is specified  
and for both eyes at all other visits as specified in the above schedule and will be sent to the reading center for evaluation (consult the reading center manual for specifics on 
image capture, processing, and transmission). Images should be captured prior to dosing on dosing days. If a subject misses a study visit or images cannot be obtained at a 
specific visit, study staff should make every effort to obtain images at the next scheduled visit. If new active CNV is suspected, SD-OCT, FFA, and OCT-A (selected sites) 
images should be collected and sent to the reading center for analysis. 
P. Postinjection assessments should be performed within 5 minutes after dosing by the unmasked physician or study staff and should include a gross assessment of vision (finger-
counting, hand motion, then light perception when applicable). If subject passes gross vision test, the subject may leave the site. If subject fails gross vision test, the tonometry 
should be performed. IOP should be ≤30 mm Hg in order for the subject to leave the site. If necessary, antiglaucomatous medication can be given to lower the IOP. If IOP is 
>30 mm Hg, assessments will continue every approximately 30 minutes from the previous measurement until the subject passes gross vision test and IOP is ≤30 mm Hg. Note: if 
the study eye is treated with a ranibizumab or aflibercept injection during the same visit as the study treatment (pegcetacoplan or sham), the treatment with ranibizumab or 
aflibercept must be performed first. The pre- and post- anti-VEGF IOP values must be measured and recorded on the eCRF. 
Q. Starting at Day 1, study subjects will be contacted by study site staff within 4 ± 2 days after each study treatment visit (through Month 3) to collect any information on any 
safety concerns, decrease in vision, eye pain, unusual ocular events, or any new ocular symptoms in the study eye. If the physician determines that there are any safety concerns, 
a follow-up visit should be scheduled as soon as possible. 
R. Record concomitant medications (ie, prescription and over-the-counter medications) used by the patient within 30 days of screening and throughout the subject's participation in 
the study.  
S. In addition to the time points indicated on the study schedule, OCT-A should be performed at the time of any suspected new active CNV. If new active CNV is confirmed in the 
study eye, OCT-A should be repeated every 2 months for the study eye.  
T. Administration of pegcetacoplan or sham can be done on separate days from the assessment visit if both days fall within the visit window. Administration of study treatment 
(pegcetacoplan or sham) can be done on a separate day from the assessment visit if both days fall within the visit window. If this occurs on the randomization visit, then the 
administration of pegcetacoplan or sham should be done within 3 days of randomization and after approval from the medical monitor. When study treatment administration is on 
a day other than a study visit, then the only assessment that must be done on the day of study treatment administration is preinjection IOP. 
 
 
 
 
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J. Perform assessments prior to dilating the eyes. 
K. In select countries, the MNREAD or Radner Reading Charts should be done during the study visit, prior to dilating the eyes. It should be performed monocularly first, then 
binocularly. 
L. Microperimetry assessments will be performed post dilation. Data will be forwarded to the reading center. 
M. To be administered by the masked site staff prior to any other assessments performed on that day. In-clinic assessments on the digital application should be completed after 
completion of all functional tests and quality of life measures prior to dilating the eyes. 
N. At select sites, and for those subjects who decide to participate, the digital application will be completed on an electronic device and will consist of assessments for visual 
function and reading speed. Subjects will receive training at Day 1 on the use of the digital applications and the electronic device and will perform the tests using the application 
in the clinic at Month 1, Month 2, Month 3, Month 6, Month 12, Month 18, and Month 24. Beginning at Day 1, subjects will complete the functional assessments weekly at 
home. Subjects should be instructed to complete the assessments on the same day each week and at approximately the same time of day each week, if possible.  
O. FAF and SD-OCT images, near infrared reflectance, fluorescein angiograms, and fundus photographs will be performed for the study eye only on days where 'SE' is specified  
and for both eyes at all other visits as specified in the above schedule and will be sent to the reading center for evaluation (consult the reading center manual for specifics on 
image capture, processing, and transmission). Images should be captured prior to dosing on dosing days. If a subject misses a study visit or images cannot be obtained at a 
specific visit, study staff should make every effort to obtain images at the next scheduled visit. If new active CNV is suspected, SD-OCT, FFA, and OCT-A (selected sites) 
images should be collected and sent to the reading center for analysis. 
P. Postinjection assessments should be performed within 5 minutes after dosing by the unmasked physician or study staff and should include a gross assessment of vision (finger-
counting, hand motion, then light perception when applicable). If subject passes gross vision test, the subject may leave the site. If subject fails gross vision test, the tonometry 
should be performed. IOP should be ≤30 mm Hg in order for the subject to leave the site. If necessary, antiglaucomatous medication can be given to lower the IOP. If IOP is 
>30 mm Hg, assessments will continue every approximately 30 minutes from the previous measurement until the subject passes gross vision test and IOP is ≤30 mm Hg. Note: if 
the study eye is treated with a ranibizumab or aflibercept injection during the same visit as the study treatment (pegcetacoplan or sham), the treatment with ranibizumab or 
aflibercept must be performed first. The pre- and post- anti-VEGF IOP values must be measured and recorded on the eCRF. 
Q. Starting at Day 1, study subjects will be contacted by study site staff within 4 ± 2 days after each study treatment visit (through Month 4) to collect any information on any 
safety concerns, decrease in vision, eye pain, unusual ocular events, or any new ocular symptoms in the study eye. If the physician determines that there are any safety concerns, 
a follow-up visit should be scheduled as soon as possible. 
R. Record concomitant medications (ie, prescription and over-the-counter medications) used by the patient within 30 days of screening and throughout the subject's participation in 
the study.  
S. In addition to the time points indicated on the study schedule, OCT-A should be performed at the time of any suspected new active CNV. If new active CNV is confirmed in the 
study eye, OCT-A should be repeated every 2 months for the study eye. 
 T. Administration of pegcetacoplan or sham can be done on separate days from the assessment visit if both days fall within the visit window. Administration of study treatment 
(pegcetacoplan or sham) can be done on a separate day from the assessment visit if both days fall within the visit window. If this occurs on the randomization visit, then the 
administration of pegcetacoplan or sham should be done within 3 days of randomization and after approval from the medical monitor. When study treatment administration is on 
a day other than a study visit, then the only assessment that must be done on the day of study treatment administration is preinjection IOP. 
 
 
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I. Height and weight should be measured at screening.  
J. Perform assessments prior to dilating the eyes. 
K. In select countries, the MNREAD or Radner Reading Charts should be done during the study visit, prior to dilating the eyes. It should be performed monocularly first, then 
binocularly. 
L. Microperimetry assessments will be performed post dilation. Data will be forwarded to the reading center. 
M. To be administered by the masked site staff prior to any other assessments performed on that day. In-clinic assessments on the digital application should be completed after 
completion of all functional tests and quality of life measures prior to dilating the eyes. 
N. At select sites, and for those subjects who decide to participate, the digital applications will be completed on an electronic device and will consist of assessments for visual 
function and reading speed. Subjects will receive training at Day 1 on the use of the digital applications and the electronic device and will perform the tests using the application 
in the clinic at Month 1, Month 2, Month 3, Month 6, Month 12, Month 18, and Month 24. Beginning at Day 1, subjects will complete the functional assessments weekly at 
home. Subjects should be instructed to complete the assessments on the same day each week and at approximately the same time of day each week, if possible.   
O. FAF and SD-OCT images, near infrared reflectance, fluorescein angiograms, and fundus photographs will be performed for the study eye only on days where 'SE' is specified  
and for both eyes at all other visits as specified in the above schedule and will be sent to the reading center for evaluation (consult the reading center manual for specifics on 
image capture, processing, and transmission). Images should be captured prior to dosing on dosing days. If a subject misses a study visit or images cannot be obtained at a 
specific visit, study staff should make every effort to obtain images at the next scheduled visit. If new active CNV is suspected, SD-OCT, FFA, and OCT-A (selected sites) 
images should be collected and sent to the reading center for analysis. 
P. Postinjection assessments should be performed within 5 minutes after dosing by the unmasked physician or study staff and should include a gross assessment of vision (finger-
counting, hand motion, then light perception when applicable). If subject passes gross vision test, the subject may leave the site. If subject fails gross vision test, the tonometry 
should be performed. IOP should be ≤30 mm Hg in order for the subject to leave the site. If necessary, antiglaucomatous medication can be given to lower the IOP. If IOP is 
>30 mm Hg, assessments will continue every approximately 30 minutes from the previous measurement until the subject passes the gross vision test and IOP is ≤30 mm Hg. 
Note: if the study eye is treated with a ranibizumab or aflibercept injection during the same visit as the study treatment (pegcetacoplan or sham), the treatment with ranibizumab 
or aflibercept must be performed first. The pre- and post- anti-VEGF IOP values must be measured and recorded on the eCRF. 
Q. Starting at Day 1, study subjects will be contacted by study site staff within 4 ± 2 days after each study treatment visit (through Month 4) to collect any information on any 
safety concerns, decrease in vision, eye pain, unusual ocular events, or any new ocular symptoms in the study eye. If the investigator determines that there are any safety 
concerns, a follow-up visit should be scheduled as soon as possible. 
R. Record concomitant medications (ie, prescription and over-the-counter medications) used by the patient within 30 days of screening and throughout the subject's participation in 
the study.  
S. In addition to the time points indicated on the study schedule, OCT-A should be performed at the time of any suspected new active CNV. If new active CNV is confirmed in the 
study eye, OCT-A should be repeated every 2 months for the study eye.  
T. Administration of pegcetacoplan or sham can be done on separate days from the assessment visit if both days fall within the visit window. Administration of study treatment 
(pegcetacoplan or sham) can be done on a separate day from the assessment visit if both days fall within the visit window. If this occurs on the randomization visit, then the 
administration of pegcetacoplan or sham should be done within 3 days of randomization and after approval from the medical monitor. When study treatment administration is on 
a day other than a study visit, then the only assessment that must be done on the day of study treatment administration is preinjection IOP. 
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APPENDIX E: NATIONAL EYE INSTITUTE VISUAL FUNCTIONING 
QUESTIONNAIRE 25-ITEM VERSION 
 
 
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APPENDIX F: FUNCTIONAL READING INDEPENDENCE INDEX (FRI)  
Kimel M, Yu R, Leidy N. The Functional Reading Independence Index (FRI Index) - User Manual 
(Version 1.2). Evidera. 2015  
 
 
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Pegaetacoplan 
APL2-304 Protocol Amendment 5
 
12 August 2020
Apellis Pharmaceuticals, Inc
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Confidential
CCI

 
Pegaetacoplan 
APL2-304 Protocol Amendment 5
 
12 August 2020
Apellis Pharmaceuticals, Inc
Page 133 of 164
Confidential
CCI

Pegcetacoplan 
APL2-304 Protocol Amendment 5 
12 August 2020 
APPENDIX G: MINNESOTA LOW-VISION READING TEST (MNREAD) 
AND RADNER READING CARDS     
The manual of procedures should be referenced for a detailed table of countries and languages to 
determine which test will be administered. Equipment and testing procedures will also be 
described in detail in the manual of procedures for both tests.  
Minnesota Low-Vision Reading Test: 
The Minnesota Low-Vision Reading Test acuity cards are continuous-text reading-acuity cards 
used for measuring the reading acuity and speed of normal and low-vision patients. These charts 
were developed at the Minnesota Laboratory for Low-Vision Research, University of Minnesota, 
Minneapolis, Minnesota, USA.  
The MNREAD Acuity Charts will be used to measure:  
• Critical Print Size: the smallest print that the patient can read with maximum speed  
• Maximum Reading Speed: the patient’s reading speed when reading is not limited by 
print size  
Radner Reading Cards: 
The Radner Reading Cards consist of sentence optotypes, which are optimized reading test 
items, standardized by construction and statistical selection. These cards allow for accurate and 
comparable measurements of reading acuity and reading speed and measurement of critical print 
size. 
 
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APPENDIX H: GRADING SCALE FOR ASSESSMENT OF ANTERIOR 
CHAMBER FLARE OR CELLS  
AQUEOUS REACTION—FLARE  
Grade 
Description 
0 
No protein is visible in the anterior chamber when viewed by an experienced observer 
using slitlamp biomicroscopy; a small, bright, focal slit-beam of white light; and high 
magnification. 
Trace 
Trace amount of protein detectable in the anterior chamber. This protein is visible only 
with careful scrutiny by an experienced observer using slitlamp biomicroscopy; a small, 
bright, focal slit-beam of white light; and high magnification. 
1+ 
Mild amount of protein detectable in the anterior chamber. This protein is immediately 
apparent to an experienced observer using slitlamp biomicroscopy and high magnification, 
but such protein is detected only with careful observation with the naked eye and a small, 
bright, focal slit-beam of white light. Note presence of any fibrin. 
2-3+ 
Moderate amount of protein detectable in the anterior chamber. These grades are similar to 
1+ but the opacity would be readily visible to the naked eye of an observer using any 
source of a focused beam of white light. This is a continuum of moderate opacification, 
with 2+ being less apparent than 3+. Note presence of any fibrin. 
4+ 
A large (severe) amount of protein is detectable in the anterior chamber. Similar to 3+, but 
the density of the protein approaches that of the lens. Additionally, frank fibrin deposition 
is frequently seen in acute circumstances. It needs to be noted that because fibrin may 
persist for a period of time after partial or complete restoration of the blood-aqueous 
barrier, it is possible to have resorbing fibrin present with lower numeric assignations for 
flare (eg, 1+ flare with fibrin). 
 
AQUEOUS REACTION—CELLS 
Grade 
Description 
0 
No cells are seen in any optical section when a large slitlamp beam is swept across the 
anterior chamber. 
Trace 
Rare (1-3) cells are observed when the slitlamp beam is swept across the anterior chamber. 
When the instrument is held stationary, not every optical section contains circulating cells. 
1+ 
3-10 cells/optical section are seen when the slitlamp beam is swept across the anterior 
chamber. When the instrument is held stationary, every optical section contains circulating 
cells. Note stage of hypopyon, if applicable. 
2+ 
10-25 cells are seen when the slitlamp beam is swept across the anterior chamber. When 
the instrument is held stationary, every optical section contains circulating cells. Note 
stage of hypopyon, if applicable. 
3+ 
25-50 cells are seen when the slitlamp beam is swept across the anterior chamber. When 
the instrument is held stationary, every optical section contains circulating cells. Keratic 
precipitates or cellular deposits on the anterior lens capsule may be present. Note stage of 
hypopyon, if applicable. 
4+ 
More than 50 cells are seen when the slitlamp beam is swept across the anterior chamber. 
When the instrument is held stationary, every optical section contains circulating cells or 
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12 August 2020 
hypopyon is noted. As for the fibrin deposition, hypopyon may persist for a period of time 
after exudation of cells into the anterior chamber has diminished or ceased entirely, 
making it possible for have 1+ circulating cells in the anterior chamber with a resolving 
hypopyon. 
 
 
 
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12 August 2020 
APPENDIX I: GRADING SCALE FOR ASSESSMENT OF VITREOUS 
CELLS  
Grade 
Description 
Cells in Retro-Illuminated Field 
0 
Clear 
0 
Trace 
Few opacities 
1-20 
1 
Scattered opacities 
21-50 
2 
Moderate opacities 
51-100 
3 
Many opacities 
101-250 
4 
Dense opacities 
≥ 251 
 
 
 
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Section revised to further define approved methods of contraception 
include:  
• 
Combined (estrogen-and progestogen-containing) hormonal 
contraception associated with inhibition of ovulation: 
o 
Oral 
o 
Intravaginal 
o 
Transdermal 
• 
Progestogen-only hormonal contraception associated with 
inhibition of ovulation: 
o 
Oral 
o 
Injectable 
o 
Implantable 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS) 
• 
Bilateral tubal occlusion 
• 
Vasectomized partner (provided that partner is the sole sexual 
partner of the WOCBP trial participant and that the 
vasectomized partner has received medical assessment of the 
surgical success) 
• 
Sexual abstinence (defined as refraining from heterosexual 
intercourse during the entire period of risk associated with the 
study treatments). Sexual abstinence is only accepted when it is 
the preferred and usual lifestyle of the subject. 
Approved methods of contraception include: oral contraceptives, 
intrauterine device, medically acceptable barrier methods 
(diaphragm or condom), implantable or injectable contraceptives 
(like DepoProvera) or removable birth control device (like 
NuvaRing or Ortho Evra patches); and/or surgical sterilization (at 
least 6 months before dosing). Subjects practicing abstinence and 
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. 
Section 6.4  Approved Methods of 
Contraception 
The following section was added: 
 
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 (e.g., in the interest of subject safety). The investigator is 
encouraged to discuss withdrawal of a subject from treatment with the 
investigational product with the medical monitor when possible. 
Subjects who discontinue treatment with the investigational product can 
continue participation in the study and should be encouraged  to return to 
the clinical site for as many follow-up visits as they can. In the event that 
a subject terminates early from the study, all early termination 
procedures should be performed even if they are outside the allowed 
study window.  
The reason for termination, date of stopping treatment with 
investigational product, all follow-up information and the total amount of 
investigational product administered must be recorded in the case report 
form (CRF) and source documents. 
Section 6.5  Discontinuation of 
Subjects 
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The requirement to notify the sponsor prior to unmasking was removed: 
 
In the event of a medical emergency where the knowledge of subject 
treatment by masked individuals (e.g., the subject or his/her physician) is 
required, an individual Investigator (or designee) will have the ability to 
unmask the treatment assignment for a specific subject and share that 
information with the appropriate parties. The Investigator (or designee) 
must endeavor to notify the Sponsor prior to unmasking a subject.  
Section 7.2.1  Unmasking 
Section was revised to allow study treatment administration to occur on a 
day separate from the assessment visit: 
 
Section was revised to allow study treatment administration to occur on a 
day separate from the assessment visit: 
 
Only qualified study staff and those delegated the responsibility of study 
drug administration on the Delegation of Authority log should perform 
this procedure. All staff should be appropriately trained on all procedures 
prior to performing the procedures. Sites should follow the Visit 
Schedule for order of procedures and assessments.  
Administration of study treatment (APL-2 or Sham) can be done on a 
separate day from the assessment visit if both days fall within the visit 
window. If this occurs on the randomization visit, then the administration 
of APL-2 or Sham should be done within 3 days of randomization and 
after approval from the medical monitor. When study treatment 
administration is on a day other than  a study visit, then the only 
assessment that must be done on the day of study treatment 
administration is the pre-injection IOP.  
If a subject falls outside the visit window for a dosing visit, the dose 
should be skipped and the subject should be scheduled on time for the 
next dosing visit. 
Section 7.3.2  Treatment 
Administration 
The description of sham injection was modified as there is no 
requirement for sham to be sterile: 
 
Sham will be provided as sterile empty stoppered glass vials and should 
be stored according to the label.   
 
Section 7.3.3.1 Identity of the 
Investigational Product 
The procedure for sham injection was further described: 
 
The procedure for sham injection will be the same as that used for IVT 
injection until the actual injection but no actual injection will occur. The 
injecting physician will only touch the study eye with the blunt end of 
the syringe. No needle or medication will be injected inside the eye. 
Section 7.4  Sham Injection 
Administration 
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Detailed instructions on sham injection procedures and post-injection 
procedures will be provided in the Manual of Procedures. 
 
The end of the trial for each subject was defined: 
 
The end of the trial for each subject is defined as when the subject either 
completes their Month 24 Visit and enrolls in the open-label extension 
study or, should a subject elect not to enter the open label extension 
study, when the subject completes their exit visit at Month 30. 
 
Through the section it has also been noted that endothelial cell count 
assessment is for “select sites only”. This was previously noted in the 
schedule of events but not consistently in the body of the protocol. In 
addition FAF and NAR are no longer “study eye only”. 
 
Section 8  Study Procedures 
The following assessments were removed as they will no longer be 
conducted at the screening Visit 1: 
• 
Low luminance BCVA 
• 
Endothelial cell count 
• 
OCT A 
The following text was moved to Section 8.1.2 as training for home-
based digital applications will now be conducted at Visit 2: 
Prior to dilating the eyes, subjects at select sites will be trained on how to 
use the home based digital applications for visual function and reading 
speed if the subject decides to participate in this portion. This training 
must occur after completion of all functional tests (NL BCVA, LL
BCVA). 
Section 8.1.1  Visit 1 All Subjects 
It was clarified that: 
All assessments should be performed on the same day. All study visits 
should be scheduled and projected based on the Day 1 visit. 
 
The following text was added as home-based digital application training 
will now occur at Visit 2: 
Subjects at select sites will be trained on how to use the home-based 
digital applications for visual function and reading speed if the subject 
decides to participate in this portion. This training must occur after 
completion of all functional tests (NL-BCVA, LL-BCVA). 
 
The following assessments were added: 
• 
Endothelial cell count 
• 
OCT-A (select sites) 
 
The following text was removed as subject discontinuation is now 
covered in Section 6.5. 
In the event that a subject is early terminated from the study, all early 
termination procedures should be performed even if they are outside the 
allowed study window.  
If the subject would like to discontinue dosing but is amenable to 
Section 8.1.2 Randomization/Initial 
Treatment—Day—Within 28 Days 
of Screening 
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continuing in the study, the site should make every effort to have the 
subject complete as many follow up visits as possible. 
 
It has been noted in the text which assessments will be conducted at 
Month 27 and Month 30. 
Section 8.1.4 Follow-up Phase 
Instructions were revised to include the following: 
 
All AEs encountered during the study will be monitored and reported in 
detail in the source documents and documented on the eCRF, from 
signing of the ICF until the Exit Visit. AEs should be recorded by 
maximum severity. AEs, especially those for which the relationship to 
test drug study treatment are considered by the Investigator to be 
possibly or definitely related, should be followed up until they have 
returned to the baseline status or stabilized. If a clear explanation is 
established, it should be recorded on the eCRF. 
Section 11.2   Recording Adverse 
Events 
Instructions modified as follows: 
If any AEs are serious, special procedures will be followed. All SAEs 
will be reported to the Safety Monitor by the Investigator via fax or 
email within one calendar day of becoming aware of the event, whether 
or not the serious events are deemed drug related. SAE reporting contact 
information will be provided separately and as included in the Safety 
Monitoring Plan. All SAEs must be reported to the applicable ethics 
committee by the Investigator in accordance with their regulations. 
 
Special procedures will be followed for reporting SAEs. All SAEs 
will be reported to the Safety Monitor by the Investigator via eCRF or 
fax/email (if eCRF is not available)  within 24 hours of becoming aware 
of the event, whether or not the event is deemed treatment-related. If the 
EDC system is not operational, the site must complete the appropriate 
paper SAE form and fax/email to the number listed on the SAE form, 
also within 24 hours of becoming aware of the event. The reported 
information submitted as a paper SAE form must be entered into the 
EDC system once it becomes operational. 
SAE reporting contact information will be provided separately and 
included in the Safety Monitoring Plan. All SAEs must be reported to the 
applicable ethics committee by the Investigator in accordance with their 
regulations. 
Section 11.5 Serious Adverse Events 
The following text was added: 
A suspected adverse reaction means any AE for which there is a 
reasonable possibility that the drug caused the AE. Reasonable 
possibility means there is evidence (such as a temporal relationship) to 
suggest a causal relationship between the drug and the AE. 
Section 11.6 Unexpected Adverse 
Events or Unexpected Suspected 
Adverse Reactions 
The analysis description was modified as follows as this will be 
conducted at all sites. This is an error correction. 
• Change from baseline at each planned assessment in the total area of 
GA lesion(s) in the study eye (in mm2) as assessed by FAF (in select 
sites)  
Section 12.7.2 Secondary Efficacy 
Analysis 
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Section 12.10 was added to describe how visit windows will be used in 
the assessment of the primary endpoint: 
 
Analysis visits will be derived with windows for the monthly visits to 
assess the primary endpoint. Baseline is defined as the date of 
randomization. If 2 or more treatment visits occur within a window, the 
closest visit to the target day will be used as that analysis visit; if 2 visits 
are equidistant from the scheduled analysis visit day, the later analysis 
visit will be used. 
Section 12.10 Visit Windows 
All study schedules were modified to align with the changes noted 
above, including removal of PK and complement profile study 
assessments. 
Appendix A, B, C, and D:  Visit 
Schedules 
 
 
 
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associated with inhibition of ovulation, oral contraceptives, intrauterine 
device, intrauterine hormone releasing system; and/or bilateral tubal 
occlusion (at least 6 months before dosing) medically acceptable barrier 
methods (diaphragm or condom), implantable or injectable 
contraceptives (like DepoProvera) or removable birth control device (like 
NuvaRing or Ortho Evra patches); and/or surgical sterilization (at least 6 
months before dosing). Subjects practicing abstinence and coitus 
interruptus (pull out method) must agree to use an approved method of 
contraception during the study and 60 90 days after their last dose of 
study drug. 
Masking language was modified to indicate that the PI is required to 
remain masked to subjects’ treatment assignments, while the treating 
physician and any associated support staff involved in IP administration 
will be unmasked. 
Section 7.2 Masking and 
Minimization of Bias 
Guidance on the treatment of new exudation related to active choroidal 
neovascularization in the study eye and/or fellow eye was modified to 
clarify that the reading center will provide a report to indicate whether or 
not there is evidence of active, exudative AMD, and the Investigator will 
then determine if anti-VEGF treatment should be initiated. The 
Investigator should wait for the reading center report before making a 
decision regarding treatment, except in cases where there is clear 
evidence of disease activity that may have a detrimental visual impact if 
not treated immediately. 
 
It was also clarified that either ranibizumab or aflibercept should be 
selected as the anti-VEGF therapy, and that the unmasked physician 
should administer anti-VEGF treatment if the treatment is administered 
on the same day as APL-2.  
 
It was also noted that any treatments of therapies administered to the 
fellow eye within 5 years of screening should be recorded as a 
concomitant medication. 
Section 7.5.1 Treatment of New 
Exudation Related to Active 
Choroidal Neovascularization in the 
Study Eye and/or Fellow Eye 
Visit Schedules A-D 
The following instruction regarding electronic devices was added: 
The subject will be instructed to bring back the electronic device for the 
visits specified in the schedule of events. 
Section 8.1.3.1 Months 1-12 
Month 6 and Month 12 were added as times of in-clinic assessment. 
It was noted that subjects will take electronic devices home at Day 1 
instead of at Screening. 
Section 9.12 Home-Based 
Functional Digital Applications (in 
select sites/countries) 
Visit Schedules A-D. 
Clarified that: 
In the event that a subject is suspected to have new active CNV in the 
study eye and/or the fellow eye, an SD-OCT and FA using the protocol 
specified procedures should be performed and sent to the Reading Center 
to confirm the diagnosis. In addition, in selected sites, OCT-A should 
also be captured according to the study imaging protocol and sent to the 
Reading Center.  
Section 9.14 Ocular Imaging 
It was clarified that if the subject does not pass the gross vision test, IOP 
must be measured at that time. Additional IOP measurement must be 
taken approximately every 30 minutes thereafter until IOP ≤ 30 mm Hg 
Section 9.15 Post-Injection 
Assessment; Visit Schedule 
Footnote “O” (all Visit Schedules) 
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and the subject is able to be released from the clinic. 
It was clarified that anti-VEGF treatment will be either ranibizumab or 
aflibercept, and that IOP should be measured before and after the anti-
VEGF injection, but prior to administration of APL-2. 
Blood volume for study assessments was updated based on the lab 
manual. 
Section 9.16 Blood Volume for 
Study Assessments 
It was clarified that 1514 mL whole blood sample will be collected at the 
specified time points for research samples. 
Section 9.17.2 Sample Collection 
Visit Schedules A-D 
The screening urine pregnancy test was removed as a serum pregnancy 
test will be performed for screening. 
 
Footnotes “M” (All Visit Schedules) was modified to indicate that 
“Beginning at Day 1 Screening, subjects will complete the functional 
assessments weekly at home.” 
Visit Schedules A and C 
 
Week 24 blood draw for clinical repository was added (error correction). 
 
Visit Schedule C 
The full version of the NEI VFQ-25 has been included in Appendix E. 
Appendix E. 
An amendment history appendix was added to show changes enacted by 
previous amendments. 
Appendix J 
 
 
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“Endothelial cell count” was removed as an assessment that will be 
provided to the reading center for objective assessment of subject 
eligibility. 
 
“Optical Coherence Tomography Angiography (OCT-A, selected sites 
only)” was added as an assessment that will be provided to the reading 
center for objective assessment of subject eligibility.  
Section 7.1 Allocation to Treatment 
Section 8.1. Study Visit Schedule 
Section 8.1.2 Randomization/Initial 
Treatment 
“Country” and “microperimetry eligibility (yes; no)” were removed as a 
stratification factor. 
Section 7.1 Allocation to Treatment 
 
References to “DSMB” updated to “DMC”. 
Section 7.2.1 Unmasking 
Section 10.1 Data Monitoring 
Committee 
Reference to preparing APL-2 for injection was removed from the 
paragraph describing sham. 
Section 7.3.3.1 Identity of the 
Investigational Product 
Text was updated to indicate that:  
 
The suspected onset or presence of new active choroidal 
neovascularization (CNV) secondary to AMD in the study eye and/or 
fellow eye must be documented in the source document and CRF.  
Section 7.5.1 Treatment of New 
Active Choroidal 
Neovascularization in the Study Eye 
and/or Fellow Eye 
Section 9.15 Ocular Imaging 
Optical Coherence Tomography Angiography (OCT-A) was added as a 
monitoring assessment for select sites to confirm the diagnosis of new 
active CNV. 
Section 7.5.1 Treatment of New 
Active Choroidal 
Neovascularization in the Study Eye 
and/or Fellow Eye 
Section 9.15 Ocular Imaging 
Text corrected as follows: 
 
The treatment method (pars plana vitrectomy vs intravitreal injection of 
antibiotics vitreous tap) and choice of antimicrobial agents are also at the 
discretion of the physician and should follow current standard practice 
patterns.  
Section 7.5.3 Endophthalmitis 
Treatment 
Content in these sections was combined. 
Section 7.5.1 Treatment of New 
Active Choroidal 
Neovascularization in the Study Eye 
and/or Fellow Eye 
 
Section 7.5.2 
Treatment of 
Neovascular AMD in the Fellow Eye 
References to “biobanking” have been replaced by references to the 
“genetic biorepository” and the “clinical repository”.  
Section 8. STUDY DESIGN 
Section 9.7 Genotyping Samples 
Section 9.17 Blood Volume for 
Study Assessments 
Protocol updated to specify that microperimetry should be conducted on 
both eyes. 
Section 8 STUDY DESIGN 
Noted that blood draws will be conducted for genotyping. 
Section 8.1.3.2 Months 13-24 
Noted that OCT-A may be conducted, if applicable as per instructions of 
the protocol. 
Section 9.6 Laboratory Analysis of 
Blood and Urine 
Text was modified to clarify that the study staff performing visual acuity 
Section 9.11 Best-corrected Visual 
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should be masked to the treatment assignment only; the protocol 
previously stated that staff should also be blinded to the study eye. 
Acuity and Low Luminance Best-
corrected Visual Acuity 
Blood volume for genetic biorepository was updated. 
Section 9.17 Blood Volume for 
Study Assessments 
The following samples were removed: 
• 
All residual serum and whole blood samples 
collected during the course of the study for PK 
analysis, genotyping and anti APL 2 antibody 
formation  
• 
Residual serum PK sample  
• 
Residual serum Anti Therapeutic Antibodies 
(ATA) sample 
 
It was noted that the 15 mL whole blood sample will be collected at 
Month 2, baseline, Month 12 and Month 24 of the study 
Section 9.18.2 Sample Collection 
It was clarified that the DMC will meet at the beginning of the study and 
every 6 months thereafter. 
Section 10.1 Data Monitoring 
Committee 
Reference to “possibly related” AEs was removed as there is no 
“possibly related” AE categorization for this study. 
 
Resolution outcome possibilities were updated to accurately align with 
the SAE report forms that will be used for this study. 
Section 11.2 Recording Adverse 
Events 
 
Section 11.4.1 Relationship of 
Events to Study Treatment 
Clarified that: 
All SAEs will be reported to the Safety Monitor by the Investigator via 
fax or email within one working calendar day of becoming aware of the 
event, whether or not the serious events are deemed drug-related. 
Section 11.5 Serious Adverse Events 
Section reorganized, modified, and updated to depict protocol 
specifications for data management and statistical considerations more 
clearly, accurately, and thoroughly. 
Section 12. DATA MANAGEMENT 
AND STATISTICAL 
CONSIDERATIONS 
Footnote was updated to indicate that: All assessments should be 
performed on the same day, with the exception of screening. 
 
The blood draw for the clinical repository was removed at baseline, 
Month 1, Month 8, Month 18, and Month 27. 
 
OCT-A was added at screening, Month 6, Month 12, Month 18, and 
Month 24 for select sites. Footnote “R” was added to note that in 
addition to the time points indicated on the study schedule, OCT-A 
should be performed at the time of any suspected new active CNV. If 
new active CNV is confirmed in the study eye, OCT-A should be 
repeated every 2 months for the study eye. 
All Study Schedules (Appendices: 
A, B, C, and D) 
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APPENDIX K: PROTOCOL CHANGES TO BE FOLLOWED DURING 
COVID-19 RESTRICTIONS 
OVERVIEW  
In response to the COVID-19 crisis, to ensure the safety of study subjects and Investigative Sites 
as well as proper conduct of the study, TEMPORARY changes to the protocol have been 
implemented. These changes should be followed only during COVID-19 restrictions and include 
extended IP administration windows, changes to masking rules, rescreening instructions, and a 
revised schedule of assessments.  
Where feasible, sites could continue to follow the full schedule of assessments (based on their 
treatment group assignment). 
EXTENDED IP ADMINISTRATION WINDOWS 
In order to allow more flexibility to sites and subjects, and to potentially mitigate missed IP 
administration, an extended IP administration window can be followed. The extended window 
can ONLY be used in situations related to COVID-19 restrictions and after medical monitor 
approval. Footnote “T” of each COVID-19 assessment table below reflects these extended IP 
options. 
Per protocol, the study window is as followed: 
• Monthly treatment group: +/–8 days for the entire study duration 
• EOM treatment group: +/–8 days for the first study year and +/–16 days for the 
second study year 
During COVID-19 restrictions, the IP administration window can be extended to the following: 
• Monthly treatment group: –8 days to +15 days. Note, interval for consecutives 
injection must be at least 14 days. 
• EOM treatment group: –8 days to +30 days for the first study year and –16 days to 
+30 days for the second study year 
MASKING RULES 
Due to current COVID-19 restrictions, clinical sites might encounter difficulties maintaining 
appropriate clinic staffing to satisfy the approved masking rules for the APL2-304 (Oaks) study. 
Based on this, and in an attempt to minimize the amount of missed data and IP administrations, 
Apellis is implementing a temporary adjustment to the study masking rules.  
This temporary change must be approved by the Apellis Medical Director prior to 
implementation and must be documented via a temporary and modified Delegation of Authority 
Log. Each masked assessment performed by an unmasked staff and vice versa (even with Apellis 
approval and following the below guidelines) should be documented.  
The principal investigator (PI) is responsible for the overall safety oversight of the study site data 
and s/he will not be allowed to switch into an unmasked role. Every masked individual that 
performs IP administration and/or postinjection assessment (all unmasked assessment) as a 
temporary measure, will permanently be considered an unmasked individual and will not be 
able to perform masked assessments once these exemptions are lifted. 
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RESCREENING PROCEDURE 
Prior to the implementation of these temporary changes, sites continuing to screen patients have 
been encouraged to complete the screening and baseline assessments in their entirety. However, 
if a subject was deemed a screen failure for not being able to meet the original screening window 
(Day –28 to Day –1 [+/–2 days]) due to COVID-19 related restrictions, a rescreening visit is 
allowed and should be followed according to the 2 scenarios below.  
Subjects Who Completed Screening and Were Considered Eligible by Reading Center and 
Investigator  
Subjects who were screened prior to 30 March 2020 and completed all screening assessments (as 
described in the Schedule of Assessments Appendix A [every month treatment group] and 
Appendix C [every-other-month [EOM] treatment group]) and considered eligible by the reading 
center and investigator and are able to return to the clinic within 90 days of initial screening, will 
receive a new subject ID number and undergo an abbreviated screening, prior to randomization, 
that includes the following assessments:   
• Informed consent/Assign new screening number  
• NL-BCVA assessment  
• Slitlamp examination  
• Dilated indirect ophthalmoscopy  
• IOP measurement  
• SD-OCT*   
• Concomitant medication/concomitant ocular procedures collection  
• AE collection  
*SD-OCT images collected at this visit will not be used by the reading center to determine 
eligibility but should be used by the investigator to detect any potential new exclusion criterion.  
If the investigator deems it necessary, additional assessments can be performed if there is a 
concern that the subject might now meet an exclusion criterion that was not the case during the 
original screening (eg, fundus fluorescein angiography to exclude the presence of CNV).  
Subjects With Incomplete Screening Assessment  
Subjects that signed the informed consent but were not able to complete all screening 
assessments due to COVID-19-related restrictions are not eligible for the abbreviated screening. 
These subjects can be rescreened but must follow the standard screening schedule of 
assessment (as described in the Schedule of Assessments Appendix A [every month treatment 
group] and Appendix C [EOM treatment group]). These subjects will also receive a new 
screening ID number.  
MINIMUM SCHEDULE OF ASSESSMENT 
Schedule of Assessments  
Where feasible, sites could continue to follow the full schedule of assessments (based on their 
treatment group assignment). The minimum assessment tables, only to be followed during this 
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COVID-19 effort and if determined necessary to use based on the investigator’s clinical 
judgment, are provided below to reduce the time required for each study visit. Subjects in the 
EOM treatment group do not need to be seen for the non-IP administration visits. Assessments 
not performed (even those that have been removed in the minimum assessment table) should be 
documented.  
Subjects that are not able to come into the clinic for a study visit due to COVID-19-related 
restrictions, including visits for the EOM group that do not include IP administration, should 
be contacted via the phone for the collection of adverse events (including SAEs) and 
concomitant medications. All SAEs are still required to be reported to Apellis within 24 
hours of site awareness, even if reported via phone call. All communications via phone call 
should also be documented in the source documentation and in the respective CRF page. In 
addition, these subjects should be instructed to self-monitor their vision at home and report any 
changes in vision or their overall health via phone call. The site must inform the Sponsor of any 
subjects lost to follow-up.  
It is critical that local, country, and regional governance regarding COVID-19 is followed along 
with your best clinical judgment when managing this situation. All visits or assessments missed 
as a result of COVID-19 will be captured in the Case Report Forms. 
The Schedule of Assessments tables shown below supersede those sent on 30 March 2020. These 
changes were previously communicated to the sites via a memorandum.  
 
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Pegcetacoplan 
APL2-304 Protocol Amendment 5 
12 August 2020 
J. Perform assessments prior to dilating the eyes.  
K. In select countries, the MNREAD or Radner Reading Charts should be done during the study visit, prior to dilating the eyes. It should be performed monocularly first, then 
binocularly.  
L. Microperimetry assessments will be performed post dilation. Data will be forwarded to the reading center.  
M. To be administered by the masked site staff prior to any other assessments performed on that day. In-clinic assessments on the digital application should be completed after 
completion of all functional tests and quality of life measures prior to dilating the eyes.  
N. At select sites, and for those subjects who decide to participate, the digital applications will be completed on an electronic device and will consist of assessments for visual 
function and reading speed. Subjects will receive training at Day 1 on the use of the digital applications and the electronic device and will perform the tests using the 
application in the clinic at Month 1, Month 2, Month 3, Month 6, Month 12, Month 18, and Month 24. Beginning at Day 1, subjects will complete the functional assessments 
weekly at home. Subjects should be instructed to complete the assessments on the same day each week and at approximately the same time of day each week, if possible.  
O. FAF and SD-OCT images, near infrared reflectance, fluorescein angiograms, and fundus photographs will be performed for the study eye only on days where 'SE' is specified 
and for both eyes at all other visits as specified in the above schedule and will be sent to the reading center for evaluation (consult the reading center manual for specifics on 
image capture, processing, and transmission). Images should be captured prior to dosing on dosing days. If a subject misses a study visit or images cannot be obtained at a 
specific visit, study staff should make every effort to obtain images at the next scheduled visit. If new active CNV is suspected, SD-OCT, FFA and OCT-A (select sites) images 
must be collected and sent to the reading center for analysis.  
P. Postinjection assessments should be performed within 5 minutes after dosing by the unmasked physician or study staff and should include a gross assessment of vision (finger-
counting, hand motion, then light perception when applicable). If subject passes gross vision test, the subject may leave the site. If subject fails gross vision test, the tonometry 
should be performed. IOP should be ≤30 mm Hg in order for the subject to leave the site. If necessary, antiglaucomatous medication can be given to lower the IOP. If IOP is 
>30 mm Hg, assessments will continue every approximately 30 minutes from the previous measurement until the subject passes gross vision test and IOP is ≤30 mm Hg. Note: if 
the study eye is treated with a ranibizumab or aflibercept injection during the same visit as the study treatment (pegcetacoplan or sham), the treatment with ranibizumab or 
aflibercept must be performed first. The pre- and  post- anti-VEGF IOP values must be measured and recorded on the eCRF.  
Q. Starting at Day 1, study subjects will be contacted by study site staff within 4 ± 2 days after each study treatment visit (through Month 3) to collect any information on any 
safety concerns, decrease in vision, eye pain, unusual ocular events, or any new ocular symptoms in the study eye. If the physician determines that there are any safety concerns, 
a follow-up visit should be scheduled as soon as possible.  
R. Record concomitant medications (ie, prescription and over-the-counter medications) used by the patient within 30 days of screening and throughout the subject's participation in 
the study.  
S. In addition to the time points indicated on the study schedule, OCT-A should be performed at the time of any suspected new active CNV. If new active CNV is confirmed in the 
study eye, OCT-A should be repeated every 2 months for the study eye.  
T. Administration of pegcetacoplan or sham can be done on separate days from the assessment visit if both days fall within the visit window. Administration of study treatment 
(pegcetacoplan or sham) can be done on a separate day from the assessment visit if both days fall within the visit window. If this occurs on the randomization visit, then the 
administration of pegcetacoplan or sham should be done within 3 days of randomization and after approval from the medical monitor. When study treatment administration is on 
a day other than  a study visit, then the only assessment that must be done on the day of study treatment administration is preinjection IOP. During the COVID-19 pandemic, the 
following flexibility is allowed for IP administration: –8 days to + 15 days after medical monitor approval. Note, interval for consecutive injections must be at least 14 days. 
Apellis Pharmaceuticals, Inc
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Pegcetacoplan 
APL2-304 Protocol Amendment 5 
12 August 2020 
J. Perform assessments prior to dilating the eyes.  
K. In select countries, the MNREAD or Radner Reading Charts should be done during the study visit, prior to dilating the eyes. It should be performed monocularly first, then 
binocularly.  
L. Microperimetry assessments will be performed post dilation. Data will be forwarded to the reading center.  
M. To be administered by the masked site staff prior to any other assessments performed on that day. In-clinic assessments on the digital application should be completed after 
completion of all functional tests and quality of life measures prior to dilating the eyes.  
N. At select sites, and for those subjects who decide to participate, the digital applications will be completed on an electronic device and will consist of assessments for visual 
function and reading speed. Subjects will receive training at Day1 on the use of the digital applications and the electronic device and will perform the tests using the 
application in the clinic at Month 1, Month 2, Month 3, Month 6, Month 12, Month 18, and Month 24. Beginning at Day 1, subjects will complete the functional assessments 
weekly at home. Subjects should be instructed to complete the assessments on the same day each week and at approximately the same time of day each week, if possible.  
O. FAF and SD-OCT images, near infrared reflectance, fluorescein angiograms, and fundus photographs will be performed for the study eye only on days where 'SE' is 
specified  and for both eyes at all other visits as specified in the above schedule and will be sent to the reading center for evaluation (consult the reading center manual for 
specifics on image capture, processing, and transmission). Images should be captured prior to dosing on dosing days. If a subject misses a study visit or images cannot be 
obtained at a specific visit, study staff should make every effort to obtain images at the next scheduled visit. If new active CNV is suspected, SD-OCT, FFA, and OCT-A 
(selected sites) images should be collected and sent to the reading center for analysis.  
P. Postinjection assessments should be performed within 5 minutes after dosing by the unmasked physician or study staff and should include a gross assessment of vision (finger-
counting, hand motion, then light perception when applicable). If subject passes gross vision test, the subject may leave the site. If subject fails gross vision test, the tonometry 
should be performed. IOP should be ≤30 mm Hg in order for the subject to leave the site. If necessary, antiglaucomatous medication can be given to lower the IOP. If IOP is 
>30 mm Hg, assessments will continue every approximately 30 minutes from the previous measurement until the subject passes gross vision test and IOP is ≤30 mm Hg. Note: if 
the study eye is treated with a ranibizumab or aflibercept injection during the same visit as the study treatment (pegcetacoplan or sham), the treatment with ranibizumab or 
aflibercept must be performed first. The pre- and  post- anti-VEGF IOP values must be measured and recorded on the eCRF.  
Q. Starting at Day 1, study subjects will be contacted by study site staff within 4 ± 2 days after each study treatment visit (through Month 3) to collect any information on any 
safety concerns, decrease in vision, eye pain, unusual ocular events, or any new ocular symptoms in the study eye. If the physician determines that there are any safety concerns, 
a follow-up visit should be scheduled as soon as possible.  
R. Record concomitant medications (ie, prescription and over-the-counter medications) used by the patient within 30 days of screening and throughout the subject's participation in 
the study.  
S. In addition to the time points indicated on the study schedule, OCT-A should be performed at the time of any suspected new active CNV. If new active CNV is confirmed in the 
study eye, OCT-A should be repeated every 2 months for the study eye.  
T. Administration of pegcetacoplan or sham can be done on separate days from the assessment visit if both days fall within the visit window. Administration of study treatment 
(pegcetacoplan or sham) can be done on a separate day from the assessment visit if both days fall within the visit window. If this occurs on the randomization visit, then the 
administration of pegcetacoplan or sham should be done within 3 days of randomization and after approval from the medical monitor. When study treatment administration is on 
a day other than  a study visit, then the only assessment that must be done on the day of study treatment administration is preinjection IOP. During the COVID-19 pandemic, the 
following flexibility is allowed for IP administration: –8 days to + 15 days after medical monitor approval. Note, interval for consecutive injections must be at least 14 days. 
Apellis Pharmaceuticals, Inc
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Pegcetacoplan 
APL2-304 Protocol Amendment 5 
12 August 2020 
K. In select countries, the MNREAD or Radner Reading Charts should be done during the study visit, prior to dilating the eyes. It should be performed monocularly first, then 
binocularly.  
L. Microperimetry assessments will be performed post dilation. Data will be forwarded to the reading center.  
M. To be administered by the masked site staff prior to any other assessments performed on that day. In-clinic assessments on the digital application should be completed after 
completion of all functional tests and quality of life measures prior to dilating the eyes.  
N. At select sites, and for those subjects who decide to participate, the digital application will be completed on an electronic device and will consist of assessments for visual 
function and reading speed. Subjects will receive training at Day 1 on the use of the digital applications and the electronic device and will perform the tests using the in the clinic 
at Month 1, Month 2, Month 3, Month 6, Month 12, Month 18, and Month 24. Beginning at Day 1, subjects will complete the functional assessments weekly at home. Subjects 
should be instructed to complete the assessments on the same day each week and at approximately the same time of day each week, if possible.  
O. FAF and SD-OCT images, near infrared reflectance, fluorescein angiograms, and fundus photographs will be performed for the study eye only on days where 'SE' is 
specified  and for both eyes at all other visits as specified in the above schedule and will be sent to the reading center for evaluation (consult the reading center manual for 
specifics on image capture, processing, and transmission). Images should be captured prior to dosing on dosing days. If a subject misses a study visit or images cannot be 
obtained at a specific visit, study staff should make every effort to obtain images at the next scheduled visit. If new active CNV is suspected, SD-OCT, FFA, and OCT-A 
(selected sites) images should be collected and sent to the reading center for analysis.  
P. Postinjection assessments should be performed within 5 minutes after dosing by the unmasked physician or study staff and should include a gross assessment of vision (finger-
counting, hand motion, then light perception when applicable). If subject passes gross vision test, the subject may leave the site. If subject fails gross vision test, the tonometry 
should be performed. IOP should be ≤30 mm Hg in order for the subject to leave the site. If necessary, antiglaucomatous medication can be given to lower the IOP. If IOP is 
>30 mm Hg, assessments will continue every approximately 30 minutes from the previous measurement until the subject passes gross vision test and IOP is ≤30 mm Hg. Note: if 
the study eye is treated with a ranibizumab or aflibercept injection during the same visit as the study treatment (pegcetacoplan or sham), the treatment with ranibizumab or 
aflibercept must be performed first. The pre- and  post- anti-VEGF IOP values must be measured and recorded on the eCRF.  
Q. Starting at Day 1, study subjects will be contacted by study site staff within 4 ± 2 days after each study treatment visit (through Month 4) to collect any information on any 
safety concerns, decrease in vision, eye pain, unusual ocular events, or any new ocular symptoms in the study eye. If the physician determines that there are any safety concerns, 
a follow-up visit should be scheduled as soon as possible.  
R. Record concomitant medications (ie, prescription and over-the-counter medications) used by the patient within 30 days of screening and throughout the subject's participation in 
the study.  
S. In addition to the time points indicated on the study schedule, OCT-A should be performed at the time of any suspected new active CNV. If new active CNV is confirmed in the 
study eye, OCT-A should be repeated every 2 months for the study eye.  
T. Administration of pegcetacoplan or sham can be done on separate days from the assessment visit if both days fall within the visit window. Administration of study treatment 
(pegcetacoplan or sham) can be done on a separate day from the assessment visit if both days fall within the visit window. If this occurs on the randomization visit, then the 
administration of pegcetacoplan or sham should be done within 3 days of randomization and after approval from the medical monitor. When study treatment administration is on 
a day other than a study visit, then the only assessment that must be done on the day of study treatment administration is preinjection IOP. During the COVID-19 pandemic, the 
following flexibility is allowed for IP administration: –8 days to + 30 days after medical monitor approval. 
 
Apellis Pharmaceuticals, Inc
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Pegcetacoplan 
APL2-304 Protocol Amendment 5 
12 August 2020 
K. In select countries, the MNREAD or Radner Reading Charts should be done during the study visit, prior to dilating the eyes. It should be performed monocularly first, then 
binocularly.  
L. Microperimetry assessments will be performed post dilation. Data will be forwarded to the reading center.  
M. To be administered by the masked site staff prior to any other assessments performed on that day. In-clinic assessments on the digital application should be completed after 
completion of all functional tests and quality of life measures prior to dilating the eyes.  
N. At select sites, and for those subjects who decide to participate, the digital applications will be completed on an electronic device and will consist of assessments for visual 
function and reading speed. Subjects will receive training at Day 1 on the use of the digital applications and the electronic device and will perform the tests using the 
application in the clinic at Month 1, Month 2, Month 3, Month 6, Month 12, Month 18, and Month 24. Beginning at Day 1, subjects will complete the functional assessments 
weekly at home. Subjects should be instructed to complete the assessments on the same day each week and at approximately the same time of day each week, if possible.  
O. FAF and SD-OCT images, near infrared reflectance, fluorescein angiograms, and fundus photographs will be performed for the study eye only on days where 'SE' is 
specified  and for both eyes at all other visits as specified in the above schedule and will be sent to the reading center for evaluation (consult the reading center manual for 
specifics on image capture, processing, and transmission). Images should be captured prior to dosing on dosing days. If a subject misses a study visit or images cannot be 
obtained at a specific visit, study staff should make every effort to obtain images at the next scheduled visit. If new active CNV is suspected, SD-OCT, FFA, and OCT-A 
(selected sites) images should be collected and sent to the reading center for analysis.  
P. Postinjection assessments should be performed within 5 minutes after dosing by the unmasked physician or study staff and should include a gross assessment of vision (finger-
counting, hand motion, then light perception when applicable). If subject passes gross vision test, the subject may leave the site. If subject fails gross vision test, 
the tonometry should be performed. IOP should be ≤30 mm Hg in order for the subject to leave the site. If necessary, antiglaucomatous medication can be given to lower the 
IOP. If IOP is >30 mm Hg, assessments will continue every approximately 30 minutes from the previous measurement until the subject passes the gross vision test and IOP is 
≤30 mm Hg. Note: if the study eye is treated with a ranibizumab or aflibercept injection during the same visit as the study treatment (pegcetacoplan or sham), the treatment with 
ranibizumab or aflibercept must be performed first. The pre- and post- anti-VEGF IOP values must be measured and recorded on the eCRF.  
Q. Starting at Day 1, study subjects will be contacted by study site staff within 4 ± 2 days after each study treatment visit (through Month 4) to collect any information on any 
safety concerns, decrease in vision, eye pain, unusual ocular events, or any new ocular symptoms in the study eye. If the investigator determines that there are any safety 
concerns, a follow-up visit should be scheduled as soon as possible.  
R. Record concomitant medications (ie, prescription and over-the-counter medications) used by the patient within 30 days of screening and throughout the subject's participation in 
the study.  
S. In addition to the time points indicated on the study schedule, OCT-A should be performed at the time of any suspected new active CNV. If new active CNV is confirmed in the 
study eye, OCT-A should be repeated every 2 months for the study eye.  
T. Administration of pegcetacoplan or sham can be done on separate days from the assessment visit if both days fall within the visit window. Administration of study treatment 
(pegcetacoplan or sham) can be done on a separate day from the assessment visit if both days fall within the visit window. If this occurs on the randomization visit, then the 
administration of pegcetacoplan or sham should be done within 3 days of randomization and after approval from the medical monitor. When study treatment administration is on 
a day other than  a study visit, then the only assessment that must be done on the day of study treatment administration is preinjection IOP. During the COVID-19 pandemic, the 
following flexibility is allowed for IP administration: –16 days to + 30 days after medical monitor approval. 
 
Apellis Pharmaceuticals, Inc
Page 164 of 164
Confidential