A Phase 2, Double-Masked, Placebo-Controlled, Dose Range Finding Study of Danicopan (ALXN2040) in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (AMD)
Phase: PHASE2
Conditions: Geographic Atrophy
Sponsor: Alexion Pharmaceuticals, Inc.

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
TITLE PAGE 
Protocol Title: A Phase 2, Double-Masked, Placebo-Controlled, Dose Range Finding Study of 
Danicopan (ALXN2040) in Patients with Geographic Atrophy (GA) Secondary to Age-Related 
Macular Degeneration (AMD) 
Protocol Number: ALXN2040-GA-201 
Amendment Number: 3.0 (Global) 
Compound: Danicopan (ALXN2040) 
Study Phase: Phase 2 
Short Title: Proof of concept and dose-finding study of danicopan in patients with geographic 
atrophy secondary to AMD 
Sponsor Name: Alexion Pharmaceuticals, Inc. 
Legal Registered Address: 
121 Seaport Boulevard 
Boston, MA 02210 
USA 
Regulatory Agency Identifier Number(s) 
IND: 153070 
EudraCT: 2021-001198-22 
EU CT: 2023-508571-37 
NCT: NCT05019521 
Release Date: 30 Oct 2023 
Sponsor Signatory: 
This document has been e-signed in Veeva. Please refer to the last page for signature details. 
 
 
 
Date 
Medical Monitor Name and Contact Information can be found in the Study Contact List. 
Page 1 of 136 
Alexion Confidential 
NCT05019521

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
INVESTIGATOR’S AGREEMENT 
I have read this study protocol amendment and agree to conduct the study in accordance with this 
protocol amendment, all applicable government regulations, the principles of the International 
Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use 
(ICH) E6 Guideline for Good Clinical Practice, and the principles of the World Medical 
Association Declaration of Helsinki. I also agree to maintain the confidentiality of all 
information received or developed in connection with this protocol amendment. 
____________________________________ 
Printed Name of Investigator  
_____________________________________ 
Signature of Investigator  
_______________ 
Date  
Page 2 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
PROTOCOL AMENDMENT SUMMARY OF CHANGES 
A complete protocol amendment history is provided in Section 10.14. 
Amendment 3.0 (Global); 30 Oct 2023 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union and in 
the European Union Clinical Trial Regulation (EU CTR) 536/2014 Article 2, 2 (13). 
Overall Rationale for the Amendment: 
This amendment was initiated to: 
•
Update secondary and exploratory study endpoints based on emerging scientific data
•
Provide new information on drug interactions based in IB Ed 13 dated 16 Oct 2023
•
Update text in preparation for transition into EU CTR
•
Add text to align with current Alexion protocol template, recently updated according
to applicable regulations
Section # and Name 
Description of Changes 
Brief Rationale 
Title page 
Section 1.1 Synopsis 
• Updated document version and
date.
• Added regulatory agency
identifier number (EU CT
number).
• Administrative changes.
All throughout the document 
• Made minor editorial and
consistency changes.
• Changed NIMP to AxMP
• For clarity, typographic
consistency, style, and
formatting edits.
• Updated in accordance with
EU CTR.
Section 1.1 Synopsis 
Section 3 Objectives and 
Endpoints 
• Exploratory endpoints for
macular ellipsoid zone (EZ),
outer retinal integrity, and
subretinal pigment epithelium
(sub-RPE)
compartment/drusen/RPE
complex were upgraded to
secondary endpoints
• Exploratory endpoint on
microperimetry revised:
Previous endpoint: 
• Change from Baseline in
macular sensitivity as assessed 
by mesopic microperimetry in 
study eye, fellow eye, and both 
• Emerging data show that EZ
and sub-RPE/drusen/RPE
complex analyses are highly
important in GA studies, thus
these exploratory endpoints
are being upgraded to
secondary endpoints.
• The microperimetry endpoint
has been revised to provide
methodology details
Page 3 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Section # and Name 
Description of Changes 
Brief Rationale 
eyes combined to Week 52 and 
Week 104 
New endpoint: 
• Incidence of patients with
predefined change in any
predefined grid pattern by
mesopic microperimetry in the
study eye, fellow eye, and both
eyes combined.
Section 1.3 Schedule of 
Activities 
Updated Tables 1 to 3 to add 
medication error, drug abuse and 
misuse- 
• To align with Section 8.4.5
and Section 10.7
Section 6.5.1 Allowed 
Medications 
Section 10.9 Allowed 
Medications 
Updated sections and associated 
table to include new information 
on potential drug interactions:  
• Added text on the need for
caution when co-administering
danicopan with drugs known to
be P-gp and/or BCRP
substrates.
• Updated Table 13: 
List of
CYP3A4, P-gp, and
UGT1A1/2B7 Sensitive
Substrates and associated
footnotes
• Updated with new information
from drug-drug interaction
study; in alignment with
updated IB Ed 13
Section 8.2.2 Secondary 
Efficacy Assessments 
Section 8.2.2.1 Anatomical 
Measures 
• Details on EZ and sub-RPE
compartment/drusen/RPE
complex moved up from
Section 8.2.3 Exploratory
Efficacy Assessments to
Section 8.2.2. Secondary
Efficacy Assessments, with
updated subsections:
-Section 8.2.2.1.1. Macular
Ellipsoid Zone and Outer
Retinal Integrity
-Section 8.2.2.1.2. Sub-RPE
Compartment/Drusen/RPE
Complex
• Added list of parameters from
SD-OCT images
• To reflect change in endpoints
(Synopsis; Section 3).
Section 8.2.3.2. Mesopic 
Microperimetry 
• Added that “a difference of 7
decibels (dB) would represent a
minimal clinically meaningful
• To provide additional
information on microperimetry
Page 4 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Section # and Name 
Description of Changes 
Brief Rationale 
change on microperimetry” 
measures. 
Section 8.4.5 and 
Section 10.7 Medication 
Error, Drug Abuse, and 
Drug Misuse 
• Updated text on data collection
and reporting details.
• Updated in accordance with
EU CTR.
Section 9.1.1. Primary 
Hypothesis 
• Updated “mean change” to
“mean rate of change” all
throughout this section
• To provide clarity
Section 9.4.5.1 Analyses of 
Primary Efficacy Endpoint 
• Updated estimand attributes
• To align with the Statistical
Analysis Plan (SAP)
Section 9.4.5.2.1 Analyses 
of Secondary Efficacy 
Endpoints at Week 52 
Section 9.4.5.2.2. Analyses 
for Secondary Efficacy 
Endpoints at Week 104’  
• Updated list and description of
endpoints
• Update description of statistical
models
• To reflect change in endpoints
(Synopsis; Section 3).
• For clarity
Section 10.1.1 Regulatory 
and Ethical Considerations 
• Updated text on process for
data protection and reporting
data breaches.
• Updated in accordance with
EU CTR and EU GDPR and
the current Alexion protocol
template.
Section 10.1.5 Data 
Protection 
• Updated text on process for
data protection and reporting
data breaches.
• Updated in accordance with
EU CTR and EU GDPR and
the current Alexion protocol
template.
Section 10.1.7 Data Quality 
Assurance 
• Added text on duration for
retention of records and
documents pertaining to the
conduct of the study.
• Updated in accordance with
EU CTR.
Section 10.1.8 Source 
Documents 
• Updated definitions and
requirements of source
documents
• Updated in accordance with
GCP and current protocol
template
Section 10.1.9 Study and 
Site Start and Closure 
• Updated text on reasons for
early study termination
• Updated in accordance with
applicable regulations and
current protocol template
Section 10.1.10 Publication 
Policy 
• Added text on publication of
results and authorship
• Updated to align with current
Alexion/AstraZeneca
publication policy
Section 10.5 Clinical 
Laboratory Test 
• Updated frequency of creatine
kinase sampling to every visit
• For safety monitoring
Page 5 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Section # and Name 
Description of Changes 
Brief Rationale 
Section 10.10 Handling of 
Human Biological Samples 
• Added new section on
biological samples
• Updated to align with current
Alexion/AstraZeneca policy
Abbreviations: AxMP = auxiliary medicinal product; Ed = edition; EU CTR = European Union Clinical Trial 
Regulation 536/2014; EU GDPR = European Union General Data Protection Regulation; GA = geographic 
atrophy; GCP = Good Clinical Practice; IB = Investigator’s Brochure; NIMP = non-investigational medicinal 
product; SD-OCT = spectral domain optical coherence tomography 
Page 6 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1
INVESTIGATOR’S AGREEMENT ...............................................................................................2
PROTOCOL AMENDMENT SUMMARY OF CHANGES ..........................................................3
TABLE OF CONTENTS .................................................................................................................7
LIST OF TABLES .........................................................................................................................14
LIST OF FIGURES .......................................................................................................................14
1.
PROTOCOL SUMMARY ..........................................................................................15
1.1.
Synopsis ......................................................................................................................15
1.2.
Study Schema .............................................................................................................21
1.3.
Schedule of Activities .................................................................................................22
2.
INTRODUCTION ......................................................................................................36
2.1.
Study Rationale ...........................................................................................................36
2.1.1.
Unmet Medical Need ..................................................................................................36
2.1.2.
Complement Dysregulation in AMD ..........................................................................37
2.1.3.
Danicopan ...................................................................................................................37
2.2.
Benefit/Risk Assessment ............................................................................................38
2.2.1.
Risk Assessment .........................................................................................................38
2.2.1.1.
Potential Risk of Meningococcal Infection ................................................................39
2.2.1.2.
Identified Risk of Liver Enzyme Elevations ..............................................................39
2.2.1.3.
Coronavirus Disease 2019 ..........................................................................................39
2.2.2.
Benefit Assessment .....................................................................................................40
2.2.2.1.
Unmet Need ................................................................................................................40
2.2.2.2.
Route of Administration .............................................................................................40
2.2.3.
Overall Benefit: Risk Conclusion ...............................................................................41
3.
OBJECTIVES AND ENDPOINTS ............................................................................42
4.
STUDY DESIGN .......................................................................................................46
4.1.
Overall Design ............................................................................................................46
4.2.
Scientific Rationale for Study Design ........................................................................47
4.2.1.
Study Eye and Fellow Eye ..........................................................................................48
4.2.2.
Study Duration ............................................................................................................48
4.2.3.
Outcome Measures .....................................................................................................48
Page 7 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
4.2.3.1.
Primary Outcomes: Square Root of GA Lesion Area ................................................48
4.2.3.2.
Secondary Outcomes: Anatomical and Functional Outcomes ...................................49
4.2.3.3.
Exploratory Outcomes ................................................................................................49
4.2.3.4.
Patient Reported Outcomes ........................................................................................49
4.2.4.
Patient Population .......................................................................................................50
4.3.
Justification for Dose ..................................................................................................50
4.4.
Definitions of Study Periods and End of Study ..........................................................50
5.
STUDY POPULATION .............................................................................................52
5.1.
Inclusion Criteria ........................................................................................................52
5.1.1.
General Inclusion Criteria ...........................................................................................52
5.1.2.
Ocular Inclusion Criteria ............................................................................................52
5.2.
Exclusion Criteria .......................................................................................................53
5.2.1.
Ocular Exclusion Criteria ...........................................................................................53
5.2.2.
General Exclusion Criteria .........................................................................................54
5.3.
Microperimetry Eligibility Criteria .............................................................................55
5.4.
Lifestyle Considerations .............................................................................................55
5.4.1.
Meals and Dietary Restrictions ...................................................................................55
5.5.
Screen Failures ............................................................................................................55
6.
STUDY INTERVENTION ........................................................................................56
6.1.
Study Intervention Administered ................................................................................56
6.1.1.
Study Drug Administration.........................................................................................56
6.1.2.
Dose Tapering .............................................................................................................57
6.1.3.
Study Drug Packaging and Labeling ..........................................................................58
6.2.
Preparation/Handling/Storage/Accountability ............................................................58
6.3.
Measures to Minimize Bias: Randomization and Masking ........................................59
6.3.1.
Randomization and Stratification ...............................................................................59
6.3.2.
Masking ......................................................................................................................60
6.3.3.
Unmasking ..................................................................................................................60
6.4.
Study Intervention Compliance ..................................................................................61
6.5.
Prior and Concomitant Therapies ...............................................................................61
6.5.1.
Allowed Medications ..................................................................................................62
6.5.1.1.
Vaccines ......................................................................................................................62
6.5.2.
Disallowed Medications and Therapy ........................................................................63
Page 8 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
6.6.
Dose Modification and Interruptions ..........................................................................63
6.6.1.
Switching to Optimal Dose .........................................................................................63
6.6.2.
Missed Doses ..............................................................................................................63
6.6.3.
Dose Interruptions ......................................................................................................63
6.6.4.
Permanent Dose Discontinuation ...............................................................................64
7.
DISCONTINUATION OF STUDY DRUG AND PATIENT
DISCONTINUATION/WITHDRAWAL ..................................................................65
7.1.
Discontinuation of Study Drug ...................................................................................65
7.2.
Patient Discontinuation/Withdrawal from the Study ..................................................66
7.3.
Lost to Follow-up .......................................................................................................66
7.4.
Intervention After the End of the Study .....................................................................67
8.
STUDY ASSESSMENTS AND PROCEDURES ......................................................68
8.1.
Screening ....................................................................................................................68
8.1.1.
General Screening .......................................................................................................68
8.1.2.
Ocular Screening ........................................................................................................69
8.2.
Efficacy Assessments .................................................................................................70
8.2.1.
Primary Efficacy Assessment .....................................................................................70
8.2.2.
Secondary Efficacy Assessments ...............................................................................71
8.2.2.1.
Anatomical Measures .................................................................................................71
8.2.2.2.
Functional Measures ...................................................................................................72
8.2.2.3.
Patient Reported Outcomes ........................................................................................72
8.2.3.
Exploratory Efficacy Assessments .............................................................................72
8.2.3.1.
GA Lesion Area by SD-OCT .....................................................................................72
8.2.3.2.
Mesopic Microperimetry ............................................................................................72
8.2.3.3.
Disease Conversion ....................................................................................................73
8.2.3.4.
Drusen Volume ...........................................................................................................73
8.3.
Safety Assessments .....................................................................................................74
8.3.1.
Physical Examinations ................................................................................................74
8.3.2.
Vital Signs ..................................................................................................................74
8.3.3.
Electrocardiograms .....................................................................................................74
8.3.4.
Clinical Safety Laboratory Assessments ....................................................................74
8.3.4.1.
Blood Collection .........................................................................................................74
8.3.4.2.
Abnormalities .............................................................................................................75
Page 9 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
8.3.5.
Pregnancy and Contraception .....................................................................................75
8.3.6.
Patient Safety Card .....................................................................................................75
8.3.7.
Monitoring for Neovascular AMD Development.......................................................76
8.4.
Adverse Events and Serious Adverse Events .............................................................76
8.4.1.
Time Period and Frequency for Collecting AE and SAE Information .......................76
8.4.2.
Method of Detecting AEs and SAEs ..........................................................................76
8.4.3.
Follow-up of AEs and SAEs .......................................................................................77
8.4.4.
Regulatory Reporting Requirements for SAEs ...........................................................77
8.4.5.
Medication Error, Drug Abuse, and Drug Misuse ......................................................77
8.4.5.1.
Timelines ....................................................................................................................77
8.4.5.2.
Medication Error .........................................................................................................77
8.4.5.3.
Drug Abuse .................................................................................................................78
8.4.5.4.
Drug Misuse ................................................................................................................78
8.5.
Treatment of Overdose ...............................................................................................78
8.6.
Pharmacokinetics ........................................................................................................78
8.7.
Pharmacodynamics .....................................................................................................79
8.8.
Genetics ......................................................................................................................79
8.9.
Exploratory Biomarkers ..............................................................................................79
8.10.
Health Related Quality of Life and Activities of Daily Living Assessments .............80
8.10.1.
National Eye Institute 25-item Visual Function Questionnaire ..................................80
8.10.2.
EuroQol 5-Dimensions 5-Level ..................................................................................80
8.10.3.
Lawton Instrumental Activities of Daily Living ........................................................81
9.
STATISTICAL CONSIDERATIONS .......................................................................82
9.1.
Statistical Hypotheses .................................................................................................82
9.1.1.
Primary Hypothesis ....................................................................................................82
9.2.
Sample Size Determination ........................................................................................82
9.3.
Populations for Analyses ............................................................................................82
9.4.
Statistical Analyses .....................................................................................................83
9.4.1.
Enrollment and Disposition ........................................................................................83
9.4.2.
Demographics, Baseline Characteristics, Inclusion and Exclusion Criteria, 
and Protocol Deviations ..............................................................................................83
9.4.3.
Medical/Surgical History, Physical Examination .......................................................83
9.4.4.
Prior and Concomitant Medications ...........................................................................84
Page 10 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
9.4.5.
Efficacy Analyses .......................................................................................................84
9.4.5.1.
Analyses of Primary Efficacy Endpoint .....................................................................84
9.4.5.2.
Analyses of Secondary Efficacy Endpoint(s) .............................................................85
9.4.5.3.
Multiplicity Adjustment..............................................................................................87
9.4.5.4.
Analyses of Exploratory Endpoint(s) .........................................................................88
9.4.6.
Safety Analyses ..........................................................................................................88
9.4.7.
PK/PD Analyses .........................................................................................................88
9.5.
Interim Analyses .........................................................................................................89
9.5.1.
Interim Analysis 1 .......................................................................................................89
9.5.2.
Interim Analysis 2 .......................................................................................................89
9.6.
Data Monitoring Committee .......................................................................................90
10.
SUPPORTING DOCUMENTATION AND OPERATIONAL
CONSIDERATIONS ..................................................................................................91
10.1.
Regulatory, Ethical, and Study Oversight Considerations .........................................91
10.1.1.
Regulatory and Ethical Considerations ......................................................................91
10.1.2.
Financial Disclosure ...................................................................................................93
10.1.3.
Informed Consent Process ..........................................................................................93
10.1.4.
Recruitment Strategy ..................................................................................................94
10.1.5.
Data Protection ...........................................................................................................94
10.1.6.
Dissemination of Clinical Study Data ........................................................................95
10.1.7.
Data Quality Assurance ..............................................................................................96
10.1.8.
Source Documents ......................................................................................................96
10.1.9.
Study and Site Start and Closure ................................................................................97
10.1.10.
Publication Policy .......................................................................................................98
10.1.11.
Good Clinical Practice Compliance............................................................................99
10.2.
Disease Classification of Age-Related Macular Degeneration ................................101
10.3.
Ocular Assessments ..................................................................................................103
10.3.1.
Best-Corrected Visual Acuity Testing ......................................................................103
10.3.2.
Low Luminance Best-Corrected Visual Acuity Testing ..........................................103
10.3.3.
Reading Speed Testing .............................................................................................103
10.3.3.1.
Minnesota Low-Vision Reading Test (MNRead) .....................................................103
10.3.3.2.
Radner Reading Cards ..............................................................................................104
10.3.4.
Mesopic Microperimetry at Selected Sites ...............................................................104
Page 11 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
10.3.5.
Slit-lamp Examination ..............................................................................................104
10.3.6.
Tonometry/Intraocular Pressure ...............................................................................104
10.3.7.
Dilated Binocular Indirect High-Magnification Ophthalmoscopy ...........................105
10.3.8.
Ocular Imaging Assessments ....................................................................................105
10.3.9.
Biometry ...................................................................................................................106
10.4.
Patient-Reported Outcome Instruments ....................................................................106
10.4.1.
National Eye Institute 25-Item Visual Function Questionnaire ...............................106
10.4.2.
EuroQol 5-Dimension 5-Level .................................................................................106
10.4.3.
Lawton Instrumental Activities of Daily Living Scale .............................................106
10.5.
Clinical Laboratory Tests .........................................................................................107
10.6.
Adverse Events: Definitions and Procedures for Recording, Evaluating, 
Follow-up, and Reporting .........................................................................................109
10.6.1.
Definition of AE .......................................................................................................109
10.6.2.
Definition of SAE .....................................................................................................110
10.6.3.
Recording and Follow-Up of AE and/or SAE ..........................................................111
10.6.4.
Reporting of SAEs ....................................................................................................113
10.6.5.
Unexpected Events ...................................................................................................113
10.7.
Medication Error, Drug Abuse, and Drug Misuse ....................................................115
10.8.
Contraceptive Guidance and Collection of Pregnancy Information .........................117
10.8.1.
Definitions ................................................................................................................117
10.8.2.
Contraception Guidance for Female Patients ...........................................................117
10.8.3.
Contraception Guidance for Male Patients ...............................................................117
10.8.3.1.
Guidance for Male Patients ......................................................................................117
10.8.3.2.
Sexual Abstinence for Male Patients ........................................................................118
10.8.4.
Collection of Pregnancy Information .......................................................................118
10.8.4.1.
Male Patients with Partners Who Become Pregnant ................................................118
10.9.
Allowed Medications ................................................................................................119
10.10.
Handling of Human Biological Samples ..................................................................120
10.10.1.
Chain of Custody ......................................................................................................120
10.10.2.
Withdrawal of Informed Consent for Donated Biological Samples .........................120
10.11.
COVID-19 Risk Assessment ....................................................................................122
10.12.
COVID-19 Vaccine Risk Assessment ......................................................................124
10.13.
Abbreviations ............................................................................................................125
Page 12 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
10.14.
Protocol Amendment History ...................................................................................129
11.
REFERENCES .........................................................................................................131
Page 13 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
LIST OF TABLES 
Table 1:
Schedule of Activities for Screening and the Primary Evaluation Period (Up 
to Week 52) .................................................................................................................22
Table 2:
Schedule of Activities for the Secondary Evaluation Period (Week 52 to 
Week 104) and Optimal Dose Transition ...................................................................27
Table 3:
Schedule of Activities for Early Termination, Taper, and Follow-up ........................31
Table 4:
Pharmacokinetic and Pharmacodynamic Blood Sampling During the 
Primary Evaluation Period (Up to Week 52) ..............................................................35
Table 5:
Potential and Identified Risks and Mitigation Strategies ...........................................38
Table 6:
Study Design Rationale for ALXN2040-GA-201 ......................................................47
Table 7:
Study Drugs ................................................................................................................56
Table 8:
Masked Study Drug Administration Weeks 1 to 104 .................................................57
Table 9:
Study Drug Taper Schedule ........................................................................................58
Table 10:
Analysis Sets ...............................................................................................................82
Table 11:
Clinical Classification of AMD ................................................................................101
Table 12:
Protocol-Required Laboratory Assessments.............................................................107
Table 13:
List of CYP3A4, P-gp, and UGT1A1/2B7 Sensitive Substrates ..............................119
Table 14:
Potential Risks and Mitigation Measures due to COVID-19 ...................................122
Table 15:
Potential Risks and Mitigation Measures due to COVID-19 Vaccine .....................124
Table 16:
Abbreviations and Specialist Terms .........................................................................125
LIST OF FIGURES 
Figure 1:
Study Design and Schematic ......................................................................................21
Page 14 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
1.
PROTOCOL SUMMARY
1.1. 
Synopsis
Protocol Title: A Phase 2, Double-Masked, Placebo-Controlled, Dose Range Finding Study of 
Danicopan (ALXN2040) in Patients with Geographic Atrophy (GA) Secondary to Age-Related 
Macular Degeneration (AMD)  
Short Title: Proof of concept and dose-finding study of danicopan in patients with geographic 
atrophy secondary to AMD 
Regulatory Agency Identifier: 
IND: 153070 
EudraCT: 2021-001198-22 
EU CT: 2023-508571-37 
NCT: NCT05019521 
Rationale: This proof of concept (POC) dose-finding study is designed to evaluate the efficacy, 
safety, and pharmacokinetics (PK) of danicopan in patients with geographic atrophy (GA) 
secondary to AMD. 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
•
To evaluate the effect of
different dosage regimens of
danicopan on the progression
of GA secondary to AMD
compared to placebo
•
Change from Baseline to Week 52 in the square root (sqrt) of
total GA lesion area (mm) in the study eye* as measured by
fundus autofluorescence (FAF)
*All patients will undergo monocular test on both eyes. The study eye
is the eye that meets eligibility criteria. If both eyes are eligible, the
right eye is taken as the study eye.
Secondary 
•
To evaluate the effect of
danicopan on disease
progression utilizing
anatomical measures in the
study eye
•
Change from Baseline to Week 104 in the sqrt of the total GA
lesion area (mm) in the study eye as measured by FAF
•
Change from Baseline to Week 52 and Week 104 in the total
GA lesion area (mm2) in the study eye as measured by FAF
Page 15 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Objectives 
Endpoints 
•
Change from Baseline to Week 52 and Week 104 in macular
ellipsoid zone (EZ) and outer retinal integrity in the study
eye, the fellow eye, and both eyes combined as measured by
SD-OCT
•
Change from Baseline to Week 52 and Week 104 in
subretinal pigment epithelium (sub-RPE)
compartment/drusen/RPE complex in the study eye, fellow
eye and both eyes combined as measured by SD-OCT
•
To evaluate the effect of
danicopan on disease
progression utilizing
functional measures in the
study eye
•
Change from Baseline to Week 52 and Week 104 in
monocular best-corrected visual acuity (BCVA) scores in the
study eye as assessed by Early Treatment Diabetic
Retinopathy Study (ETDRS) chart
•
Change from Baseline to Week 52 and Week 104 in
monocular low luminance visual acuity (LLVA) scores in the
study eye as assessed by ETDRS chart
•
Change from Baseline to Week 52 and Week 104 in low
luminance deficit (BCVA-LLVA) in the study eye
•
Change from Baseline to Week 52 and Week 104 in
monocular reading speeds in the study eye as assessed by
Minnesota Low Vision Reading Test (MNRead) Acuity
Charts or Radner Reading Charts
•
To evaluate the effect of
danicopan on patient reported
outcomes (PROs) in patients
with GA secondary to AMD
•
Change from Baseline to Week 52 and Week 104 in National
Eye Institute Visual Function Questionnaire (NEI VFQ-25)
scores
•
To evaluate the PK and
pharmacodynamics (PD) of
danicopan in patients with GA
secondary to AMD
•
Plasma concentrations of danicopan over time
•
PD biomarkers, ex vivo serum AP activity, and plasma Bb
concentration over time
•
To evaluate the safety and
tolerability of danicopan in
patients with GA secondary to
AMD
•
Incidence of treatment-emergent adverse events (TEAEs),
serious adverse events (SAEs), and ocular TEAEs, SAEs, and
clinical laboratory abnormalities, and events leading to
discontinuation of study drug throughout the study
Page 16 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Objectives 
Endpoints 
Exploratory 
•
To evaluate the effect of
danicopan on health-related
quality of life and activities of
daily living
•
Change from Baseline to Week 52 and Week 104 in
EQ-5D-5L
•
Change from Baseline to Week 52 and Week 104 in Lawton
Instrumental Activities of Daily Living (IADL)
•
To evaluate the effect of
danicopan on disease
progression utilizing
exploratory anatomical
measures
•
Change from Baseline to Week 52 and Week 104 in the sqrt
of the total GA lesion area (mm) in fellow eye and both eyes
as measured by FAF
•
Change from Baseline to Week 52 and Week 104 in the total
GA lesion area (mm2) in fellow eye and both eyes as
measured by FAF
•
Percent change from Baseline to Week 52 and Week 104 in
the total GA lesion area (mm2) in the study eye, fellow eye
and both eyes combined as measured by FAF
•
Percent change from Baseline to Week 52 and Week 104 in
the sqrt of the total GA lesion area (mm) in the study eye,
fellow eye and both eyes combined as measured by FAF
•
Incidence of patients with conversion from incomplete to
complete retinal pigment epithelium and outer retinal atrophy
(iRORA to cRORA) from Baseline to Week 52 and
Week 104 in the study eye, fellow eye, either eye, and both
eyes combined using spectral domain optical coherence
tomography (SD-OCT) images
•
Incidence of patients with conversion from high-risk drusen
to late AMD from Baseline to Week 52 and Week 104 in the
study eye, fellow eye, either eye, and both eyes combined
using SD-OCT images
•
Incidence of patients with conversion from intermediate
AMD (iAMD) to late AMD from Baseline to Week 52 and
Week 104 in the study eye, fellow eye, either eye, and both
eyes combined using SD-OCT images
•
Number of conversions from iAMD to late AMD from
Baseline in the study eye, fellow eye, and both eyes combined
to Week 52 and Week 104
•
Change from Baseline to Week 52 and Week 104 in drusen
volume (mm3) in the fellow eye with early or iAMD as
measured by SD-OCT
Page 17 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Objectives 
Endpoints 
•
Change from Baseline to Week 52 and Week 104 in total GA
lesion area (mm2) and sqrt of the total GA lesion area (mm) in
the study eye, the fellow eye, and both eyes combined as
measured by SD-OCT
•
Percent change from Baseline to Week 52 and Week 104 in
the total GA lesion area (mm2) and sqrt of the total GA lesion
area (mm) in study eye, fellow eye and both eyes combined as
measured by SD-OCT
•
To evaluate the effect of
danicopan on disease
progression utilizing
exploratory functional
measures
•
Change from Baseline to Week 52 and Week 104 in BCVA
scores in the fellow eye as assessed by ETDRS chart
•
Change from Baseline to Week 52 and Week 104 in LLVA
scores in the fellow eye as assessed by ETDRS chart
•
Change from Baseline to Week 52 and Week 104 in low
luminance deficit (BCVA-LLVA) in the fellow eye
•
Change from Baseline to Week 52 and Week 104 in binocular
BCVA scores as assessed ETDRS chart
•
Change from Baseline to Week 52 and Week 104 in binocular
LLVA scores as assessed by ETDRS chart
•
Change from Baseline to Week 52 and Week 104 in binocular
low luminance deficit (BCVA-LLVA)
•
Change from Baseline to Week 52 and Week 104 in
monocular reading speeds in fellow eye as assessed by
MNRead Acuity Charts or Radner Reading Charts
•
Change from Baseline to Week 52 and Week 104 in binocular
reading speeds as assessed by MNRead Acuity Charts or
Radner Reading Charts
•
Number of scotomatous points assessed by mesopic
microperimetry for the evaluation of the macular functional
response in study eye, fellow eye, and both eyes combined at
Week 52 and Week 104a
•
Incidence of patients with predefined change in any
predefined grid pattern by mesopic microperimetry in the
study eye, fellow eye, and both eyes combined.
Page 18 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Objectives 
Endpoints 
•
To evaluate the effect of
optimal danicopan dose on
disease progression at the end
of delayed-start period
(Week 104) compared to the
end of early-start period
(Week 52) for the study eye
•
Change from Baseline to Week 52 and Week 104 in the sqrt
of the total GA lesion area (mm) in the study eye as measured
by FAF
•
To evaluate exploratory PD
biomarkers
•
Concentrations of exploratory biomarkers over time,
including serum CP activity and serum (or plasma) C3 and
FD concentrations
a Microperimetry endpoints will be assessed in the microperimetry subpopulation 
Abbreviations: AMD = age-related macular degeneration; AP = alternative pathway; Bb = Bb fragment of complement factor B; 
BCVA = best-corrected visual acuity; C3 = complement component 3; CP = classical pathway; cRORA = complete retinal 
pigment epithelium and outer retinal atrophy; EQ-5D-5L = EuroQol 5-dimension 5-level questionnaire; ETDRS = Early 
Treatment Diabetic Retinopathy Study; EZ = ellipsoid zone; FAF = fundus autofluorescence; FD = factor D; GA = geographic 
atrophy; IADL = Instrumental Activities of Daily Living; iAMD = intermediate age-related macular degeneration; 
iRORA = incomplete retinal pigment epithelium and outer retinal atrophy; LLVA = low luminance visual acuity; 
MNRead = Minnesota Low Vision Reading Test; NEI VFQ-25 = National Eye Institute Visual Function Questionnaire, 25-
item version; PD = pharmacodynamic(s); PK = pharmacokinetic(s); PRO = patient reported outcome; RPE = retinal pigment 
epithelium; SAE = serious adverse event; sqrt = square root; SD-OCT = spectral-domain optical coherence tomography; 
TEAE = treatment-emergent adverse event 
Overall Design: 
This is a multicenter Phase 2, randomized, double-masked, placebo-controlled, dose-finding, 
parallel-group study to evaluate the efficacy, safety, and PK of danicopan compared to placebo 
in patients ≥ 60 years with GA secondary to AMD. Eligible patients will be randomized (1:1:1:1) 
with stratification to 1 of 4 treatment groups (3 active treatment groups and 1 placebo group). 
The primary efficacy analysis will be performed when all patients complete the Week 52 Visit or 
discontinued. Secondary efficacy and safety analyses, and exploratory analyses will be 
performed when all patients complete the Week 104 Visit or discontinue.  
There are 2 potential interim analyses (IA) planned for this study. The first interim analysis (IA1) 
for futility may be conducted when approximately 50% patients have completed the Week 28 
Visit. The second interim analysis (IA2) may be conducted when approximately 50% of patients 
complete Week 52 Visit. At IA2, a futility analysis will be conducted first. If the study is not 
considered futile, dose response analysis will be performed. If the dose response analysis is 
positive, a pair-wise comparison of each dose compared to placebo will be conducted.  
A dose with the optimal benefit-risk profile could be identified at the IA2 or primary analysis for 
Phase 3 development. Placebo patients will be re-randomized to one of the 3 active treatment 
groups at Week 52, or switched to the optimal dose, if already identified. If an optimal dose is 
identified, all patients who have at least 52 weeks of treatment on their originally assigned dose 
will be switched to the selected optimal dose for the remainder of the study. Masked treatment 
paradigm will be maintained throughout the study.  
Disclosure Statement: This is a Phase 2, placebo-controlled, double-masked, parallel-treatment 
study. 
Page 19 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Number of Patients: Approximately 332 patients aged ≥ 60 years will be enrolled, with 
83 patients per dose group. 
Intervention Groups and Duration: 
This study has 4 treatments arms: 100 mg twice daily (bid) dose group, 200 mg bid dose group, 
400 mg once daily (qd) dose group, and a placebo group. The study consists of a Screening 
Period of up to 6 weeks and a Masked Treatment Period (approximately 2 years). Treatment ends 
with a 6-day Taper, followed by a Follow-up Visit 30 days after the last taper dose. The potential 
total study duration per patient is approximately 115 weeks.  
Data Monitoring Committee: Yes 
Ethical Considerations and Benefit-Risk Assessment 
This study will be conducted as specified in this protocol and in accordance with the following: 
•
Consensus ethical principles derived from international guidelines including the
Declaration of Helsinki and Council for International Organizations of Medical
Sciences (CIOMS) International Ethical Guidelines
•
Applicable ICH Good Clinical Practice (GCP) Guidelines
•
Applicable laws and regulations
A thorough benefit-risk assessment has been performed for danicopan. Measures will be taken to 
minimize risk to study participants. The potential risks identified in association with danicopan 
are justified by the anticipated benefits that may be afforded to participants with GA secondary 
to AMD. 
Page 20 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
1.2. 
Study Schema 
Figure 1: 
Study Design and Schematic 
a The futility analysis (interim analysis 1 [IA1]) may be conducted when approximately 50% patients complete 
Week 28 Visit.  
b The futility and dose-response analyses (interim analysis 2 [IA2] may be conducted when approximately 50% 
patients complete Week 52 Visit. If the dose-response is positive, pairwise comparisons will be performed at IA2. 
c Placebo patients will be transitioned after 52 weeks to the optimal dose, or, if not identified, will be re-randomized 
at Week 52 to 1 of the active treatment groups until the optimal dose has been determined. 
Abbreviations: bid = twice daily; EOS = end of study; IA = interim analysis; qd = once daily 
Page 21 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
1.3. 
Schedule of Activities 
Table 1: 
Schedule of Activities for Screening and the Primary Evaluation Period (Up to Week 52) 
Procedure 
Screening 
Primary Evaluation Period (Masked Treatment) 
Notes 
Visit 
Up to 6 
weeks 
1 
2 
3 
4 
5 
6 
7 
8 
X = in-clinic visit; 
HV = home visit by VHS; 
HV may be turned into in-clinic 
visit per agreement between patient 
and site but following the same HV 
assessments. 
Weeks 
-6 to 0
2 
4 
8 
16 
28 
40 
52 
Days and Window 
-42 to -1
1 
15 
± 2 
29 
± 4 
57 
± 4 
113 
± 4 
197 
± 4 
281 
± 4 
365 
± 4 
Visit Type 
X 
X 
HV 
X 
X 
X 
X 
X 
X 
Informed consent 
X 
To be obtained before any study-
related procedures are performed 
Inclusion and exclusion 
criteria 
X 
X 
Eligibility to be confirmed prior to 
randomization. See Section 5 
Randomization 
X 
Demography 
X 
Full PE including height and 
weight 
X 
X 
X 
X 
Height only required at Screening 
Abbreviated PE 
X 
X 
X 
X 
Abbreviated PE = a targeted PE 
that includes, at a minimum, body 
system relevant examination based 
on Investigator judgement and 
patient symptoms 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Medical history 
X 
Prior and current medications 
X 
X 
FSH for females 
X 
Screening tests for HIV, HBV, 
HCV 
X 
Page 22 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Table 1: 
Schedule of Activities for Screening and the Primary Evaluation Period (Up to Week 52) 
Procedure 
Screening 
Primary Evaluation Period (Masked Treatment) 
Notes 
Visit 
Up to 6 
weeks 
1 
2 
3 
4 
5 
6 
7 
8 
X = in-clinic visit; 
HV = home visit by VHS; 
HV may be turned into in-clinic 
visit per agreement between patient 
and site but following the same HV 
assessments. 
Weeks 
-6 to 0
2 
4 
8 
16 
28 
40 
52 
Days and Window 
-42 to -1
1 
15 
± 2 
29 
± 4 
57 
± 4 
113 
± 4 
197 
± 4 
281 
± 4 
365 
± 4 
Visit Type 
X 
X 
HV 
X 
X 
X 
X 
X 
X 
Vaccination or confirmation 
of vaccination against 
Neisseria meningitidis
X 
< -----------------------continuous monitoring --------------------------- 
See Section 6.5.1.1 
Laboratory assessments 
(including chemistry, 
hematology, urinalysis, and 
LFTs)  
X 
X 
X 
X 
X 
X 
X 
X 
X 
VHS will collect blood samples at 
HV. 
PK 
X 
X 
X 
X 
X 
X 
PK samples will be collected 
predose, and 2 h postdose for all 
visits except for Week 4. For 
Week 4, PK samples should be 
collected on predose, 2 h, and 4 h 
post dose.  
PD (Bb and AP activity) 
X 
X 
X 
X 
X 
X 
AP activity samples will be 
collected at the same time points as 
PK samples; Bb samples will be 
collected at predose; at ET; Bb and 
AP activity samples will be 
collected once.  
Biomarkers 
X 
X 
X 
X 
X 
X 
Biomarkers will be collected 
predose and also once at ET 
Genetic samples (optional) 
X 
12-lead ECG
X 
X 
Single tracing 
Drug dispensing 
X 
X 
X 
X 
X 
X 
X 
At each clinic visit, site should 
ensure patient has sufficient study 
drug till their next clinic visit 
Page 23 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Table 1: 
Schedule of Activities for Screening and the Primary Evaluation Period (Up to Week 52) 
Procedure 
Screening 
Primary Evaluation Period (Masked Treatment) 
Notes 
Visit 
Up to 6 
weeks 
1 
2 
3 
4 
5 
6 
7 
8 
X = in-clinic visit; 
HV = home visit by VHS; 
HV may be turned into in-clinic 
visit per agreement between patient 
and site but following the same HV 
assessments. 
Weeks 
-6 to 0
2 
4 
8 
16 
28 
40 
52 
Days and Window 
-42 to -1
1 
15 
± 2 
29 
± 4 
57 
± 4 
113 
± 4 
197 
± 4 
281 
± 4 
365 
± 4 
Visit Type 
X 
X 
HV 
X 
X 
X 
X 
X 
X 
Drug accountability 
X 
X 
X 
X 
X 
X 
X 
Patients are instructed to bring 
their study drugs at each clinic visit 
AE/SAE monitoring 
< ------------------------------- continuous monitoring ------------------------------------- > 
Continuous monitoring of 
AE/SAEs (including pregnancy in 
female partners of male patients) 
starts at time of signing the ICF 
and continues until EOS 
Medication error, drug abuse 
and misuse 
< ------------------------------- continuous monitoring ------------------------------------- > 
See Section 8.4.5 and Section 10.7. 
Monitoring started with PA 2.0 
Concomitant medications 
monitoring 
< --------------------------------- continuous monitoring ----------------------------------- > 
Continuous monitoring (reporting 
of concomitant medications) starts 
at time of signing the ICF and 
continues until EOS 
Review patient safety card 
< -------------------------------- continuous monitoring ------------------------------------ > 
Patients to carry card at all times 
PATIENT-REPORTED OUTCOMES 
All PROs and QoL assessments 
should be completed as early as 
possible during visits, before 
ocular assessments 
NEI VFQ-25 
X 
X 
X 
X 
X 
EQ-5D-5L 
X 
X 
X 
X 
X 
Lawton IADL 
X 
X 
X 
X 
X 
Page 24 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Table 1: 
Schedule of Activities for Screening and the Primary Evaluation Period (Up to Week 52) 
Procedure 
Screening 
Primary Evaluation Period (Masked Treatment) 
Notes 
Visit 
Up to 6 
weeks 
1 
2 
3 
4 
5 
6 
7 
8 
X = in-clinic visit; 
HV = home visit by VHS; 
HV may be turned into in-clinic 
visit per agreement between patient 
and site but following the same HV 
assessments. 
Weeks 
-6 to 0
2 
4 
8 
16 
28 
40 
52 
Days and Window 
-42 to -1
1 
15 
± 2 
29 
± 4 
57 
± 4 
113 
± 4 
197 
± 4 
281 
± 4 
365 
± 4 
Visit Type 
X 
X 
HV 
X 
X 
X 
X 
X 
X 
OCULAR ASSESSMENTS 
Ocular assessments are to be 
performed on both eyes (OU); tests 
that do not need pupil dilation 
should be done first 
BCVA testing on ETDRS 
chart (starting at 4 m) 
X 
X 
X 
X 
X 
X 
X 
Non-dilated, to be administered 
first monocularly (right/left eye) 
and then binocularly (both eyes). 
LL BCVA testing on ETDRS 
chart (starting at 4 m) 
X 
X 
X 
Non-dilated, to be administered 
first monocularly (right/left eye) 
and then binocularly (both eyes). 
Reading Speed (MNRead or 
Radner Reading Charts)a 
X 
X 
X 
Non-dilated, to be administered 
first monocularly (right/left eye) 
and then binocularly (both eyes). 
Mesopic microperimetryb 
Xc 
X 
X 
Non-dilated, only in 
microperimetry subpopulation 
Slit lamp examination 
X 
X 
X 
X 
X 
X 
X 
Tonometry/IOP 
X 
X 
X 
X 
X 
X 
X 
Goldmann applanation tonometry 
must be used at Screening. Tono-
pen or other calibrated tonometers 
can be used at other times. IOP 
measurement recommended prior 
to dilation. Goldmann applanation 
tonometry must also be used to 
verify the reading of ≥ 30 mmHg 
occurring at any time. 
Page 25 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Table 1: 
Schedule of Activities for Screening and the Primary Evaluation Period (Up to Week 52) 
Procedure 
Screening 
Primary Evaluation Period (Masked Treatment) 
Notes 
Visit 
Up to 6 
weeks 
1 
2 
3 
4 
5 
6 
7 
8 
X = in-clinic visit; 
HV = home visit by VHS; 
HV may be turned into in-clinic 
visit per agreement between patient 
and site but following the same HV 
assessments. 
Weeks 
-6 to 0
2 
4 
8 
16 
28 
40 
52 
Days and Window 
-42 to -1
1 
15 
± 2 
29 
± 4 
57 
± 4 
113 
± 4 
197 
± 4 
281 
± 4 
365 
± 4 
Visit Type 
X 
X 
HV 
X 
X 
X 
X 
X 
X 
Dilated binocular indirect 
ophthalmoscopy 
X 
X 
X 
X 
X 
X 
X 
FAF 
X 
X 
X 
X 
X 
X 
X 
Recommended order of imaging is 
FAF, NIR, SD-OCT, FA, CFP. 
Administration of artificial tears 
between acquisition of each eye for 
FAF/NIR and SD-OCT is 
recommended. 
NIR 
X 
X 
X 
X 
X 
X 
X 
SD-OCT 
X 
X 
X 
X 
X 
X 
X 
Fluorescein angiography 
X 
X 
X 
CFP 
X 
X 
X 
Biometry (if available)d 
X 
a Reading speeds will only be assessed if charts are available in the local language. 
b Microperimetry should be performed prior to any imaging.  
c Microperimetry should be carried out twice per eye during Screening. 
d Biometry should be performed if the site has the equipment; otherwise, spherical equivalent refractive error should be determined. 
Abbreviations: AE = adverse event; AP = alternative pathway; Bb = Bb fragment of complement factor B; BCVA = best-corrected visual acuity; CFP = color fundus photography; 
ECG = electrocardiogram; ETDRS = Early Treatment Diabetic Retinopathy Study; EOS = end of study; EQ-5D -5L = EuroQol 5-dimension 5-level questionnaire; ET = early 
termination; FA = fluorescein angiography; FAF = fundus autofluorescence; FSH = follicle stimulating hormone; h = hour; HBV = hepatitis B virus; HCV = hepatitis C virus; 
HIV = human immunodeficiency virus; HV = home visit; IADL = Instrumental Activities of Daily Living; ICF = informed consent form; IOP = intraocular pressure; LFT = liver 
function test; LL BCVA= low luminance best-corrected visual acuity; MNRead = Minnesota Low-Vision Reading Test; NEI VFQ-25 = National Eye Institute Visual Function 
Questionnaire, 25-item version; NIR = near infrared reflectance; OU = oculus uterque/both eyes; PA = protocol amendment; PD = pharmacodynamic; PE = physical 
examination; PK = pharmacokinetics; PRO = patient-reported outcome; QoL = quality of life; SAE = serious adverse event; SD-OCT = spectral domain optical coherence 
tomography; VHS = visiting health service  
Page 26 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Table 2: 
Schedule of Activities for the Secondary Evaluation Period (Week 52 to Week 104) and Optimal Dose 
Transition 
Procedure 
Secondary Evaluation Period (Masked Treatment) 
Weeks 52 to 104 
Optimal Dose Transitiona
After Week 52 
Notes 
Visit 
9 
10 
11 
12 
13 
14 
15 
X = in-clinic visit; 
HV = home visit by VHS 
HV may be turned into in-clinic 
visit per agreement between 
patient and site but following the 
same HV assessments. 
Weeks 
54 
56 
60 
68 
80 
92 
104 
Opti
mal 
Dose 
+2
+4
+8
Days and Window 
379 
±2 
393 
±4 
421 
±4 
477±4 
561±4 
645±4 
729 
±4 
±2 
±4 
±4 
Visit Type 
HV 
X 
X 
X 
X 
X 
X 
X 
HV 
X 
X 
Full PE including weight 
X 
X 
X 
X 
X 
Abbreviated PE 
X 
X 
X 
Abbreviated PE = a targeted PE 
that includes, at a minimum, body 
system relevant examination 
based on Investigator judgement 
and patient symptoms. 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
N meningitidis
vaccination status 
assessment/ vaccination, 
if needed 
< -------------------continuous monitoring ------------------------- > 
< -continuous monitoring- >
See Section 6.5.1.1 
Laboratory assessments 
(including chemistry, 
hematology, urinalysis, 
and LFTs) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
VHS will collect blood samples at 
HV. 
12-lead ECG
X 
Drug dispensing 
X 
X 
X 
X 
X 
X 
At each clinic visit, site should 
ensure patient has sufficient study 
drug till their next clinic visit 
Drug accountability 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Patients are instructed to bring 
their study drugs at each clinic 
visit 
Page 27 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Table 2: 
Schedule of Activities for the Secondary Evaluation Period (Week 52 to Week 104) and Optimal Dose 
Transition 
Procedure 
Secondary Evaluation Period (Masked Treatment) 
Weeks 52 to 104 
Optimal Dose Transitiona
After Week 52 
Notes 
Visit 
9 
10 
11 
12 
13 
14 
15 
X = in-clinic visit; 
HV = home visit by VHS 
HV may be turned into in-clinic 
visit per agreement between 
patient and site but following the 
same HV assessments. 
Weeks 
54 
56 
60 
68 
80 
92 
104 
Opti
mal 
Dose 
+2
+4
+8
Days and Window 
379 
±2 
393 
±4 
421 
±4 
477±4 
561±4 
645±4 
729 
±4 
±2 
±4 
±4 
Visit Type 
HV 
X 
X 
X 
X 
X 
X 
X 
HV 
X 
X 
AE/SAE monitoring 
< -------------------continuous monitoring ------------------------- > 
< -continuous monitoring- >
Concomitant medications 
monitoring 
< -------------------continuous monitoring ------------------------- > 
< -continuous monitoring- >
Medication error, drug 
abuse and misuse 
< -------------------continuous monitoring ------------------------- > 
< -continuous monitoring- >
See Section 8.4.5 and 
Section 10.7; Monitoring started 
with PA 2.0 
Review patient safety 
card 
< -------------------continuous monitoring ------------------------- > 
< -continuous monitoring- >
Patients to carry card at all times 
PATIENT REPORTED OUTCOMES 
All PROs and QoL assessments 
should be completed as early as 
possible during visits, before 
ocular assessments 
NEI VFQ-25 
X 
X 
X 
EQ-5D-5L 
X 
X 
X 
Lawton IADL 
X 
X 
X 
OCULAR ASSESSMENTS 
Ocular assessments are to be 
performed on both eyes (OU); 
tests that do not need pupil 
dilation should be done first 
BCVA testing on 
ETDRS chart’(starting at 
4 m) 
X 
X 
X 
X 
X 
Non-dilated, the test will be 
administered first monocularly 
(right/left eye) and then 
binocularly (both eyes). 
Page 28 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Table 2: 
Schedule of Activities for the Secondary Evaluation Period (Week 52 to Week 104) and Optimal Dose 
Transition 
Procedure 
Secondary Evaluation Period (Masked Treatment) 
Weeks 52 to 104 
Optimal Dose Transitiona
After Week 52 
Notes 
Visit 
9 
10 
11 
12 
13 
14 
15 
X = in-clinic visit; 
HV = home visit by VHS 
HV may be turned into in-clinic 
visit per agreement between 
patient and site but following the 
same HV assessments. 
Weeks 
54 
56 
60 
68 
80 
92 
104 
Opti
mal 
Dose 
+2
+4
+8
Days and Window 
379 
±2 
393 
±4 
421 
±4 
477±4 
561±4 
645±4 
729 
±4 
±2 
±4 
±4 
Visit Type 
HV 
X 
X 
X 
X 
X 
X 
X 
HV 
X 
X 
LL BCVA testing on 
ETDRS chart’(starting at 
4 m) 
X 
Non-dilated, the test will be 
administered first monocularly 
(right/left eye) and then 
binocularly (both eyes). 
Reading Speed (MNRead 
or Radner Reading 
Charts)b 
X 
Non-dilated, the test will be 
administered first monocularly 
(right/left eye) and then 
binocularly (both eyes). 
Mesopic microperimetryc 
X 
Non-dilated, only in 
microperimetry subpopulation 
Slit lamp examination 
X 
X 
X 
X 
X 
Dilated binocular indirect 
ophthalmoscopy 
X 
X 
X 
X 
X 
Tonometry/IOP 
X 
X 
X 
X 
X 
Tono-pen or other calibrated 
tonometers can be used. IOP 
measurement recommended prior 
to dilation. Goldmann applanation 
tonometry must also be used to 
verify the reading of ≥ 30 mmHg 
occurring at any time. 
FAF 
X 
X 
X 
X 
X 
Recommended order of imaging 
is FAF, NIR, SD-OCT, 
NIR 
X 
X 
X 
X 
X 
Page 29 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Table 2: 
Schedule of Activities for the Secondary Evaluation Period (Week 52 to Week 104) and Optimal Dose 
Transition 
Procedure 
Secondary Evaluation Period (Masked Treatment) 
Weeks 52 to 104 
Optimal Dose Transitiona
After Week 52 
Notes 
Visit 
9 
10 
11 
12 
13 
14 
15 
X = in-clinic visit; 
HV = home visit by VHS 
HV may be turned into in-clinic 
visit per agreement between 
patient and site but following the 
same HV assessments. 
Weeks 
54 
56 
60 
68 
80 
92 
104 
Opti
mal 
Dose 
+2
+4
+8
Days and Window 
379 
±2 
393 
±4 
421 
±4 
477±4 
561±4 
645±4 
729 
±4 
±2 
±4 
±4 
Visit Type 
HV 
X 
X 
X 
X 
X 
X 
X 
HV 
X 
X 
SD-OCT 
X 
X 
X 
X 
X 
fluorescein angiography, CFP. 
Administration of artificial tears 
between acquisition of each eye 
for FAF/NIR and SD-OCT is 
recommended. 
Fluorescein angiography 
X 
CFP 
X 
a If optimal dose is identified, all patients who have completed Week 52 will start the transition to the optimal dose at the next scheduled visit. See Section 6.6.1. 
b Reading speeds will only be assessed if charts are available in the local language. 
c Microperimetry should be performed prior to any imaging. 
Abbreviations: AE = adverse event; BCVA = best-corrected visual acuity; CFP = color fundus photography; ECG = electrocardiogram; ETDRS = Early Treatment Diabetic 
Retinopathy Study; EQ‑5D‑5L = EuroQol 5-dimension 5-level questionnaire; FAF = fundus autofluorescence; h = hours; HV = home visit; IADL= Instrumental Activities of 
Daily Living; IOP = intraocular pressure; LFT = liver function test; LL BCVA= low luminance best-corrected visual acuity; MNRead = Minnesota Low-Vision Reading Test; 
NEI VFQ-25 = National Eye Institute Visual Function Questionnaire, 25-item version; NIR = near infrared reflectance; PA = protocol amendment; PE = physical examination; 
OU = oculus uterque/both eyes; PRO = patient reported outcome; QoL = quality of life; SAE = serious adverse event; SD-OCT = spectral domain optical coherence tomography; 
VHS = visiting health service 
Page 30 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Table 3: 
Schedule of Activities for Early Termination, Taper, and Follow-up 
Un-
scheduled 
Visita 
Early 
Termination 
Taper 
6 daysb
Follow-up 
(EOS) 
30 days 
Notes 
Visit 
T1 
T2 
X = in-clinic visit; 
HV = home visit by VHS; HV may be turned into in-
clinic visit per agreement between patient and site but 
following the same HV assessments. 
Weeks 
Days and Window 
D1 to D3 
D4 to D6 
30 +7 post last 
dose 
Visit Type 
X 
X 
HV 
HV 
X 
Full physical examination 
including weight 
X 
X 
X 
Abbreviated PE 
Abbreviated PE = a targeted PE that includes, at a 
minimum, body system relevant examination based on 
Investigator judgement and patient symptoms 
Vital signs 
X 
X 
X 
N meningitidis vaccination
status assessment/ vaccination, 
if needed 
X 
X 
X 
X 
See Section 6.5.1.1 
Laboratory assessments 
(including chemistry, 
hematology, urinalysis, and 
LFTs) 
X 
X 
X 
VHS will collect blood samples at HV. 
PD (Bb and AP activity) 
X 
ET samples for PD and biomarkers only applicable for 
the first 52 weeks. No samples after Week 52. 
Biomarkers 
X 
12-lead ECG
X 
X 
Single tracing. 
Drug dispensing 
Xb 
Patients are provided with sufficient study drug to last 
until their next clinic visit. 
Drug accountability 
X 
X 
X 
X 
Patients are instructed to bring their study drugs at each 
visit. 
AE/SAE review 
X 
X 
X 
X 
X 
Page 31 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Table 3: 
Schedule of Activities for Early Termination, Taper, and Follow-up 
Un-
scheduled 
Visita 
Early 
Termination 
Taper 
6 daysb
Follow-up 
(EOS) 
30 days 
Notes 
Visit 
T1 
T2 
X = in-clinic visit; 
HV = home visit by VHS; HV may be turned into in-
clinic visit per agreement between patient and site but 
following the same HV assessments. 
Weeks 
Days and Window 
D1 to D3 
D4 to D6 
30 +7 post last 
dose 
Visit Type 
X 
X 
HV 
HV 
X 
Medication error, drug abuse 
and misuse 
X 
X 
X 
X 
X 
See Section 8.4.5 and Section 10.7; Monitoring started 
with PA 2.0 
Concomitant medications 
review 
X 
X 
X 
X 
X 
Review patient safety card 
X 
X 
X 
X 
X 
Patients to carry card at all times. 
PATIENT REPORTED OUTCOMES 
All PROs and QoL assessments should be completed as 
early as possible during visits. 
NEI VFQ-25 
X 
EQ-5D-5L 
X 
Lawton IADL 
X 
OCULAR ASSESSMENTS 
Ocular assessments are to be performed on both eyes 
(OU); tests that do not need pupil dilation should be 
done first. 
BCVA testing on ETDRS chart 
(starting at 4 m) 
X 
X 
Non-dilated, the test will be administered first 
monocularly (right/left eye) and then binocularly (both 
eyes). 
LL BCVA testing on ETDRS 
chart (starting at 4 m) 
X 
Non-dilated, the test will be administered first 
monocularly (right/left eye) and then binocularly (both 
eyes). 
Page 32 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Table 3: 
Schedule of Activities for Early Termination, Taper, and Follow-up 
Un-
scheduled 
Visita 
Early 
Termination 
Taper 
6 daysb
Follow-up 
(EOS) 
30 days 
Notes 
Visit 
T1 
T2 
X = in-clinic visit; 
HV = home visit by VHS; HV may be turned into in-
clinic visit per agreement between patient and site but 
following the same HV assessments. 
Weeks 
Days and Window 
D1 to D3 
D4 to D6 
30 +7 post last 
dose 
Visit Type 
X 
X 
HV 
HV 
X 
Reading Speed (MNRead or 
Radner Reading Charts)c  
X 
Non-dilated, the test will be administered first 
monocularly (right/left eye) and then binocularly (both 
eyes). 
Mesopic microperimetryd 
X 
Non-dilated; only in microperimetry subpopulation. 
Slit lamp examination 
X 
X 
Dilated binocular indirect 
ophthalmoscopy 
X 
X 
Tonometry/IOP 
X 
X 
Tono-pen or other calibrated tonometers can be used. 
IOP measurement recommended prior to dilation. 
Goldmann applanation tonometry must also be used to 
verify the reading of ≥ 30 mmHg occurring at any time. 
FAF 
X 
X 
Recommended order of imaging is FAF, NIR, SD-OCT, 
fluorescein angiography, CFP. Administration of 
artificial tears between acquisition of each eye for 
FAF/NIR and SD-OCT is recommended. 
NIR 
X 
X 
SD-OCT 
X 
X 
Fluorescein angiography 
X 
CFP 
X 
X 
a Unscheduled visits for safety and worsening of vision; indicated and additional assessments may be performed if deemed necessary by the Investigator 
b Tapering will be masked; masked blister packs will be provided to patients possibly at ET, Week 104, or unscheduled visit. See Table 9. 
c Reading speeds will only be assessed if charts are available in the local language. 
d Microperimetry should be performed prior to any imaging. 
Page 33 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Table 3: 
Schedule of Activities for Early Termination, Taper, and Follow-up 
Abbreviations: AE = adverse event; AP = alternative pathway; Bb = Bb fragment of complement factor B; BCVA = best-corrected visual acuity; CFP = color fundus photography; 
D = Day; ECG = electrocardiogram; ETDRS = Early Treatment Diabetic Retinopathy Study; EOS = end of study; EQ-5D-5L = EuroQol 5-dimension 5-level questionnaire; 
ET = early termination; FAF = fundus autofluorescence; IADL= Instrumental Activities of Daily Living; IOP = intraocular pressure; LFT = liver function test; LL BCVA= low 
luminance best-corrected visual acuity; MNRead = Minnesota Low-Vision Reading Test; NEI VFQ-25 = National Eye Institute Visual Function Questionnaire, 25-item version; 
NIR = near infrared reflectance; OU = oculus uterque/both eyes; PA = protocol amendment; PE = physical examination; QoL = quality of life; SAE = serious adverse event; 
SD-OCT = spectral domain optical coherence tomography; VHS = visiting health service 
Page 34 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Table 4: 
Pharmacokinetic and Pharmacodynamic Blood Sampling During the Primary Evaluation Period (Up to 
Week 52) 
BL 
Week 4 
Week 16, 28, 40, 52 
ET 
Time After Dosing (Hour ± 10 
min) 
Predosea 
2h 
Predosea 
2h 
4h 
Predosea 
2h 
PK plasma samplesb 
X 
X 
X 
X 
X 
X 
X 
PD: AP activityc 
X 
X 
X 
X 
X 
X 
X 
X 
PD: Bb concentrationc 
X 
X 
X 
X 
Plasma/serum samples for 
additional non-genetic biomarker 
testingc 
X 
X 
X 
X 
a Predose samples: Patients should be instructed to take their dose onsite, with a snack or meal. The time when the previous 2 doses were taken (12 and 24 hours prior to blood 
draw) should be recorded. 
b PK samples will be drawn predose and postdose. 
c AP activity samples will be collected at the same time as the PK samples and once at ET. Bb and biomarkers will be collected predose and also once at ET.  
Abbreviations: AP = alternative pathway; Bb = Bb fragment of complement factor B; bid = twice daily; BL = Baseline; ET = early termination; h = hour; min = minutes; 
PD = pharmacodynamic(s); PK = pharmacokinetic(s); qd = once daily. 
Page 35 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
2.
INTRODUCTION
Age-related macular degeneration is a leading cause of blindness in the developed world by 
causing 2 advanced forms of disease: 1) neovascular age related macular degeneration (nAMD; 
wet form), and 2) GA (dry form). Both advanced forms of AMD are preceded by a decades-long 
process of retinal degeneration beginning at the boundary (Bruch’s membrane) between the 
vascular-rich choroid and the photoreceptor-supporting retinal pigment epithelium (RPE). This 
results in the development of retinal and subretinal pigment epithelial deposits of protein /lipid 
/inflammatory products known as drusen. Some as yet undetermined trigger predisposes disease 
progression to either an initial nAMD path or a GA path, but neither are mutually exclusive, as it 
is possible for both to occur in 1 eye, or even for the drusen to resolve without sequelae (Danis, 
2015). The development of nAMD results in structural alterations, exudation, hemorrhage, 
disciform scarring, and disruption of the photoreceptors leading to loss of vision. If untreated, 
this can result in legal blindness within 12 months (Guyer, 1986; Wong, 2008). The development 
of GA is heralded by the loss of RPE which progresses in an ever-expanding radius to eventually 
encompass the center of the macula (eg, the fovea), resulting in photoreceptor loss, central 
scotoma, legal blindness, and significant reduction of independence and quality of life (QoL) 
(Nielsen, 2020). 
Approximately 8.7% of the world population between age 30 to 97 years old has some stage of 
AMD (Wong, 2014), with a projected increase of ~50% from 2020 to 2040, to affect up to 288 
million people (Leng, 2023). Disease risk is multifactorial, with age, genetics, environment, 
behavior, diet, and lifestyle all implicated in development and progression of the disease. 
Epidemiology shows a substantial increase in AMD risk with advanced age. In the US, the 
prevalence of nAMD in individuals 65 to 69 years is 0.63% and increases to 8.18% in 
individuals 80 years and older. Estimated GA prevalence is 0.48% in the 65 to 69 age group, and 
6.89% in those aged over 80 years (Friedman, 2004). 
2.1. 
Study Rationale 
This proof of concept (POC) dose-finding study is designed to evaluate the efficacy, safety, and 
PK of danicopan in the treatment of patients with GA secondary to AMD. 
2.1.1. 
Unmet Medical Need 
Multiple agents with different mechanism of actions, including neuroprotectors, 
immunomodulators, anti-inflammatory agents, and complement inhibitors have been investigated 
or are under clinical investigation for the treatment of GA (Nebbioso, 2019; Sastre-Ibáñez, 
2018).  
As of 17 Feb 2023, pegcetacoplan intravitreal injection has been approved in the US for 
treatment of GA secondary to AMD. Modest efficacy of pegcetacoplan observed in the OAKS 
and DERBY trials was accompanied with increased risk of conversion to neovascular AMD 
compared to sham injection (Singh, 2023). Frequent intravitreal injections come with high 
patient burden. There is a high unmet clinical need for treatments with less invasive and 
burdensome mode of administration.  
Page 36 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
2.1.2. 
Complement Dysregulation in AMD 
The complement pathway of immune regulation consists of 3 parallel arms: the classical 
pathway (CP), the lectin pathway, and the alternative pathway (AP). Unlike the other two 
pathways, the AP is continuously activated to surveil for pathogens for prompt elimination. To 
prevent damage to the surrounding normal host tissues during activation, AP is tightly controlled 
by various complement regulatory proteins. Otherwise, the products formed during the 
activation, such as complement component 3 (C3) fragments, complement component 5a, and 
membrane attack complex, will cause host tissue damage by inducing phagocytosis, 
inflammation, and cell lysis. In fact, dysregulation of AP has been implicated in the pathogenesis 
of AMD. In 2005, multiple genetic studies showed that complement factor H (FH; a key 
regulator in AP) polymorphism has been associated with AMD (Edwards, 2005; Hageman, 2005; 
Haines, 2005; Klein, 2005). Later studies have confirmed the dysregulation of the complement 
system, particularly the AP, in the pathogenesis of AMD (Lynch, 2019; McHarg, 2015; Merle, 
2015; Merle, 2015b; Scholl, 2008; Yates, 2007). Recently, another large AMD genetics study 
(Fritsche, 2013) using a meta-analysis of 17,000 AMD cases and more than 60,000 control 
identified multiple genetic risk loci, including complement factors H, B and I and C3 provided 
additional evidence of the role of dysregulation of AP in the development of AMD. Factor D 
(FD) is an essential molecule required for AP activation. By inhibiting FD, we hypothesize that 
the tissue damage precipitated by AP dysregulation can be prevented, positioning FD inhibition 
strategy as a potential therapeutic strategy for the treatment of GA secondary to AMD. 
2.1.3. 
Danicopan 
Danicopan (ALXN2040, formerly ACH-0144471) is an oral small molecule inhibitor of FD 
being developed for AP - mediated diseases. Danicopan was shown to be safe and efficacious as 
add-on treatment in patients with paroxysmal nocturnal hemoglobinuria (PNH) concurrently 
receiving background complement component 5 (C5) inhibitors.  
Danicopan binds reversibly to FD with high affinity (KD = 0.44 nM) and demonstrates potent 
inhibition of AP activity under both in vitro and in vivo conditions. Danicopan can also bind 
reversibly to melanin but with ~ 20,000-fold lower affinity (KD = 8.56 µM, the mean value of KD 
determined with synthetic melanin and melanin from Sepia officinalis), leading to the
observation of selective retention and accumulation of danicopan in ocular melanin-containing 
tissues of rats and rabbits including RPE and choroid, 2 tissues of critical importance in the 
development of GA. 
Additionally, based on data from rabbit studies, danicopan is able to pass the blood-retina 
barrier, distributing to the retinal tissue following oral dosing. This has 2 potential advantages: 1) 
oral administration results in selective retention of danicopan in ocular tissues containing 
melanin (eg, choroid and RPE) as well as delivery to the retina, 2) systemic administration 
effectively targets both eyes. 
Danicopan inhibition of FD represents an opportunity to interrupt the complement cascade and, 
thus, prevent progression and vision loss. 
A description of the properties, toxicology, pharmacology, efficacy, and safety of danicopan is 
provided in the Investigator’s Brochure (IB) and Investigational Medicinal Product Dossier. 
Page 37 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
2.2. 
Benefit/Risk Assessment 
2.2.1. 
Risk Assessment 
Based on clinical trial experience and cumulative clinical trial safety data of danicopan at doses 
with similar systemic exposures, danicopan has been demonstrated to be well tolerated and safe. 
Treatment with danicopan in humans has not raised any unexpected safety concerns. 
There are 2 risks closely monitored in clinical trials: liver enzyme elevations and Neisseria 
meningitidis infection.
Table 5: 
Potential and Identified Risks and Mitigation Strategies 
Risks of Clinical 
Significance 
Summary of Data/ 
Rationale for Risk 
Mitigation Strategy 
Meningococcal 
infections 
(potential risk) 
Patients receiving Factor D 
complement inhibitor therapy 
may have increased risk of 
infections, particularly N 
meningitidis.
Patients must be vaccinated or 
revaccinated against meningococcal 
infections as described in this protocol. 
Patients should be monitored for early 
signs of meningococcal infection and 
treated with appropriate antibiotics, if 
necessary. 
Patients must carry the Patient Safety 
Card at all time for quick disclosure of 
any potential signs or symptoms of 
infection. 
See Section 2.2.1.1 and Section 6.5.1.1 
for more information on vaccinations. 
Liver enzyme elevations 
(identified risk) 
Hepatobiliary cholestasis was 
seen in dog toxicology studies and 
was characterized by icterus, 
elevated AST, ALT, ALP, GGT, 
and TBIL (primarily direct 
bilirubin), with histological 
findings.  
Dose limiting toxicity of transient 
and self-limiting liver enzyme 
elevation was observed in healthy 
volunteer study at doses of 500 
mg bid and 800 mg bid. 
Based on the PNH program, 
elevations in liver enzymes are 
considered as an identified risk. 
The majority of these cases were 
transient and nonserious. All 
participants were asymptomatic 
without any significant clinical 
consequence.  
Exclusion of patients with abnormal 
liver function tests as specified in the 
exclusion criteria in Section 5.2.2. 
Liver function tests are routinely 
performed to monitor for potential 
cases of drug-induced liver toxicity. 
Strict stopping criteria are included 
ensuring prompt discontinuation of 
any patient with evidence of liver 
enzyme elevation. 
See Section 2.2.1.2. 
Abbreviations: ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; 
bid = twice daily; GGT = gamma-glutamyl transferase; PNH = paroxysmal nocturnal hemoglobinuria; 
TBIL = total bilirubin 
Page 38 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
2.2.1.1. 
Potential Risk of Meningococcal Infection 
Since a primary function of the complement system is to fight infections, pharmacologic 
inhibition of the complement system could theoretically result in an increased rate or severity of 
infections. As suggested by individual case reports with complement system deficiencies, 
including FD, inhibition of the complement system may result in a lifetime increased risk of 
infection, notably with N meningitidis (Biesma, 2001; Granoff, 2019; Hiemstra, 1989; Sprong,
2006; van den Broek, 2019). 
Patients receiving terminal complement inhibitor therapy such as C5 inhibitor, in general, have 
increased susceptibility to N meningitidis (Socié, 2019). FD inhibition does not affect the CP and
does not completely inhibit the terminal portion of the complement system. FD inhibition 
appears to have little impact on bactericidal and opsonophagocytic activity in vaccinated 
individuals (Granoff, 2019; Konar, 2017; van den Broek, 2019). 
To increase risk awareness and promote quick disclosure of any potential signs or symptoms of 
infection experienced by the patients during the course of the study, patients will be provided a 
Patient Safety Card as described in Section 8.3.6. 
2.2.1.2. 
Identified Risk of Liver Enzyme Elevations 
In dog toxicology studies, hepatobiliary cholestasis has been observed at systemic exposures 
higher than those intended for clinical use. This effect was reversible and could be monitored 
with hepatic safety biomarkers. 
In human healthy volunteers, elevations in alanine aminotransferase (ALT) and aspartate amino 
transferase (AST) with no increase in bilirubin levels have been observed in 2 subjects in the 
multiple ascending dose study (MAD; ACH471-002) with the high doses of 500 mg bid and 
800 mg bid for 14 days.  
Based on results in the PNH program, elevations in liver enzymes are considered as an identified 
risk. The majority of cases were transient and nonserious. All participants were asymptomatic 
without any significant clinical consequence. 
These elevations were not associated with signs or symptoms of hepatic failure, occurred several 
days after completion of dosing, and were self-limiting. A dose taper was instituted in 
subsequent studies as a risk mitigation measure. See Section 6.1.2 for details on dose tapering. 
Exclusion of patients with abnormal liver function tests are clearly specified in Section 5.2.2. 
Rigorous stopping criteria are included ensuring prompt discontinuation of any patient with 
evidence of liver enzyme elevation (see Section 7). 
A detailed description of the potential and identified risks of danicopan is provided in the IB. 
2.2.1.3. 
Coronavirus Disease 2019 
The coronavirus disease 2019 (COVID-19) pandemic is active in many countries at the time of 
this original protocol. Given this unique circumstance, specific consideration has been given to 
the risks and benefits of the study as they relate to COVID-19, and the global and local changes 
that exist as a result of the pandemic. This assessment is described in Section 10.11. Risk 
assessment for COVID-19 vaccination is described in Section 10.12. 
Page 39 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
2.2.2. 
Benefit Assessment 
2.2.2.1. 
Unmet Need 
Age-related macular degeneration is a leading cause of blindness in the developed world and GA 
as the late form of AMD has a significant impact on patient’s QoL. In the early stages of GA 
without foveal involvement, patients typically show minimal changes in central visual acuity 
(VA). However, patients often still experience significant symptoms from visual dysfunction, 
such as dense parafoveal scotomas (eg, leading to difficulties with face recognition), difficulty 
driving, delayed dark adaptation, reduced contrast sensitivity, and decreased reading speed 
(Heier, 2020; Sunness, 1996; Sunness, 1999a; Sunness, 1995). In the later stages, as the GA 
lesion expands into the fovea, a profound decrease in central VA occurs with a decline in 
activities of daily living (Heier, 2020; Lindblad, 2005). GA is bilateral in most patients with 
advanced AMD (Lindblad, 2009; Sunness, 1999b). 
Based on data from pegcetacoplan (a C3 inhibitor) and avacincaptad pegol (a C5 inhibitor) 
studies (Jaffe, 2020; Liao, 2020; Nebbioso, 2019), complement modulation strategies have 
demonstrated a signal for the ability to slow the growth of GA. Both treatments are administered 
as frequent intravitreal injections, presenting a significant patient burden. There exists a need for 
GA treatments that are less invasive and burdensome. 
Danicopan has been shown to be an efficacious inhibitor of FD in studies on paroxysmal 
nocturnal hemoglobinuria. This efficacy, alongside the specific affinity for melanin-containing 
tissues and the ability to cross the blood retina barrier, makes danicopan a logical candidate for 
the treatment of GA. The potential benefit of danicopan for treatment of GA, if demonstrated to 
be efficacious, is slowing or halting the disease progression or conversion from early to late stage 
at which irreversible anatomical and functional loss happens. 
2.2.2.2. 
Route of Administration 
Danicopan as an oral FD inhibitor has potential benefits over intravitreal injections (eg, C3 and 
C5 inhibitors), including 
•
Potential improvement in treatment adherence, especially among patients with fear of
injections
•
Reduction of patient and caregiver burden for avoiding frequent clinic visit for treatments
ie, intravitreal injection.
•
Potential minimization of the risk of ocular injection-related adverse events (AEs).
•
Oral administration of danicopan in patients with GA will result in systemic exposure and
enable concurrent treatment of both eyes, which is a significant benefit for patients with
GA since most patients have both eyes involved.
•
Relative to the previous systemic administration of C5 inhibitors, danicopan offers the
advantage of localization and retention at the target tissues.
•
Oral administration of danicopan may have the potential benefit of allowing the
opportunity of the intervention at the early stage of the disease in which patients may not
have noticeable VA change, to potentially reduce the risk of disease progression to late
Page 40 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
stage, whereas therapies using intravitreal injection may be difficult to be accepted by 
GA patients at the early stage with no visual symptoms. 
2.2.3. 
Overall Benefit: Risk Conclusion 
Considering the measures taken to minimize risk to patients in this study, the risks identified in 
association with danicopan are justified by the anticipated benefits that may be afforded to 
patients with GA secondary to AMD. 
More detailed information about danicopan may be found in the IB. 
Page 41 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
3.
OBJECTIVES AND ENDPOINTS
Objectives 
Endpoints 
Primary 
•
To evaluate the effect of
different dosage regimens of
danicopan on the progression
of GA secondary to AMD
compared to placebo
•
Change from Baseline to Week 52 in the square root (sqrt) of
total GA lesion area (mm) in the study eye* as measured by
fundus autofluorescence (FAF)
*All patients will undergo monocular test on both eyes. The study eye
is the eye that meets eligibility criteria. If both eyes are eligible, the
right eye is taken as the study eye.
Secondary 
•
To evaluate the effect of
danicopan on disease
progression utilizing
anatomical measures in the
study eye
•
Change from Baseline to Week 104 in the sqrt of the total GA
lesion area (mm) in the study eye as measured by FAF
•
Change from Baseline to Week 52 and Week 104 in the total
GA lesion area (mm2) in the study eye as measured by FAF
•
Change from Baseline to Week 52 and Week 104 in macular
ellipsoid zone (EZ) and outer retinal integrity in the study eye,
the fellow eye, and both eyes combined as measured by SD-
OCT
•
Change from Baseline to Week 52 and Week 104 in
subretinal pigment epithelium (sub-RPE)
compartment/drusen/RPE complex in the study eye, fellow
eye and both eyes combined as measured by SD-OCT.
•
To evaluate the effect of
danicopan on disease
progression utilizing
functional measures in the
study eye
•
Change from Baseline to Week 52 and Week 104 in
monocular best-corrected visual acuity (BCVA) scores in the
study eye as assessed by Early Treatment Diabetic
Retinopathy Study (ETDRS) chart
•
Change from Baseline to Week 52 and Week 104 in
monocular low luminance visual acuity (LLVA) scores in the
study eye as assessed by ETDRS chart
•
Change from Baseline to Week 52 and Week 104 in low
luminance deficit (BCVA-LLVA) in the study eye
•
Change from Baseline to Week 52 and Week 104 in
monocular reading speeds in the study eye as assessed by
Minnesota Low Vision Reading Test (MNRead) Acuity
Charts or Radner Reading Charts
Page 42 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Objectives 
Endpoints 
•
To evaluate the effect of
danicopan on patient reported
outcomes (PROs) in patients
with GA secondary to AMD
•
Change from Baseline to Week 52 and Week 104 in National
Eye Institute Visual Function Questionnaire (NEI VFQ-25)
scores
•
To evaluate the PK and
pharmacodynamics (PD) of
danicopan in patients with GA
secondary to AMD
•
Plasma concentrations of danicopan over time
•
PD biomarkers, ex vivo serum AP activity, and plasma Bb
concentration over time
•
To evaluate the safety and
tolerability of danicopan in
patients with GA secondary to
AMD
•
Incidence of treatment-emergent adverse events (TEAEs),
serious adverse events (SAEs), and ocular TEAEs, SAEs, and
clinical laboratory abnormalities, and events leading to
discontinuation of study drug throughout the study
Exploratory 
•
To evaluate the effect of
danicopan on health-related
quality of life and activities of
daily living
•
Change from Baseline to Week 52 and Week 104 in
EQ-5D-5L
•
Change from Baseline to Week 52 and Week 104 in Lawton
Instrumental Activities of Daily Living (IADL)
•
To evaluate the effect of
danicopan on disease
progression utilizing
exploratory anatomical
measures
•
Change from Baseline to Week 52 and Week 104 in the sqrt
of the total GA lesion area (mm) in fellow eye and both eyes
as measured by FAF
•
Change from Baseline to Week 52 and Week 104 in the total
GA lesion area (mm2) in fellow eye and both eyes as
measured by FAF
•
Percent change from Baseline to Week 52 and Week 104 in
the total GA lesion area (mm2) in the study eye, fellow eye
and both eyes combined as measured by FAF
•
Percent change from Baseline to Week 52 and Week 104 in
the sqrt of the total GA lesion area (mm) in the study eye,
fellow eye and both eyes combined as measured by FAF
•
Incidence of patients with conversion from incomplete to
complete retinal pigment epithelium and outer retinal atrophy
(iRORA to cRORA) from Baseline to Week 52 and
Week 104 in the study eye, fellow eye, either eye, and both
eyes combined using spectral domain optical coherence
tomography (SD-OCT) images
•
Incidence of patients with conversion from high-risk drusen
to late AMD from Baseline to Week 52 and Week 104 in the
Page 43 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Objectives 
Endpoints 
study eye, fellow eye, either eye, and both eyes combined 
using SD-OCT images 
•
Incidence of patients with conversion from intermediate
AMD (iAMD) to late AMD from Baseline to Week 52 and
Week 104 in the study eye, fellow eye, either eye, and both
eyes combined using SD-OCT images
•
Number of conversions from iAMD to late AMD from
Baseline in the study eye, fellow eye, and both eyes combined
to Week 52 and Week 104
•
Change from Baseline to Week 52 and Week 104 in drusen
volume (mm3) in the fellow eye with early or iAMD as
measured by SD-OCT
•
Change from Baseline to Week 52 and Week 104 in total GA
lesion area (mm2) and sqrt of the total GA lesion area (mm) in
the study eye, the fellow eye, and both eyes combined as
measured by SD-OCT
•
Percent change from Baseline to Week 52 and Week 104 in
the total GA lesion area (mm2) and sqrt of the total GA lesion
area (mm) in study eye, fellow eye and both eyes combined as
measured by SD-OCT
•
To evaluate the effect of
danicopan on disease
progression utilizing
exploratory functional
measures
•
Change from Baseline to Week 52 and Week 104 in BCVA
scores in the fellow eye as assessed by ETDRS chart
•
Change from Baseline to Week 52 and Week 104 in LLVA
scores in the fellow eye as assessed by ETDRS chart
•
Change from Baseline to Week 52 and Week 104 in low
luminance deficit (BCVA-LLVA) in the fellow eye
•
Change from Baseline to Week 52 and Week 104 in binocular
BCVA scores as assessed ETDRS chart
•
Change from Baseline to Week 52 and Week 104 in binocular
LLVA scores as assessed by ETDRS chart
•
Change from Baseline to Week 52 and Week 104 in binocular
low luminance deficit (BCVA-LLVA)
•
Change from Baseline to Week 52 and Week 104 in
monocular reading speeds in fellow eye as assessed by
MNRead Acuity Charts or Radner Reading Charts
•
Change from Baseline to Week 52 and Week 104 in binocular
reading speeds as assessed by MNRead Acuity Charts or
Radner Reading Charts
Page 44 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Objectives 
Endpoints 
•
Number of scotomatous points assessed by mesopic
microperimetry for the evaluation of the macular functional
response in study eye, fellow eye, and both eyes combined at
Week 52 and Week 104a
•
Incidence of patients with predefined change in any
predefined grid pattern by mesopic microperimetry in the
study eye, fellow eye, and both eyes combined
•
To evaluate the effect of
optimal danicopan dose on
disease progression at the end
of delayed-start period
(Week 104) compared to the
end of early-start period
(Week 52) for the study eye
•
Change from Baseline to Week 52 and Week 104 in the sqrt
of the total GA lesion area (mm) in the study eye as measured
by FAF
•
To evaluate exploratory PD
biomarkers
•
Concentrations of exploratory biomarkers over time,
including serum CP activity and serum (or plasma) C3 and
FD concentrations
a Microperimetry endpoints will be assessed in the microperimetry subpopulation 
Abbreviations: AMD = age-related macular degeneration; AP = alternative pathway; Bb = Bb fragment of complement factor B; 
BCVA = best-corrected visual acuity; C3 = complement component 3; CP = classical pathway; cRORA = complete retinal 
pigment epithelium and outer retinal atrophy; EQ-5D-5L = EuroQol 5-dimension 5-level questionnaire; ETDRS = Early 
Treatment Diabetic Retinopathy Study; EZ = ellipsoid zone; FAF = fundus autofluorescence; FD = factor D; GA = geographic 
atrophy; IADL = Instrumental Activities of Daily Living; iAMD = intermediate age-related macular degeneration; 
iRORA = incomplete retinal pigment epithelium and outer retinal atrophy; LLVA = low luminance visual acuity; 
MNRead = Minnesota Low Vision Reading Test; NEI VFQ-25 = National Eye Institute Visual Function Questionnaire, 25-
item version; PD = pharmacodynamic(s); PK = pharmacokinetic(s); PRO = patient reported outcome; RPE = retinal pigment 
epithelium; SAE = serious adverse event; sqrt = square root; SD-OCT = spectral-domain optical coherence tomography; 
TEAE = treatment-emergent adverse event 
Page 45 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
4.
STUDY DESIGN
4.1. 
Overall Design
Study ALXN2040-GA-201 is a multicenter, double-masked, randomized, placebo-controlled, 
parallel-group, dose-finding study to evaluate 3 dose levels of danicopan compared to placebo in 
patients with GA secondary to AMD.  
Patients will be assigned (1:1:1:1) by stratified randomization (with 3 stratification factors 
described in Section 6.3.1) to 1of 4 dose groups: 
•
100 mg bid
•
200 mg bid
•
400 mg qd
•
Placebo
Approximately 332 patients aged ≥ 60 years will be enrolled, with 83 patients per dose group. 
This study evaluates the efficacy, safety, and PK of danicopan compared to placebo in patients 
≥ 60 years with GA secondary to AMD. Eligible patients will be randomized (1:1:1:1) with 
stratification to one of four treatment groups (3 active treatment groups and 1 placebo group). 
The primary efficacy analysis will be performed when all patients complete the Week 52 Visit or 
discontinue (Section 6.6.4). Secondary efficacy and safety analyses, and exploratory analyses 
will be performed when all patients complete the Week 104 Visit or discontinue.  
There are 2 potential interim analyses (IA) planned for this study. The first interim analysis (IA1) 
for futility may be conducted when approximately 50% patients have completed the Week 28 
Visit. The second interim analysis (IA2) may be conducted when approximately 50% of patients 
complete Week 52 Visit. At IA2, a futility analysis will be conducted first. If the study is not 
considered futile, dose response analysis will be performed. If the dose response analysis is 
positive, a pair-wise comparison of each dose compared to placebo will be conducted. Placebo 
patients will be re-randomized to 1 of the 3 active treatment groups at Week 52, or switched to 
the optimal dose, if identified. A dose with the optimal benefit-risk profile (see Section 9.5.2) 
could be identified at the IA2 or primary analysis for Phase 3 development. If an optimal dose is 
identified, all patients who have at least 52 weeks of treatment on their originally assigned dose 
will be switched to the selected optimal dose for the remainder of the study. Masked treatment 
paradigm will be maintained all throughout the study.  
Page 46 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
4.2. 
Scientific Rationale for Study Design 
Table 6: 
Study Design Rationale for ALXN2040-GA-201 
Design Element 
Rationale 
This is a double-masked, randomized, placebo-
controlled study. 
o
A randomized, double-masked study design
minimizes bias to treatment allocation.
o
The term “masked” (used in lieu of “blinded”)
is considered appropriate in the therapeutic
area of ophthalmology.
o
Comparison with placebo will look at the
intrinsic pharmacological action of danicopan.
Patients will be randomized across 4 dose groups 
in a 1:1:1:1 ratio using randomization with 
stratification 
o
Stratification according to study eye
characteristics ensures balanced distribution
of patients across the different dose groups
with respect to GA severity. See
Section 6.3.1.
The study is conducted in patients with GA aged 
≥ 60 years 
o
This age group assures a balanced
representation of the GA patient population,
while focusing on patients who are more
likely to suffer from an accelerated
deterioration of their GA status. See
Section 4.2.4.
The primary endpoint is change from Baseline at 
Week 52 in the sqrt of total GA lesion area in the 
study eye of an individual patient 
o
To minimize variability, the eye that meets all
eligibility criteria is designated as the study
eye. In case both eyes are eligible, the right
eye is designated as the study eye.
o
Square root of GA lesion area has been used
as a US FDA approvable anatomical marker
for disease progression in clinical studies.
o
See Section 4.2.1 and Section 4.2.3.
Duration of study 
o
Based on current knowledge on GA lesion
growth, a clinically meaningful effect is
expected to be observed at 1 year, hence the
Primary Treatment Period of 52 weeks was
chosen.
o
Functional outcomes trail anatomical findings
(typically seen at 12 months), making a
104-week outcome a more reliable indicator
of stability and durability of visual functional
outcomes.
o
See Section 4.2.2.
Secondary endpoints consist of anatomical and 
functional outcomes  
o
A combined anatomical (with multimodal
imaging techniques) and functional
assessment strategy allows to capture changes
Page 47 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Table 6: 
Study Design Rationale for ALXN2040-GA-201 
Design Element 
Rationale 
in retinal function associated with progressive 
GA changes from AMD.  
o
Oral administration of danicopan in patients
with GA will result in systemic exposure and
enable concurrent treatment of both eyes.
o
See Section 4.2.3.2.
Abbreviations: AMD = age-related macular degeneration; GA = geographic atrophy; sqrt = square root 
4.2.1. 
Study Eye and Fellow Eye 
Systemic treatment with danicopan affects both eyes. For standardization purposes, the primary 
and secondary efficacy analyses will be measured in the pre-specified study eye per individual 
patient. In this study, ocular assessments will be performed in both eyes at Screening. The eye 
that meets all eligibility criteria is designated as the study eye and the other eye will be used as 
the fellow eye. In case of bilateral GA wherein both eyes are eligible, the right eye is designated 
as the study eye. 
Exploratory analyses may be performed on the study eye, the fellow eye, and both eyes 
combined. 
4.2.2. 
Study Duration 
The study consists of a Screening Period of up to 6 weeks and a 104-week Masked Treatment 
Period. Treatment is followed by a 6-day Taper and a 30-day Follow-up is scheduled after the 
last taper dose. The total study duration per patient is approximately 115 weeks. 
The 52-week time point for primary efficacy analysis was selected based on current knowledge 
about the rate of GA lesion growth (Dugel, 2020; Liao, 2020), and the projected duration of 
observation required to detect a clinically meaningful effect of treatment (eg, prevention of 
photoreceptor death through inhibition of GA growth) on slowing lesion growth relative to 
placebo. 
Functional outcomes trail anatomical findings typically seen at 1 year (52 weeks). An overall 
duration of 104 weeks of the randomized double-masked treatment period allows for a more 
reliable indicator of stability and durability of visual functional outcomes and for the assessment 
of prevention of disease progression. 
The total study duration of approximately 115 weeks allows an evaluation period relevant to the 
course of disease progression. 
4.2.3. 
Outcome Measures 
4.2.3.1. 
Primary Outcomes: Square Root of GA Lesion Area 
The primary efficacy outcome measure of this study is the change in the square root (sqrt) of 
total GA lesion area (in mm) from Baseline at Week 52 as assessed by fundus autofluorescence 
(FAF) in the study eye. Although the kinetics of GA progression are highly variable among 
Page 48 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
individual patients, a growing body of evidence suggests that specific characteristics of the 
lesions may be important in predicting disease progression and outcomes. Therefore, the 
quantitative measurement of total GA lesion area progression by FAF imaging has become an 
acceptable anatomic marker used as clinical endpoint for clinical studies (Holz, 2007; Holz, 
2018; Liao, 2020; Sadda, 2016). The sqrt transformation of the GA lesion area measurements 
eliminates variability dependence on baseline lesion size (Feuer, 2013; Yehoshua, 2014). 
4.2.3.2. 
Secondary Outcomes: Anatomical and Functional Outcomes 
A combined anatomical (with multimodal imaging techniques) and corresponding functional 
assessment strategy that incorporates many different aspects of visual function is appropriate in 
capturing changes in visual function associated with progressive GA changes from AMD.  
In this study, a combination of anatomical and functional tests to assess disease progression and 
visual deficits will be used as outcome measures. 
Anatomical outcomes will be based on changes in GA lesion area using different imaging 
modalities. 
Functional outcomes will be based on changes in best-corrected visual acuity (BCVA) scores, 
low luminance visual acuity (LLVA) scores, the low luminance deficit (LLD) calculated from 
these 2 scores (BCVA-LLVA), and reading speeds. 
Patient-reported outcomes (PRO) will be assessed using the National Eye Institute Visual 
Function Questionnaire, 25-item version (NEI VFQ-25).  
These tests are described in Section 10.3 and Section 10.4. 
4.2.3.3. 
Exploratory Outcomes 
Exploratory analyses will be performed based on anatomical and functional outcomes. 
Disease progression of AMD will be followed by quantifying conversion from 1 disease stage to 
another based on disease classification described in Section 10.2. 
Functional outcomes will be based on changes in BCVA scores, LLVA scores, the LLD 
calculated from these 2 scores in fellow eye and both eyes. Functional retinal response including 
number of scotomatous points and change in macular sensitivity will be assessed by mesopic 
microperimetry in the microperimetry eligible subpopulation. 
Anatomical outcomes will be based on anatomical measures on the fellow eye and both eyes 
combined, including changes in the area and sqrt area of the total GA lesion, changes in drusen 
volume, and incidence of patients with conversion from incomplete retinal pigment epithelium 
and outer retinal atrophy (iRORA) to complete retinal pigment epithelium and outer retinal 
atrophy (cRORA), as measured by spectral-domain optical coherence tomography (SD-OCT). 
The ellipsoid zone (EZ) and subretinal pigment epithelium (sub-RPE) compartment/drusen/RPE 
complex analyses will also be included.  
4.2.3.4. 
Patient Reported Outcomes 
Both nAMD and GA can lead to the loss of vision that may be severe and irreversible, resulting 
in a significant loss of QoL and inability to perform activities of daily living. Collection of PROs 
using QoL instruments and visual functioning questionnaires in clinical trials has been 
Page 49 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
recommended by regulatory bodies (Csaky, 2017). Change in QoL and daily living functioning 
are measured as exploratory endpoints using validated instruments, as described in Section 10.4. 
4.2.4. 
Patient Population 
Epidemiology studies show a substantial increase in AMD risk with age. Prevalence is highest in 
age groups ≥ 75 years (Augood, 2006; Lambert, 2016). 
The study population of ≥ 60 years of age supports a balanced representation of the GA patient 
population with a reported mean (± standard deviation [SD]) age of 79 ± 8 years (Yaspan, 2017). 
This also provides the opportunity to capture the photoreceptor degeneration and conversion 
events and rules out unilateral GA in younger patients that may be due to other diseases such as 
myopia, uveitis, post trauma, or radiation. 
4.3. 
Justification for Dose 
One of the key objectives for this study is to test potentially efficacious and safe doses and dose 
regimens of danicopan and to support the selection of an appropriate dose for subsequent clinical 
development. 
The 100 mg bid, 200 mg bid, and 400 mg qd dose regimens proposed for 
Study ALXN2040-GA-201 are based on the simulation results. Plasma PK exposures for these 
proposed doses are predicted to remain below the identified exposures where tolerability limit 
was observed in the MAD study (ACH471-002, see IB for further details). These doses are 
predicted to achieve > 90% alternative pathway hemolysis (APH) inhibition for the entire dose 
interval in the potential eye tissue targets: the retina and the choroid-RPE retinal side 
(melanosomes), and partial-to-complete APH inhibition in the choroid-RPE capillary-bed side 
(peripheral). Based on data from the literature, retina, and choroid-RPE on the retinal side are 
more likely to be the target eye tissues. However, the choroid-RPE on the capillary-bed side 
cannot be completely ruled out as a potential target. The proposed doses allow for the assessment 
of two different dosing intervals, ie, bid vs qd. The 400 mg qd dose regimen, if shown to be safe 
and effective, would be more convenient for patients and encourage better compliance relative to 
bid dosing. An up to 2-fold uncertainty of model prediction on PK and APH inhibition in the 
target eye tissues is anticipated as the physiological eye parameters in humans were translated 
from Dutch-Belted rabbits. 
4.4. 
Definitions of Study Periods and End of Study 
The Primary Evaluation Period is from Day 1 to Week 52 (Table 1). 
The Secondary Evaluation Period starts from Week 52 and ends at Week 104 (Table 2). 
Study completion (patient level): A patient is considered to have completed the study if they 
have completed all periods of the study, including the Taper, Follow-up, and the last scheduled 
procedure shown in the Schedule of Activities (SoA). 
Early termination (ET) or discontinuation: A patient is considered to early terminate from the 
study if they discontinued from the study before completing the last visit as described in Table 3. 
See details in Section 7. 
Page 50 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Follow-up: A follow-up visit is scheduled 30 (+ 7) days after the last dose (including taper doses, 
Table 3) of study drug. 
End of study (EOS; study level completion): The end of the study is defined as the date the last 
patient completes the last visit (including the Taper and Follow-up, Table 4). 
Refer to the SoA in Section 1.3. 
Page 51 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
5.
STUDY POPULATION
Each consented patient must meet all eligibility criteria at both the Screening Period and the 
Day 1 Visit. Prospective approval of protocol deviations to recruitment and enrollment criteria, 
also known as protocol waivers or exemptions, is not permitted. 
5.1. 
Inclusion Criteria 
5.1.1. 
General Inclusion Criteria 
1. Age ≥ 60 years, male or female.
2. All patients must be vaccinated against meningococcal infections within 3 years prior to,
or at the time of, initiating study drug. Patients who initiate study drug treatment less than
2 weeks after receiving a meningococcal vaccine must receive treatment with appropriate
prophylactic antibiotics until 2 weeks after vaccination.
3. For female patients, confirmation of non-childbearing potential based on
follicle-stimulating hormone (FSH) test at Screening only.
4. For nonsterile male patients, agreement to use a highly effective or acceptable method of
contraception with their partner(s) of childbearing potential from the first day of dosing
to 90 days after their last dose of study drug. Males who are surgically sterile do not need
to employ additional contraception.
5. For male patients, agreement not to donate sperm while enrolled in this study and for
90 days after their last dose of study drug.
6. Capable of giving signed informed consent, which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in this
protocol.
5.1.2. 
Ocular Inclusion Criteria 
At Screening, the eye that meets all eligibility criteria is designated as the study eye and the other 
eye will be the fellow eye. In case of bilateral GA wherein both eyes are eligible, the right eye is 
designated as the study eye (see Section 4.2.1). In cases where both eyes are eligible, if eligibility 
status of the designated study eye changes during review of eligibility criteria on Day 1 prior to 
randomization, the other eye can be designated as the study eye if all eligibility criteria are met. 
To be eligible, there should be a presentation of GA secondary to AMD in at least one eye, 
characterized by: 
7. The study eye must have the specified VA (range of 84 to 24 letters; 20/20 to 20/320)
using Early Treatment Diabetic Retinopathy Study (ETDRS) charts at starting distance of
4 meters.
8. Adequate clarity of ocular media, adequate pupillary dilation, and fixation assessed by
slit lamp examination and indirect ophthalmoscopy to permit the collection of good
quality images as determined by the Investigator.
9. Axial length ≤ 26.0 mm measured by biometry (if available) or spherical equivalent
refractive error ≤ 6.0 diopter of myopia.
Page 52 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
−
For patients with history of refractive or cataract surgery in the study eye, axial
length ≤ 26.0 mm measured by biometry (if available) OR preoperative spherical
equivalent refractive error ≤ 6.0 diopter of myopia.
10. The entire GA lesion must be completely visualized on the macula centered field 2 of the
FAF image, must be able to be imaged in its entirety, and must not be contiguous with
any areas of peripapillary atrophy.
11. Total GA lesion area of 0.5 to 17.76 mm2 (~0.2 to 7 disc area [DA]) per eye measured by
FAF. If GA is multifocal, at least one focal lesion must be ≥ 0.5 mm2 (~0.2 DA).
12. The entire GA lesion must be > 1 µm outside of the foveal center.
5.2. 
Exclusion Criteria 
Patients who meet any of the following criteria will be excluded from study entry: 
5.2.1. 
Ocular Exclusion Criteria 
1. GA in the study eye due to cause other than AMD (pathological myopia, monogenetic
macular dystrophies eg, Stargardt/cone-rod dystrophy) or toxic maculopathies (eg,
chloroquine/ hydroxychloroquine maculopathy) per Investigator's judgement.
2. GA and concomitant nAMD in the study eye.
3. Have previously received intravitreal anti-vascular endothelial growth factor (VEGF)
injections in study eye for intraocular vascular disease.
4. Have previously received any stem cell or gene therapy for any ophthalmological
condition in either eye.
5. Use of any investigational medicinal product (ie, participation in interventional clinical
studies for any ophthalmic indications) or use of any regulatory approved treatment for
GA in the study eye regardless of route of administration within the last 3 months or 5
half-lives of the last dose of the investigational or commercial product (whichever is
longer).
6. Previous laser photocoagulation for nAMD, diabetic macular edema, retinal vein
occlusion and proliferative diabetic retinopathy in the study eye.
7. Previous photodynamic therapy (Visudyne) or transpupillary thermotherapy in the study
eye.
8. Previous external beam radiation therapy and/or any other irradiation (eg, isotope,
charged particle, photon, x-ray) to the study eye and respective orbit, head, and/or neck.
9. Previous intravitreal delivery of steroid or device implantation, with the exception of
intraocular lens, in the study eye. A single intravitreal steroid injection for cystoid
macular edema after cataract surgery ≥ 3 months prior to Screening is permitted in the
study eye.
10. Presence of an active ocular disease in the study eye that in the opinion of the
Investigator compromises or confounds visual function or interferes with study
assessments, including but not limited to cataract, uveitis, keratitis, scleritis or
Page 53 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
endophthalmitis, vitreous hemorrhage, other macular diseases (eg, clinically significant 
epiretinal membrane, full thickness macular hole, RPE tear in macula), central serous 
retinopathy, uncontrolled glaucoma, proliferative diabetic retinopathy. 
11. History of any of the following in the study eye:
a.
retinal detachment or full thickness macular hole
b. glaucoma-filtering surgery including microinvasive glaucoma surgery (MIGS)
c.
vitrectomy, submacular surgery, or any surgical intervention for AMD
d. prophylactic subthreshold laser treatment for AMD
e.
intraocular surgery (including lens replacement surgery) within 3 months prior to
Screening.
12. History of any of recurrent infectious or inflammatory eye disease in either eye.
13. If the following changes occur between Screening and Day 1 in the study eye, as
determined by eligibility review before randomization at Day 1:
a.
the Snellen equivalent is no longer between 20/20 to 20/320 OR
b. significant anatomical changes (ie, large subretinal hemorrhage, RPE rip, pigment
epithelial detachment, or other conditions that meet the exclusion criteria per
Investigator’s discretion).
5.2.2. 
General Exclusion Criteria
14. Known or suspected complement deficiency
15. History of N meningitidis infection.
16. Active bacterial or viral infection, a body temperature > 38°C (100.4°F) on 2 consecutive
daily measures, evidence of other infection, or history of any febrile illness within
14 days prior to first study drug administration.
17. History of malignant disease within the past 5 years or ongoing, including solid tumors
and hematologic malignancies (with the exception of basal cell and squamous cell
carcinomas of the skin that have been completely excised and are considered cured).
18. Abnormal liver function tests, defined as:
a.
ALT, AST, alkaline phosphatase (ALP) or direct bilirubin > 2 × upper limit of normal
(ULN) at Screening
b. Patients with Gilbert's Syndrome will not be excluded. If increased bilirubin is
suggestive of Gilbert's syndrome, the patient has to provide documentation of the
diagnosis or will be tested for this condition.
19. Evidence of hepatitis B infection (positive hepatitis B surface antigen [HBsAg] or
positive core antibody (anti-HBc) with negative surface antibody [anti-HBs]) or hepatitis
C viral infection (HCV antibody positive), except for patients with documented
successful treatment and documented sustained virologic response (SVR) at Screening.
20. Evidence of human immunodeficiency virus (HIV antibody positive) infection at
Screening.
Page 54 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
21. Estimated glomerular filtration rate < 30 mL/min/1.73 m2 and/or are on dialysis. eGFR
will be calculated using the Chronic Kidney Disease Epidemiology Collaboration
(CKD-EPI) equation.
22. Hypersensitivity to the investigational drug (danicopan) or any of its excipients, or to
fluorescein sodium for injection (known fluorescein hypersensitivity previously
successfully pre-medicated can be performed per Investigator discretion).
23. Participation in non-ophthalmologic clinical trials involving last dose administration of
another investigational medicinal product within 5 half-lives (if known) or within 30 days
for systemic non-biologics or 6 months for biologics, whichever is longer.
24. History or presence of any medical or psychological condition that, in the opinion of the
Principal Investigator, would make the patient inappropriate for the study or unable to
comply with study procedures or put the patient at undue risk or confound the results of
the study.
5.3. 
Microperimetry Eligibility Criteria 
A subset of patients will be included in a microperimetry subpopulation. The eligibility criteria 
for microperimetry are as follows: 
•
Meeting all the inclusion criteria in Section 5.1 and none of the exclusion criteria in
Section 5.2.
•
Eyes able to detect fixation target.
•
Total elapsed time to complete a microperimetry test is ≤ 30 minutes in duration per test
•
Fixation losses must be ≤ 20%.
5.4. 
Lifestyle Considerations 
5.4.1. 
Meals and Dietary Restrictions 
Danicopan is taken orally with food. See Section 6.1.1 for details of study drug administration. 
5.5. 
Screen Failures 
Screen failures are defined as patients who consent to participate in the clinical study but are not 
subsequently randomly assigned to study drug. A minimal set of screen failure information is 
required to ensure transparent reporting of screen failure patients to meet the Consolidated 
Standards of Reporting Trials publishing requirements and to respond to queries from regulatory 
authorities. Minimal information includes demography, screen failure details (eg, failed 
eligibility criteria), and any AEs, including any serious adverse events (SAEs) and any related 
concomitant medication, occurring during the Screening Period. 
Individuals who do not meet the criteria for participation in this study (screen failure) due to a 
reason that is expected to resolve or has resolved may be rescreened based on discussion and 
agreement between the Investigator and the Medical Monitor. Participants who are rescreened 
outside of the Screening window are required to sign a new ICF. During rescreening, the patient 
must repeat all required screening assessments as defined in Screening Visit in the SOA.  
Page 55 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
6.
STUDY INTERVENTION
6.1. 
Study Intervention Administered 
For this study, the intervention is the administration of study drugs shown in Table 7. 
Table 7: 
Study Drugs 
Danicopan 
Placebo 
IMP and AxMP 
IMP 
IMP 
Type 
small molecule drug 
placebo 
Dose formulation 
tablet 
tablet 
Unit dose strength 
100 mg 
N/A 
Dose levels 
100 mg bid, 200 mg bid, 400 mg 
qd 
matching placebo 
Route of administration 
oral 
oral 
Use 
experimental 
placebo control 
Sourcing 
provided by Sponsor 
provided by Sponsor 
Packaging and labeling 
tablets are provided in blister 
packs and bottles 
tablets are provided in blister 
packs and bottles 
Other names and aliases 
ALXN2040, ACH-0144471 
N/A 
Abbreviations: bid= twice daily; IMP = investigational medicinal product; N/A = not applicable; AxMP = auxiliary 
medicinal product; qd = once daily 
6.1.1. 
Study Drug Administration 
The study drugs will be dispensed to the patients at the clinic visits, mostly to be taken at home 
at the specified dosing regimen. At each clinic visit, the site should ensure that the patient has 
sufficient drug supply until the next clinic visit. Patients will be instructed to bring back all 
unused tablets at each clinic visit for accountability. 
At certain clinic visits (see SoA) that require PK sample collection, patients should be instructed 
to administer their study drugs at the clinic for predose blood sample collection (Table 4). 
The study drugs (danicopan or matching placebo) will be provided as tablets which are identical 
in appearance. The composition of the masked study treatments is shown in Table 8. 
At home, patients will take their tablets twice daily with food and water, one dose of 4 tablets in 
the morning, and a second dose of 2 tablets in the evening. The time interval between the 2 doses 
should be approximately 12 hours. 
At certain clinic visits (see SoA Section 1.3), patients will be instructed to take their morning 
dose of 4 tablets at the clinic to enable predose blood collection. 
Page 56 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Table 8: 
Masked Study Drug Administration Weeks 1 to 104 
Timing 
Dose Groupa 
100 mg bid 
200 mg bid 
400 mg qd 
Placebo 
Morning dose, with food 
and water 
100 mg 
100 mg 
100 mg 
placebo 
placebo 
100 mg 
100 mg 
placebo 
placebo 
placebo 
100 mg 
placebo 
placebo 
placebo 
100 mg 
placebo 
Approximately 12 hours 
Evening dose, with food 
and water 
100 mg 
100 mg 
placebo 
placebo 
placebo 
100 mg 
placebo 
placebo 
a Doses are given as tablets in 100 mg strengths 
Abbreviations: bid = twice daily; qd = once daily 
6.1.2. 
Dose Tapering 
In the MAD Study ACH471-002, ALT elevations were observed at high doses in 2 subjects after 
dosing was ceased. The elevations were transient and not considered of clinical significance. 
However, this temporal relationship suggests that the sudden withdrawal of FD inhibition may be 
associated with liver enzyme elevations. A dose taper was instituted in subsequent studies as a 
risk mitigation measure. 
If possible, tapering should be initiated during dose interruptions, study discontinuation, or study 
completion. The dose of danicopan or placebo will be tapered over a 6-day period according to 
the dose tapering regimen described in Table 9. In case of discontinuation, the patient will 
complete the ET Visit, if possible, prior to tapering and should take the study drug per protocol 
until the tapering period begins.  
Taper doses will be taken only in the morning with food and water. Masking must be maintained 
during tapering as shown in Table 9.  
Page 57 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Table 9: 
Study Drug Taper Schedule 
Dose group 
100 mg bid 
200 mg bid 
400 mg qd 
Placebo 
Taper 
dose 
Masked 
(tablets 
to be 
taken) 
Taper 
dose 
Masked 
(tablets 
to be 
taken) 
Taper 
dose 
Masked 
(tablets 
to be 
taken) 
Taper 
dose 
Masked 
(tablets 
to be 
taken) 
Taper Period 
1 
(Taper Days 1 
to 3), 
morningsa  
100 mg 
qd 
100 mg 
200 mg 
qd 
100 mg 
200 mg 
qd 
100 mg 
placebo 
placebo 
placebo 
100 mg 
100 mg 
placebo 
Taper Period 
2 
(Taper Days 4 
to 6), 
morningsa 
0 mg 
placebo 
100 mg 
qd 
100 mg 
100 mg 
qd 
100 mg 
placebo 
placebo 
a During taper, patients will take tablets in the morning with food and water. 
Abbreviations: bid = twice daily; D = day; qd = once daily; T = taper 
T1 and T2 visits are done on Taper D1 to D3 and Taper D4 to D6, respectively, by visiting healthcare service. 
T1 Visit should assess safety and give instructions to taper dosing. T2 Visit should assess safety and give 
instructions to terminate dosing. 
In case the tapering is not tolerated, there should be a discussion between the Investigator and the 
Medical Monitor. 
At the end of the Tapering Period, the patient will be scheduled for a Follow-up Visit 30 (+ 7) 
days after the last taper dose of the study drug. 
Data collected at the time of study drug discontinuation, Taper, and Follow-up and for any 
further evaluations that need to be completed are provided in the SoA (Section 1.3). 
6.1.3. 
Study Drug Packaging and Labeling 
The study drugs will be labeled according to the country’s regulatory requirements. At a 
minimum, the label should contain: 
•
The protocol number
•
Lot number/expiry date
•
Alexion name and address
•
Instructions for use and storage
6.2. 
Preparation/Handling/Storage/Accountability
The study drugs will be formulated and packaged by the Sponsor or its designee; therefore, no 
specific preparation instructions are required. 
Page 58 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
At the pharmacy, the study drug must be stored at 15°C to 30°C (59°F to 86°F). Patients must be 
instructed to keep their study drugs in the original container at room temperature.  
The Principal Investigator or designee (eg, pharmacist) is responsible for ensuring storage as per 
the label on the drug product at the site and adequate accountability of all used and unused study 
drugs. 
The Investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study drugs received and that any discrepancies are reported and 
resolved before use of the study drugs. 
Only patients enrolled in the study may receive the study drugs and only authorized site staff 
may supply or administer the study drugs. All study drugs must be stored in a secure, 
environmentally controlled, and monitored (manual or automated) area in accordance with the 
labeled storage conditions with access limited to the Investigator and authorized site staff. 
The Investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance (ie, 
receipt, reconciliation, and final disposition records). 
This responsibility includes the reporting of any temperature excursions and product complaints 
to AlexionIMPTE@alexion.com and productcomplaints@alexion.com within 1 business day of 
awareness. A product complaint is defined as any written, electronic, or oral communication that 
alleges deficiencies related to the identity, quality, durability, reliability, usability, safety, 
effectiveness, or performance of a product or clinical study material and/or its packaging 
components after it is has been released for distribution to an end customer that affects the 
performance of such product. 
The Investigator or designee (eg, pharmacist) will maintain records of interventional product 
delivered to the study site, the inventory at the study site, the distribution to and use by each 
participant, the storage or disposal of materials at the study site or the return of materials to the 
sponsor. These records should include dates, quantities, batch/serial numbers, expiration dates, 
in-clinic temperature log, and unique code numbers assigned to the interventional product and 
study participants. 
Investigational product will not be returned to the Sponsor or disposed of until accountability has 
been fully monitored. 
Further guidance regarding preparation, handling, storage, and accountability and information 
for the final disposition of unused study drugs is provided in the IB or Pharmacy Manual. 
6.3. 
Measures to Minimize Bias: Randomization and Masking 
6.3.1. 
Randomization and Stratification 
This is a double-masked, placebo-controlled study with randomization. After Screening, eligible 
patients will be assigned across the 4 dose groups in a 1:1:1:1 ratio using stratified 
randomization. Stratification will be performed according to the study eye characteristics listed 
below to ensure balanced distribution of patients across the different dose groups with respect to 
GA severity. Three stratification factors will be used, namely: 
•
GA lesion size < 1 disc area (DA) versus ≥ 1 DA
Page 59 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
•
Subfoveal* versus extrafoveal* GA lesion and microperimetry eligibility (Yes) versus
extrafoveal GA lesion and microperimetry eligibility (No)**
•
Unifocal vs multifocal GA lesion
Note: 
*For this study, extrafoveal is defined as > 1 µm from the center of the fovea and subfoveal is
≤ 1 μm from the center of the fovea (Heier, 2022).
**Patients who are unable to provide microperimetry data (eg, patients do not undergo 
microperimetry eligibility screening or patients do not meet microperimetry eligibility criteria) 
will be categorized as “microperimetry eligibility (No)”. 
All patients will be centrally assigned to randomized study treatment using an interactive voice 
or web response system (IVRS/IWRS) or other automated tool. 
At the start of the study, patients will be assigned a unique randomization number. The 
randomization number encodes the patient’s assignment to one of the 4 treatment arms of the 
study, according to the randomization schedule generated prior to the study. 
6.3.2. 
Masking 
Masking of treatment allocation will be observed during the entire study. The masked drug 
administration is described in Section 6.1.1 and Table 8. 
During this period, images will be read centrally by masked graders according to the Central 
Reading Manual. 
The Investigator and the study staff must ensure keeping the treatment masked unless unmasking 
is absolutely necessary. 
6.3.3. 
Unmasking 
In rare cases, masking may need to be broken due to an AE or other medical emergency. 
Unmasking (breaking randomization code) should only be performed/done in 
extraordinary/rare/exceptional circumstances when knowledge of the treatment assignment is 
important for patient safety.  
In case of an emergency, the Investigator has the sole responsibility for determining if 
unmasking of a patients’ treatment assignment is warranted. Patient safety must always be the 
first consideration in making such a determination. 
If a patient’s treatment assignment is unmasked, Alexion must be notified within 24 hours after 
breaking the masking. The IVRS/IWRS will be programmed with mask-breaking instructions. In 
the event that emergency unmasking is necessary, the IVRS/IWRS will provide clear 
step-by-step instructions for the Investigator to follow. 
If the Investigator decides that unmasking is warranted, the unmasking will be done for that 
specific patient only. In addition, the Investigator has to ensure that disclosure of treatment 
allocation for that specific patient will only be restricted to the relevant personnel and health 
authorities. The Investigator should not reveal the treatment allocation to the Medical Monitor or 
Page 60 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
any other individuals (eg, clinical study team, contract research organization [CRO] or 
investigational site), unless absolutely necessary. 
Any patient who is unmasked before study completion will be discontinued from the study. 
6.4. 
Study Intervention Compliance 
Patients will continuously self-administer the study drug, unless instructed otherwise. 
Compliance with the study drug will be assessed by direct questioning and counting returned 
tablets during the site visits and recorded in the source documents. Deviation(s) from the 
prescribed dosage regimen should be recorded in the electronic case report form (eCRF). 
A record of the quantity of the number of tablets dispensed to and taken by each patient must be 
maintained and reconciled with the number of tablets and compliance records. Treatment start 
and stop dates, including dates for planned and unplanned dose delays and/or dose reductions 
will also be recorded in the eCRF. 
See Section 6.6.2 and Section 6.6.3 for more information about missed doses and dose 
interruptions, respectively. 
Patients should be advised on the importance of taking the study drug according to the protocol 
(Section 6.1.1). Patients who do not adhere to protocol specified visit schedule and procedures, 
and who do not adhere to study drug administration (eg, generally considered as having < 80% 
treatment compliance during the identified treatment period) may be regarded as non-compliant 
to the protocol. If poor compliance with the study protocol continues, discontinuation should be 
considered. See also information on missed doses and dose interruptions in Section 6.6. 
6.5. 
Prior and Concomitant Therapies 
Any medication (including over-the-counter or prescription medicines, vitamins, and/or herbal 
supplements) other than protocol-specified procedural medications (eg, dilating drops, anesthetic 
drops, fluorescein dyes, vaccines) that the patient is receiving at the time of enrollment or 
receives during the study must be recorded in the electronic case report form (eCRF) along with: 
•
Reason for use
•
Dates of administration, including start and end dates
•
Dosage information including dose and frequency
The Medical Monitor should be contacted if there are any questions regarding concomitant or 
prior procedures and therapy. 
Prior and concomitant medications, including background therapy, will be reviewed as specified 
in the SoA (Section 1.3). 
Prior medications and/or vaccines (including vitamins, herbal preparations, and those discussed 
in the eligibility criteria [Section 5]) and procedures (eg, surgery, biopsy, physical therapy) that 
the patient receives or undergoes ≤ 30 days prior to Screening or during the Screening Period, as 
well as any meningococcal vaccine administered within the last 3 years, will be recorded in the 
patient’s eCRF. 
Page 61 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Concomitant medications (including any medication, vitamins, herbal preparation or 
supplements) and procedures are those received on or after the first study intervention date 
(Day 1), including those started before Day 1 and continued after Day 1. 
Any concomitant medication deemed necessary for the patient’s care during the study, or for the 
treatment of any AE, along with any other medications, other than those listed as disallowed 
medications in Section 6.5.2, may be given at the discretion of the Investigator. However, it is 
the responsibility of the Investigator to ensure that details regarding all medications are recorded 
in full, in the patient’s source documents and eCRF. 
Vaccination and antibiotics administered for prophylaxis of meningococcal infection (if 
applicable) during the study will also be recorded. 
6.5.1. 
Allowed Medications 
At the discretion of the Investigator, patients may continue to receive medications and standard 
treatments administered for other conditions. Patients enrolled may have previously taken oral 
supplements of vitamins and minerals for treatment of dry AMD, and these may be continued 
during the study. Previous and ongoing regulatory approved intravitreal fellow eye treatment of 
GA and anti-VEGF treatment for exudative and/or non-exudative nAMD is permitted. If, during 
the study, the Investigator suspects development of neovascularization in the study eye or fellow 
eye, administration of an anti-VEGF agent according to product label is allowed. 
For ease of reference, see Section 10.9 for a non-comprehensive list of medications allowed in 
this patient population. 
Use of specific concomitant medications with a narrow therapeutic index (ie, P-glycoprotein 
[P-gp] or breast cancer resistance protein [BCRP] substrates) will be considered on a case-by-
case basis with decisions made by the Principal Investigator in discussion with the Medical 
Monitor, based on available knowledge of danicopan as well as the characteristics of the 
potential concomitant medication. Concomitant administration of tacrolimus is permitted if 
therapeutic drug monitoring of tacrolimus exposure is conducted in accordance with 
recommendations in the product label.  
Clinical drug-drug interaction studies indicate that danicopan is an inhibitor of P-gp and BCRP 
transporters. Caution may be needed when co-administering danicopan with drugs known to be 
P-gp and/or BCRP substrates (eg, some statins). Details are provided in the Investigator’s
Brochure.
6.5.1.1. 
Vaccines 
To reduce the risk of meningococcal infection, all patients must be vaccinated against 
meningococcal infections within 3 years prior to, or at the time of, initiating study drug. 
Vaccines against serotypes A, C, Y, W135, and B where available, are recommended to prevent 
common pathogenic meningococcal serotypes. Patients who initiate study drug treatment less 
than 2 weeks after receiving a meningococcal vaccine must receive treatment with appropriate 
prophylactic antibiotics from the first day of study drug treatment until 2 weeks after 
vaccination.  
Patients must be vaccinated or revaccinated according to current national vaccination guidelines 
or local practice for vaccination use with complement inhibitors. Vaccination may not be 
Page 62 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
sufficient to prevent meningococcal infection. All patients should be monitored for early signs of 
meningococcal infection, evaluated immediately if infection is suspected, and treated with 
appropriate antibiotics, if necessary. 
Patients should be vaccinated or revaccinated against other pathogens according to current 
national vaccination guidelines or local practice for vaccination use as part of standard of care of 
underlying disease and age group. 
6.5.2. 
Disallowed Medications and Therapy 
There are no disallowed medications or procedures during the study. 
6.6. 
Dose Modification and Interruptions 
Decisions regarding dose interruptions or modifications will be made by the Investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the patient. 
Regardless of modifications or interruptions, masking of dose assignment should be maintained 
all throughout the study unless emergency unmasking (Section 6.3.2 and Section 6.3.3) is 
necessary. 
6.6.1. 
Switching to Optimal Dose 
If an optimal dose is identified, all patients with at least 52 weeks of treatment, as specified in the 
SoA (Section 1.3) will transition to the optimal dose at the next scheduled visit when drug supply 
is made available. Placebo patients will be rerandomized to one of the 3 active treatment groups 
at Week 52, or switched to the optimal dose, if already identified. Masking of dose assignment 
will be maintained till the end of the study. 
The timing of transitioning to optimal dose will be programmed into the IVRS/IWRS to ensure 
that masking is maintained till then end of the study. 
6.6.2. 
Missed Doses 
The study drug (danicopan or placebo) should be taken as prescribed by the protocol and without 
interruption during the course of the study, whenever possible. In case of a dose missed (defined 
as dose at a single timepoint, morning or evening) inadvertently, the patient should continue with 
administration of a regularly scheduled next dose. Adding the missed dose at the next dosing 
time is not allowed. Information on missed doses should be recorded in the eCRF. See 
Section 6.6.3 for information about dose interruptions. 
6.6.3. 
Dose Interruptions 
If the study drug (danicopan or placebo) has to be stopped or interrupted for any reason, dose 
tapering should occur per Table 3 and Table 9, and assessment should be made if the stop is 
temporary and discussion about the reasons for interruption and plans for potential re-initiation 
should occur between the Investigator and the Medical Monitor. Re-initiation of treatment with 
the study drug should be done under careful clinical monitoring, including laboratory monitoring 
and after consultation with the Medical Monitor. If upon resumption of treatment, the patient has 
a recurrence of the event, permanent discontinuation should be considered as described in 
Section 7. 
Page 63 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Any temporary preplanned treatment interruption should be discussed between the Investigator 
and the Medical Monitor and tapering should be considered (refer to Section 6.1.2). 
The patient should continue participation until the end of the study and continue all scheduled 
assessments as per SoA (see Section 1.3) unless the pre-specified events for treatment 
discontinuation have been met. Any interruption of study drug and the reason for the interruption 
should be fully documented in the source documents and eCRF. 
6.6.4. 
Permanent Dose Discontinuation 
If the study drug (danicopan or placebo) is permanently discontinued for any reason (see 
Section 7), the dose of danicopan or placebo will be tapered over a 6-day period, and the patient 
will complete the ET Visit, if possible, prior to tapering as described in Section 6.1.2, (Table 9). 
A patient who permanently discontinues the study drug is also permanently discontinued from 
the study. 
Page 64 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
7.
DISCONTINUATION OF STUDY DRUG AND PATIENT
DISCONTINUATION/WITHDRAWAL
7.1. 
Discontinuation of Study Drug
In rare instances, it may be necessary for a patient to permanently discontinue (definitive 
discontinuation) the study drug. If the study drug is definitively discontinued, the patient will be 
dose tapered as described in Section 6.1.2, and have a final follow-up 30 days after the last dose 
of the study drug. 
A patient is free to withdraw from the study at any time without jeopardizing future medical 
care. In addition, the Principal Investigator (or designee) may decide, for reasons of medical 
prudence or patient noncompliance, to discontinue dosing of study drug for an individual patient. 
The Principal Investigator will discontinue the study drug in any patient who meets any reasons 
listed below, and should notify the Medical Monitor immediately, and if possible, before dosing 
is terminated. Anytime a patient has to discontinue the study drug, the dose tapering instructions 
and schedule (see Section 6.1.2, Table 9) should be followed unless the patient cannot tolerate 
tapering of study drug or the discontinuation is due to an SAE. In case tapering is not tolerated, 
there should be a discussion between the Investigator and the Medical Monitor. 
Patients will discontinue the study drug if any of the following occur during the study: 
•
Illness that would, in the judgment of the Investigator, affect assessment of clinical
status to a significant degree.
•
Development of any of the following liver function test abnormalities:
−
ALT or AST > 8 × ULN
−
ALT or AST > 5 × ULN for more than 2 weeks
−
ALT or AST > 3 × ULN and total bilirubin > 2 × ULN or international
normalized ratio > 1.5, in the absence of warfarin anticoagulation
−
ALT or AST > 3 × ULN with the appearance of fatigue, nausea, vomiting, right
upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (> 5%)
•
Persistent Grade 3-4 toxicity (including a clinically significant laboratory
abnormality) despite appropriate intervention necessitating discontinuation of study
participation or that, in the judgment of the Investigator, compromises the ability to
continue study-specific procedures, or it is considered not to be in the patient’s best
interest to continue the study.
•
Development of rhegmatogenous retinal detachment or Stage 3 or 4 macular hole
during the course of the study.
•
Development of malignancy in eye, orbit, head, or neck that needs radiation therapy.
•
Patient request to discontinue for any reason.
•
Patient non-compliance with the protocol. In case of significant deviations from the
protocol for any reason (eg, oversight, accident, inadvertent error, etc), the
Investigator (or designee) and Sponsor Medical Monitor will discuss and reach a joint
Page 65 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
decision about patient discontinuation from the study. This joint decision will be fully 
documented per study procedures. 
•
Discontinuation of the study at the request of the Sponsor, regulatory agency, or
Ethics Committee or Institutional Review Board (IRB).
•
Any other condition or circumstance that would jeopardize the welfare of the patient
if s/he were to continue in the study.
Details on early termination/discontinuation are detailed in Section 7.2. 
7.2. 
Patient Discontinuation/Withdrawal from the Study 
All efforts should be made to ensure patients are willing to comply with study participation prior 
to conducting the screening procedures. 
A patient may withdraw from the study at any time at his/her own request, or may be withdrawn 
at any time at the discretion of the Investigator for safety, behavioral, compliance, or 
administrative reasons. This activity is expected to be uncommon. At the time of discontinuing 
from the study, if possible, an ET Visit should be conducted as shown in the SoA (Section 1.3). 
The reason for patient discontinuation must be recorded in the source documents and eCRF at 
the ET Visit. The ET Visit marks the end of efficacy assessments. This will be followed by a 
6-day tapering and a final Follow-up Visit (EOS Visit) scheduled 30 days after the last dose
(including taper doses). Safety assessments will continue during the taper and the follow-up until
study completion. The Follow-up Visit can be omitted if it falls within 5 days of the ET Visit.
Refer to the SoA for data to be collected at the time of study discontinuation/ET Visit, Taper 
period, and Follow-up, and for any further evaluations that need to be completed. 
If the patient withdraws consent for disclosure of future information, Alexion may retain and 
continue to use any data collected before such a withdrawal of consent. If a patient withdraws 
from the study, the patient may request destruction of any samples taken and not tested, and the 
Investigator must document this in the site study records. 
7.3. 
Lost to Follow-up 
A patient will be considered lost to follow-up if the patient repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a patient fails to return to the clinic for a required study 
visit: 
•
The site must attempt to contact the patient to reschedule the missed visit as soon as
possible, counsel the patient on the importance of maintaining the assigned visit
schedule, and ascertain whether or not the patient wishes to and/or should continue in
the study.
•
Before a patient is deemed lost to follow-up, the Investigator or designee must make
every effort to regain contact with the patient. An example of contact effort
escalation/due diligence would include 3 telephone calls, followed by a certified letter
to the patient's last known mailing address or local equivalent, if earlier attempts fail
Page 66 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
to regain contact with patient. These contact attempts should be documented in the 
patient’s medical record. 
•
Should the patient continue to be unreachable, s/he will be considered lost to
Follow-up.
Discontinuation of specific sites or of the study as a whole are handled as part of Section 10.1.9. 
7.4. 
Intervention After the End of the Study 
The study drug will not be provided to the patients after the last scheduled dosing. See SoA in 
Section 1.3. Upon completion of the last study visit (EOS), patients will return to the care of their 
treating physician. 
See Section 4.4 for definition of EOS. 
Page 67 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
8.
STUDY ASSESSMENTS AND PROCEDURES
Study procedures and their timing are summarized in the SoA (Section 1.3). Protocol waivers or 
exemptions are not allowed. 
There are two types of study visits: in-clinic visits and home visits by a visiting health service (in 
countries where available). All visits must be complied with according to the SoA (Section 1.3). 
Patients may opt to convert home visits to in-clinic visits per agreement with site personnel, but 
the home visit assessments will still be followed. Changes in visit type should be noted in source 
documentation. 
Immediate safety concerns should be discussed with Alexion immediately upon occurrence or 
awareness to determine if the patient should continue or discontinue study drug. 
Adherence to the study design requirements, including those specified in the SoA (Section 1.3), 
is essential and required for study conduct. 
Procedures conducted as part of the patient’s routine clinical management (eg, blood count) and 
obtained before signing of the ICF may be utilized for screening or baseline purposes provided 
the procedures met the protocol-specified criteria and were performed within the time frame 
defined in the SoA (Section 1.3). See Section 10.5 for the list of clinical laboratory tests. 
8.1. 
Screening 
During Screening, there should be an ongoing discussion between the Investigator and the 
Medical Monitor regarding eligibility criteria. 
The Principal Investigator or designee is responsible for administering and obtaining freely given 
informed consent before the patient enters the study and before any study related procedures are 
performed. Each patient will sign (written or electronic) an ICF (see Section 10.1.3). This may 
include additional consent forms for HIV testing or other procedures which may be performed 
prior to patients being accepted into the study. 
All screening evaluations (SoA, Section 1.3, Table 1) must be completed during the Screening 
Period and then reviewed at Day 1 to confirm that potential patients meet all eligibility criteria. 
The Investigator will maintain a screening log to record details of all patients screened and to 
confirm eligibility or record reasons for screening failure, as applicable. 
Individuals who do not meet the criteria for participation in this study (screen failure) due to a 
reason that is expected to resolve or has resolved may be rescreened based on discussion and 
agreement between the Investigator and the Medical Monitor. Participants who are rescreened 
outside of the Screening window are required to sign a new ICF. During rescreening, the patient 
must repeat all required screening assessments as defined in Screening Visit in the SoA. 
8.1.1. 
General Screening 
As part of the screening process, patients will be evaluated for vaccination requirements as 
detailed in Section 6.5.1.1. A Patient Safety Card will be issued at Screening. 
A window of up to 6 weeks is permitted to allow screening and any required vaccinations. 
Screening procedures may be spread over more than 1 visit within the 6-week Screening Period. 
The screening clinic and laboratory procedures listed in Section 10.5 must be performed and 
Page 68 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
documented prior to dosing. This will include a review of the inclusion and exclusion criteria. 
The patient’s medical history will be reviewed, and a complete physical examination will be 
conducted. 
Female participants in this study are postmenopausal and therefore not of child-bearing potential. 
See definitions in Section 10.8.1. An FSH test will be performed at Screening for confirmation. 
If screening laboratory assessments show elevated indirect bilirubin levels in conjunction with 
normal liver function tests (AST and ALT), or if the patient has a history of unexplained 
jaundice, unexplained high bilirubin levels, or a history otherwise suggestive of Gilbert's 
syndrome, the patient will be tested for this condition. If the patient has a history of Gilbert’s 
syndrome it should be documented as the patient’s medical history. Refer to the Laboratory 
Manual for testing procedure. 
8.1.2. 
Ocular Screening 
At Screening, all patients will undergo a monocular test on both eyes. The “study eye” is defined 
as the eye that meets all eligibility criteria at Screening. For patients with bilateral GA with both 
eyes meeting the eligibility criteria, the right eye will be taken as the study eye. The other eye 
will be used as the “fellow eye”. 
The following ocular assessments will be conducted for both eyes during Screening. It is 
recommended to follow the order of the procedures as listed below. Assessments that require 
non-dilation of the pupils must be performed first: 
•
BCVA assessed on ETDRS chart at a starting distance of 4 m (perform prior to
dilating eyes). The test will be administered first monocularly (right/left eye) and then
binocularly (both eyes)
•
For the microperimetry subpopulation: mesopic microperimetry will be performed on
both eyes without dilation. Two tests per eye will be performed and up to 3 attempts
are allowed to meet the eligibility criteria during the Screening Visit
•
Slit-lamp examination on both eyes
•
Intraocular pressure (IOP) measurement of both eyes (recommended prior to dilating
eyes; Goldmann applanation tonometry must be used at Screening)
•
Dilated binocular indirect high-magnification ophthalmoscopy on both eyes
•
Retinal imaging to be performed in the following recommended order: FAF, near
infrared reflectance (NIR), SD-OCT, fluorescein angiography (FA), and color fundus
photography (CFP) will be performed per Central Reading Manual and training
materials. Administration of artificial tears between acquisition of each eye for
FAF/NIR and SD-OCT is recommended. Before any study images and
microperimetry are obtained, site personnel, test images, and systems and software
(where applicable) will be certified/validated by the reading center as specified in the
Central Reading Manual. During the eligibility assessment, if the FAF images were
reviewed to be ungradable per Central Reading Center, the FAF images will be
repeated as soon as feasible
Page 69 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
•
If available, biometry (preferred) on both eyes to measure axial length. If biometry is
not available, spherical equivalent refractive error is to be used.
Details of these ocular assessments are provided in Section 10.3. 
All ocular images at Screening will be read centrally by trained graders according to a Central 
Reading Manual. Eligibility assessment by the Central Reading Center based on reading of 
screening images should be considered by the Investigator when confirming that potential 
patients meet all eligibility criteria. Discrepancies in eligibility confirmation may be discussed 
between the Investigator, Medical Monitor, and Central Reading Center. 
Prior to randomization at Day 1, the inclusion and exclusion criteria will be reviewed to confirm 
eligibility. If eligibility status of the designated study eye changes during review of eligibility 
criteria on Day 1 prior to randomization, the other eye can be designated as the study eye if all 
eligibility criteria are met. 
8.2. 
Efficacy Assessments 
Efficacy will be based on anatomical, functional and health-related QoL assessments at in-clinic 
visits. The assessments should be done in the sequence shown and detailed in the SoA 
(Section 1.3) and Section 10.3. 
•
Patient-reported outcomes
•
BCVA testing (starting at 4 m)
•
LL BCVA testing (starting at 4 m)
•
Reading Speed (MNRead or Radner Reading Charts)
•
Mesopic microperimetry for microperimetry subpopulation
•
Slit lamp examination
•
Tonometry/IOP, measurement of both eyes (recommended prior to dilating eyes).
•
Dilated binocular indirect ophthalmoscopy
•
Ocular imaging, recommended to be done in the following order: FAF, NIR, SD-OCT,
FA, and CFP. Administration of artificial tears between acquisition of each eye for
FAF/NIR and SD-OCT is recommended.
All ocular images at Screening will be read centrally by trained graders according to a Central 
Reading Manual. 
8.2.1. 
Primary Efficacy Assessment 
The primary objective of this study is to evaluate the effect of different dosage regimens of 
danicopan on the progression of GA secondary to AMD. 
GA lesion area in mm2 will be measured by FAF in the study eye at the time points indicated in 
Section 1.3. The total GA lesion area (mm2) will be transformed into sqrt (mm). 
FAF provides high-contrast retinal images particularly valuable for the detection of atrophic 
areas. FAF images will be taken according to the SoA (Section 1.3) and sent to reading center for 
Page 70 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
total GA lesion area measurement. Grading of FAF images for the primary efficacy assessment 
will be centrally performed by trained masked graders per the Central Reading Manual. 
A detailed description of FAF is provided in Section 10.3. 
8.2.2. 
Secondary Efficacy Assessments 
Several anatomical and functional measures will be utilized to evaluate the effect of danicopan 
on GA progression in the study eye. In all cases, assessments that require non-dilated eyes 
should be performed first prior to dilation. 
8.2.2.1. 
Anatomical Measures 
GA lesion area in mm2 will be measured by FAF for both eyes at the time points indicated in 
Section 1.3. The total lesion area will be transformed into sqrt. 
A description of the FAF procedure is provided in Section 10.3. 
8.2.2.1.1. Macular Ellipsoid Zone and Outer Retinal Integrity 
Photoreceptor loss will be assessed by measuring the percent of macular EZ total attenuation 
using SD-OCT. The EZ is considered to be formed mainly by mitochondria within the ellipsoid 
layer of the outer portion of the inner segments of the photoreceptors. In SD-OCT, decreases in 
the integrity and intensity of the EZ have been correlated with the reduction in cone 
photoreceptors and retinal sensitivity in retinal degenerative diseases, including AMD and 
macular telangiectasia type 2 (Lara-Medina, 2019; Mukherjee, 2017; Pfau, 2020b; Tao, 2016). 
The following parameters will be assessed from SD-OCT images: 
•
EZ-RPE mean central 1-mm subfield thickness
•
EZ-RPE mean central macular 2 mm thickness
•
Outer nuclear layer (ONL)-RPE mean central 1 mm subfield thickness
•
ONL-RPE mean central macular 2 mm thickness
•
EZ-RPE macular volume
•
Percent macular EZ total attenuation
•
Percent macular EZ partial attenuation
•
Percent central 1 mm subfield EZ total attenuation
•
Percent central macular 2 mm subfield EZ total attenuation
•
Percent central 1 mm subfield EZ partial attenuation
•
Percent central macular 2 mm subfield EZ partial attenuation
•
Targeted EZ integrity based on other analysis targets (eg, correlation with
microperimetry patterns)
Page 71 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
8.2.2.1.2. Sub-RPE Compartment/Drusen/RPE Complex 
Sub-RPE compartment measures reflect the disease burden between the RPE and Bruch’s 
membrane. Generally, this measure should be close to zero in normal eyes. In this volumetric 
assessment and higher order optical coherence tomography (OCT) analysis, the following 
parameters will be assessed: 
•
Sub-RPE central 1 mm subfield mean thickness
•
Sub-RPE central macular 2 mm subfield mean thickness
•
Panmacular sub-RPE volume
•
Percent macular Total RPE Attenuation (ie, surrogate for SD-OCT-based measure of
GA area).
•
Percent central 1 mm subfield Total RPE attenuation
•
Percent central macular 2 mm subfield Total RPE attenuation
8.2.2.2. 
Functional Measures
Monocular BCVA scores, and LLVA scores, and LLD score (BCVA-LLVA) will be assessed by 
ETDRS chart at a starting distance of 4 meters at the time points indicated in Section 1.3. The 
test will be administered first monocularly (right/left eye) and then binocularly (both eyes). 
These measures must be performed prior to dilation of the eyes. 
Reading speeds will be assessed by MNRead Acuity Charts or Radner Reading Charts at the 
time points indicated in the SoA in Section 1.3. The test will be administered first monocularly 
(right/left eye) and then binocularly (both eyes). Reading speed testing is only applicable if the 
charts are available in the local language. 
For a description of the reading charts and other functional measures, refer to Section 10.3. 
8.2.2.3. 
Patient Reported Outcomes 
The NEI VFQ-25 scores will be assessed as a secondary endpoint. See details of PROs in 
Section 8.10 and Section 10.4. 
8.2.3. 
Exploratory Efficacy Assessments 
Other anatomical and functional outcomes will be measured and analyzed in an exploratory 
manner. 
8.2.3.1. 
GA Lesion Area by SD-OCT 
GA lesion area measured by SD-OCT will also be evaluated by masked graders per the Central 
Reading Manual. A description of the SD-OCT procedure is provided in Section 10.3. 
8.2.3.2. 
Mesopic Microperimetry 
Mesopic microperimetry using the grid customized for our study will be conducted in a subset of 
patients who meet the eligibility criteria for microperimetry (microperimetry subpopulation, 
Section 23). Microperimetry should be performed prior to eye dilation and any imaging 
Page 72 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
procedure. Two microperimetry tests per eye should be conducted during Screening Visit and 
once per eye in the follow-up visits. 
A grid customized for this study will be utilized to measure the macular sensitivity by patterns of 
up to 61 testing points in the study eye and fellow eye.  
Microperimetry will evaluate retinal sensitivity which has been shown to be well correlated with 
anatomical changes in intermediate age related macular degeneration (iAMD) and GA patients in 
multiple studies (Alibhai, 2020; Jones, 2016; Pfau, 2020a; Welker, 2018; Wu, 2015). A 
difference of 7 decibels (dB) would represent a minimal clinically meaningful change on 
microperimetry (Weinreb, 2009).  
A scotoma is an area of reduced sensitivity in the visual field. Mesopic microperimetry evaluates 
macular functional response and macular sensitivity by quantifying scotomatous points 
(nonresponding points or “dense” scotomas) in the macula (Csaky, 2019). The number of 
scotomatous points and mean changes from Baseline in macular sensitivity within the grid 
customized for the study in the study and fellow eyes will be evaluated by the reading center. See 
Section 10.3. 
8.2.3.3. 
Disease Conversion 
SD-OCT along with other imaging techniques including FAF, FA, NIR (Section 10.3) will be 
used to evaluate the disease conversion in both eyes, according to classification of AMD (see 
Section 10.2). SD-OCT has become an essential imaging technology to evaluate the macula. 
SD-OCT affords us an opportunity to identify the early stages of the atrophic process before 
lesions are clinically visible or detected as atrophy by CFP or FAF. In addition, the depth 
resolved nature of SD-OCT imaging allows us to evaluate tissue layer by layer, which is 
important because the severity of cellular loss in atrophic disease may vary among layers. 
SD-OCT has been widely used in recent clinical studies for GA (Holz, 2017; Sadda, 2018). 
Anatomical lesion features from iAMD including high risk drusen, iRORA, non-exudative 
nAMD will be identified from SD-OCT images by masked graders per the Central Reading 
Manual, the conversion to late AMD including complete retinal pigment epithelium and outer 
retinal atrophy (cRORA) and exudative nAMD will be tracked over time including: 
•
Conversion from iRORA to cRORA will be assessed at Week 52 and Week 104.
•
Conversion from high risk drusen to late AMD at Week 52 and Week 104
•
Conversion from iAMD to late AMD will be assessed at Week 52 and Week 104.
The assessment will be based on standard disease classification definitions provided in 
Section 10.2, Table 11. 
8.2.3.4. 
Drusen Volume 
Evidence from previous study demonstrated that patients with a drusen volume over 0.03 mm3 
had an increased risk for developing late AMD compared with those with lower drusen volumes 
(Abdelfattah, 2016; Folgar, 2016). Drusen volume in the fellow eye with early/iAMD will be 
measured using SD-OCT images by masked graders per the Central Reading Manual at the time 
points indicated in Section 1.3. 
Page 73 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
8.3. 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA (Section 1.3). 
8.3.1. 
Physical Examinations 
A complete physical examination will be performed as indicated in the SoA (Section 1.3). A 
complete physical examination will include, at a minimum, an assessment of general appearance 
and a review of systems. Height (at Screening only) and weight will also be measured and 
recorded. Measurements of height and weight should be taken with the patients in light clothing 
or underwear and without shoes. 
An abbreviated physical examination will be conducted at all other in-clinic visits, as indicated 
in the SoA (Section 1.3). An abbreviated physical examination includes, at a minimum, body 
system relevant examination based on Investigator judgement and patient symptoms. Additional 
brief, complete, or symptom-driven physical examinations may be conducted at the discretion of 
the Investigator or designee and/or when patients present with AEs. Investigators should pay 
special attention to clinical signs related to previous serious illnesses.  
8.3.2. 
Vital Signs 
Body temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure (mmHg) 
will be assessed. 
Vital signs will be measured after 5 min rest and will include temperature, systolic and diastolic 
blood pressure, and pulse, and respiratory rate.  
8.3.3. 
Electrocardiograms 
A single 12-lead electrocardiogram (ECG) will be conducted as outlined in the SoA (Section 1.3) 
to obtain heart rate (HR), PR, QRS, QT, and QTcF intervals. All ECG recordings will be 12-lead 
and will be performed after the patient has rested quietly for at least 5 minutes in a supine 
position and before blood is drawn (whenever possible). The occurrence of depolarization or 
repolarization disorders, arrhythmic disorders or other abnormalities will be noted. 
In some cases, it may be appropriate to repeat an abnormal ECG to rule out improper lead 
placement as contributing to the ECG abnormality. It is important that the leads are placed in 
approximately the same positions each time in order to achieve precise ECG recordings. 
All ECGs will be reviewed by a central ECG reader. All ECG parameters and assessments must 
be recorded or stored in the patient’s source documents. ECG reports will be reviewed by the 
Investigator or designee. Any clinically significant ECG finding must be reported as an AE. 
8.3.4. 
Clinical Safety Laboratory Assessments 
All protocol-required laboratory assessments, as defined in Section 10.5, Table 12, must be 
collected in accordance with the Laboratory Manual and the SoA (Section 1.3). 
8.3.4.1. 
Blood Collection 
Patients should refrain from heavy exercise 24 hours before blood collection. Walking and light 
exercise are acceptable. Patients will be in a seated or supine position during the blood 
Page 74 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
collection. Specific instructions for sample collection, processing, and shipping will be provided 
in a separate Laboratory Manual. If central laboratory tests results are not obtainable in a timely 
manner, samples may be collected at an unscheduled visit and analyzed locally. See the 
Laboratory Manual for additional information. 
8.3.4.2. 
Abnormalities 
The Investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the eCRF. The 
laboratory reports must be filed with the source documents. Clinically significant abnormal 
laboratory findings are those which are not associated with the underlying disease, unless judged 
by the Investigator to be more severe than expected for the patient’s condition. 
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study or within 30 days after the final dose of study drug should be repeated until the 
values return to normal or Baseline or are no longer considered clinically significant by the 
Investigator or medical monitor. 
•
If such values do not return to normal/Baseline within a period of time judged
reasonable by the Investigator, the etiology should be identified, and Alexion notified.
•
Laboratory assessments performed at the institution’s local laboratory that require a
change in patient management or are considered clinically significant by the
Investigator must be recorded in the AE or SAE eCRF. When possible, parameter
value outside of the reference range should be entered in a free text field.
8.3.5. 
Pregnancy and Contraception
•
Female participants in this study are postmenopausal and therefore not of child-bearing
potential. This will be confirmed following FSH testing at Screening.
•
Contraception guidance for male patients with partners of childbearing potential is
provided in Section 10.8.
•
Pregnancy data from female spouses/partners of male patients will be collected from the
first dose of the study drug during safety monitoring. If a pregnancy is reported, the
Investigator must immediately inform Alexion within 24 hours of awareness of the
pregnancy and follow the procedures outlined in Section 10.8.4
8.3.6. 
Patient Safety Card 
Before the first dose of the study drug, a Patient Safety Card will be provided to patients to carry 
with them at all times until 30 days after the final dose of the study drug. The card is provided to 
increase patient awareness of the risk of meningococcal infections and promote quick 
recognition and disclosure of any potential signs or symptoms of infection experienced during 
the course of the study and to inform patients on what actions must be taken if they are 
experiencing signs or symptoms of infection. 
At each visit throughout the study, the study staff will ensure that the patient has the Patient 
Safety Card. Additional discussion and explanation of the potential risks, signs, and symptoms 
Page 75 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
will occur at specific time points as part of the review of the Patient Safety Card and throughout 
the study as described in the SoA in Section 1.3. 
8.3.7. 
Monitoring for Neovascular AMD Development 
During the study, the development of nAMD (non-exudative and exudative) will be monitored. 
Neovascularization is suspected if the patient has > 5 ETDRS letters of VA loss between the 
current visit and the immediate past visit. If possible, this diagnosis should be assessed by FAF, 
FA, SD-OCT, and CFP, and confirmed by the reading center prior to initiation of anti-VEGF 
treatment per product label. The development of nAMD will be captured as an AE and recorded. 
Following development of nAMD in either eye, study drug should be continued and patients are 
encouraged to continue all study procedures as per protocol. 
8.4. 
Adverse Events and Serious Adverse Events 
The definitions of AEs and SAEs can be found in Section 10.6. 
All AEs will be reported to the Investigator or qualified designee by the patient (or, when 
appropriate, by a caregiver, surrogate, or the patient’s legally authorized representative). 
The Investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up AEs that are serious, considered related to the study drug or study procedures, or that caused 
the patient to discontinue the study drug (see Section 8). 
Procedures for recording, evaluating, follow-up, and reporting AEs and SAEs are outlined in 
Section 10.6. 
8.4.1. 
Time Period and Frequency for Collecting AE and SAE Information 
All AEs and SAEs will be collected from the signing of the ICF until 30 days after final 
(including taper) dose of study drug is administered. 
All SAEs will be recorded and reported to Alexion immediately and under no circumstance 
should this exceed 24 hours, as indicated in Section 10.6. The Investigator will submit any 
updated SAE data to Alexion within 24 hours of the date the investigational site became aware of 
the event. 
Investigators are not obligated to actively seek AE or SAE data after conclusion of the study 
participation. However, if the Investigator learns of any SAE, including a death, at any time after 
a patient has been discharged from the study, and he/she considers the event to be reasonably 
related to the study drug or study participation, the Investigator must promptly notify Alexion. 
8.4.2. 
Method of Detecting AEs and SAEs 
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Section 10.6.  
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the patient will be the preferred method to inquire about AE 
occurrences. 
Page 76 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
8.4.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow-up on each 
patient at subsequent visits/contacts. All SAEs will be followed up until resolution, stabilization, 
the event is otherwise explained, or the patient is lost to follow-up (as defined in Section 7.3). 
Further information on follow-up procedures is provided in Section 10.6. 
8.4.4. 
Regulatory Reporting Requirements for SAEs 
Prompt notification of an SAE by the Investigator to Alexion is essential so that legal obligations 
and ethical responsibilities towards the safety of patients and the safety of a study drug under 
clinical investigation are met. 
Alexion has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study drug under clinical investigation. Alexion will 
comply with country-specific regulatory requirements relating to safety reporting to the 
regulatory authority, IRBs/Independent Ethics Committees (IECs), and Investigators. 
Alexion is required to submit individual suspected unexpected serious adverse reaction reports 
(defined in Section 10.6.2 in the format of MedWatch 3500 or Council for International 
Organizations of Medical Sciences (CIOMS) I Form to health authorities and Investigators as 
required. Forms submitted to Investigators will be masked to treatment assignment. In limited 
circumstances, the masking may be broken in the case of urgent safety issues that could 
compromise patient safety. 
An Investigator who receives an Investigator safety report describing an SAE or other specific 
safety information (eg, summary or listing of SAEs) from Alexion will review and then file it 
along with the IB and will notify the IRB/IEC, if appropriate according to local requirements. 
Under the EU CTR 536/2014, events other than SAEs (eg, unexpected events) that may impact 
the benefit-risk balance should be reported. See definitions in Section 10.6.5. 
8.4.5. 
Medication Error, Drug Abuse, and Drug Misuse 
Medication error, drug abuse, and drug misuse will be collected from signing of the applicable 
version of ICF through the last scheduled procedure shown in the SoA (Section 1.3). 
8.4.5.1. 
Timelines 
If an event of medication error, drug abuse, or drug misuse occurs during the study, then the 
Investigator or other site personnel will report to Alexion or designee immediately but no later 
than 24 hours of when they become aware of it.  
The full definitions and examples of medication error, drug abuse, and drug misuse can be found 
in Section 10.7. 
8.4.5.2. 
Medication Error 
For the purposes of this clinical study a medication error is an unintended failure or mistake in 
the treatment process for an investigational medicinal product (IMP) or an auxiliary medicinal 
product (AxMP) that either causes harm to the participant or has the potential to cause harm to 
the participant. 
Page 77 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
8.4.5.3. 
Drug Abuse 
Drug abuse is the persistent or sporadic intentional, non-therapeutic excessive use of IMP or 
Alexion AxMP for a perceived reward or desired non-therapeutic effect. 
8.4.5.4. 
Drug Misuse 
Drug misuse is the intentional and inappropriate use of IMP or Alexion AxMP for medicinal 
purposes outside of the authorized product information, or for unauthorized IMPs or Alexion 
AxMPs, outside the intended use as specified in the protocol, including deliberate administration 
of the product by the wrong route. 
8.5. 
Treatment of Overdose 
For this study, any dose of the masked study drug greater than that specified in the protocol will 
be considered an overdose. Overdoses are medication errors that are not considered AEs unless 
there is an untoward medical occurrence resulting from the overdose. 
The Sponsor does not recommend specific treatment for an overdose; general supportive 
measures are recommended below. 
In the event of an overdose, the Investigator/Treating Physician should: 
1. Contact the Medical Monitor immediately.
2. Closely monitor the patient for any AE/SAE.
3. If necessary, based on consultation with the Medical Monitor, obtain a plasma sample for
PK analysis or safety laboratory assessments.
4. Document the quantity of the excess dose as well as the duration of the overdose in the
eCRF.
Decisions regarding dose interruptions or modifications will be made by the Investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the patient. 
8.6. 
Pharmacokinetics 
•
Biomatrix samples (eg, plasma, serum, whole blood, and urine) will be collected from
all patients for measurement of concentrations of the study drug as specified in the
SoA (Section 1.3, Table 4).
•
Samples may be collected at additional time points during the study if warranted and
agreed upon between the Investigator and Alexion. The timing of sampling may be
altered during the course of the study, based on newly available data (eg, to obtain
data closer to the time of peak plasma concentrations) to ensure appropriate
monitoring.
•
Instructions for the collection and handling of biological samples will be provided in
the Laboratory Manual. The actual date and time (24-hour clock time) of each sample
will be recorded.
Page 78 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
•
Samples will be used to evaluate the PK of danicopan. Samples collected for analyses
of drug concentration may also be used to evaluate safety or efficacy aspects related
to concerns arising during or after the study.
•
Study drug concentration information that may unmask the study will not be reported
to investigational sites or masked personnel until the study has been unmasked.
Additional information on sample collection and shipping instructions will be
provided in a separate Laboratory Manual.
8.7. 
Pharmacodynamics
•
For all patients, blood samples for pharmacodynamic (PD) evaluations (serum AP
activity and plasma Bb fragment of complement factor B (Bb) concentration) will be
collected at scheduled time points as delineated in the SoA (Section 1.3). The
allowable deviation window for postdose PD blood sample collection is detailed in
Table 4.
•
Instructions for blood sampling, collection, processing to serum and plasma, and
sample shipment will be provided in the Laboratory Manual. The actual date and time
(24hour clock time) of each sample will be recorded.
•
Samples from all patients will be assayed even if the patients do not complete the
study.
•
PD assessments that may unmask the study will not be reported to investigative sites
or masked personnel until the study has been unmasked.
8.8. 
Genetics
Subject to patient consent, a sample will be collected at Day 1 for potential genetic analysis. The 
genes encoding the following proteins, but not limited to, may be examined: complement 
factor D (FD), factor B (FB), factor H (FH), factor I (FI) and factor H related 1-5 (FHR1-5) 
proteins.  
The results of genetic analyses may be reported in the clinical study report (CSR) or in a separate 
study summary. 
Alexion or designee will store the collected samples in a secure storage space with adequate 
measures to protect confidentiality. The samples will be retained while research on danicopan 
continues but no longer than 5 years after the study ends or other period as per local 
requirements. 
8.9. 
Exploratory Biomarkers 
•
Collection of samples for exploratory biomarker research is also part of this study.
•
The following samples for biomarker research are required and will be collected from
all patients in this study as specified in the SoA (Section 1.3, Table 4).
−
Biomarkers to be assessed include but are not limited to serum CP activity, serum
C3 concentration, plasma FD concentration.
Page 79 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
•
Plasma samples will be stored and analysis may be performed on biomarkers
including, but not limited to, FHR4 concentration (Cipriani, 2020), for their
association with disease progression and clinical responses to danicopan.
The samples may be used to develop methods, assays for prognosis, diagnostics, and/or 
treatment monitoring related to the disease (early AMD to advanced AMD and complement 
inhibition). 
The results of biomarker analyses may be reported in the CSR or in a separate study summary. 
Alexion or designee will store the collected samples in a secure storage space with adequate 
measures to protect confidentiality. The samples will be retained while research on danicopan 
continues but no longer than 5 years after the study ends or other period as per local 
requirements. 
8.10. 
Health Related Quality of Life and Activities of Daily Living 
Assessments 
Health-related QoL will be evaluated using the EuroQol 5-dimension 5-level (EQ-5D-5L) and 
NEI VFQ-25 questionnaires. Activity of daily living will be assessed using the Lawton 
Instrumental Activities of Daily Living (IADL) Scale. 
Patient reported outcomes will be captured on paper. Validated local language versions of each 
of the tools will be provided, as needed. All measures should be administered by the Investigator 
or a qualified site staff, if possible, prior to other study procedures at visits specified in the SoAs. 
8.10.1. 
National Eye Institute 25-item Visual Function Questionnaire 
The NEI VFQ-25 scores will be analyzed as a secondary endpoint. The instrument (Mangione, 
2001) measures dimensions of self-reported vision-targeted health status of individuals with 
chronic eye conditions. The NEI VFQ-25 consists of 11 vision related domains: global vision 
rating, difficulty with near vision activities, difficulty with distance vision activities, limitations 
in social function related to vision, role limitations, dependency on others due to vision, mental 
health symptoms due to vision, driving difficulties, limitations with peripheral- and color-vision, 
and ocular pain. The NEI VFQ-25 also includes a single item measuring general health. A 
composite score averages the vision related domains and ranges from 0 (worse) to 100 (best). 
The NEI VFQ-25 in patients with GA has been demonstrated to be a reliable and valid measure 
(Sivaprasad, 2018). If possible, the NEI VFQ-25 should be administered by the Investigator or a 
qualified site staff prior to other study procedures at visits specified in the SoAs. 
8.10.2. 
EuroQol 5-Dimensions 5-Level 
The EQ-5D-5L scores will be analyzed as an exploratory endpoint. This is a standardized 
instrument to measure health-related QoL and has been used in a wide range of health 
conditions. The EQ-5D-5L is defined by 5 dimensions: mobility, usual activities, self-care, 
pain/discomfort, and anxiety/depression. A 0 to 100 health state visual analog scale (VAS) 
accompanies the 5 dimensions, where 0 indicates worst health and 100 best health. A 0 to 1 
index or utility score is calculated from the 5 dimensions using a preference-based value set, 
where 0 indicates a health state equivalent to death and 1 indicates perfect health. Negative 
values indicate health states considered worse than death. If possible, the EQ-5D-5L should be 
Page 80 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
administered by the Investigator or a qualified site staff prior to other study procedures at visits 
specified in the SoAs. 
8.10.3. 
Lawton Instrumental Activities of Daily Living 
The Lawton IADL (Lawton, 1969) scores will be analyzed as an exploratory endpoint. This is an 
assessment that evaluates the patient’s ability for independent living. The IADL is used to 
capture the ability in functioning at the present time and in evaluating functioning improvements 
or deterioration over time. The Lawton IADL scale consists of 8 domains of functioning (food 
preparation, housekeeping, laundry, ability to use the telephone, mode of transportation, 
shopping, financial, and medication management). The instrument includes 8 dichotomous 
questions and its total score can range from 0 to 8. Low scores depict low function and 
dependence, whereas high scores high function and independence. The change from Baseline 
scores will be calculated at its prespecified time points as shown in the SoAs. If possible, the 
IADL should be administered by the Investigator or a qualified site staff prior to other study 
procedures at visits specified in the SoAs. 
Page 81 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
9.
STATISTICAL CONSIDERATIONS
9.1. 
Statistical Hypotheses
9.1.1. 
Primary Hypothesis
The primary null hypothesis is that there is no dose-response effect for danicopan treatment in 
mean rate of change from Baseline in sqrt of total GA lesion area (mm) at Week 52 in the study 
eye (the mean rate of change in danicopan treatment arms are the same as the mean change in 
placebo).  
The alternative hypothesis is that there is a dose-response effect for danicopan treatment 
compared to placebo in change from Baseline in sqrt of total GA lesion area (mm) at Week 52 in 
the study eye (the mean rate of change in at least one danicopan treatment arm is less than the 
mean rate of change in placebo). 
9.2. 
Sample Size Determination 
A total of approximately 332 patients will be randomized in 1:1:1:1 ratio to one of the four 
treatment arms within each stratum, assuming a 15% discontinuation rate within the first 52 
weeks. According to assumptions made based on published data (Jaffe, 2020; Steinle, 2021), the 
mean annual increase in sqrt of GA lesion area of a single eye for the placebo group is estimated 
to be 0.41 mm. The common SD for all treatment groups is assumed to be 0.25 mm (Holz, 2018; 
Liao, 2020). Furthermore, the expected mean annual increase in at least one danicopan dose is 
assumed to be 0.3034 mm, which is equivalent to approximately 26% relative reduction 
compared to placebo or an absolute treatment difference of 0.1066 mm between placebo and 
danicopan treatment in the mean change from baseline in sqrt of GA lesion area at Week 52. The 
Multiple Comparison Procedure and Modeling (MCP-Mod) approach is used to establish the 
proof of concept (POC) with 4 candidate dose-response models at IA2 and Week 52. Further 
details will be provided in the statistical analysis plan (SAP). Based on simulations, this sample 
size will provide at least 90% power to detect the dose-response effect at Week 52 with 1-sided 
type I error rate of 0.05 after adjusting for multiplicity. If the POC is established, this sample size 
will also provide at least 90% power to detect a statistically significant difference between at 
least one danicopan treatment arm and placebo at Week 52 after appropriate multiplicity 
adjustment for pairwise comparison. 
9.3. 
Populations for Analyses 
The analysis sets are defined as follows: 
Table 10: 
Analysis Sets 
Analysis Set 
Description 
Randomized Set 
All randomized patients grouped by randomized treatment group (for 
reporting disposition, demographics, and baseline characteristics). 
Full Analysis Set 
All randomized patients who receive at least 1 dose (full or partial) of 
study drug grouped by randomized treatment group. 
Page 82 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Table 10: 
Analysis Sets 
Analysis Set 
Description 
Safety Set 
All patients who receive at least 1 dose (full or partial) of study drug 
grouped by treatment actually received (for reporting exposure and 
safety data).  
Per Protocol Set 
All randomized patients who receive at least 1 dose (full or partial) of 
study drug and have no important protocol deviations that are likely to 
impact efficacy. 
Pharmacokinetic (PK) 
Analysis Set 
All patients who receive at least 1 dose (full or partial) of study drug 
and have at least 1 measurable concentration value 
Pharmacodynamic (PD) 
Analysis Set 
All patients who receive at least 1 dose (full or partial) of study drug 
and have at least 1 measurable PD value. 
Abbreviations: PD = pharmacodynamic; PK = pharmacokinetic 
9.4. 
Statistical Analyses 
Statistical methods described in this section will be further elaborated in a separate SAP. 
Inference from efficacy analyses will be based on a 2-sided Type I error of 0.1 unless stated 
otherwise. The efficacy analysis population will be the full analysis set (FAS) unless stated 
otherwise. Summary statistics will be computed and displayed by treatment group and by visit, 
where applicable. Descriptive statistics for continuous variables will minimally include the 
number of patients, mean, SD, minimum, median, and maximum. For categorical variables, 
frequencies, and percentages will be presented. Graphical displays will be provided as 
appropriate. 
9.4.1. 
Enrollment and Disposition 
The number of patients screened, screen failures, and randomized patients will be presented. 
Enrollment information will be presented by randomization strata and treatment groups. The 
number of patients discontinued and reasons for discontinuation from the Primary Evaluation 
Period (Day 1 to Week 52), the Secondary Evaluation Period (Weeks 52 to 104), and the overall 
study will be summarized.  
9.4.2. 
Demographics, Baseline Characteristics, Inclusion and Exclusion Criteria, and 
Protocol Deviations 
All demographic information and baseline characteristics will be reported by the assigned 
treatment group and overall. The number and percentage of patients not meeting specific 
inclusion or exclusion criterion will be summarized. A similar summary will be provided for 
important protocol deviations based on prespecified categories. 
9.4.3. 
Medical/Surgical History, Physical Examination 
The medical and surgical history will be summarized by System Organ Class (SOC) and 
Preferred Term using the Medical Dictionary for Regulatory Activities (MedDRA) Version 23.1 
or higher. Baseline physical examination information will also be summarized. 
Page 83 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
9.4.4. 
Prior and Concomitant Medications 
For analysis and reporting purposes, any medication started prior to first dose of study drug will 
be considered as prior medication and any medication taken by a patient that overlaps with the 
intake of the study drug will be considered as concomitant medication. All prior and concomitant 
medications will be summarized. Medications will be coded using the World Health 
Organization Drug Dictionary. 
9.4.5. 
Efficacy Analyses 
All efficacy analyses will be conducted on the FAS. Summary statistics will be computed and 
displayed by treatment group and visit for all efficacy endpoints. 
9.4.5.1. 
Analyses of Primary Efficacy Endpoint 
The attributes for the primary estimand are as follows: 
•
Treatment: Danicopan and placebo.
•
Population: Patients with GA secondary to AMD as defined by the protocol
inclusion/exclusion criteria.
•
Variable: Change from Baseline to Week 52 in sqrt of total GA lesion area in the
study eye as measured by FAF.
•
Intercurrent events: Any treatment discontinuation. The treatment policy strategy will
be used. For the primary analysis, all available data will be used for the analysis
regardless of treatment discontinuation and no imputations for missing data will be
performed, assuming the data are missing at random.
•
Summary measure: Treatment difference in mean rate of change from Baseline in sqrt
of total GA lesion area at Week 52 between danicopan and placebo.
The objective of the primary analysis is to establish the proof of concept by detecting a dose 
response effect of danicopan treatment compared to placebo. The MCP-Mod approach (Bretz, 
2005) will be used to establish the proof of concept with the pre-specified 4 candidate dose 
response models. Model-specific optimal contrast will be constructed based on the estimated 
mean change from Baseline at week 52 for each treatment group derived from the mixed-effect 
model for repeated measures (MMRM) approach as follows: 
The model will include change from Baseline at postbaseline visits in the sqrt GA lesion area as 
the dependent variable and the following list of independent variables as fixed effects: time 
(years, continuous), the interaction between time (years, continuous) and treatment, baseline sqrt 
of GA lesion area, and the randomization strata.  
In addition, the patient-specific random slope will be added to the model with an unstructured 
variance-covariance matrix to model the correlations among repeated measurements within each 
patient. Other covariance structures will be implemented if a convergence issue occurs. The 
Kenward-Rogers method will be used to estimate the denominator degrees of freedom. No 
imputation for missing data will be performed after discontinuation from the study, assuming the 
data are missing at random. Further details will be provided in the SAP. 
Page 84 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Given that the study may conduct an early proof of concept assessment at interim analysis 2 (see 
Section 9.5), adjusted Type I error boundaries will be derived using an alpha spending function 
(Hwang, Shih, and DeCani Gamma family) (Hwang, 1990) for IA2 and Week 52 analyses. 
Given the 1-sided nature of the dose-response hypothesis, the overall Type I error is considered 
for the primary analysis is 0.05. The multiplicity-adjusted p-values corresponding to the 4 
optimal contrasts will be compared to the alpha boundary applicable for the Week 52 analysis. 
The POC will be established if at least one multiplicity-adjusted p-value is less than the alpha 
boundary. 
If the POC is established, pairwise comparisons versus placebo will be performed to identify 
treatment arm(s) superior to placebo with statistical significance, with Hommel’s multiplicity 
adjustment based on the estimated mean change derived from the MMRM approach described 
above. Same adjusted Type I error boundaries will be used as defined above. 
The rate of change from Baseline (mm/year) for each treatment group will be estimated based on 
the coefficients for time and the interaction of time and treatment from the above mentioned 
MMRM model. 
Sensitivity analyses using MMRM will be performed, the model will include change from 
Baseline in the sqrt GA lesion area as the dependent variable and the following list of 
independent variables as fixed effects: treatment, visit (categorical), the interaction between visit 
(categorical) and treatment, baseline sqrt of GA lesion area, and the randomization strata.  
9.4.5.2. 
Analyses of Secondary Efficacy Endpoint(s) 
9.4.5.2.1. Analyses for Secondary Efficacy Endpoints at Week 52 
The objectives of the secondary analyses are to evaluate the effect of danicopan on anatomical 
and functional outcomes of GA. The null hypotheses associated with the secondary objectives 
are that there are no difference between danicopan treatment arms and placebo for the mean of 
the respective endpoints at Week 52; the alternative hypotheses are that at least one danicopan 
treatment arm is different than placebo for the mean of the respective endpoints at Week 52. 
The secondary efficacy endpoints at Week 52 include: 
•
Change from Baseline to Week 52 in the total GA lesion area (mm2) in the study eye
•
Change from Baseline to Week 52 in monocular BCVA score in the study eye
•
Change from Baseline to Week 52 in monocular LLVA score in the study eye
•
Change from Baseline to Week 52 in low luminance deficit LLD score (BCVA-LLVA)
in the study eye
•
Change from Baseline to Week 52 in monocular reading speeds in the study eye
•
Change from Baseline to Week 52 in NEI VFQ-25 score
•
Change from Baseline to Week 52 in macular EZ and outer retinal integrity in the study
eye, the fellow eye, and both eyes combined as measured by SD-OCT
•
Change from Baseline to Week 52 in sub-RPE compartment/drusen/RPE complex in the
study eye, fellow eye and both eyes combined as measured by SD-OCT
Page 85 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
The treatment effect at Week 52 for secondary efficacy endpoints described above will be 
estimated based on MMRM approach using all available longitudinal data up to and including 
Week 52. 
The model for change from Baseline in the total GA lesion area (mm2) includes the following list 
of independent variables as fixed effects: time (years, continuous), the interaction between time 
(years, continuous) and treatment, baseline total GA lesion area, and the randomization strata. 
Treatment will include 4 groups: placebo, 100 mg bid, 200 mg bid, and 400 mg qd. The rate of 
change from Baseline (mm2/year) for each treatment group will be estimated based on the 
coefficients for time and the interaction of time and treatment from the MMRM. In addition, the 
patient-specific random slope will be added to the model. The Kenward-Rogers method will be 
used to estimate the denominator degrees of freedom. No imputation for missing data will be 
performed after discontinuation from the study, assuming the data are missing at random. 
A sensitivity analysis using MMRM will be performed, the model will include change from 
Baseline in the total GA lesion area as the dependent variable and the following list of 
independent variables as fixed effects: treatment, visit (categorical), the interaction between visit 
(categorical) and treatment, baseline total GA lesion area, and the randomization strata. 
The models for change from Baseline in BCVA, LLVA, LLD (BCVA-LLVA), monocular 
reading speed, NEI VFQ-25, macular EZ and sub-RPE compartment/drusen/RPE complex 
parameters include the following list of independent variables as fixed effects: treatment, visit 
(categorical), the interaction between visit (categorical) and treatment, corresponding baseline, 
and the randomization strata. Treatment group will include placebo, 100 mg bid, 200 mg bid, and 
400 mg qd. In addition, the patient-specific random effect for visit will be added to the model 
with an unstructured variance-covariance matrix to model the correlations among repeated 
measurements within each patient. Other covariance structures will be implemented if a 
convergence issue occurs. Further details will be provided in the SAP. The Kenward-Rogers 
method will be used to estimate the denominator degrees of freedom. No imputation for missing 
data will be performed after discontinuation from the study, assuming the data are missing at 
random. 
9.4.5.2.2. Analyses for Secondary Efficacy Endpoints at Week 104 
The objectives of the secondary analyses at are to evaluate the effect of danicopan on anatomical 
and functional outcomes of GA. Placebo patients will be re-randomized to one of the 3 active 
treatment groups at Week 52. The new treatment groups without placebo for Week 104 analyses 
are: placebo:100 mg bid, placebo:200 mg bid, placebo:400 mg qd, 100 mg bid, 200 mg bid, and 
400 mg qd. 
The null hypotheses associated with the secondary objectives are that treatment groups are not 
different for the mean of the respective endpoints at Week 104; the alternative hypotheses are 
that at least two treatment groups are different for the mean of the respective endpoints at 
Week 104. 
The secondary efficacy endpoints at Week 104 include: 
•
Change from Baseline to Week 104 in the sqrt of the total GA lesion area (mm) in the
study eye
Page 86 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
•
Change from Baseline to Week 104 in the total GA lesion area (mm2) in the study eye
•
Change from Baseline to Week 104 in monocular BCVA score in the study eye
•
Change from Baseline to Week 104 in monocular LLVA score in the study eye
•
Change from Baseline to Week 104 in low luminance deficit LLD score (BCVA-LLVA)
in the study eye
•
Change from Baseline to Week 104 in monocular reading speed
•
Change from Baseline to Week 104 in NEI VFQ-25 score
•
Change from Baseline to Week 104 in macular EZ and outer retinal integrity in the study
eye, the fellow eye, and both eyes combined as measured by SD-OCT
•
Change from Baseline to Week 104 in sub-RPE compartment/drusen/RPE complex in the
study eye, fellow eye and both eyes combined as measured by SD-OCT
The treatment effect at Week 104 for secondary efficacy endpoints described above will be 
estimated based on MMRM approach using all available longitudinal data up to and including 
Week 104 and prior to optimal dose switch. 
The models for change from Baseline in the sqrt of GA lesion area (mm) and the total GA lesion 
area (mm2) include the following list of independent variables as fixed effects: time (years, 
continuous), the interaction between time (continuous) and treatment, corresponding baseline, 
and the randomization strata. Treatment will include 6 groups: placebo:100 mg bid, 
placebo:200 mg bid, placebo:400 mg qd, 100 mg bid, 200 mg bid, and 400 mg qd. In addition, 
the patient-specific random slope will be added to the model. The Kenward-Rogers method will 
be used to estimate the denominator degrees of freedom. No imputation for missing data will be 
performed after discontinuation from the study, assuming the data are missing at random. 
The models for change from Baseline in BCVA, LLVA, LLD (BCVA-LLVA), monocular 
reading speeds, NEI VFQ-25, macular EZ, and sub-RPE compartment/drusen/RPE complex 
parameters include the following list of independent variables as fixed effects: treatment, visit 
(categorical), the interaction between visit (categorical) and treatment, corresponding baseline, 
and the randomization strata. Treatment will include 6 groups: placebo:100 mg bid, 
placebo:200 mg bid, placebo:400 mg qd, 100 mg bid, 200 mg bid, and 400 mg qd. In addition, 
the patient-specific random effect for visit will be added to the model with an unstructured 
variance-covariance matrix to model the correlations among repeated measurements within each 
patient. Other covariance structures will be implemented if a convergence issue occurs. The 
Kenward-Rogers method will be used to estimate the denominator degrees of freedom. No 
imputation for missing data will be performed after discontinuation from the study, assuming the 
data are missing at random. 
9.4.5.3. 
Multiplicity Adjustment 
Multiplicity adjustment will be conducted to control the family-wise error rate associated with 
multiple dose-response analyses and pairwise comparisons versus placebo at IA2 and Week 52. 
The Gamma spending function (Hwang, 1990) will be used for the alpha adjustment at IA2 and 
Week 52 analyses. If POC is established based on dose-response analysis, pairwise comparisons 
versus placebo will be performed with Hommel’s step-up multiplicity adjustment. No 
Page 87 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
multiplicity adjustment will be done for secondary endpoint analyses. Further details will be 
provided in the SAP. 
9.4.5.4. 
Analyses of Exploratory Endpoint(s) 
If optimal danicopan dose is established, to assess the effect of danicopan on disease progression 
in the sqrt of the total GA lesion area, a delayed-start analysis will be conducted by incorporating 
all data from the first 52 weeks (referred as early-start period) and second 52 weeks (referred as 
delayed-start period). The analysis population will include a subset of patients in the FAS who 
were randomized to optimal danicopan dose and the placebo patients re-randomized to the 
optimal dose. The delayed-start analysis will be performed if the treatment effect at the end of 
early-start period for the population is statistically significant at 2-sided nominal alpha level of 
0.1. The treatment effects will be quantified by the estimated differences between the groups 
based on their original treatment arms (optimal dose vs. placebo) for both early-start and 
delayed-start periods. Additional details will be provided in the SAP. 
Other analyses of exploratory endpoints, including the microperimetry subgroup analyses of the 
microperimetry endpoints will be described in the SAP. The MP subgroup includes all 
randomized patients who receive at least 1 dose of study drug and meet the eligibility criteria for 
microperimetry. 
9.4.6. 
Safety Analyses 
All safety analyses will be made on the Safety Set. The safety and tolerability of danicopan will 
be assessed based on AEs, clinical laboratory findings, vital sign findings, and ECG results. 
Analysis and reporting for AEs will be based on ocular and non-ocular TEAEs, including 
treatment-emergent serious adverse events (TESAEs), defined as AEs with onset on or after the 
date of the first dose of study drug.  
Treatment-emergent AEs and TESAEs will be summarized by MedDRA SOC and Preferred 
Term and by relationship to the study drug; TEAEs will also be summarized by severity. 
Patient-years adjusted event rates will be generated to characterize the long-term safety profile. 
Laboratory measurements, including changes from Baseline at each visit and shifts from 
Baseline, if applicable, will be summarized descriptively. Weight, ECG, and vital signs will also 
be summarized using descriptive analyses. 
9.4.7. 
PK/PD Analyses 
PK exposure parameters such as AUC, Cmax, and Ctrough are going to be derived using the 
population PK modeling approach and will be reported in a separate population PK report. 
Descriptive statistics (number of patients, mean/geometric mean, SD, median, minimum, and 
maximum) will be used to summarize the PK concentration data. 
Descriptive statistics will be presented for all danicopan PD endpoints at each sampling time. 
The PD effects of danicopan will be evaluated by assessing the absolute values and changes and 
percentage changes from Baseline in serum or plasma concentrations over time, as appropriate.  
Assessments of danicopan PK/PD relationships may be explored using data from this study or in 
combination with data from other studies. 
Page 88 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
In addition, the exposure response (PD biomarkers, clinical endpoints) relationship may be 
explored. 
9.5. 
Interim Analyses 
9.5.1. 
Interim Analysis 1 
The IA1 for futility may be conducted when approximately 50% of patients have completed the 
Week 28 Visit. The conditional power rule (probability of statistical significance at Week 52 
based on the trend observed at the interim analysis) will be used for the futility analysis at IA1. 
The estimated treatment effect and variance at IA1 from MMRM as in Section 9.4.5 will be used 
for the conditional power calculation. 
•
If conditional power is < 10% for each active treatment compared with placebo, the
study can be considered futile.
The Data Monitoring Committee (DMC) will capture the outcome of IA1 on the 
recommendation form in the charter. At IA1, additional assessment for macular EZ, outer retinal 
integrity, RPE compartment/drusen/RPE complex may be done by the unmasked Sponsor team 
(independent of the study team) for potential considerations of study futility and signal of 
anatomical response. 
9.5.2. 
Interim Analysis 2 
The IA2 may be conducted when approximately 50% of patients complete Week 52 Visit. There 
are two objectives of IA2. 
•
Futility assessment
•
Early establishment of POC
A futility analysis that is similar to the IA1 will be conducted first. If the criterion for futility is 
not met, a dose-response analysis will be performed similarly as described in the Interim 
Analysis SAP and Section 9.4.5.1. The early dose-response effect at IA2 will be established if 
any multiplicity adjusted p-value from MCP-Mod is less than the alpha boundary from the
Gamma spending function at IA2. All patients will continue in the study regardless of the 
establishment of early POC at IA2.  
If early dose-response effect is established, pairwise comparison of each active treatment versus 
placebo will be performed with Hommel’s step-up multiplicity adjustment method. The adjusted 
p-values will be compared to the same alpha boundary used for dose-response analysis at IA2.
Provided deemed safe, a statistically significant danicopan treatment will constitute a set of 
potential danicopan regimens for optimal dose selection at IA2.  
The DMC will capture the outcome of IA2 on the recommendation form in the charter. 
At IA2, additional assessments for macular EZ and outer retinal integrity, and RPE 
compartment/drusen/RPE complex may be done by unmasked Sponsor team for potential 
considerations of study futility and signal of POC. 
Page 89 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Upon receipt of the DMC recommendation, the final determination if the optimal dose can be 
identified, will be made by an unmasked Sponsor team (independent of the study team) based on 
the totality of the data.  
If the optimal dose is not identified at IA2, optimal dose selection will be performed again at the 
primary analysis when all patients either complete the Week 52 Visit or discontinue, and will be 
based on the totality of data. 
The detailed analysis strategies will be pre-specified in interim analysis plan (IAP). 
9.6. 
Data Monitoring Committee 
An independent DMC will be appointed by Alexion and is composed of experts in relevant fields 
with no direct relationship to the study. In this study, the independent DMC will be responsible 
for the review of efficacy and safety data, including data from the IA. 
The structure and the specific roles and responsibilities of the DMC and a schedule of meetings 
will be described in the DMC Charter. 
Page 90 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
10.
SUPPORTING DOCUMENTATION AND OPERATIONAL
CONSIDERATIONS
10.1. 
Regulatory, Ethical, and Study Oversight Considerations
10.1.1. 
Regulatory and Ethical Considerations
•
This study will be conducted in accordance with the protocol and the following:
−
Consensus ethical principles derived from international guidelines including the
Declaration of Helsinki and CIOMS International Ethical Guidelines
−
Applicable ICH Good Clinical Practice (GCP) Guidelines
−
Applicable laws and regulations
•
The protocol, substantial protocol amendments (ie, modifications), ICF, IB, and other
relevant documents (eg, advertisements) must be submitted to an IRB/IEC by the
Investigator/Alexion and reviewed and approved by the IRB/IEC before the study is
initiated.
−
If any of these documents require regulatory/health authority approval per local
regulations, Alexion will also obtain such approval before the study is initiated.
•
Any substantial amendments to the protocol will require IRB/IEC and
regulatory/health authority approval before implementation of changes made to the
study design, except for changes necessary to eliminate an immediate hazard to study
participants.
•
For studies to be approved by the Medicines and Healthcare products Regulatory
Agency: The Investigator will notify the IRB/IEC of deviations from the study
protocol or GCP as defined by UK legislation as a serious breach or as required by
IRB/IEC procedures.
•
The Investigator will be responsible for the following:
−
Providing written summaries of the status of the study to the IRB/IEC annually or
more frequently in accordance with the requirements, policies, and procedures
established by the IRB/IEC
−
Notifying the IRB/IEC of SAEs or other significant safety findings as required by
IRB/IEC procedures per local regulations
−
Providing oversight of the conduct of the study at the site and adherence to
requirements of 21 Code of Federal Regulations (CFR), ICH guidelines, the
IRB/IEC, EU Directive 2001/20/EC, EU CTR 536/2014 for clinical studies, and
all other applicable local regulations
−
Promptly notifying Alexion of any (potential) serious breach of the protocol or
regulations (including if a data breach compromises the integrity, confidentiality,
or availability of the personal data of participants) so that legal and ethical
obligations are met. A ‘serious breach’ means a breach likely to affect to a
Page 91 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
significant degree the safety and rights of a participant or the reliability and 
robustness of the data generated in the clinical study. 
•
In certain regions/countries, Alexion has a legal responsibility to notify both the local
regulatory authority and other regulatory agencies about such breaches.
−
Alexion will comply with country-specific regulatory requirements relating to
serious breach reporting to the regulatory authority (including data protection
authorities and, if applicable, affected participants in case of a personal data
breach), IRB/IEC, and Investigators. Under EU CTR 536/2014, Alexion is
required to enter details of serious breaches into the European Medicines Agency
(EMA) Clinical Trials Information System (CTIS). It is important to note that
redacted versions of serious breach reports will be available to the public via
CTIS.
•
The Investigator should have a process in place to ensure that:
−
The site staff or service providers delegated by the Investigator/institution are able
to identify the occurrence of a (potential) serious breach, including personal data
breaches.
−
A (potential) serious breach is promptly reported to Alexion or delegated party,
through the contacts (email address or telephone number) provided by Alexion.
•
Where applicable:
−
Alexion and the site have taken all necessary steps to avoid personal data
breaches and have undertaken measures to prevent such breaches from occurring
in the first place and to mitigate the impact of occurred data breaches (eg,
applying encryption, maintaining and keeping systems and information
technology (IT) security measures up-to-date, regular reviews and testing, regular
training of employees, and developed security policies and standards).
−
Both Alexion and the study site have developed an internal data breach reporting
and investigation process and internal protocols with guidance on how to respond
swiftly and diligently to the occurrence of a personal data breach.
−
In compliance with applicable laws, the data controller for the processing activity
where the personal data breach occurred (Alexion or respectively the study site)
will notify the data protection authorities without undue delay within the legal
terms provided for such notification and within the prescribed form and content.
−
If participants need to be notified of a personal data breach, the notification to
participants is done by the site for the data breaches that occur within the
processing activities for which the site is the data controller. For data breaches
that occur within the processing activities of Alexion as the data controller, the
notification is done in collaboration with the site and is performed by the site
and/or Investigator, acting on behalf of Alexion, so that Alexion has no access to
the identifying personal information of the participants. The site and/or
Investigator shall conduct the notification by contacting the participants using the
information that they gave for communication purposes in clinical research.
Page 92 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
−
If a personal data breach occurs in a processor's systems engaged by Alexion, the
processor under contractual obligations with Alexion promptly and in due course
after discovering the breach, notifies Alexion and provides full cooperation with
the investigation. In these cases, to the extent Alexion is the data controller for the
processing activity where the breach occurred, it will be responsible for the
notification to data protection authorities and, if applicable, to participants. If the
personal data breach needs to be notified to the participants, the notification is
done in collaboration with the site and is performed by the site and/or
Investigator, acting on behalf of Alexion, so that Alexion has no access to the
identifying personal information of the participants.
•
The Coordinating Investigator will be identified among the enrolling Investigators
during the course of the study and will be responsible for reviewing the CSR and
confirming that it accurately describes the conduct and results of the study.
10.1.2. 
Financial Disclosure 
Investigators and Sub-investigators will provide Alexion with sufficient, accurate financial 
information as requested to allow Alexion to submit complete and accurate financial certification 
or disclosure statements to the appropriate regulatory authorities. Investigators are responsible 
for providing information on financial interests during the course of the study and for 1 year after 
completion of the study. 
10.1.3. 
Informed Consent Process 
•
It is the responsibility of the Investigator or designee to obtain signed (written or
electronic signature) informed consent from all participants, or the participant’s
legally authorized representative, prior to performing any study-related procedures
including screening assessments.
•
The Investigator or designee will explain the nature of the study (including but not
limited to the objectives, potential benefits and risks, inconveniences, and the
participant’s rights and responsibilities) to the participant or his/her legally authorized
representative, defined according to local and country regulations where the study is
taking place, and answer all questions regarding the study.
•
Participants must be informed that their participation is voluntary. Participants or
their legally authorized representative will be required to sign a statement of informed
consent or a certified translation, if applicable, that meets the requirements of
21 CFR 50, local regulations, EU General Data Protection Regulation (GDPR), ICH
GCP guidelines, Health Insurance Portability and Accountability Act (HIPAA)
requirements, where applicable, and the IRB/IEC or study center.
•
The participant’s medical record must include a statement that signed (written or
electronic) informed consent was obtained before any screening procedures were
performed with a participant, and the date the written consent was obtained. The
authorized person obtaining the informed consent must also sign the ICF(s).
•
Participants must be reconsented to the most current version of the ICF(s) during their
participation in the study, as applicable.
Page 93 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
•
A copy of the signed (written or electronic) informed consent documentation (ie, a
complete set of participant information sheets and fully executed signature pages)
must be provided to the participant or the participant’s legally authorized
representative, as applicable. This document may require translation into the local
language. Original signed (written or electronic) consent forms must remain in each
participant’s study file and must be available for verification at any time.
10.1.4. 
Recruitment Strategy 
Participants will be identified by qualified research staff. This may be done through a review of 
medical records, external referrals or using databases. Recruitment strategies may include study 
posters, referral letters, recruitment brochures, advertisements, social media posts, and websites, 
where permitted by local regulations. All recruitment materials will be submitted to local 
IRB/EC as required, for review and approval for use. 
10.1.5. 
Data Protection 
•
Participants will be assigned a unique identifier by a Trusted Third Party contracted
by Alexion. Any participant records or datasets that are transferred to Alexion will
contain the identifier only; participant names, initials, or any information which
would make the participant identifiable will not be transferred.
•
Participants must be informed that their personal study-related and coded
(pseudonymized) data, who will have access to their personal data, how and how long
it will be used, and that it will be used by Alexion in accordance with local data
protection law. In addition, multiple local laws require that participants must also be
informed of any individuals rights they may have with regard to their personal data.
Participants will be informed about how their personal study-related data will be
disclosed, and are provided with the appropriate legal basis for which a controller
processes their personal data. The level of disclosure, the security controls used to
protect their data, and information regarding any transfer of their personal data
outside of their country or region must also be explained to the participant.
•
Participants must be informed that their medical records may be examined by Clinical
Quality Assurance auditors or other authorized personnel appointed by Alexion,
appropriate IRB/IEC members, any third parties acting on behalf of Alexion, and
inspectors from regulatory authorities.
•
Alexion and the site as a data controller have implemented privacy and security
controls designed to help protect participant personal data, including information
security controls, firewalls, incident detection, and secure transfer measures.
•
The contract between Alexion and study sites specifies responsibilities of the parties
related to data protection, including handling of data security breaches and respective
communication and cooperation of the parties.
•
Information technology systems used to collect, process, and store study-related data
are secured by technical and organizational security measures designed to protect
such data against accidental or unlawful loss, alteration, or unauthorized disclosure or
access.
Page 94 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
•
The EU GDPR defines pseudonymization as the processing of personal data in such a
way that the personal data can no longer be attributed to a specific individual without
the use of additional information, provided that such additional information is kept
separately and protected by technical and organizational measures to ensure that the
personal data are not attributed to an identified or identifiable natural person.
•
Appropriate safeguards will be implemented to protect coded data during and after
the study that include:
−
Access to the coded data will be limited to specific individuals subject to
confidentiality obligations (including the obligation to not attempt to re-identify
individuals/decode the clinical data).
−
The coded data will be protected with security measures to avoid data alteration,
loss, and unauthorized accesses and further de-identification techniques may be
applied.
−
A data protection impact assessment (DPIA), where required, will apply to
identify and mitigate privacy risks, if any, associated with each scientific research.
−
The coded data will not be shared for direct marketing purposes or other purposes
that are not legal duties or are not considered scientific research according to the
applicable data protection legislation. In particular, it will not be used to make
decisions about future services available to the participant, such as insurance.
•
In addition to having the participants’ data and biosamples coded, the data is also
protected by high-standard technical security means, such as strong access control
and encryption.
•
Participants are also protected legally by the following means if the level of
disclosure of the coded data includes sharing of the latter with other third parties, as
the participants will be explained in the ICF:
−
The participants’ coded data are protected by contractual arrangements, Codes of
Conduct, or certifications that set the rules for personal information protection to
those available in European countries or other alternatives set forth in the law, as
well as any supplementary technical and organizational measures that may results
out of conducted transfer impact assessments.
10.1.6. 
Dissemination of Clinical Study Data 
Study-related information and study results may be posted on publicly accessible clinical study 
databases (eg, the US website www.clinicaltrials.gov or the EU website 
www.clinicaltrialsregister.eu), as appropriate, and in accordance with national, regional, and 
local regulations. 
However, posting of study results per local regulations may be deferred to a later date for one of 
the following reasons: 
•
Study is still ongoing in other countries or regions
Page 95 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
•
Study is part of an ongoing review for approval by Health Authorities; study result
data deferral request can be submitted.
10.1.7. 
Data Quality Assurance
•
All participant data relating to the study will be recorded on eCRF unless transmitted
to Alexion or designee electronically (eg, laboratory data). The Investigator is
responsible for verifying that data entries are accurate and correct by physically or
electronically signing the eCRF.
•
The Investigator must maintain accurate documentation (source data) that supports
the information entered in the eCRF.
•
The Investigator must permit study-related monitoring, audits, IRB/IEC review, and
regulatory agency inspections and provide direct access to source data documents.
•
Quality tolerance limits (QTLs) will be predefined to identify systematic issues that
can impact participant safety and/or reliability of study results. These predefined
parameters will be monitored during the study, and important deviations from the
QTLs and remedial actions taken will be summarized in the CSR.
•
Alexion or designee is responsible for the data management of this study including
quality checking of the data.
•
Study monitors will perform ongoing source data verification to confirm that data
entered into the eCRF by authorized site personnel are accurate, complete, and
verifiable from source documents; that the safety and rights of participants are being
protected; and that the study is being conducted in accordance with the currently
approved protocol and any other study agreements, ICH GCP, and all applicable
regulatory requirements.
−
Remote source data verification may be employed where permitted by local
regulations.
−
The scope of the source data verification will be described in detail in the Clinical
Monitoring Plan.
•
Records and documents, including signed ICFs, pertaining to the conduct of this
study must be retained by the Investigator for at least 25 years after study completion
or per local regulations or institutional policies. No records may be destroyed without
the written approval of Alexion. No records may be transferred to another location or
party without written notification to Alexion. Clinical study documents and records
required as part of the trial master file (TMF) are archived and stored by Alexion for
at least 30 years.
10.1.8. 
Source Documents
•
Source documents provide evidence for the existence of the participant and
substantiate the integrity of the data collected. The Investigator or designee will
prepare and maintain adequate and accurate source documents (eg, medical records,
Page 96 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
ECGs, AE and concomitant medication reporting, raw data collection forms) 
designed to record all observations and other pertinent data for each participant. 
•
Data reported on the eCRF that are transcribed from source documents must be
consistent with the source documents or the discrepancies must be explained. The
eCRFs must be completed by the Investigator or designee as indicated in the site
delegation log. Source documents are filed at the investigational site. The Investigator
may need to request previous medical records or transfer records, depending on the
study. Also, current medical records must be available to Alexion, Alexion delegates,
and health authorities, as requested.
•
Definition of what constitutes source data and its origin can be found in monitoring
guidelines.
•
The Investigator must maintain accurate documentation (source data) that supports
the information entered in the CRF.
•
Alexion or designee will perform monitoring to confirm that data entered into the
CRF by authorized site personnel are accurate, complete, and verifiable from source
documents; that the safety and rights of participants are being protected; and that the
study is being conducted in accordance with the currently approved protocol and any
other study agreements, ICH GCP, and all applicable regulatory requirements.
•
Per ICH E6 (R2) guidelines and good documentation practice requirements, source
documents and study records in all media (eg, paper, electronic) must be Attributable,
Legible, Contemporaneous, Original, Accurate, and Complete.
10.1.9. 
Study and Site Start and Closure
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
The first act of recruitment is the first site activation and will be the study start date. 
Study sites will be closed after the study is completed or following the decision to close or 
terminate the study. A study site is considered closed when all participants have completed the 
EOS or ET Visit, all data have been collected and entered into the electronic data capture (EDC) 
system, all required documents and study supplies have been collected and reconciled, and a 
study-site closure visit has been performed. 
The Investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by Alexion or Investigator may include but are not 
limited to: 
•
Failure of the Investigator to comply with the protocol, the requirements of the
IRB/IEC or local health authorities, Alexion’s procedures, or ICH GCP guidelines
•
Inadequate recruitment of participants by the Investigator
•
Total number of participants included earlier than expected
•
Discontinuation of further study drug development
Page 97 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Alexion or health authority may terminate the study for reasonable cause. Conditions that may 
warrant stopping or discontinuing the study may include but are not limited to: 
•
The incidence or severity of AEs in this study indicate a potential health hazard to
participants taking part in the trial.
•
If any information leads to conclude that the benefit/risk ratio of the clinical trial is
negative.
•
Alexion decision to suspend or discontinue testing, evaluation, or development of the
study intervention
If the study is prematurely terminated or suspended, Alexion shall promptly inform the 
Investigators, the IECs/IRBs, the regulatory authorities, and any CROs used in the study of the 
reason for termination or suspension, as specified by the applicable regulatory requirements. The 
Investigator shall promptly inform the participant and should assure appropriate patient therapy 
and/or follow-up. 
10.1.10. 
Publication Policy 
•
Alexion strives to publish results from all research studies regardless of whether the
findings are positive, negative, or inconclusive, or whether the product is
investigational, licensed, or has been discontinued or withdrawn from the market. The
minimum commitment is to all Phase 2 and Phase 3 clinical studies. Alexion also
commits to publish other studies of significant scientific or medical importance
including, but not limited to Phase 1 clinical studies, discovery, research,
epidemiology, and health economics and outcomes research.
•
Where possible, primary manuscripts reporting results of the primary efficacy
endpoint or the final results will be submitted for publication to peer-reviewed,
indexed (eg, PubMed, Scopus, Embase) journals within 12 to 18 months of the
primary evaluation date or EOS, whichever is earlier.
•
Investigators who participate as authors in manuscripts derived from
Alexion-sponsored studies will agree to the prerequisites as outlined in the Alexion
Author Letter of Agreement prior to engaging in manuscript development.
•
The Investigator agrees to submit proposals for new manuscripts (whether or not the
proposed analyses are derived from protocol-specified endpoints) to Alexion for
review and consideration. All manuscripts or abstracts emanating from approved
proposals are to be submitted to Alexion for review before submission to the
journal/society. This allows Alexion to protect proprietary information and provide
comments.
−
The proprietary nature of some development work may preclude publication. In
some cases, it may be necessary to delay a publication to allow Alexion to ensure
protection of intellectual property.
•
Primary publications, including congress and journal publications, containing the
protocol-specified results of a study should occur prior to the publication of
individual study site results or case reports. Alexion’s policy prohibits duplicate
Page 98 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
publication, whereby the same results must not be published in multiple 
peer-reviewed journal manuscripts. 
−
Encore congress publications may be appropriate to allow communication of
research findings to relevant audience and geographical regions.
•
Alexion will comply with the requirements for publication of study results as defined
by the Pharmaceutical Research and Manufacturers of America and the International
Committee of Medical Journal Editors and per the Alexion Publication Policy. In
accordance with standard editorial and ethical practice, Alexion will generally
support publication of multicenter studies only in their entirety and not as individual
site data. In this case, a Coordinating Investigator will be designated by mutual
agreement.
•
Authorship will be determined by mutual agreement and in line with International
Committee of Medical Journal Editors authorship recommendations and per the
Alexion Publication Policy.
−
Alexion will publish Plain Language Summaries and include patients and/or
caregivers as reviewers for readability and understanding of lay person language.
•
No compensation shall be provided to external Authors for authorship of publication,
including drafting or revising a publication. Alexion may reimburse the presenting
Author of an Alexion-supported publication for travel, lodging, and registration to
present a poster or oral presentation at scientific meeting, consistent with the Alexion
Global Procurement and Sourcing Procedure, the Alexion Antibribery Anticorruption
Policy, and the Alexion Global Travel and Expense Policy.
•
Authors must disclose financial or personal affiliations that could be considered a
conflict of interest in the publication.
−
Investigators who participate as authors in manuscripts derived from Alexion
sponsored studies will agree to the prerequisites as outlined in the Alexion Author
Letter of Agreement prior to engaging in manuscript development.
•
More details are provided in the Alexion/AstraZeneca Publication Policy
10.1.11. 
Good Clinical Practice Compliance 
Alexion and any third party to whom aspects of the study management or monitoring have been 
delegated will undertake their assigned roles for this study in compliance with all applicable 
industry regulations, ICH GCP Guideline E6 R2, EU Directive 2001/20/EC, EU CTR 536/2014 
as well as all applicable national and local laws and regulations. 
Visits to sites are conducted by representatives of Alexion and/or the company 
organizing/managing the research on behalf of Alexion to inspect study data, participants’ 
medical records, and eCRFs in accordance with current GCP and respective local and 
(inter)national government regulations and guidelines. Records and data may additionally be 
reviewed by auditors or by regulatory authorities. 
Alexion ensures that local regulatory authority requirements are met before the start of the study. 
Alexion (or designee) is responsible for the preparation, submission, and confirmation of receipt 
Page 99 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
of any regulatory authority approvals required prior to release of the study drug for shipment to 
the site. 
Page 100 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
10.2. 
Disease Classification of Age-Related Macular Degeneration 
The disease classification of AMD is presented in Table 11. The definitions to be used in 
analyses will be outlined by the Reading Center documentations. 
Table 11: 
Clinical Classification of AMD 
Classification of 
AMD 
Subcategory 
Definition 
No apparent aging 
changesa 
N/A 
•
No drusen AND
•
No AMD pigmentary abnormalitiesb
Normal aging 
changesa 
N/A 
•
Only drupelets (small drusen ≤ 63 µm) AND
•
No AMD pigmentary abnormalitiesb
Early dry AMDa 
N/A 
•
Medium drusen > 63 µm and ≤ 125 µm AND
•
No AMD pigmentary abnormalitiesb
Intermediate dry 
AMDa  
(iAMD) 
High-risk drusen 
Large soft drusen, drusen with hollow core, or 
subretinal drusenoid deposit observed in SD-OCTc 
Non-exudative 
neovascular AMDd 
Evidence of macular neovascularization by SD-OCT, 
but no leakage on FA and no macular fluid by SD-OCT 
imaging 
iRORAe 
•
A region of signal hypertransmission into the
choroid, AND
•
A corresponding zone of attenuation or disruption
of the RPE, with or without persistence of basal
laminar deposits, AND
•
Evidence of overlying photoreceptor
degeneration, that is, subsidence of the INL and
OPL, presence of a hyporeflective wedge in the
HFL, thinning of the ONL, disruption of the
ELM, or disintegrity of the EZ, AND
•
When these criteria do not meet the definition of
cRORA
Page 101 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Table 11: 
Clinical Classification of AMD 
Classification of 
AMD 
Subcategory 
Definition 
Late wet (exudative 
neovascular) or dry 
(geographic atrophy) 
AMDa 
cRORAf 
•
Region of hypertransmission of at least 250 μm in
diameter in any lateral dimension, AND
•
Zone of attenuation or disruption of the RPE of at
least 250 μm in diameter, AND
•
Evidence of overlying photoreceptor
degeneration. Features of photoreceptor
degeneration include all of the following:
−
loss of the IZ, EZ, and ELM and
thinning of the ONL.
•
AND absence of scrolled RPE or other signs of an
RPE tear.
Exudative 
neovascular AMDd 
•
Evidence of macular neovascularization and
macular fluid by SD-OCT, evidence of leakage on
FA.
a Ferris (2013) Beckman Initiative for Macular Research Classification Committee
b AMD pigmentary abnormalities are any definite hyper- or hypopigmentary abnormalities associated with medium 
or large drusen but not associated with known disease entities
c Zweifel (2010)
d Laiginhas (2020)
e Guymer (2020) Classification of Atrophy Meeting Report 4
f Sadda (2018) Classification of Atrophy Meeting Report 3
Abbreviations: AMD = age-related macular degeneration; cRORA = complete RPE and outer retinal atrophy; 
ELM = external limiting membrane; EZ = ellipsoid zone; FA = fluorescein angiography; HFL = Henle fiber layer; 
iAMD = intermediate AMD; INL = inner nuclear layer; iRORA = incomplete RPE and outer retinal atrophy; 
IZ = interdigitation zone; N/A = not applicable; OCT = optical coherence tomography; ONL = outer nuclear layer; 
OPL = outer plexiform layer; RPE = retinal pigment epithelium; SD-OCT = spectral-domain optical coherence 
tomography 
Page 102 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
10.3. 
Ocular Assessments 
It is recommended that ocular assessments should be performed according to the sequence 
described below. Assessments that do not require dilation must be performed before dilation is 
implemented. 
All assessments must be performed by trained and certified personnel (eg, a licensed medical 
doctor of ophthalmology or ocular technician) according to the Central Reading Manual. 
10.3.1. 
Best-Corrected Visual Acuity Testing 
BCVA will be measured at following schedule specified in the SoA (Section 1.3) prior to 
dilation. Monocular BCVA for both eyes and binocular BCVA tests will be conducted. 
•
The following are needed to conduct the examination:
a.
Examination lane of adequate dimensions to allow testing at required starting
distance of 4 meters
b. Standard chair with a firm back
c.
Set of 3 visual acuity charts (Original Series ETDRS Charts R, 1, and 2, EU Wide
ETDRS Charts 1, 2, 3, or PV Number Charts 2750, 2750A, and 2750B)
d. Retro-illuminated fluorescent or LED lightbox
e.
Study frame
f.
Study lens set
•
A VA specifications document, procedure manual, and training materials will be
provided to the investigational sites.
•
The VA examination room and equipment must be validated before any VA
examinations are performed.
10.3.2. 
Low Luminance Best-Corrected Visual Acuity Testing
The same requirements as the BCVA described in Section 10.3.1 apply for LL BCVA. In 
addition, LLVA will be measured by placing a 2.0-log-unit neutral density filter (Kodak Wratten 
2.0 Neutral Density Filter) over the best correction for that eye and having the patient read the 
normally illuminated ETDRS charts. 
10.3.3. 
Reading Speed Testing 
One of two reading speed instruments may be used. Reading speed testing is only applicable if 
the charts are available in the local language. 
10.3.3.1. Minnesota Low-Vision Reading Test (MNRead) 
The MNRead acuity cards can be used to measure the reading speed according to the schedule 
specified in the SoA (Section 1.3). Both monocular and binocular reading speed will be 
recorded. The MNRead acuity cards consist of single, simple sentences with equal numbers of 
characters. The print is a proportionally spaced font, similar to that found in many newspapers 
and books. The cards contain sentences with 19 different print sizes. The text is printed with high 
contrast (approximately 85%). Each sentence contains 60 characters (including space between 
each word and at the end of each line) printed as three lines with even left and right margins. The 
Page 103 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
vocabulary used in the sentences is selected from words appearing with high frequency in 
second- to third-grade reading materials (Calabrèse, 2016). The detailed information about 
equipment required, card illumination, viewing distance, test procedure and instruction to 
patients will be provided to the study sites prior to the start of the study. Examples of the 
MNReading Charts are found in https://www.precision-vision.com/products/visual-acuity-
reading-charts/reading-charts/hand-held-reading-charts/mnread-chart-in-english-spanish/. 
10.3.3.2. Radner Reading Cards 
The Radner Reading Cards (Radner, 2017) can be used to measure the reading speed if MNRead 
card is not available. The assessment is to be conducted in each eye separately and then with 
both eyes open at the schedule specified in the SoA (Section 1.3). The test consists of 24 short 
sentences that are highly comparable in terms of number of words, word length, position of 
words, lexical difficulty, and syntactical complexity. The detailed information about equipment 
required, card illumination, viewing distance, test procedure and instruction to patients will be 
provided to the study sites prior to the start of the study. Examples of the Radner Reading Card 
are found in https://www.precision-vision.com/products/visual-acuity-reading-charts/reading-
charts/hand-held-reading-charts/radner-reading-chart-in-multiple-languages/. 
10.3.4. 
Mesopic Microperimetry at Selected Sites 
Mesopic microperimetry will be performed in a subset of patients (microperimetry 
subpopulation). 
Assessments with a validated microperimetry device will be performed at the schedule specified 
in the SoA (Section 1.3). 
The test should be performed by certified personnel trained on the microperimetry device using 
grid customized for the study.  
The microperimetry will be performed on patients who meet eligibility criteria as defined in the 
inclusion and exclusion criteria (Section 5). If the Investigator determines that both eyes of a 
patient meet the eligibility criteria for study eye, mesopic microperimetry will be performed on 
both eyes at Screening. Two tests per eye will be performed and up to 3 attempts are allowed to 
meet eligibility criteria during the Screening Visit. 
The Central Reading Center will provide the study manual and training materials. 
Microperimetry operators, systems, and software will be certified prior to any evaluation of 
patients. 
10.3.5. 
Slit-lamp Examination 
Slit lamp biomicroscopy must be completed by a licensed medical doctor of ophthalmology or 
ocular technician. 
It will be performed for both eyes at the schedule specified in the SoA (Section 1.3) to assess 
eyelids/conjunctiva, cornea, iris, pupil, lens, anterior chamber, and anterior vitreous. 
10.3.6. 
Tonometry/Intraocular Pressure 
Intraocular pressure will be conducted for both eyes after all VA assessments have been 
conducted. 
Page 104 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
•
Measure IOP according to the Investigator’s standard of care, recommended prior to
dilating the eyes. Goldmann applanation tonometry must be used at Screening. Tono-pen
or other calibrated tonometers can be used at other times. Goldmann applanation
tonometry must also be used to verify the reading of ≥ 30 mmHg occurring at any time
•
Within a single patient, utilize the same instrument type to measure IOP during each visit
after screening.
•
Record the measurement in mmHg.
10.3.7. 
Dilated Binocular Indirect High-Magnification Ophthalmoscopy 
Dilated fundus examination for both eyes will be performed using indirect high magnification 
ophthalmoscopy by a licensed medical doctor of ophthalmology or ocular technician. 
•
Assess the vitreous, retina, macula, choroid, optic nerve, and cup/disc ratio.
•
Document all clinical observations.
10.3.8. 
Ocular Imaging Assessments 
•
Ocular images will be taken after dilation.
•
The Central Reading Center will provide sites with the Central Reading Manual and
training materials for specified study ocular images and microperimetry (at selected
sites). Before any study images and microperimetry are obtained, site personnel, test
images, and systems and software (where applicable) will be certified/validated by the
Central Reading Center as specified in the Central Reading Manual.
•
All ocular images and microperimetry results will be obtained by trained site personnel at
the study sites and forwarded to the Central Reading Center for independent analysis
and/or storage.
•
All images will be transferred to the Central Reading Center as digital files (ie, no printed
images will be sent).
•
For angiography, digital angiograms must be used while conducting angiographic
evaluations. Film-based angiography is not acceptable.
•
All images will be pseudonymized to protect patient privacy.
•
Images will be assessed centrally by graders masked to the patient treatment allocation
•
As much as possible, the same equipment and system will be used for the duration of the
study.
•
Refer to the Central Reading Manual
•
The following imaging assessments will be performed for both eyes, recommended to be
done in the following order:
1. FAF
2. NIR
3. SD-OCT
Page 105 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
4. FA
5. CFP
•
Administration of artificial tears between acquisition of each eye for FAF/NIR and
SD-OCT is recommended.
10.3.9. 
Biometry 
At Screening, if equipment is available, axial length will be measured for both eyes using 
biometry according to the Investigator’s standard of care.  
10.4. 
Patient-Reported Outcome Instruments 
10.4.1. 
National Eye Institute 25-Item Visual Function Questionnaire 
Detailed information about this questionnaire with the correct version and the validated language 
versions, if needed, will be provided to the study sites prior to the start of the study. More 
information about this questionnaire can be found in https://www.rand.org/health-
care/surveys_tools/vfq.html (Mangione, 2001; Radner, 2017). 
10.4.2. 
EuroQol 5-Dimension 5-Level 
Detailed information about this questionnaire with the correct version and the validated language 
versions, if needed, will be provided to the study sites prior to the start of the study. More 
information about this instrument is found in https://euroqol.org/eq-5d-instruments/eq-5d-5l-
about/. 
10.4.3. 
Lawton Instrumental Activities of Daily Living Scale 
Detailed information about this questionnaire with the correct version and the validated language 
versions, if needed, will be provided to the study sites prior to the start of the study (Graf, 2008). 
Page 106 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
10.5. 
Clinical Laboratory Tests 
•
The tests detailed in Table 12 will be performed by the central laboratory as
indicated.
•
Local laboratory results are only required in the event that the central laboratory
results are not available in time for either study intervention administration and/or
response evaluation. If a local sample is required, it is important that the sample for
central analysis is obtained at the same time. Additionally, if the local laboratory
results are used to make either a study intervention decision or response evaluation,
the results must be available in the patient’s source documents.
•
Protocol-specific requirements for inclusion or exclusion of patients are detailed in
Section 5.
•
Additional tests may be performed at any time during the study as determined
necessary by the Investigator or required by local regulations.
Table 12: 
Protocol-Required Laboratory Assessments 
Hematology 
Chemistry 
Urinalysis 
Other Assessments1 
Complete blood count 
(CBC), including: 
Red blood cell (RBC) 
count 
White blood cell 
(WBC) count 
WBC differential 
(absolute and 
percent): 
- neutrophils
- lymphocytes
- monocytes
- eosinophils
- basophils
Hematocrit (Hct) 
Hemoglobin (Hgb) 
Mean corpuscular 
volume (MCV)  
Mean corpuscular 
hemoglobin (MCH) 
Mean corpuscular 
hemoglobin 
concentration (MCHC) 
Mean platelet volume 
(MPV) 
Liver function tests: 
-Alanine
aminotransferase
(ALT)
-Alkaline phosphatase
-Aspartate
aminotransferase (AST)
-Gamma-glutamyl
transferase (GGT)
Albumin 
Bicarbonate (HCO3) 
Bilirubin (fractionated)2 
Blood urea nitrogen 
(BUN) 
Calcium 
Calculated eGFR3 
Chloride 
C-reactive protein 
(CRP) 
Creatine kinase4 
Creatinine 
Glucose5 
HbA1c (glycated 
hemoglobin) 
Analysis including: 
Bilirubin 
Color 
Glucose 
Ketones 
Leukocytes 
Nitrite 
Occult blood 
pH 
Protein 
Specific gravity 
Urobilinogen 
Microscopic 
examination of 
sediment 
Biomarkers: 
Alternative pathway 
activity  
Bb 
C3 
Classical pathway 
activity 
Factor D 
Serology: 
-HCV antibody and
HBV antigen
-HIV-1 and HIV-2
antibodies
UGT1A1 (Gilbert’s)6 
Genetic biomarkers 
(optional) 
Drug concentrations for 
PK 
FSH for females 
Page 107 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Table 12: 
Protocol-Required Laboratory Assessments 
Hematology 
Chemistry 
Urinalysis 
Other Assessments1 
Platelet count 
PT/PTT/INR  
Red cell distribution 
width (RDW) 
Reticulocyte count 
(absolute and percent) 
Lactate dehydrogenase 
Lipid profile 
including: 
Cholesterol/HDL ratio 
High-density 
lipoprotein cholesterol 
(HDL-C) 
Low-density 
lipoprotein cholesterol 
(LDL-C) 
Non-HDL-C 
Total cholesterol 
Triglycerides 
Very low-density 
lipoprotein cholesterol 
(VLDLC) 
Potassium 
Sodium 
Total protein 
Uric acid 
1.
Check the SoA for specific time points when these tests should be done.
2.
Fractionate and obtain measurements of direct and indirect bilirubin for all patients. If indirect bilirubin levels
are > ULN at Screening but ALT and AST are normal, test for Gilbert’s syndrome.
3.
Provide estimated glomerular filtration rate (eGFR) based on Chronic Kidney Disease-Epidemiology
Collaboration (CKD-EPI) creatinine equation (2009) for patients ≥ 19 years of age and based on the “bedside
Schwartz” equation (2009) for patients < 19 years of age.
4.
Perform at Baseline, and then subsequently at every visit, a lab sample is collected.
5.
If glucose is > ULN, reflexively test HbA1c.
6.
Test only if medical or family history suggestive of Gilbert’s Syndrome.
Investigators must document their review of each laboratory safety report. 
Laboratory/analyte results that could unmask the study will not be reported to investigative sites 
or other masked personnel until the study has been unmasked. In case emergency unmasking is 
necessary, see Section 6.3.3. 
Page 108 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
10.6. 
Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting 
10.6.1. 
Definition of AE 
AE Definition 
•
An AE is any untoward medical occurrence in a patient administered a pharmaceutical product
and which does not necessarily have to have a causal relationship with this treatment (ICH E2A).
•
Note: An AE can therefore be any unfavorable and unintended sign (including an abnormal
laboratory finding), symptom, or disease [new or exacerbated] temporally associated with the use
of the study drug, whether or not considered related to the study drug.
Events Meeting the AE Definition 
•
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other safety
assessments (eg, ECG, radiological scans, vital signs measurements), including those that worsen
from baseline, considered clinically significant in the medical and scientific judgment of the
Investigator (ie, not related to progression of underlying disease).
•
Exacerbation of a chronic or intermittent pre-existing condition including either an increase in
frequency and/or intensity of the condition.
•
New conditions detected or diagnosed after study drug administration even though it may have
been present before the start of the study.
•
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.
•
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study drug or a
concomitant medication. Overdose per se will not be reported as an AE/SAE unless it is an
intentional overdose taken with possible suicidal/self-harming intent. Such overdoses should be
reported regardless of sequelae.
Events Not Meeting the AE Definition 
•
Medical or surgical procedure (eg, endoscopy, appendectomy): The condition that leads to the
procedure is the AE. Situations in which an untoward medical occurrence did not occur (eg,
hospitalization for elective surgery if planned before the signing the ICF, admissions for social
reasons or for convenience).
•
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or detected at
the start of the study that do not worsen.
•
A medication error (including intentional misuse, abuse, and overdose of the product) or use other
than what is defined in the protocol is not considered an AE unless there is an untoward medical
occurrence as a result of a medication error.
•
Cases of pregnancy that occur during maternal or paternal exposure to study drug are to be reported
within 24 hours of Investigator/site awareness. Data on fetal outcome and breastfeeding will be
collected for regulatory reporting and safety evaluation.
Page 109 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Events Not Meeting the AE Definition 
•
Any clinically significant abnormal laboratory findings or other abnormal safety assessments
which are associated with the underlying disease, unless judged by the Investigator to be more
severe than expected for the patient’s condition.
•
The disease/disorder being studied or expected progression, signs, or symptoms of the
disease/disorder being studied, unless more severe than expected for the patient’s condition.
•
Situations in which an untoward medical occurrence did not occur (social and/or convenience
admission to a hospital).
•
“Lack of efficacy” or “failure of expected pharmacological action” per se will not be reported as an
AE or SAE. Such instances will be captured in the efficacy assessments. However, the signs,
symptoms, and/or clinical sequelae resulting from lack of efficacy will be reported as AE or SAE if
they fulfil the definition of an AE or SAE.
10.6.2. 
Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (eg, hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease). 
An SAE is defined as any untoward medical occurrence that, at any dose: 
1.
Results in death
2.
Is life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which the patient was at 
risk of death at the time of the event. It does not refer to an event, which hypothetically might have 
caused death, if it was more severe. 
3.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the patient has been detained (usually involving at least an 
overnight stay) at the hospital or emergency ward for observation and/or treatment that would not have 
been appropriate in the physician’s office or outpatient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfills any other serious criteria, 
the event is serious. When in doubt as to whether “hospitalization” occurred or was necessary, the AE 
should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from Baseline is 
not considered an AE. 
4.
Results in persistent disability/incapacity
•
The term disability means a substantial disruption of a person’s ability to conduct normal life
functions.
•
This definition is not intended to include experiences of relatively minor medical significance such
as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma (eg,
sprained ankle) which may interfere with or prevent everyday life functions but do not constitute a
substantial disruption.
5.
Is a congenital anomaly/birth defect
6.
Other situations:
•
Medical or scientific judgment should be exercised in deciding whether SAE reporting is
appropriate in other situations such as important medical events that may not be immediately life-
Page 110 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
An SAE is defined as any untoward medical occurrence that, at any dose: 
threatening or result in death or hospitalization but may jeopardize the patient or may require 
medical or surgical intervention to prevent one of the other outcomes listed in the above 
definition. These events should usually be considered serious. 
•
Examples of such events include invasive or malignant cancers, intensive treatment in an
emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that do
not result in hospitalization, or development of drug dependency or drug abuse.
A suspected unexpected serious adverse reaction (SUSAR) is defined as: 
An event that is assessed as serious by the Investigator and/or Alexion that is not listed in the 
appropriate Reference Safety Information (RSI) and has been assessed that there is at least a reasonable 
possibility that the event is related to the investigational medicinal product by the Investigator and/or 
Alexion. 
Alexion has procedures that will be followed for the recording, medical assessment, and expedited 
reporting of SUSARs that are consistent with global regulations, legislation, and guidance documents. 
Suspected unexpected serious adverse reactions will undergo expedited reporting to the national 
regulatory authorities, IRBs/IECs, and Investigators following local regulatory reporting requirements 
where applicable. 
10.6.3. 
Recording and Follow-Up of AE and/or SAE 
Recording of AE and/or SAE 
•
When an AE/SAE occurs, it is the responsibility of the Investigator to review all documentation
(eg, hospital progress notes, laboratory reports, and diagnostics reports) related to the event.
•
The Investigator will then record all relevant AE/SAE information in the eCRF.
•
It is not acceptable for the Investigator to send photocopies of the patient’s medical records to
Alexion in lieu of completion of the Alexion AE/SAE eCRF page.
•
There may be instances when copies of medical records for certain cases are requested by
Alexion. In this case, all patient identifiers, with the exception of the patient number, will be
redacted on the copies of the medical records before submission to Alexion.
•
The Investigator will attempt to establish a diagnosis of the event based on signs, symptoms,
and/or other clinical information. Whenever possible, the diagnosis (not the individual
signs/symptoms) will be documented as the AE/SAE.
Assessment of Intensity 
The Investigator will make an assessment of intensity for each AE and SAE reported during the study 
and assign it to one of the following categories from National Cancer Institute Common Terminology 
Criteria for Adverse Events (CTCAE) v5.0, published 27 Nov 2017:  
•
Grade 1: Mild (awareness of sign or symptom, but easily tolerated)
•
Grade 2: Moderate (discomfort sufficient to cause interference with normal activities)
•
Grade 3: Severe (incapacitating, with inability to perform normal activities)
•
Grade 4: Life-threatening
•
Grade 5: Fatal
Page 111 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Recording of AE and/or SAE 
An event is defined as “serious” when it meets at least one of the predefined outcomes as described in 
the definition of an SAE, not when it is rated as severe. 
Assessment of Causality 
•
The Investigator is obligated to assess the relationship between the study drug and each
occurrence of each AE or SAE. An Investigator causality assessment must be provided for all AEs
(both nonserious and serious). This assessment must be recorded in the eCRF and on any
additional forms, as appropriate. The definitions for the causality assessments are as follows:
−
Not related: There is no reasonable possibility the study drug caused the AE.
−
The AE has a more likely alternative etiology; it may be due to
underlying or concurrent illness, complications, concurrent treatments, or
effects of another concurrent drug.
−
The event does not follow a reasonable temporal relationship to
administration of the study drug.
−
Related: There is a reasonable possibility the study drug caused the AE.
−
The AE has a temporal relationship to the administration of the study
drug.
−
The event does not have a likely alternative etiology.
−
The event corresponds with the known pharmaceutical profile of the
study drug.
−
There is improvement on discontinuation and/or reappearance on
rechallenge.
•
The Investigator will use clinical judgment to determine the relationship.
•
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, as
well as the temporal relationship of the event to study drug administration will be considered and
investigated.
•
The Investigator will also consult the IB and/or Product Information, for marketed products, in
his/her assessment.
•
For each AE/SAE, the Investigator must document in the medical notes that he/she has reviewed
the AE/SAE and has provided an assessment of causality.
•
There may be situations in which an SAE has occurred, and the Investigator has minimal
information to include in the initial report to Alexion. However, it is very important that the
Investigator always make an assessment of causality for every event before the initial transmission
of the SAE data to Alexion.
•
The Investigator may change his/her opinion of causality in light of follow-up information and
send an SAE follow-up report with the updated causality assessment.
•
The causality assessment is one of the criteria used when determining regulatory reporting
requirements.
Follow-up of AEs and SAEs 
•
The Investigator is obligated to perform or arrange for the conduct of supplemental
measurements and/or evaluations as medically indicated or as requested by Alexion to elucidate
Page 112 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Follow-up of AEs and SAEs 
the nature and/or causality of the AE or SAE as fully as possible. This may include additional 
laboratory tests or investigations, histopathological examinations, or consultation with other 
health care professionals. 
•
New or updated information will be recorded in the originally completed eCRF.
•
The Investigator will submit any updated SAE data to Alexion within 24 hours of receipt of the
information.
10.6.4. 
Reporting of SAEs 
SAE Reporting to Alexion via an Electronic Data Collection Tool 
•
All SAEs will be recorded and reported to Alexion immediately and within 24 hours of
awareness.
•
The primary mechanism for reporting an SAE to Alexion will be the EDC system.
•
If the electronic system is unavailable or site staff is unable to process the SAE via the EDC
system at the time that the Investigator or site becomes aware of an SAE, the site will use the
paper Contingency Form for SAE Reporting via facsimile or email. Facsimile transmission or
email may also be used in the event of electronic submission failure.
−
Email: clinicalsae@alexion.com or Fax: + 1.203.439.9347
•
The site will enter the SAE data into the EDC system as soon as it becomes available.
•
When further information becomes available, the EDC should be updated immediately with the
new information and an updated SAE report should be submitted to Alexion Global Drug Safety
(GDS) within 24 hours of Investigator/site awareness.
•
After the patient has completed the study, no new data or changes to existing data are expected to
be entered in the EDC system.
o
If a site receives a report of a new SAE from a study patient which the Investigator
considers to be related to the study drug, or the site receives updated data on a
previously reported SAE after the EDC system has been taken offline, then the site can
report this information on a paper Contingency Form for SAE Reporting via facsimile
or email.
10.6.5. 
Unexpected Events 
Apart from the reporting of SUSARs, there may be other events which are relevant in terms of 
benefit-risk balance and which should be reported in a timely manner according to regional and 
national requirements eg, EU CTR 536/2014 (48). It is important for patient safety that, in 
addition to SAEs and reactions, all unexpected events that might materially influence the benefit-
risk assessment of the study intervention or that would lead to changes in the administration of 
the study intervention or in overall conduct of a clinical trial should be reported. Examples of 
such unexpected events include an increase in the rate of occurrence of expected serious adverse 
reactions which may be clinically important, a significant hazard to the patient population, such 
as lack of efficacy of a medicinal product, or a major safety finding from a newly completed 
animal study (such as, carcinogenicity). 
Under the EU CTR 536/2014 (49), where unexpected events require an urgent modification of a 
clinical trial, it should be possible for Alexion and the Investigator to take urgent safety measures 
Page 113 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
without awaiting prior authorization. If such measures constitute a temporary halt of the clinical 
trial, Alexion should apply for a substantial modification before restarting the clinical trial. 
Page 114 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
10.7. 
Medication Error, Drug Abuse, and Drug Misuse 
Medication Error 
For the purposes of this clinical study a medication error is an unintended failure or mistake in 
the treatment process for an IMP or Alexion AxMP that either causes harm to the participant or 
has the potential to cause harm to the participant.  
Any events of medication error, with or without associated AEs, are to be captured and 
forwarded to Alexion Global Patient Safety via email or facsimile (clinicalsae@alexion.com or + 
1.203.439.9347) using the Alexion Clinical Study Medication Error Report Form. 
A medication error is not lack of efficacy of the drug, but rather a human or process related 
failure while the drug is under the control of the study site staff or participant. 
Medication error includes situations where an error: 
•
Occurred
•
Was identified and intercepted before the participant received the drug
•
Did not occur, but circumstances were recognized that could have led to an error
Examples of events to be reported in clinical studies as medication errors: 
•
Drug name confusion
•
Dispensing error, eg, medication prepared incorrectly, even if it was not actually
given to the participant
•
Drug not administered as indicated, eg, wrong route or wrong site of administration
•
Drug not taken as indicated, eg, tablet dissolved in water when it should be taken as a
solid tablet
•
Drug not stored as instructed, eg, kept in the refrigerator when it should be at room
temperature
•
Wrong participant received the medication (excluding Interactive Response
Technology [IRT]/Randomization and Trial Supply Management [RTSM] errors)
•
Wrong drug administered to participant (excluding IRT/RTSM errors)
Examples of events that do not require reporting as medication errors in clinical studies: 
•
Errors related to or resulting from IRT/RTSM - including those which led to one of
the above listed events that would otherwise have been a medication error
•
Participant accidentally missed drug dose(s), eg, forgot to take medication
•
Accidental overdose (will be captured as an overdose (refer to Section 8.5) for
information on overdose])
•
Participant failed to return unused medication or empty packaging
Medication errors are not regarded as AEs but AEs may occur as a consequence of the 
medication error. 
Page 115 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Drug Abuse 
For the purpose of this study, drug abuse is defined as the persistent or sporadic intentional, 
non-therapeutic excessive use of IMP or Alexion AxMP for a perceived reward or desired 
non-therapeutic effect. 
Any events of drug abuse, with or without associated AEs, are to be captured and forwarded to 
Alexion Global Patient Safety via email or facsimile (clinicalsae@alexion.com or + 
1.203.439.9347) using the Alexion Clinical Study Drug Misuse or Drug Abuse Report Form. 
This form should be used both if the drug abuse happened in a study participant or if the drug 
abuse involves a person not enrolled in the study (such as a relative of the study participant). 
Examples of drug abuse include but are not limited to: 
•
The drug is used with the intent of getting a perceived reward (by the study
participant or a person not enrolled in the study)
•
The drug in the form of a tablet is crushed and injected or snorted with the intent of
getting high
Drug Misuse 
Drug misuse is the intentional and inappropriate use (by a study participant) of IMP or Alexion 
AxMP for medicinal purposes outside of the authorized product information, or for unauthorized 
IMPs or Alexion AxMPs, outside the intended use as specified in the protocol, including 
deliberate administration of the product by the wrong route. 
Events of drug misuse, with or without associated AEs, are to be captured and forwarded to 
Alexion Global Patient Safety via email or facsimile (clinicalsae@alexion.com or + 
1.203.439.9347) using the Alexion Clinical Study Drug Misuse or Drug Abuse Report Form. 
This form should be used both if the drug misuse happened in a study participant or if the drug 
misuse involves a person not enrolled in the study (such as a relative of the study participant). 
Examples of drug misuse include but are not limited to: 
•
The drug is used with the intention to cause an effect in another person
•
The drug is sold to other people for recreational purposes
•
The drug is used to facilitate assault in another person
•
The drug is deliberately administered by the wrong route
•
The drug is split in half because it is easier to swallow, when it is stated in the
protocol that it must be swallowed whole
•
Only half the dose is taken because the study participant feels that he/she is feeling
better when not taking the whole dose
•
Someone who is not enrolled in the study intentionally takes the drug
Page 116 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
10.8. 
Contraceptive Guidance and Collection of Pregnancy Information 
10.8.1. 
Definitions 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile. Permanent sterilization methods include hysterectomy, bilateral 
salpingectomy, and bilateral oophorectomy. 
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study intervention, additional evaluation should be considered. 
Postmenopausal Female 
A postmenopausal state is defined as no menses for 12 months without an alternative medical 
cause prior to the Day 1 Visit. 
A high FSH level in the postmenopausal range will be used to confirm a postmenopausal state in 
women not using hormonal contraception or hormone replacement therapy (HRT). However, in 
the absence of 12 months of amenorrhea, confirmation with more than one FSH measurement 
may be required.  
Females on HRT and whose menopausal status is in doubt will be required to use one of the non-
estrogen hormonal, highly effective contraception methods if they wish to continue their HRT 
during the study. Otherwise, they must discontinue HRT to allow confirmation of 
postmenopausal status before study enrollment. 
10.8.2. 
Contraception Guidance for Female Patients 
All female patients in this study are postmenopausal and of non-child-bearing potential as 
confirmed by FSH test at Screening. Contraception for female patients is not needed. 
10.8.3. 
Contraception Guidance for Male Patients 
Contraceptive use by male patients should be consistent with local regulations regarding the 
methods of contraception utilized for those participating in clinical studies. If teratogenic effects 
are suspected to be transferred to a fetus/embryo from a female spouse/partner of a male patient, 
pregnancy follow-up information will be obtained for the partner who becomes pregnant (refer to 
Section 10.8.4.1). In these cases, follow-up will be conducted on the pregnant partner in the same 
manner as a female patient who becomes pregnant during the study. 
10.8.3.1. Guidance for Male Patients 
Contraception is the responsibility of the heterosexually active male patients in the study, 
regardless of his female partner’s method of contraception. 
Male patients who have had a vasectomy > 6 months prior to the first dose of the study drug 
must use a condom with or without spermicide during heterosexual intercourse. Male patients 
who have had a vasectomy < 6 months prior to the first dose of the study drug and those who 
have not had a vasectomy must use a condom with or without spermicide during heterosexual 
intercourse for at least 90 days after their final dose of the study drug. 
Page 117 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
10.8.3.2. Sexual Abstinence for Male Patients 
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse. In this study, abstinence is only acceptable if consistent with the 
patient’s preferred and usual lifestyle. Abstinent male patients who become heterosexually active 
must use a condom with or without spermicide during intercourse. 
Periodic abstinence (eg, calendar, symptothermal, or post ovulation methods for a female 
partner) is not considered a highly effective method of contraception for male patients. 
Male patients must not donate sperm from the Day 1 Visit until 90 days after their final dose of 
the study drug. 
10.8.4. 
Collection of Pregnancy Information 
Pregnancy data will be collected during this study for all female spouses/partners of male 
patients after the first dose of study drug.  
Exposure during pregnancy (also referred to as exposure in utero) can be the result of either 
maternal exposure or transmission of study drug via semen following paternal exposure. If a 
male patient’s female spouse/partner becomes pregnant during the conduct of this study, the 
Investigator must submit the “Pregnancy/Breastfeeding Reporting and Outcome Form” to 
Alexion GDS via facsimile or email. When the outcome of the pregnancy becomes known, the 
form should be updated and submitted to Alexion GDS. If additional follow-up is required, the 
Investigator will be requested to provide the information. 
Pregnancy is not regarded as an AE unless there is a suspicion that the study drug may have 
interfered with the effectiveness of a contraceptive medication. However, complications of 
pregnancy and abnormal outcomes of pregnancy are AEs and may meet the criteria for an SAE 
(eg, ectopic pregnancy, spontaneous abortion, intrauterine fetal demise, neonatal death, or 
congenital anomaly). Elective abortions without complications should not be reported as AEs. 
10.8.4.1. Male Patients with Partners Who Become Pregnant 
•
The Investigator will attempt to collect pregnancy information on any male patient’s
female partner who becomes pregnant while the male patient is in this study. This
applies only to male patients who receive the study drug.
•
After obtaining the necessary signed informed consent from the pregnant female
partner directly, the Investigator will record pregnancy information on the appropriate
“Pregnancy/Breastfeeding Reporting and Outcome Form” and submit it to Alexion
within 24 hours of learning of the partner’s pregnancy. The female partner will also
be followed to determine the outcome of the pregnancy. Information on the status of
the mother and child will be forwarded to Alexion. Generally, the follow-up will be
no longer than 3 months following the delivery date. Any termination of the
pregnancy will be reported regardless of fetal status (presence or absence of
anomalies) or indication for the procedure.
Page 118 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
10.9. 
Allowed Medications 
Clinically significant drug-drug interaction between danicopan and medications that are 
substrates of cytochrome P450 subfamily 3A4 (CYP3A4), and/or uridine 5’-diphospho-
glucuronosyltransferase (UGT) are not anticipated (see Investigator’s Brochure).  
Clinical drug-drug interaction studies indicate that danicopan is an inhibitor of P-gp and BCRP 
transporters. Caution may be needed when co-administering danicopan with drugs known to be 
P-gp and/or BCRP substrates (eg, some statins). For more details, refer to the Investigator’s
Brochure.
For ease of reference, a non-comprehensive list of medications that are sensitive substrates for 
CYP3A4, P-gp, and/or UGT1A1/2B7, which are allowed in this patient population, is provided 
in Error! Reference source not found. below. 
Use of specific concomitant medications with a narrow therapeutic index (ie, P-gp or BCRP 
substrates) will be considered on a case-by-case basis with decisions made by the Principal 
Investigator in discussion with the Medical Monitor, based on available knowledge of danicopan 
as well as the characteristics of the potential concomitant medication. 
Table 13: 
List of CYP3A4, P-gp, and UGT1A1/2B7 Sensitive Substrates 
Classification 
Medication 
CYP3A4 substrate 
alfentanil, aliskirenb, ambrisentanb, apixabanb, atorvastatina, avanafil, 
azithromycinb, budesonide, buprenorphine, buspirone, cannabidiol, 
cerivastatina,b, colchicineb, conivaptan, cyclosporineb, dabigatran etexilateb, 
darifenacin, darunavir, dasatinib, domperidoneb, dronedarone, ebastine, 
eletriptan, eplerenone, everolimus, felodipine, fentanyl, ibrutinib, 
indinavir, irinotecan, lomitapide, loperamideb, lovastatina, lurasidone, 
maraviroc, midazolam, naloxegol, nisoldipine, quetiapine, quinidineb, 
ranolazineb, rivaroxabanb, saquinavir, sildenafil, simvastatina, sirolimusb, 
tacrolimusb, ticagrelorb, tipranavir, tolvaptan, triazolam, upadacitinibb, 
vardenafil, venetoclaxb 
P-gp substratec 
aliskiren, ambrisentan, apixaban, atorvastatin, azithromycin, berotralstat, 
cerivastatin, colchicine, cyclosporine, dabigatran etexilate, digoxin, 
domperidone, edoxaban, fexofenadine, loperamide, phenytoin, quinidine, 
ranolazine, rivaroxaban, sirolimus, tacrolimus, ticagrelor, upadacitinib, 
venetoclax 
UGT1A1 substrate 
buprenorphine, carvedilol, dabigatran etexilate, irinotecan, telmisartan 
UGT2B7 substrate 
acemetacin, ambrisentan, buprenorphine, cannabidiol, carvedilol, codeine, 
dabigatran etexilate, diclofenac, etodolac, flurbiprofen, ibuprofen, 
indomethacin, ketorolac, lorazepam, loxoprofen, naloxone, naproxen, 
oxazepam, suprofen, zaltoprofen 
Abbreviations: CYP = cytochrome P450 subfamily 3A4; P-gp = P-glycoprotein; 
UGT = uridine 5’-diphospho-glucuronosyltransferase 
a These CYP3A substrates are also BCRP substrates; caution may be needed in co-administering with danicopan. 
b These CYP3A substrates are also P-gp substrates; caution may be needed in co-administering with danicopan.  
c Caution may be needed in co-administering with danicopan.
Page 119 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
10.10. 
Handling of Human Biological Samples 
All research and biological samples, including those for possible future research, are subject to 
national regulations and will only be conducted in a specified country if approved in that 
country. 
Handling, storage, and shipment of biological samples are detailed in the laboratory manual. 
10.10.1. 
Chain of Custody 
A full chain of custody is maintained for all samples throughout their lifecycle. 
The Investigator [at each site] keeps full traceability of collected biological samples from the 
participants while in storage at the site until shipment or disposal (where appropriate) and 
records relevant processing information related to the samples while at the site. 
The sample receiver keeps full traceability of the samples while in storage and during use until 
used or disposed of or until further shipment and keeps record of receipt of arrival and onward 
shipment or disposal. 
Alexion or delegated representatives will keep oversight of the entire life cycle through internal 
procedures, monitoring of study sites, auditing or process checks, and contractual requirements 
of external laboratory providers. 
Samples retained for further use will be stored in the Alexion-assigned biobanks or other sample 
archive facilities and will be tracked by the appropriate Alexion team for the remainder of the 
sample life cycle. 
All appropriately consented samples will be retained will be retained for a maximum of 25 years 
from study completion or as per applicable requirements. 
If required, Alexion will ensure that remaining biological samples are returned to the site 
according to local regulations or at the end of the retention period, whichever is sooner. 
10.10.2. 
Withdrawal of Informed Consent for Donated Biological Samples 
If applicable, Alexion ensures that biological samples are returned to the source or destroyed at 
the end of a specified period as described in the informed consent. 
If a participant withdraws consent to the use of donated biological samples, the samples will be 
disposed of/destroyed/repatriated, and the action documented. If samples are already analyzed, 
Alexion is not obliged to destroy the results of this research. 
Following withdrawal of consent for biological samples, further study participation should be 
considered in relation to the withdrawal processes outlined in the informed consent. 
The Investigator: 
•
Ensures the participant’s withdrawal of informed consent to the use of donated samples is
communicated immediately to Alexion or delegate.
•
Ensures that relevant human biological samples from that participant, if stored at the
study site, are immediately identified, disposed of as appropriate, and the action
documented.
Page 120 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
•
Ensures that the participant and Alexion are informed about the sample disposal.
Alexion ensures the organization(s) holding the samples is/are informed about the withdrawn 
consent immediately and that samples are disposed of or repatriated as appropriate, the action is 
documented, and study site is notified. 
Page 121 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
10.11. 
COVID-19 Risk Assessment 
As such, the benefit a patient may receive from treatment with danicopan is potentially 
significant. Based on the mechanism of action of danicopan and clinical experience, there is no 
evidence to suggest patients will have a higher risk of severe acute respiratory syndrome 
coronavirus 2 (SARS-CoV-2) infection or a more severe course of disease than the general 
population. Risk factors for severe illness as those already observed in the general population 
remain for patients receiving danicopan. The site Investigator will therefore balance the 
risk/benefit considerations in the study patient taking these factors into account.  
The potential operational risks identified, and mitigation measures put in place in light of the 
COVID-19 pandemic are provided in Table 14. 
Table 14: 
Potential Risks and Mitigation Measures due to COVID-19 
Risks category 
Summary of Data/ 
Rationale for Risk 
Mitigation Strategy 
Potential risks 
Healthcare 
institution 
availability for 
non-COVID-19 
related activities 
COVID-19 pandemic may impact the 
workload of healthcare institutions globally 
and may reduce staff availability to perform 
non-urgent activities and non-COVID-19 
related activities. 
During the time that the 
COVID-19 pandemic is active, 
Alexion will not open study sites 
or enroll new patients at sites 
unless the sites have the 
resourcing and capabilities to 
implement the study per 
protocol. 
Data quality and 
integrity 
Lack of availability of site personnel to 
perform study assessments and capture 
study specific data in a timely manner and 
to maintain adequate quality standards. 
Lack of availability of site personnel to 
ensure adequate and continuous chain of 
custody, storage conditions, and monitoring 
for investigational product and biological 
samples. 
Inability of study monitors and quality 
personnel to conduct in-person visits to 
exercise adequate oversight of study 
execution at investigational sites. 
Missing data (COVID-19 pandemic may 
impact study visit schedules and increase 
missed visits and/or patient study 
discontinuations inadvertently resulting in 
During the time that the 
COVID-19 pandemic is active, 
Alexion will only open study 
sites that report enough 
personnel capacity to sufficiently 
conduct clinical study-related 
activities.  
During this timeframe, patient 
eligibility as well as site capacity 
will be reviewed by the site 
Investigator and the study 
Medical Monitor prior to 
Screening. Each site is also 
evaluated for the capacity to 
perform remote monitoring visits 
and remote source data 
verification. 
During the time that the 
COVID-19 pandemic is active, it 
will be important to capture 
Page 122 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Table 14: 
Potential Risks and Mitigation Measures due to COVID-19 
Risks category 
Summary of Data/ 
Rationale for Risk 
Mitigation Strategy 
missing data [eg, for protocol-specified 
procedures]). 
specific information in the eCRF 
that explains the reason the data 
is missing (eg, missed study 
visits or patient study 
discontinuations due to 
COVID-19). 
Abbreviations: COVID-19 = coronavirus disease 2019; eCRF = electronic case report form 
Page 123 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
10.12. 
COVID-19 Vaccine Risk Assessment 
There is currently no information available evaluating the safety and efficacy of COVID-19 
vaccines in participants treated with ALXN2040. It is unlikely that the immune response to a 
COVID-19 vaccine (and therefore the efficacy of the vaccination) would be diminished by 
danicopan administration, based on danicopan’s mechanism of action. It is also unlikely that 
COVID-19 vaccination would impact danicopan’s mechanism of action. 
Vaccination may further activate complement. As a result, patients with complement-mediated 
diseases may experience increased signs and symptoms of their underlying disease. Therefore, 
patients should be closely monitored for disease symptoms after recommended vaccination. 
Because vaccines may activate complement, if possible, consider vaccination when the 
underlying complement-mediated disease is clinically controlled and subsequent complement 
blockade is relatively high, shortly after administration. 
Local and national guidelines should be consulted for recommendations related to COVID-19 
vaccination.  
The potential risks identified and mitigation measures put in place in light of the COVID-19 
vaccination rollout are provided in Table 15. 
Table 15: 
Potential Risks and Mitigation Measures due to COVID-19 Vaccine 
Risks category 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Potential risks 
Data quality and 
integrity 
Missing data due to appointments for 
COVID-19 vaccination or side effects of 
COVID-19 vaccine may impact study visit 
schedules and increase missed visits and/or 
participant study discontinuations, 
inadvertently resulting in missing data (eg, 
for protocol-specified procedures). 
Capture specific information in 
the eCRF that explains the 
reason the data are missing (eg, 
missed study visits due to 
appointments for COVID-19 
vaccination or side effects of 
COVID-19 vaccine).  
Abbreviation: COVID-19 = coronavirus disease 2019; eCRF = electronic case report form 
Page 124 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
10.13. 
Abbreviations 
The following abbreviations and terms are used in this study protocol. 
Table 16: 
Abbreviations and Specialist Terms 
Abbreviation 
Definition 
AE 
adverse event 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AMD 
age-related macular degeneration 
AP 
alternative pathway 
APH 
alternative pathway hemolysis 
AST 
aspartate aminotransferase 
AUC 
area under the concentration-time curve 
AxMP 
auxiliary medicinal product 
Bb 
Bb fragment of complement factor B 
BCRP 
breast cancer resistance protein 
BCVA 
best-corrected visual acuity 
bid 
twice daily 
C3 
complement component 3 
C5 
complement component 5 
CFP 
color fundus photography 
CFR 
Code of Federal Regulations 
CIOMS 
Council for International Organizations of Medical Sciences 
Cmax 
maximum (peak) plasma concentration of the drug 
COVID-19 
coronavirus disease 2019 
CP 
classical pathway 
CRO 
contract research organization 
cRORA 
complete retinal pigment epithelium and outer retinal atrophy 
CSR 
clinical study report 
Ctrough 
concentration at the end of the dosage interval 
CTIS 
Clinical Trials Information System 
CYP3A4 
cytochrome P450 subfamily 3A4 
DA 
disc area 
Page 125 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Table 16: 
Abbreviations and Specialist Terms 
Abbreviation 
Definition 
dB 
decibel 
DMC 
Data Monitoring Committee 
DPIA 
data protection impact assessment 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EOS 
end of study 
EQ‑5D‑5L 
EuroQol 5-dimension 5-level questionnaire 
ET 
early termination 
ETDRS 
Early Treatment Diabetic Retinopathy Study 
EU CTR 
European Union Clinical Trial Regulation 
EU GDPR 
European Union General Data Protection Regulation 
EZ 
ellipsoid zone 
FA 
fluorescein angiography 
FAF 
fundus autofluorescence 
FAS 
full analysis set 
FD 
factor D 
FH 
factor H 
FSH 
follicle-stimulating hormone 
GA 
geographic atrophy 
GCP 
Good Clinical Practice 
GDS 
Global Drug Safety 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
HRT 
hormone replacement therapy 
IA 
interim analysis or interim analyses 
IADL 
Instrumental Activities of Daily Living 
iAMD 
intermediate age-related macular degeneration 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
Page 126 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Table 16: 
Abbreviations and Specialist Terms 
Abbreviation 
Definition 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IEC 
Independent Ethics Committee 
IMP 
investigational medicinal product 
IOP 
intraocular pressure 
IRB 
Institutional Review Board 
iRORA 
incomplete retinal pigment epithelium and outer retinal atrophy 
IRT 
Integrated Response Technology 
IVRS 
interactive voice response system 
IWRS 
interactive web response system 
LL BCVA 
low luminance best-corrected visual acuity 
LLD 
low luminance deficit 
LLVA 
low luminance visual acuity 
MAD 
multiple ascending dose 
MCP-Mod 
Multiple Comparison Procedure and Modeling 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMRM 
mixed-effect model for repeated measures 
MNRead 
Minnesota Low-Vision Reading Test 
nAMD 
neovascular age-related macular degeneration 
NEI VFQ-25 
National Eye Institute Visual Function Questionnaire, 25-item version 
NIR 
near infrared reflectance 
ONL 
outer nuclear layer 
PA 
Protocol amendment 
PD 
pharmacodynamic(s) 
P-gp 
P-glycoprotein 
PK 
pharmacokinetic(s) 
PNH 
paroxysmal nocturnal hemoglobinuria 
POC 
proof of concept 
PRO 
patient reported outcome 
qd 
once daily 
QoL 
quality of life 
Page 127 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Table 16: 
Abbreviations and Specialist Terms 
Abbreviation 
Definition 
QTL 
quality tolerance limit 
RPE 
retinal pigment epithelium 
RTSM 
Randomization and Trial Supply Management 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
standard deviation 
SD-OCT 
spectral-domain optical coherence tomography 
SoA 
schedule of activities 
SOC 
System Organ Class 
sqrt 
square root 
SUSAR 
suspected unexpected serious adverse reaction 
TEAE 
treatment-emergent adverse event 
TESAE 
treatment-emergent serious adverse event 
UGT 
uridine 5’-diphospho-glucuronosyltransferase 
ULN 
upper limit of normal 
VA 
visual acuity 
VEGF 
vascular endothelial growth factor 
WOCBP 
woman of childbearing potential 
Page 128 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
10.14. 
Protocol Amendment History 
The protocol amendment summary of changes table for the current amendment is located 
directly before the Table of Contents. 
DOCUMENT HISTORY 
Document 
Type of 
Amendment 
(Global or 
Country-specific) 
Date 
Summary of Key Changes in the 
Amendment 
Protocol 
Amendment 
2.0 
Global 
30 Mar 2023 
To add exploratory anatomical endpoints 
To add text in preparation for transition 
into EU CTR 
To incorporate changes from 
Administrative Letter #1 
Protocol 
Amendment 
1.0 
Global 
10 May 2022 
To streamline the study design and 
schedule of activities to reduce complexity 
and minimize burden to sites and patients. 
To update objectives and endpoints and 
statistical sections to reflect changes in 
study design and emerging data, 
streamline SoA to minimize complexity 
and patient burden, and incorporate. 
To provide clarification on several 
eligibility criteria based on feedback from 
sites. The changes had no impact on the 
eligibility of randomized patients. 
To update the statistical analysis sections 
to add details on the interim analyses and 
reflect changes in endpoints. 
To include changes implemented in 
country-specific amendments as requested 
by local health authorities. 
Amendment 
0.10 
France 
03 May 2022 
To address feedback on PA 0.8 from the 
French health authorities  
Amendment 
0.9 
Germany 
03 Mar 2022 
To address feedback on PA 0.6 from the 
German health authorities (BfArM) and to 
update inclusion criteria. 
Amendment 
0.8 
France 
15 Feb 2022 
To address feedback from the Independent 
Ethics Committee in France. 
Amendment 
0.7 
Italy 
15 Feb 2022 
To address feedback from health 
authorities in Italy (AIFA) and to add an 
inclusion criterion for extrafoveal GA 
lesions from PA 0.4. 
Page 129 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
DOCUMENT HISTORY 
Amendment 
0.6 
Germany 
10 Feb 2022 
To address questions from the German 
health authorities (BfArM). 
Amendment 
0.5 
UK 
07 Dec 2021 
To add an inclusion criterion for 
extrafoveal GA lesions that was 
implemented in PA 0.4. 
Amendment 
0.4 
Local, Multiple 
Countries 
23 Nov 2021 
To add an inclusion criterion for 
extrafoveal GA lesions. 
Amendment 
0.3 
UK 
22 Nov 2021 
To address questions from MHRA 
Amendment 
0.2 
Local, Multiple 
Countries 
08 Nov 2021 
To add the EudraCT and NCT numbers on 
the 
cover page of the protocol. 
Amendment 
0.1 
Local, Multiple 
Countries 
28 Jul 2021 
To clarify eligibility criteria with respect 
to the use of biometry and for patients 
with history of cataract surgery or 
pathological myopia. 
Original 
Protocol 
Not applicable 
24 Feb 2021 
Not applicable. 
Page 130 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
11.
REFERENCES
Abdelfattah NS, Zhang H, Boyer DS, et al. Drusen volume as a predictor of disease progression 
in patients with late age-related macular degeneration in the fellow eye. Invest Ophthalmol Vis 
Sci. 2016;57(4):1839-1846. 
Alibhai AY, Mehta N, Hickson-Curran S, et al. Test-retest variability of microperimetry in 
geographic atrophy. Int J Retin Vitr. 2020;6:16-16. 
Augood CA, Vingerling JR, de Jong PT, et al. Prevalence of age-related maculopathy in older 
Europeans: the European Eye Study (EUREYE). Arch Ophthalmol. 2006;124(4):529-535. 
Biesma DH, Hannema AJ, van Velzen-Blad H, et al. A family with complement factor D 
deficiency. J Clin Invest. 2001;108(2):233-240. 
Bretz F, Pinheiro JC, Branson M. Combining multiple comparisons and modeling techniques in 
dose-response studies. Biometrics. 2005;61(3):738-748. 
Calabrèse A, Owsley C, McGwin G, Legge GE. Development of a reading accessibility index 
using the MNREAD Acuity Chart. JAMA Ophthalmology. 2016;134(4):398-405. 
Cipriani V, Lorés-Motta L, He F, et al. Increased circulating levels of factor H-related protein 4 
are strongly associated with age-related macular degeneration. Nat Commun. 2020;11(1):778. 
Csaky K, Ferris F, 3rd, Chew EY, Nair P, Cheetham JK, Duncan JL. Report from the NEI/FDA 
endpoints workshop on age-related macular degeneration and inherited retinal diseases. Invest 
Ophthalmol Vis Sci. 2017;58(9):3456-3463. 
Csaky KG, Patel PJ, Sepah YJ, et al. Microperimetry for geographic atrophy secondary to age-
related macular degeneration. Surv Ophthalmol. 2019;64(3):353-364. 
Danis RP, Lavine JA, Domalpally A. Geographic atrophy in patients with advanced dry age-
related macular degeneration: current challenges and future prospects. Clin Ophthalmol. 
2015;9:2159-2174. 
Dugel PU, Singh RP, Koh A, et al. HAWK and HARRIER: Ninety-six-week outcomes from the 
phase 3 trials of brolucizumab for neovascular age-related macular degeneration. 
Ophthalmology. 2020. 
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. 
Ferris FL, 3rd, Wilkinson CP, Bird A, et al. Clinical classification of age-related macular 
degeneration. Ophthalmology. 2013;120(4):844-851. 
Feuer WJ, Yehoshua Z, Gregori G, et al. Square root transformation of geographic atrophy area 
measurements to eliminate dependence of growth rates on baseline lesion measurements: A 
reanalysis of Age-Related Eye Disease Study Report No. 26. JAMA Ophthalmology. 
2013;131(1):110-111. 
Page 131 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Folgar FA, Yuan EL, Sevilla MB, et al. Drusen volume and retinal pigment epithelium abnormal 
thinning volume predict 2-year progression of age-related macular degeneration. 
Ophthalmology. 2016;123(1):39-50.e31. 
Friedman DS, O'Colmain BJ, Muñoz B, et al. Prevalence of age-related macular degeneration in 
the United States. Arch Ophthalmol. 2004;122(4):564-572. 
Fritsche LG, Chen W, Schu M, et al. Seven new loci associated with age-related macular 
degeneration. Nat Genet. 2013;45(4):433-439, 439e431-432. 
Graf C. The Lawton instrumental activities of daily living scale. Am J Nurs. 2008;108(4):52-62; 
quiz 62-53. 
Granoff DM, Kim H, Topaz N, MacNeil J, Wang X, McNamara LA. Differential effects of 
therapeutic complement inhibitors on serum bactericidal activity against non-groupable 
meningococcal isolates recovered from patients treated with eculizumab. Haematologica. 
2019;104(8):e340-e344. 
Guyer DR, Fine SL, Maguire MG, Hawkins BS, Owens SL, Murphy RP. Subfoveal choroidal 
neovascular membranes in age-related macular degeneration. Visual prognosis in eyes with 
relatively good initial visual acuity. Arch Ophthalmol. 1986;104(5):702-705. 
Guymer RH, Rosenfeld PJ, Curcio CA, et al. Incomplete retinal pigment epithelial and outer 
retinal atrophy in age-related macular degeneration: Classification of Atrophy Meeting Report 4. 
Ophthalmology. 2020;127(3):394-409. 
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. Proc Natl Acad Sci U S A. 2005;102(20):7227-7232. 
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. 
Heier J, Singh R, Wykoff C, et al. Efficacy of intravitreal pegcetacoplan in geographic atrophy: 
24 month results from the phase 3 OAKS and DERBY trials.  Retina Society 2022; Pasadena, 
California2022. 
Heier JS, Pieramici D, Chakravarthy U, et al. Visual function decline resulting from geographic 
atrophy: results from the CHROMA and SPECTRI phase 3 trials. Ophthalmol Retina. 
2020;4(7):673-688. 
Hiemstra PS, Langeler E, Compier B, et al. Complete and partial deficiencies of complement 
factor D in a Dutch family. J Clin Invest. 1989;84(6):1957-1961. 
Holz FG, Bindewald-Wittich A, Fleckenstein M, Dreyhaupt J, Scholl HP, Schmitz-Valckenberg 
S. Progression of geographic atrophy and impact of fundus autofluorescence patterns in age-
related macular degeneration. Am J Ophthalmol. 2007;143(3):463-472.
Page 132 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Holz FG, Sadda SR, Busbee B, et al. Efficacy and safety of lampalizumab for geographic 
atrophy due to age-related macular degeneration: CHROMA and SPECTRI phase 3 randomized 
clinical trials. JAMA Ophthalmol. 2018;136(6):666-677. 
Holz FG, Sadda SR, Staurenghi G, et al. Imaging protocols in clinical studies in advanced age-
related macular degeneration: Recommendations from Classification of Atrophy Consensus 
Meetings. Ophthalmology. 2017;124(4):464-478. 
Hwang IK, Shih WJ, De Cani JS. Group sequential designs using a family of type I error 
probability spending functions. Stat Med. 1990;9(12):1439-1445. 
Jaffe GJ, Westby K, Csaky KG, et al. C5 inhibitor avacincaptad pegol for geographic atrophy 
due to age-related macular degeneration: A randomized pivotal phase 2/3 trial. Ophthalmology. 
2020. 
Jones PR, Yasoubi N, Nardini M, Rubin GS. Feasibility of macular integrity assessment (MAIA) 
microperimetry in children: sensitivity, reliability, and fixation stability in healthy observers. 
Invest Ophthalmol Vis Sci. 2016;57(14):6349-6359. 
Klein RJ, Zeiss C, Chew EY, et al. Complement factor H polymorphism in age-related macular 
degeneration. Science. 2005;308(5720):385-389. 
Konar M, Granoff DM. Eculizumab treatment and impaired opsonophagocytic killing of 
meningococci by whole blood from immunized adults. Blood. 2017;130(7):891-899. 
Laiginhas R, Yang J, Rosenfeld PJ, Falcão M. Nonexudative macular neovascularization - A 
systematic review of prevalence, natural history, and recent insights from OCT angiography. 
Ophthalmol Retina. 2020;4(7):651-661. 
Lambert NG, ElShelmani H, Singh MK, et al. Risk factors and biomarkers of age-related 
macular degeneration. Prog Retin Eye Res. 2016;54:64-102. 
Lara-Medina FJ, Esteban O, Bartolome I, C I, Mateo J, Javier AF. New landmarks, signs, and 
findings in optical coherence tomography. In: Michele L, editor. A Practical Guide to Clinical 
Application of OCT in Ophthalmology: IntechOpen; 2019. 
Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities 
of daily living. Gerontologist. 1969;9(3):179-186. 
Leng T, Schwartz J, Nimke D, et al. Dry age-related macular degeneration: distribution of visual 
acuity and progression risk in a large registry. Ophthalmol Ther. 2023;12(1):325-340. 
Liao DS, Grossi FV, El Mehdi D, et al. Complement C3 inhibitor pegcetacoplan for geographic 
atrophy secondary to age-related macular degeneration: a randomized phase 2 trial. 
Ophthalmology. 2020;127(2):186-195. 
Page 133 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Lindblad AS, Clemons TE. Responsiveness of the National Eye Institute Visual Function 
Questionnaire to progression to advanced age-related macular degeneration, vision loss, and lens 
opacity: AREDS Report no. 14. Arch Ophthalmol. 2005;123(9):1207-1214. 
Lindblad AS, Lloyd PC, Clemons TE, et al. Change in area of geographic atrophy in the Age-
Related Eye Disease Study: AREDS report number 26. Arch Ophthalmol. 2009;127(9):1168-
1174. 
Lynch AM, Mandava N, Patnaik JL, et al. Systemic activation of the complement system in 
patients with advanced age-related macular degeneration. Eur J Ophthalmol. 2019;30(5):1061-
1068. 
Mangione CM, Lee PP, Gutierrez PR, Spritzer K, Berry S, Hays RD. Development of the 25-
item National Eye Institute Visual Function Questionnaire. Arch Ophthalmol. 2001;119(7):1050-
1058. 
McHarg S, Clark SJ, Day AJ, Bishop PN. Age-related macular degeneration and the role of the 
complement system. Mol Immunol. 2015;67(1):43-50. 
Merle NS, Church SE, Fremeaux-Bacchi V, Roumenina LT. Complement system part I - 
molecular mechanisms of activation and regulation. Front Immunol. 2015;6:262. 
Merle NS, Noe R, Halbwachs-Mecarelli L, Fremeaux-Bacchi V, Roumenina LT. Complement 
system part II: role in immunity. Front Immunol. 2015b;6:257. 
Mukherjee D, Lad EM, Vann RR, et al. Correlation between macular integrity assessment and 
optical coherence tomography imaging of ellipsoid zone in macular telangiectasia type 2. Invest 
Ophthalmol Vis Sci. 2017;58(6):Bio291-bio299. 
Nebbioso M, Lambiase A, Cerini A, Limoli PG, La Cava M, Greco A. Therapeutic approaches 
with intravitreal injections in geographic atrophy secondary to age-related macular degeneration: 
current drugs and potential molecules. Int J Mol Sci. 2019;20(7). 
Nielsen MK, Lim JI, Bhagat N. Geographic atrophy.: EyeWiki. Am Ac Ophthal; 2020 [cited 
2020 15 Sep]. Available from: https://eyewiki.aao.org/Geographic_atrophy#cite_note-4. 
Pfau M, Müller PL, von der Emde L, et al. Mesopic and dark-adapted two-color fundus-
controlled perimetry in geographic atrophy secondary to age-related macular degeneration. 
Retina. 2020a;40(1):169-180. 
Pfau M, von der Emde L, de Sisternes L, et al. Progression of photoreceptor degeneration in 
geographic atrophy secondary to age-related macular degeneration. JAMA Ophthalmol. 
2020b;138(10):1026-1034. 
Radner W. Reading charts in ophthalmology. Graefes Arch Clin Exp Ophthalmol. 
2017;255(8):1465-1482. 
Page 134 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
Sadda SR, Chakravarthy U, Birch DG, Staurenghi G, Henry EC, Brittain C. Clinical endpoints 
for the study of geographic atrophy secondary to age-related macular degeneration. Retina. 
2016;36(10):1806-1822. 
Sadda SR, Guymer R, Holz FG, et al. Consensus definition for atrophy associated with age-
related macular degeneration on OCT: classification of atrophy report 3. Ophthalmology. 
2018;125(4):537-548. 
Sastre-Ibáñez M, Barreiro-González A, Gallego-Pinazo R, Dolz-Marco R, García-Armendariz B. 
Geographic atrophy: etiopathogenesis and current therapies. Arch Soc Esp Oftalmol. 
2018;93(1):22-34. 
Scholl HP, Charbel Issa P, Walier M, et al. Systemic complement activation in age-related 
macular degeneration. PLoS One. 2008;3(7):e2593. 
Singh R. 2-year outcomes of the pegcetacoplan phase 3 DERBY and OAKS clinical trials for 
GA: Safety and exudative changes.  Angiogenesis, Exudation, and Degeneration 2023; Virtual 
Edition: Bascom Palmer Eye Institute; 2023. 
Sivaprasad S, Tschosik E, Kapre A, et al. Reliability and construct validity of the NEI VFQ-25 in 
a subset of patients with geographic atrophy from the phase 2 Mahalo study. Am J Ophthalmol. 
2018;190:1-8. 
Socié G, Caby-Tosi MP, Marantz JL, et al. Eculizumab in paroxysmal nocturnal 
haemoglobinuria and atypical haemolytic uraemic syndrome: 10-year pharmacovigilance 
analysis. Br J Haematol. 2019;185(2):297-310. 
Sprong T, Roos D, Weemaes C, et al. Deficient alternative complement pathway activation due 
to factor D deficiency by 2 novel mutations in the complement factor D gene in a family with 
meningococcal infections. Blood. 2006;107(12):4865-4870. 
Steinle NC, Pearce I, Monés J, et al. Impact of baseline characteristics on geographic atrophy 
progression in the FILLY trial evaluating the complement C3 inhibitor pegcetacoplan. Am J 
Ophthalmol. 2021;227:116-124. 
Sunness JS, Applegate CA, Haselwood D, Rubin GS. Fixation patterns and reading rates in eyes 
with central scotomas from advanced atrophic age-related macular degeneration and Stargardt 
disease. Ophthalmology. 1996;103(9):1458-1466. 
Sunness JS, Bressler NM, Tian Y, Alexander J, Applegate CA. Measuring geographic atrophy in 
advanced age-related macular degeneration. Invest Ophthalmol Vis Sci. 1999a;40(8):1761-1769. 
Sunness JS, Schuchard RA, Shen N, Rubin GS, Dagnelie G, Haselwood DM. Landmark-driven 
fundus perimetry using the scanning laser ophthalmoscope. Invest Ophthalmol Vis Sci. 
1995;36(9):1863-1874. 
Page 135 of 136 
Alexion Confidential 

Protocol Amendment 3.0 (Global) 
ALXN2040-GA-201 
30 Oct 2023 
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. 
1999b;106(9):1768-1779. 
Tao LW, Wu Z, Guymer RH, Luu CD. Ellipsoid zone on optical coherence tomography: a 
review. Clin Exp Ophthalmol. 2016;44(5):422-430. 
van den Broek B, van Els C, Kuipers B, et al. Multi-component meningococcal serogroup B 
(MenB)-4C vaccine induces effective opsonophagocytic killing in children with a complement 
deficiency. Clin Exp Immunol. 2019;198(3):381-389. 
Weinreb RN, Kaufman PL. The glaucoma research community and FDA look to the future: A 
report from the NEI/FDA CDER Glaucoma Clinical Trial Design and Endpoints Symposium *. 
Investigative Ophthalmology & Visual Science. 2009;50(4):1497-1505. 
Welker SG, Pfau M, Heinemann M, Schmitz-Valckenberg S, Holz FG, Finger RP. Retest 
reliability of mesopic and dark-adapted microperimetry in patients with intermediate age-related 
macular degeneration and age-matched controls. Invest Ophthalmol Vis Sci. 
2018;59(4):Amd152-amd159. 
Wong TY, Chakravarthy U, Klein R, et al. The natural history and prognosis of neovascular age-
related macular degeneration: a systematic review of the literature and meta-analysis. 
Ophthalmology. 2008;115(1):116-126. 
Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease 
burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob 
Health. 2014;2(2):e106-e116. 
Wu Z, Luu CD, Ayton LN, et al. Fundus autofluorescence characteristics of nascent geographic 
atrophy in age-related macular degeneration. Invest Ophthalmol Vis Sci. 2015;56(3):1546-1552. 
Yaspan BL, Williams DF, Holz FG, et al. Targeting factor D of the alternative complement 
pathway reduces geographic atrophy progression secondary to age-related macular degeneration. 
Sci Transl Med. 2017;9(395). 
Yates JR, Sepp T, Matharu BK, et al. Complement C3 variant and the risk of age-related macular 
degeneration. N Engl J Med. 2007;357(6):553-561. 
Yehoshua Z, de Amorim Garcia Filho CA, Nunes RP, et al. Systemic complement inhibition 
with eculizumab for geographic atrophy in age-related macular degeneration: the COMPLETE 
study. Ophthalmology. 2014;121(3):693-701. 
Zweifel SA, Imamura Y, Spaide TC, Fujiwara T, Spaide RF. Prevalence and significance of 
subretinal drusenoid deposits (reticular pseudodrusen) in age-related macular degeneration. 
Ophthalmology. 2010;117(9):1775-1781. 
Page 136 of 136 
Alexion Confidential 

Signature Page for VV-CLIN-012935 v1.0
Signature Page for VV-CLIN-012935 v1.0
Approval
31-Oct-2023 20:53:44 GMT+0000