A Phase IV, Randomised, Single Masked Study Investigating the Efficacy and Safety of Ranibizumab "Inject and Extend" Using an Intensive Retinal Fluid Retreatment Regimen Compared to a Relaxed Retinal Fluid Retreatment Regimen in Patients With Wet Age-related Macular Degeneration (AMD)
Phase: PHASE4
Conditions: Subfoveal Choroidal Neovascularization CNV Secondary to Wet Age-related Macular Degeneration AMD
Sponsor: Novartis Pharmaceuticals

Clinical Development 
RFB002/ranibizumab / NCT01972789
A Phase IV, randomised, controlled, single masked study 
investigating the efficacy and safety of ranibizumab “inject 
and extend” using an intensive retinal fluid retreatment 
regimen compared to a relaxed retinal fluid retreatment 
regimen in patients with wet age-related macular 
degeneration (AMD). 
Project standard In-text and Post-text and appendix 
deliverables 
AUTHOR(S): 
 
DOCUMENT TYPE: 
MAP Documentation 
DOCUMENT STATUS: 
Final version 2.0 
RELEASE DATE: 
19 June 2017 
NUMBER OF PAGES: 
218 
Property of Novartis 
Confidential 
May not be used, divulged, published or otherwise disclosed 
without the consent of Novartis 
Template version 3.1 July 2014 

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CRFB002AAU15/RFB002/Ranibizumab 
 
Deliverables Approval 
 
By my signature, I confirm that this deliverables document has been reviewed by 
Novartis Australia, and has been approved for use on the CRFB002AAU15 study: 
 
Name 
Title / Company 
Signature 
Date 
 
 
 
 
 
 
 
 
 
 
 

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Table of contents 
Table of contents 3 
General guidance .................................................................................................. 5 
1.1 
General guidance on shells in this document ............................................. 5 
1.1.1 
Document headers .................................................................... 5 
1.1.2 
Presentation of table numbering and titles within this document
 5 
1.2 
General strategies of data presentation ...................................................... 5 
1.2.1 
Treatment group labels and ordering ......................................... 5 
1.2.2 
Missing treatment columns ........................................................ 5 
1.2.3 
Order of entries in listings .......................................................... 6 
1.2.4 
Decimal places .......................................................................... 6 
1.2.5 
Baseline Definition ..................................................................... 6 
Overall table of contents for IIS outputs ...................................................................... 7 
2 
Shells and specifications ......................................................... 14 
2.1 
Shells and specifications for Sections 10, 11 and 12 of a standard CSR 
(Text tables and figures) ........................................................................... 14 
Section 10 Study patients ............................................................................... 14 
Section 11 Efficacy ......................................................................................... 16 
Section 12 Safety evaluation .......................................................................... 33 
2.2 
Shells and specifications for Sections 14 and 16 of a standard CSR ....... 38 
Section 14 – Tables, figures referred to but not included in the text ............... 38 
Section 14.1 – Demographic data ................................................................... 38 
Section 14.2 – Efficacy and other non-safety data (e.g. PK, PK/PD, health 
economics, QoL) ..................................................................... 84 
Section 14.3 – Safety data ............................................................................ 145 
Section 14.3.1 – Displays of adverse events ................................................ 152 
Section 14.3.2 – Listings of deaths, other serious and significant adverse 
events .................................................................................... 170 
Section 14.3.3 – Narratives of deaths, other serious and significant adverse 
events (non Biometric deliverables) ....................................... 175 
Section 14.3.4 – Abnormal laboratory value listings ..................................... 175 
Section 16.2 – Patient data listings ............................................................... 178 
Section 16.2.1 – Discontinued patients ......................................................... 178 
Section 16.2.2 – Protocol deviations ............................................................. 180 
Section 16.2.3 – Patients excluded from the efficacy analysis ...................... 181 
Section 16.2.4 – Demographic data .............................................................. 182 

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Section 16.2.5  Compliance and/or drug concentration data ........................ 190 
Section 16.2.6 – Individual efficacy response data and other non-safety data
 196 
Section 16.2.7 – Adverse event listings ........................................................ 207 
Section 16.2.8 – Laboratory measurements ................................................. 213 
Section 16.2.9 – Vital signs, physical findings and other observations related 
to safety listings ..................................................................... 214 
Section 16.2.10 – Listing of subject numbers who reported at least one safety 
event of special interest by event and treatment ................... 218 
Section 16.2.11 – Case retrieval strategy listing ........................................... 218 

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General guidance 
1.1 
General guidance on shells in this document 
1.1.1 
Document headers 
The following header will be used for all Section 14 and Section 16 tables, listings and 
figures outlined in this document:  CRFB002AAU15/RFB002/Ranibizumab. 
1.1.2 
Presentation of table numbering and titles within this document 
In order to facilitate the inclusion of a table of contents for all output, the format of the 
number and title for each layout should be in the Novstyle format “Non-TOC Heading” 
and therefore does not exactly match the layout that is intended for the final deliverable. 
In practice, the numbering and title for all Section 14 and Section 16 tables and listings 
defined in this document will be of the following formats respectively: 
 
Table XX.X-X.X 
Title Title Title Title Title Title 
Analysis set 
 
Listing XX.X-X.X 
Title Title Title Title Title Title 
Analysis set 
1.2 
General strategies of data presentation 
1.2.1 
Treatment group labels and ordering 
The following treatment labels will be used for all tables, listings and figures in the order 
provided here: 
• Intensive 
• Relaxed 
• Total (where applicable) 
1.2.2 
Missing treatment columns 
All treatment columns should be presented as long as data is available for at least one 
treatment group. When information is not available for any treatment groups then “No 
observations available” will be used to reflect that observations are not available for a 
specific table/figure/listing. 
In the case where treatment columns are automatically dropped due to lack of 
events/data etc. output the following footnote will be added: 
Note:  Treatment groups which do not contribute events are not displayed. 

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1.2.3 
Order of entries in listings 
All listings should be sorted by treatment group, site, patient, visit date/event date (in 
the case of multiple observations per visit date/event date, the observations should be 
sorted alphabetically within visit date/event date). 
1.2.4 
Decimal places 
Decimal places for demographic, background and duration of exposure variables will 
be as follows: 
• 3 decimal places for p-values; if p-value is less than 0.001, display <0.001. 
• 2 decimal places for standard errors and standard deviations. 
• 1 decimal place for means and medians. 
• 1 decimal place for min and max. 
• 1 decimal place for percentages. 
• If percentage = 100, no decimal is required. 
Decimal places for efficacy and other safety summary tables and listings will be as 
follows: 
• p-value: 3 decimal places; if p-value is less than 0.001, display <0.001. 
• Standard errors and standard deviations: data precision + 2 decimal places  
• Means and medians: data precision + 1 decimal place  
• Minimums and maximums: same as data precision  
• Percentages: 1 decimal place 
• If percentage = 100, no decimal is required. 
Please ignore current examples of precision in shells. 
1.2.5 
Baseline Definition 
For statistical purposes, baseline will be defined as the last available non-missing value 
collected just prior to the start of treatment in the study eye. 

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Overall table of contents for IIS outputs 
Deliverables Approval ................................................................................................. 2 
Table 10-1 
Patient disposition – n (%) of patients...................................... 14 
Table 10-2 
Protocol Deviations – n (%) of patients and total counts.......... 15 
Table 11.1-1 
Analysis sets – n (%) of patients .............................................. 16 
Table 11.2-1 
Demographic summary by treatment group ............................. 17 
Table 11.2-2 
Baseline Medical History Questions by treatment group ......... 19 
Table 11.2-3 
Medical History - Arterial Thomboembolic Events ................... 20 
Table 11.2-4 
Baseline AMD characteristics (STUDY EYE) by treatment group
 ................................................................................................ 21 
Table 11.4-1.1 
Mean absolute change in BCVA from baseline to months 2, 12 
and 24 ...................................................................................... 29 
Table 11.4-1.2 
Mean absolute change in BCVA from baseline to months 2, 12 
and 24 ...................................................................................... 30 
Table 11.4-2 
Mean change in Central Retinal Thickness from baseline to 
months 2, 12 and 24 (STUDY EYE) ........................................ 31 
Table 11.4-3 
Number of Injections from baseline to month 12 and 24.......... 32 
Table 12.1-1 
Overall exposure ..................................................................... 33 
Table 12.1-2 
Treatment Frequency and Intervals at 12 and 24 months ....... 34 
Table 12.2-1 
Number (%) of patients with AEs by primary system organ class
 ................................................................................................ 35 
Table 14.1-1 
Patient disposition, by treatment .............................................. 39 
Table 14.1-2 
Screening phase subject disposition........................................ 40 
Table 14.1-3 
Protocol deviations, by treatment ............................................ 41 
Table 14.1-4 
Protocol deviations leading to exclusion from analysis sets .... 42 
Table 14.1-5 
Out of Window visits ................................................................ 43 
Table 14.1-6 
Under and Over Treatment due to treatment interval error ...... 44 
Table 14.1-7 
Analysis sets, by treatment ...................................................... 45 
Table 14.1-8 
Randomisation by Site ............................................................. 46 
Table 14.1-9 
Demographics, by treatment .................................................... 47 
Table 14.1-10 
Baseline characteristics by Treatment Group .......................... 49 
Table 14.1-11 
Baseline characteristics by genotyping status ......................... 60 
Table 14.1-12 
Baseline Medical History Questions by treatment group ......... 71 
Table 14.1-13 
Medical History, by primary system organ class, preferred terms 
and treatment .......................................................................... 72 
Table 14.1-14 
Ocular Medical History, by primary system organ class, 
preferred terms ........................................................................ 73 
Table 14.1-15 
Medical History - Arterial Thomboembolic Events ................... 74 

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Table 14.1-16  
Baseline AMD characteristics (STUDY EYE) by treatment group
 ................................................................................................ 75 
Table 14.1-17 
Baseline AMD characteristics (FELLOW EYE) by treatment 
group ....................................................................................... 83 
Figure 14.2-1 
Absolute BCVA over time by treatment ................................... 85 
Figure 14.2-2 
Absolute change in BCVA over time by treatment ................... 86 
Figure 14.2-3 
Visual Acuity over time, stratified by baseline acuity ............... 87 
Figure 14.2-4 
Visual Acuity over time, stratified by baseline acuity ............... 88 
Figure 14.2-5 
Change in BCVA from baseline stratified by visual acuity ....... 89 
Figure 14.2-6 
Change in BCVA from baseline stratified by visual acuity ....... 90 
Figure 14.2-7 
Proportion of Patients with >= 15 letter increase in BCVA from 
baseline, over time by treatment .............................................. 91 
Figure 14.2-8 
Proportion of Patients with >= 15 letter increase in BCVA from 
baseline at Month 12 and 24 ................................................... 92 
Figure 14.2-9 
Proportion of patients achieving >=6/12 vision, over time by 
treatment ................................................................................. 93 
Figure 14.2-10 
Proportion of of patients achieving >=6/12 vision at Month 12 
and 24 ...................................................................................... 94 
Figure 14.2-11 
Proportion of patients showing worse than 6/60 vision, over time 
by treatment ............................................................................. 95 
Figure 14.2-12 
Proportion of of patients showing worse than 6/60 vision at 
Month 12 and 24 ...................................................................... 96 
Figure 14.2-13 
Proportion of patients with IRF and BCVA, over time by 
treatment ................................................................................. 97 
Figure 14.2-14 
Proportion of patients with SRF and BCVA, over time by 
treatment ................................................................................. 98 
Figure 14.2-15 
Proportion of patients with IRF and SRF, and BCVA, over time 
by treatment ............................................................................. 99 
Figure 14.2-16 
Proportion of patients with neither IRF or SRF, and BCVA, over 
time by treatment ................................................................... 100 
Figure 14.2-17 
Proportion of patients with Geographic Atrophy and BCVA, over 
time by treatment ................................................................... 101 
Figure 14.2-18 
Proportion of Patients with IRF over time by treatment ......... 102 
Figure 14.2-19 
Proportion of Patients with SRF over time by treatment ........ 103 
Figure 14.2-20 
Proportion of Patients with IRF and SRF over time by treatment
 .............................................................................................. 104 
Figure 14.2-21 
Proportion of Patients with neither IRF or SRF over time by 
treatment ............................................................................... 105 
Figure 14.2-22 
Proportion of Patients with Geographic Atrophy over time by 
treatment ............................................................................... 106 

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Figure 14.2-23 
Change in geographic atrophy area from baseline over time by 
treatment ............................................................................... 107 
Figure 14.2-24 
Change in Central Subfield Foveal Thickness from baseline, 
over time by treatment ........................................................... 108 
Figure 14.2-25 
Number of injections by treatment at 12 and 24 months........ 109 
Table 14.2-1 
Visual Acuity – Summary and Change from Baseline ........... 110 
Table 14.2-2 
Visual Acuity – Mixed Model Analysis.................................... 111 
Table 14.2-3 
Visual Acuity – Mixed Model Analysis.................................... 111 
Table 14.2-4 
Proportion of Patients with >=15 letters change from baseline – 
Logistic Regression ............................................................... 112 
Table 14.2-4 
Proportion of Patients with less than 15 letters lost change from 
baseline – Logistic Regression .............................................. 114 
Table 14.2-5 
Proportion of Patients who achieve >=6/12 visual acuity – 
Logistic Regression ............................................................... 116 
Table 14.2-6 
Proportion of Patients who achieve <=6/60 visual acuity – 
Logistic Regression ............................................................... 117 
Table 14.2-7 
Interval Decision Summary Table .......................................... 118 
Table 14.2-8 
Number of Injections .............................................................. 119 
Table 14.2-9 
Number of Injections from Baseline to Months 12 and 24 – 
Negative Binomial Regression ............................................... 120 
Table 14.2-10 
Treatment Interval Summary (Based on Interval Decision) ... 121 
Table 14.2-11 
Treatment Interval Summary (Based on Actual Intervals 
between Visits) ...................................................................... 122 
Table 14.2-12 
Treatment Interval Visit Summary (Based on Interval Decision)
 .............................................................................................. 123 
Table 14.2-13 
Treatment Interval Visit Summary (Based on Actual Intervals 
between Visits) ...................................................................... 124 
Table 14.2-14 
Breakpoint Set Interval - Summary ........................................ 125 
Table 14.2-15 
Post-Breakpoint Maximum Inteval - Summary ....................... 126 
Table 14.2-16 
Time to Breakpoint - Summary .............................................. 127 
Table 14.2-17 
Time to Breakpoint – Survival Analysis .................................. 128 
Table 14.2-18 
Geographic Atrophy Area – Summary and Change from 
Baseline (Central Reading Center Data) ............................... 129 
Table 14.2-19 
Geographic Atrophy – Categorical Summary ........................ 130 
Table 14.2-20 
Geographic Atrophy – Survival Analysis ................................ 131 
Table 14.2-21 
Geographic Atrophy – Mixed Model Analysis ........................ 132 
Table 14.2-22 
Geographic Atrophy – Mixed Model Analysis ........................ 133 
Table 14.2-23 
Proportion of Patients with Geographic Atrophy from Baseline to 
Month 24 – Logistic Regression ............................................ 134 

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Table 14.2-24 
Proportion of Patients showing intra-retinal /  sub-retinal fluid, by 
visit ........................................................................................ 135 
Table 14.2-25 
Proportion of patients with SRF at baseline who never resolve 
their SRF (irrespective of their IRF) – Logistic Regression .... 136 
Table 14.2-26 
Proportion of patients with IRF at baseline who never resolve 
their IRF (irrespective of their SRF) – Logistic Regression .... 137 
Table 14.2-27 
Proportion of patients with IRF and SRF at baseline who never 
resolve either their IRF or SRF – Logistic Regression ........... 138 
Table 14.2-28 
Intra-Retinal and Sub-Retinal Fluid – Generalized Estimating 
Equation ................................................................................ 139 
Table 14.2-29 
Central Retinal Thickness – Summary and Change from 
Baseline, by treatment ........................................................... 140 
Table 14.2-30 
Central Retinal Thickness – Mixed Model Analysis ............... 141 
Table 14.2-31 
Genotyping by Treatment ...................................................... 142 
Table 14.2-32 
Genotyping by Race .............................................................. 143 
Table 14.3-1 
Number (%) of patients receiving each dose and regimen of 
study medication by treatment and visit ................................. 145 
Table 14.3-2 
Duration of exposure to study drug, by treatment .................. 146 
Table 14.3-3 
Medications and significant non-drug therapies taken prior to 
the start of study drug by ATC class, preferred term and 
treatment ............................................................................... 147 
Table 14.3-4 
Forbidden concomitant medications and significant non-drug 
therapies after start of study drug by ATC class, preferred term 
and treatment ........................................................................ 148 
Table 14.3-5 
Vital signs by visit and treatment ........................................... 149 
Table 14.3-6 
Ophthalmic Examination – Intraocular Pressure (IOP) by 
treatment ............................................................................... 150 
Listing 14.3-1 
Patients with notably abnormal vital signs ............................. 151 
Table 14.3.1-1 
Incidence of adverse events, regardless of study drug 
relationship, by primary system organ class, preferred term and 
treatment ............................................................................... 153 
Table 14.3.1-2 
Incidence of ocular adverse events, regardless of study drug 
relationship, by primary system organ class, preferred term and 
treatment ............................................................................... 154 
Table 14.3.1-3 
Incidence of adverse events, regardless of study drug 
relationship by primary system organ class, preferred term, 
maximum severity and treatment ........................................... 155 
Table 14.3.1-4 
Incidence of ocular adverse events, regardless of study drug 
relationship by primary system organ class, preferred term, 
maximum severity and treatment ........................................... 156 

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Table 14.3.1-5 
Incidence of adverse events, by primary system organ class, 
preferred term, maximum relationship to study drug and 
treatment ............................................................................... 157 
Table 14.3.1-6 
Incidence of adverse events suspected to be related to study 
drug, by primary system organ class, preferred term and 
treatment ............................................................................... 158 
Table 14.3.1-7 
Incidence of ocular adverse events suspected to be related to 
study drug, by primary system organ class, preferred term and 
treatment ............................................................................... 159 
Table 14.3.1-8 
Incidence of serious adverse events, regardless of study drug 
relationship, by primary system organ class, preferred term and 
treatment ............................................................................... 160 
Table 14.3.1-9 
Incidence of ocular serious adverse events, regardless of study 
drug relationship, by primary system organ class, preferred term 
and treatment ........................................................................ 161 
Table 14.3.1-10 
Incidence of adverse events leading to treatment withdrawal, 
regardless of study drug relationship, by primary system organ 
class, preferred term and treatment ....................................... 162 
Table 14.3.1-11 
Incidence of ocular adverse events leading to treatment 
withdrawal, regardless of study drug relationship, by primary 
system organ class, preferred term and treatment ................ 163 
Table 14.3.1-12 
Incidence of adverse events leading to study drug interruption, 
regardless of study drug relationship, by primary system organ 
class, preferred term and treatment ....................................... 164 
Table 14.3.1-13 
Incidence of ocular adverse events leading to study drug 
interruption, regardless of study drug relationship, by primary 
system organ class, preferred term and treatment ................ 165 
Table 14.3.1-14 
Incidence of adverse events requiring significant additional 
therapy, regardless of study drug relationship, by primary 
system organ class, preferred term and treatment ................ 166 
Table 14.3.1-15 
Incidence of ocular adverse events requiring significant 
additional therapy, regardless of study drug relationship, by 
primary system organ class, preferred term and treatment ... 167 
Table 14.3.1-16 
Deaths, by primary system organ class, preferred term and 
treatment ............................................................................... 168 
Table 14.3.1-17 
Arterial Thomboembolic Events ............................................. 169 
Listing 14.3.2-1 
Deaths, by treatment ............................................................. 170 
Listing 14.3.2-2 
Serious adverse events, by treatment ................................... 171 
Listing 14.3.2-3 
Adverse events causing study drug discontinuation by treatment
 .............................................................................................. 172 
Listing 14.3.2-4 
Adverse events requiring interruption by treatment ............... 173 

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Listing 14.3.2-5 
Adverse events requiring significant additional therapy ......... 174 
Listing 16.1.7-1 
Randomized allocation to treatment ...................................... 176 
Listing 16.2.1-1 
Study phase completion by treatment.................................... 178 
Listing 16.2.1-2 
Screened subjects discontinued from study prior to 
randomization ........................................................................ 179 
Listing 16.2.2-1.1 
Protocol deviations by treatment ........................................... 180 
Listing 16.2.3-1 
Patients excluded from Per-Protocol efficacy analysis by 
treatment ............................................................................... 181 
Listing 16.2.4-1 
Patient Disposition ................................................................. 182 
Listing 16.2.4-2 
Eligibility Criteria .................................................................... 183 
Listing 16.2.4-3 
Patient demographics by treatment ....................................... 184 
Listing 16.2.4-4 
Patient demographic questions by treatment ......................... 185 
Listing 16.2.4-5 
Relevant medical history and current medical conditions by 
treatment ............................................................................... 186 
Listing 16.2.4-6 
AMD Treatment History (STUDY eye) ................................... 187 
Listing 16.2.4-7 
AMD Treatment History (FELLOW eye) ................................ 188 
Listing 16.2.4-8 
AMD Treatment at Baseline ................................................... 189 
Listing 16.2.5-1 
Dose administration record by treatment (STUDY eye) ......... 190 
Listing 16.2.5-2 
Dose administration record by treatment (FELLOW eye) ...... 191 
Listing 16.2.5-3 
Medications and significant non-drug therapies prior to start of 
study drug by treatment ......................................................... 192 
Listing 16.2.5-4 
Medications and significant non-drug therapies after start of 
study drug by treatment ......................................................... 193 
Listing 16.2.5-5 
Medications and significant non-drug therapies after start of 
study drug by treatment (STUDY EYE) ................................. 194 
Listing 16.2.5-6 
Medications and significant non-drug therapies after start of 
study drug by treatment (FELLOW EYE) ............................... 195 
Listing 16.2.6-1 
CF/FA/AF by treatment (STUDY EYE) (CRF Data) ............... 196 
Listing 16.2.6-2 
CF/FA/AF by treatment (FELLOW EYE) ................................ 197 
Listing 16.2.6-3 
Fluorescein Angiography Assessments by treatment (STUDY 
EYE) (Central Reading Center Data) ..................................... 198 
Listing 16.2.6-4 
Colour Fundus Assessments by treatment (STUDY EYE) 
(Central Reading Center Data) .............................................. 199 
Listing 16.2.6-5 
Visual Acuity by Treatment (STUDY EYE) ............................ 200 
Listing 16.2.6-6 
Visual Acuity by Treatment (FELLOW EYE) .......................... 201 
Listing 16.2.6-7 
Optical Coherence Tomography (OCT) by Treatment (STUDY 
EYE) (CRF Data) ................................................................... 202 

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Listing 16.2.6-8 
Optical Coherence Tomography (OCT) by Treatment (FELLOW 
EYE) (CRF Data) ................................................................... 203 
Listing 16.2.6-9 
Optical Coherence Tomography (OCT) by treatment (STUDY 
EYE) (Central Reading Center Data) ..................................... 204 
Listing 16.2.6-10 
Genotyping Sampling ............................................................ 205 
Listing 16.2.6-11 
Genotyping SNPs .................................................................. 206 
Listing 16.2.7-1 
Adverse events ...................................................................... 207 
Listing 16.2.7-2 
Ocular adverse events ........................................................... 208 
Listing 16.2.7-3 
Adverse events suspect to be related to study drug and/or 
ocular injection ....................................................................... 209 
Listing 16.2.7-4 
Serious adverse events ......................................................... 210 
Listing 16.2.7-5 
Adverse events leading to treatment withdrawal ................... 211 
Listing 16.2.7-6 
Adverse events leading to treatment interruption .................. 212 
Listing 16.2.9-1 
Vital signs by treatment ......................................................... 214 
Listing 16.2.9-2 
Ophthalmic Examinations by treatment (STUDY EYE).......... 215 
Listing 16.2.9-3 
Ophthalmic Examinations by treatment (FELLOW EYE) ....... 216 
Listing 16.2.9-4 
Pregnancy test data by treatment .......................................... 217 
 

 
 
 
2 
Shells and specifications 
2.1 
Shells and specifications for Sections 10, 11 and 12 of a standard CSR (Text tables and figures) 
Section 10 Study patients 
PATIENT DISPOSITION 
Table 10-1 
Patient disposition – n (%) of patients  
Randomised Set 
 
n(%) 
Intensive 
(N=X) 
 Relaxed  
(N=X) 
 Total  
(N=X) 
 
All Enrolled 
 
x (xx.x) 
 
x (xx.x) 
 
x (xx.x) 
Number of Subjects Started Treatment 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Number of Subjects Completed Treatment 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Number of Subjects Discontinued Early  
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
Primary Reason for Early Discontinuation 
 
 
 
Adverse Event  
x (xx.x) 
x (xx.x) 
x (xx.x) 
Subject withdrew consent 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Lost to follow-up 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Site administrative problems 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Death 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Protocol deviation 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Physician’s decision 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Source: Table 14.1-1 

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PROTOCOL DEVIATIONS 
Table 10-2 
Protocol Deviations – n (%) of patients and total counts 
Full Analysis Set 
 
Population n (%) 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
 Total  
(N=X) 
 
 
 
 
Subjects with at least one protocol deviation 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Number of deviations 
x 
x 
x 
 
Type of Deviation 
 
 
 
 
I (inclusion criteria) 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
E (Exclusion criteria) 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
M (Medication) 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
O (other)  
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
Source: Table 14.1-3 

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Section 11 Efficacy  
ANALYSIS SETS 
Table 11.1-1 
Analysis sets – n (%) of patients 
Randomised Set 
 
Population n(%) 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
 Total  
(N=X) 
 
 
 
 
Randomised Set 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Full Analysis Set 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Safety Set  
x (xx.x) 
x (xx.x) 
x (xx.x) 
Per-Protocol Set* 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
* Includes all patients who contributed at least one data point to per-protocol analyses. Individual data points or visits may have been excluded from per-
protocol analyses based on protocol deviation assessments. 
Source: Table 14.1-7 
Note to Programmer: Table needs to include all analysis sets used in the output. This includes any 
derived analysis sets used for sensitivity analyses 

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MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS 
Table 11.2-1 
Demographic summary by treatment group 
Randomised Set 
 
 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
 
 
 
 
 
Study Eye 
 
 
Left 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Right 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Age (years)* 
 
 
 
n 
x 
x 
x 
 
Mean 
x.x 
x.x 
x.x 
 
Median 
x.x 
x.x 
x.x 
 
SD 
x.x 
x.x 
x.x 
 
Minimum 
x 
x 
x 
 
Maximum 
x 
x 
x 
 
 
 
 
 
Gender n(%) 
 
 
 
Female 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Male 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Predominate Race n(%) 
 
 
 
Caucasian: Afghan, Caucasian, 
Egypt, Egyptian, El Salvadore, Greek, 
Hispanic, Israeli, Italian, Maltese, 
Middle East, Middle Eastern, South 
American, Turkish, Yugoslavian  
x (xx.x) 
x (xx.x) 
x (xx.x) 

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CRFB002AAU15/RFB002/Ranibizumab 
 
 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
 
Black African 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Asian: Asian and Indian 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Aboriginal and Torres Strait Islander 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Pacific Islander 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Not Sure 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Ethnicity n(%) 
 
 
 
Anglo Saxon 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Northern European 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Southern European 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Asian Indian 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Other 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Not Sure 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Do you have a family history of AMD? 
 
 
 
Yes 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
No 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Is there any history of arterial thromboembolic events? 
 
 
Yes 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
No 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Has the participant ever smoked cigarettes, pipes or cigars? 
 
 
Yes 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
No 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
*Age calculated at date of informed consent 
SD: Standard Deviation 
Source: Table 14.1-6 

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MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
Table 11.2-2 
Baseline Medical History Questions by treatment group  
Randomised Set 
 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
Medical history/Current medical conditions to be reported* 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
* Refer to Table 14.1-9 and 14.1-10 for further details 
Source: Table 14.1-7 
 
 
 
 

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CRFB002AAU15/RFB002/Ranibizumab 
 
Table 11.2-3 Medical History - Arterial Thomboembolic Events 
Randomised Set 
 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
 
 
 
 
 
 
 
 
Arterial Thomboembolic Events (ATEs)* 
xx.x 
x 
xx.x 
x 
xx.x 
x 
Nonfatal myocardial infarction 
xx.x 
x 
xx.x 
x 
xx.x 
x 
Nonfatal stroke 
xx.x 
x 
xx.x 
x 
xx.x 
x 
 
 
 
 
 
 
 
* ATEs defined as nonfatal myocardial infarction, nonfatal stroke, vascular death and death of unknown cause 
AE: Adverse Event 
Note: Some patients may have experienced multiple events 
 
 
 
 
 
 
 
 
 
 
 

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Table 11.2-4 
Baseline AMD characteristics (STUDY EYE) by treatment group  
Randomised Set 
 
 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
 
 
 
 
 
Was any treatment ever given to the fellow eye prior to Screening? 
 
 
No 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Yes 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Lucentis 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Eylea 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Visudyne 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Avastin 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Steroids 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Other 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Total BCVA Score (ETDRS letters) 
 
 
 
 
n 
x 
x 
x 
 
Mean 
x.x 
x.x 
x.x 
 
Median 
x.x 
x.x 
x.x 
 
SD 
x.x 
x.x 
x.x 
 
Minimum 
x 
x 
x 
 
Maximum 
x 
x 
x 
 
 
 
 
 
Visual Acuity - Categorical (20/40) 
 
 
 
 
>=70 letters 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
<70 letters 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
 

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CRFB002AAU15/RFB002/Ranibizumab 
 
 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
Central Subfield Foveal Thickness (µm)* 
 
 
 
 
n 
x 
x 
x 
 
Mean 
x.x 
x.x 
x.x 
 
Median 
x.x 
x.x 
x.x 
 
SD 
x.x 
x.x 
x.x 
 
Minimum 
x 
x 
x 
 
Maximum 
x 
x 
x 
 
 
 
 
 
Central Subfield Volume (mm3)* 
 
 
 
 
n 
x 
x 
x 
 
Mean 
x.x 
x.x 
x.x 
 
Median 
x.x 
x.x 
x.x 
 
SD 
x.x 
x.x 
x.x 
 
Minimum 
x 
x 
x 
 
Maximum 
x 
x 
x 
 
 
 
 
 
Area of Lesion (mm2)* 
 
 
 
 
n 
x 
x 
x 
 
Mean 
x.x 
x.x 
x.x 
 
Median 
x.x 
x.x 
x.x 
 
SD 
x.x 
x.x 
x.x 
 
Minimum 
x 
x 
x 
 
Maximum 
x 
x 
x 
 
 
 
 
 
Intra-Retinal Fluid Status 
 
 
 
 
Absent 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Present 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Can’t Grade 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 

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CRFB002AAU15/RFB002/Ranibizumab 
 
 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
Intra-Retinal Fluid Status* 
 
 
 
 
Absent 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Present 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Can’t Grade 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Intra-Retinal Fluid Centre Involvement* 
 
 
 
 
Absent 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Present 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Can’t Grade 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Intra-Retinal Cysts* 
 
 
 
 
Absent 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Present 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Intra-Retinal Cysts Centre Involvement* 
 
 
 
 
Absent 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Present 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Sub-Retinal Fluid Status 
 
 
 
 
Absent 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Present 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Can’t Grade 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
 
 
 
 
 
Sub-Retinal Fluid Status* 
 
 
 
 
Absent 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Present 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Can’t Grade 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 

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MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
Sub-Retinal Fluid Centre Involvement* 
 
 
 
 
Absent 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Present 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Can’t Grade 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Sub-Retinal Fluid at Centrepoint* 
 
 
 
 
Absent 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Present 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Can’t Grade 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Sub-Retinal Fluid Height at Centrepoint 
 
 
 
 
<=200μm 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
>200 μm 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Not Applicable 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Sub-Retinal Fluid Height at Centrepoint* 
 
 
 
 
<=200μm 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
>200 μm 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Not Applicable 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Morphologic Changes* 
 
 
 
 
Epiretinal Membrane 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Vitreoretinal Traction 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Macular Hole 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Atrophy 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Other 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 

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MAP Module 7.1 
 
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Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
Area of CNV (mm2)* 
 
 
 
 
n 
x 
x 
x 
 
Mean 
x.x 
x.x 
x.x 
 
Median 
x.x 
x.x 
x.x 
 
SD 
x.x 
x.x 
x.x 
 
Minimum 
x 
x 
x 
 
Maximum 
x 
x 
x 
 
 
 
 
CNV Complex (lesion) 
 
 
 
 
Absent 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Definite 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Questionable 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
…… 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
CNV Complex (lesion)* 
 
 
 
 
Absent 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Definite 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Questionable 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
…… 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
CNV Complex (lesion) Location 
 
 
 
 
Subfoveal 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Juxtafoveal 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Juxtafoveal with centre 
involvement 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Extrafoveal 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Extrafoveal with centre 
involvement 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Can’t grade 
x (xx.x) 
x (xx.x) 
x (xx.x) 

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MAP Module 7.1 
 
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Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
CNV Location 
 
 
 
 
Subfoveal 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Juxtafoveal 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Extrafoveal 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Can’t grade 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
CNV Location* 
 
 
 
 
Subfoveal 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Juxtafoveal 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Juxtafoveal with centre 
involvement 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Extrafoveal 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Extrafoveal with centre 
involvement 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Can’t grade 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
CNV Secondary to …..* 
 
 
 
 
AMD 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Angioid Streaks 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Idiopathic 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Pathologic Myopia 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Other 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Type of CNV* 
 
 
 
 
Predominantly classic 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Occult 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Fibrovascular PED 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Serous PED 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Other 
x (xx.x) 
x (xx.x) 
x (xx.x) 

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Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
CNV Leakage* 
 
 
 
 
Absent 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Present 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Lesion Components* 
 
 
 
 
Blood 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
CNV 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Serous PED 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
RPE Tear 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Other 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Can’t Grade 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Geographic Atrophy (Status)* 
 
 
 
 
Absent 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Definite 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Can’t Grade 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Not Applicable 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Geographic Atrophy Location* 
 
 
 
 
Central Subfield 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Inner Subfield 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Outer Subfield 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Geographic Atrophy Area (mm2)* 
 
 
 
 
n 
x 
x 
x 
 
Mean 
x.x 
x.x 
x.x 
 
Median 
x.x 
x.x 
x.x 
 
SD 
x.x 
x.x 
x.x 
 
Minimum 
x 
x 
x 
 
Maximum 
x 
x 
x 

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Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
 
 
 
 
 
Haemorrhage* 
 
 
 
 
Yes 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
No 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Haemorrhage Location* 
 
 
 
 
Central Subfield 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Inner Subfield  
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Outer Subfield 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Retinal Abnormality* 
 
 
 
 
Drusen 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Atrophy 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Fibrosis 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
PED 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Other 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Retinal Abnormality Location* 
 
 
 
 
Central 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Periphery 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
* Source: 
 
Source: Table 14.1-8 
Note to Programmer: Footnote is to appear on all pages 

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MAP Module 7.1 
 
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ANALYSIS OF EFFICACY 
Table 11.4-1.1 
Mean absolute change in BCVA from baseline to months 2, 12 and 24  
Full analysis set 
 
Visit 
Statistic 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
Actual Value 
Absolute 
Change from 
Baseline* 
Actual Value 
Absolute 
Change from 
Baseline 
Actual Value 
Absolute 
Change from 
Baseline 
 
 
 
 
 
 
 
 
Baseline 
n 
x 
- 
x 
- 
x 
- 
 
Mean (SD) 
x.x (x.x) 
- 
x.x (x.x) 
- 
x.x (x.x) 
- 
 
Min; Max 
x;x 
- 
x;x 
- 
x;x 
- 
 
 
 
 
 
 
 
 
Month 2 
n 
x 
x 
x 
x 
x 
x 
 
Mean (SD) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
 
Min; Max 
x;x 
x;x 
x;x 
x;x 
x;x 
x;x 
 
 
 
 
 
 
 
 
Month 12 
n 
x 
x 
x 
x 
x 
x 
 
Mean (SD) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
 
Min; Max 
x;x 
x;x 
x;x 
x;x 
x;x 
x;x 
 
 
 
 
 
 
 
 
Month 24 
n 
x 
x 
x 
x 
x 
x 
 
Mean (SD) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
 
Min; Max 
x;x 
x;x 
x;x 
x;x 
x;x 
x;x 
 
 
*Baseline: The last available non-missing value collected just prior to the start of treatment in the study eye 
SD: Standard Deviation 
Source: Table 14.2-1 

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Table 11.4-1.2 
Mean absolute change in BCVA from baseline to months 2, 12 and 24  
Per Protocol Set 
 
Visit 
Statistic 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
Actual Value 
Absolute 
Change from 
Baseline* 
Actual Value 
Absolute 
Change from 
Baseline 
Actual Value 
Absolute 
Change from 
Baseline 
 
 
 
 
 
 
 
 
Baseline 
n 
x 
- 
x 
- 
x 
- 
 
Mean (SD) 
x.x (x.x) 
- 
x.x (x.x) 
- 
x.x (x.x) 
- 
 
Min; Max 
x;x 
- 
x;x 
- 
x;x 
- 
 
 
 
 
 
 
 
 
Month 2 
n 
x 
x 
x 
x 
x 
x 
 
Mean (SD) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
 
Min; Max 
x;x 
x;x 
x;x 
x;x 
x;x 
x;x 
 
 
 
 
 
 
 
 
Month 12 
n 
x 
x 
x 
x 
x 
x 
 
Mean (SD) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
 
Min; Max 
x;x 
x;x 
x;x 
x;x 
x;x 
x;x 
 
 
 
 
 
 
 
 
Month 24 
n 
x 
x 
x 
x 
x 
x 
 
Mean (SD) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
 
Min; Max 
x;x 
x;x 
x;x 
x;x 
x;x 
x;x 
 
 
*Baseline: The last available non-missing value collected just prior to the start of treatment in the study eye 
SD: Standard Deviation 
Source: Table 14.2-1 
 
 
 
 

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Table 11.4-2 
Mean change in Central Retinal Thickness from baseline to months 2, 12 and 24 (STUDY EYE) 
Full Analysis Set 
 
Visit 
Statistic 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
Actual Value 
Absolute 
Change from 
Baseline* 
Actual Value 
Absolute 
Change from 
Baseline 
Actual Value 
Absolute 
Change from 
Baseline 
 
 
 
 
 
 
 
 
Baseline 
n 
x 
- 
x 
- 
x 
- 
 
Mean (SD) 
x.x (x.x) 
- 
x.x (x.x) 
- 
x.x (x.x) 
- 
 
Min; Max 
x;x 
- 
x;x 
- 
x;x 
- 
 
 
 
 
 
 
 
 
Month 2 
n 
x 
- 
x 
- 
x 
- 
 
Mean (SD) 
x.x (x.x) 
- 
x.x (x.x) 
- 
x.x (x.x) 
- 
 
Min; Max 
x;x 
- 
x;x 
- 
x;x 
- 
 
 
 
 
 
 
 
 
Month 12 
n 
x 
- 
x 
- 
x 
- 
 
Mean (SD) 
x.x (x.x) 
- 
x.x (x.x) 
- 
x.x (x.x) 
- 
 
Min; Max 
x;x 
- 
x;x 
- 
x;x 
- 
 
 
 
 
 
 
 
 
Month 24 
n 
x 
- 
x 
- 
x 
- 
 
Mean (SD) 
x.x (x.x) 
- 
x.x (x.x) 
- 
x.x (x.x) 
- 
 
Min; Max 
x;x 
- 
x;x 
- 
x;x 
- 
 
 
*Baseline: The last available non-missing value collected just prior to the start of treatment in the study eye 
SD: Standard Deviation 
NOTE: Data based on Central Reading Center data 
Source: Table 14.2-5 
 
 
 
 

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Table 11.4-3 
Number of Injections from baseline to month 12 and 24  
Full Analysis Set 
 
Visit 
 
Intensive 
(N=X)  
 Relaxed 
(N=X)  
Total 
(N=X) 
 
 
 
 
 
Number of Injections 
(First Year) 
n 
x 
x 
x 
 
Mean (SD) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
 
Min; Max 
x;x 
x;x 
x;x 
 
 
 
 
 
Number of Injections 
(Second Year) 
n 
x 
x 
x 
 
Mean (SD) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
 
Min; Max 
x;x 
x;x 
x;x 
 
 
 
 
 
Number of Injections 
(Total) 
n 
x 
x 
x 
 
Mean (SD) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
 
Min; Max 
x;x 
x;x 
x;x 
 
 
 
 
 
Exposure (year) 
n 
x 
x 
x 
 
Mean (SD) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
 
Min; Max 
x;x 
x;x 
x;x 
 
 
 
 
 
Injections per year* 
 
xx 
xx 
xx 
 
 
 
 
 
* Injections per year = Total number of injections / total exposure to treatment (years) 
Source: Table 14.2-8 
 

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Section 12 Safety evaluation 
EXTENT OF EXPOSURE 
Table 12.1-1 
Overall exposure 
Safety Set 
 
 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
 
 
 
 
 
Duration of Exposure (days)* 
 
 
 
 
n 
x 
x 
x 
 
Mean 
x.x 
x.x 
x.x 
 
Median 
x.x 
x.x 
x.x 
 
SD 
x.x 
x.x 
x.x 
 
Minimum 
x 
x 
x 
 
Maximum 
x 
x 
x 
 
 
 
 
 
SD: Standard Deviation 
*Duration of Exposure = Date of first treatment to date of End of Treatment + 1 
Source:  Table 14.3-2 
 
 
 
 
 
 
 

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Table 12.1-2 
Treatment Frequency and Intervals at 12 and 24 months 
Safety set 
 
Visit 
Interval 
n (%) 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
 
 
 
 
 
Month 12 
4 weeks 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
6 weeks 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
8 weeks 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
10 weeks 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
12 weeks 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Month 24 
4 weeks 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
6 weeks 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
8 weeks 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
10 weeks 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
12 weeks 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Source: Table 14.3-1 
 
 Note to Programmer: This table counts what interval schedule each patient is on at the static 
timepoints of Month 12 and Month 24. Knowing the Month 12 date, look at the injection visit immediately 
prior to that date and use the Interval Decision value. If the patient’s injection visit was held at the same 
time as the Month 12 visit then use the Interval leading up to the visit rather than the Injection Decision. 

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ADVERSE EVENTS 
Table 12.2-1 
Number (%) of patients with AEs by primary system organ class  
Safety set 
 
System Organ Class (SOC) 
           Preferred Term (PT) 
Intensive 
(N=X) 
Relaxed 
(N=X) 
Total 
(N=X) 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
 
 
 
 
 
 
 
 
All Body Systems 
x (xx.x) 
x 
x (xx.x) 
x 
x (xx.x) 
x 
 
 
 
 
 
 
 
 
SOC1 
x (xx.x) 
x 
x (xx.x) 
x 
x (xx.x) 
x 
 
PT1 
x (xx.x) 
x 
x (xx.x) 
x 
x (xx.x) 
x 
 
PT2 
x (xx.x) 
x 
x (xx.x) 
x 
x (xx.x) 
x 
 
…. 
…. 
…. 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x) 
x 
x (xx.x) 
x 
x (xx.x) 
x 
 
 
 
 
 
 
 
 
SOC2 
x (xx.x) 
x 
x (xx.x) 
x 
x (xx.x) 
x 
 
PT1 
x (xx.x) 
x 
x (xx.x) 
x 
x (xx.x) 
x 
 
PT2 
x (xx.x) 
x 
x (xx.x) 
x 
x (xx.x) 
x 
 
…. 
…. 
…. 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x) 
x 
x (xx.x) 
x 
x (xx.x) 
x 
……….. 
 
 
 
 
 
 
AE: Adverse Event 
A patient with multiple occurrences of an AE under one treatment is counted only once in the AE category for that treatment. 
A patient with multiple adverse events within a primary system organ class is counted only once in the total row. 
Source: Table 14.3.1-1 
 
 

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DEATHS, OTHER SERIOUS ADVERSE EVENTS, AND OTHER SIGNIFICANT ADVERSE EVENTS 
 
None 

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LABORATORY EVALUATIONS 
 
None 
 
LIVER TOXICITY 
 
None 
 
VITAL SIGNS, PHYSICAL FINDING, OTHER OBSERVATION RELATED TO SAFETY 
 
None 
 

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2.2 
Shells and specifications for Sections 14 and 16 of a standard CSR 
Section 14 – Tables, figures referred to but not included in the text 
Section 14.1 – Demographic data 
Figures (Section 14.1) 
No Output 
 
 

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Tables (Section 14.1) 
Table 14.1-1 
Patient disposition, by treatment     
Randomised Set 
 
Disposition 
               Reason 
Intensive 
(N=X) 
n (%) 
 Relaxed  
(N=X) 
n (%) 
 Total  
(N=X) 
n (%) 
 
All Enrolled 
 
x (xx.x) 
 
x (xx.x) 
 
x (xx.x) 
 
 
 
 
Number of Subjects Started Treatment 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Number of Subjects Completed Treatment 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Number of Subjects Terminated Early  
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
Primary Reason for Termination 
 
 
 
Adverse Event  
x (xx.x) 
x (xx.x) 
x (xx.x) 
Subject withdrew consent 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Lost to follow-up 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Site administrative problems 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Death 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Protocol deviation 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Physician’s decision 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 

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Table 14.1-2 
Screening phase subject disposition 
Randomised Set 
 
Disposition 
               Reason 
 Total  
(N=X) 
n (%) 
 
Completed Screening phase 
 
x (xx.x) 
Discontinued prior to screening phase completion 
x (xx.x) 
 
 
Primary Reason for Termination 
 
Adverse Event  
x (xx.x) 
Lost to follow-up 
x (xx.x) 
Physician’s decision 
x (xx.x) 
Screen failure 
x (xx.x) 
Study terminated by Sponsor 
x (xx.x) 
Technical problems 
x (xx.x) 
Subject/guardian decision 
x (xx.x) 
Death 
x (xx.x) 
 
 
Note: Percentage is out of total number screened 

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Table 14.1-3 
Protocol deviations, by treatment 
Full Analysis Set 
 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
 Total  
(N=X) 
 
 
 
 
Subjects with at least one protocol deviation 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Number of deviations 
x 
x 
x 
 
 
 
 
Category 1 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Category 2 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Category 3 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Category 4 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Category n 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
Note: Patients with multiple occurrences of a protocol deviation category are counted only once in the protocol deviation category. 
Note: Patients may have protocol deviations in more than one protocol deviation category. 

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Table 14.1-4 
Protocol deviations leading to exclusion from analysis sets 
Full Analysis Set 
 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
 Total  
(N=X) 
 
 
 
 
Excluded from Full Analysis Set (FAS) 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
Total 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Category 1 
x (xx.x) 
x (xx.x) 
x (xx.x) 
PD term 1 
 
 
 
PD term 2 
 
 
 
…. 
 
 
 
Category 2 
x (xx.x) 
x (xx.x) 
x (xx.x) 
PD term 1 
 
 
 
PD term 2 
 
 
 
…. 
 
 
 
Category 3 
x (xx.x) 
x (xx.x) 
x (xx.x) 
PD term 1 
 
 
 
PD term 2 
 
 
 
…. 
 
 
 
Category 4 
x (xx.x) 
x (xx.x) 
x (xx.x) 
PD term 1 
 
 
 
PD term 2 
 
 
 
…. 
 
 
 
Category n 
 
 
 
…. 
 
 
 
 
 
 
 
Excluded from …… Set 
 
 
 
…. 
 
 
 
 
 
 
 
Note: Patients with multiple occurrences of a protocol deviation category are counted only once for that specific protocol deviation criterion. 
Note: Patients may have multiple protocol deviations. 

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Table 14.1-5 
Out of Window visits 
Full Analysis Set 
 
 
 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
 Total  
(N=X) 
 
 
 
 
 
Number of days 
earlier than planned 
1 - 7 days 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
8 – 14 days 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
15 - 28 days 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
29 - 42 days 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
>42 days 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Number of days later 
than planned 
1 - 7 days 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
8 – 14 days 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
15 - 28 days 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
29 - 42 days 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
>42 days 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
 
 
 

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Table 14.1-6 
Under and Over Treatment due to treatment interval error 
Full Analysis Set 
 
 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
 Total  
(N=X) 
 
 
 
 
 
Under-Treated at least once 
n(%) 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Number of Times Under-Treated 
n 
x 
x 
x 
 
Mean 
x.x 
x.x 
x.x 
 
Median 
x.x 
x.x 
x.x 
 
SD 
x.x 
x.x 
x.x 
 
Minimum 
x 
x 
x 
 
Maximum 
x 
x 
x 
 
 
 
 
 
Over-Treated at least once 
n(%) 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Number of Times Over-Treated 
n 
x 
x 
x 
 
Mean 
x.x 
x.x 
x.x 
 
Median 
x.x 
x.x 
x.x 
 
SD 
x.x 
x.x 
x.x 
 
Minimum 
x 
x 
x 
 
Maximum 
x 
x 
X 
 
 
 
 
 
SD: Standard Deviation 
 
 
 

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Table 14.1-7 
Analysis sets, by treatment 
All Enrolled 
 
Analysis Set 
Intensive  
(N=X) 
n (%) 
 Relaxed  
(N=X) 
n (%) 
 Total  
(N=X) 
n (%) 
 
 
 
 
Randomized Set 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Full Analysis Set 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Safety Set  
x (xx.x) 
x (xx.x) 
x (xx.x) 
Per-Protocol Set* 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
Note: Percentages are based on the number of patients in the Randomized set. 
* Includes all patients who contributed at least one data point to per-protocol analyses. Individual data points or visits may have been excluded from per-
protocol analyses based on protocol deviation assessments. 
 
Randomized Set: The Randomised Population will consist of all randomised patients. 
Full Analysis Set (FAS): The Full Analysis Set (FAS) compromises all subjects randomised and whom have at least one post-baseline efficacy value for the primary 
endpoint. 
Safety Set: The Safety Set will consist of all patients who received at least one application of study treatment and had at least one post-baseline safety assessment. The 
statement that a patient had no adverse events also constitutes a safety assessment.  
Per-Protocol Set: The Per-Protocol Set (PPS) will consist of all patients in the FAS who followed the treatment regimen as randomised and completed the study without 
clinically significant protocol deviations.  Clinically significant protocol deviations will be identified and documented prior to the database lock.  Refer to “Protocol 
Deviations” study document for further details. 
 
 
 
 
 
 
 
 
Note to Programmer: Table needs to include all analysis sets used in the output. This includes any 
derived analysis sets used for sensitivity analyses 

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Table 14.1-8 
Randomisation by Site 
All Enrolled 
 
Site 
Intensive  
(N=X) 
n (%) 
 Relaxed  
(N=X) 
n (%) 
P Value 
 Total  
(N=X) 
n (%) 
 
 
 
 
 
 
 
 
x.xxxx 
 
Site A 
x (xx.x) 
x (xx.x) 
 
x (xx.x) 
Site B 
x (xx.x) 
x (xx.x) 
 
x (xx.x) 
Site C  
x (xx.x) 
x (xx.x) 
 
x (xx.x) 
Site D 
x (xx.x) 
x (xx.x) 
 
x (xx.x) 
 
 
 
 
 
 
 
 

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Table 14.1-9 
Demographics, by treatment 
Randomised Set 
 
 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
 
 
 
 
 
Study Eye 
 
 
Left 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Right 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Age (years)* 
 
 
 
n 
x 
x 
x 
 
Mean 
x.x 
x.x 
x.x 
 
Median 
x.x 
x.x 
x.x 
 
SD 
x.x 
x.x 
x.x 
 
Minimum 
x 
x 
x 
 
Maximum 
x 
x 
x 
 
 
 
 
 
Gender n(%) 
 
 
 
Female 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Male 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Predominate Race n(%) 
 
 
 
Caucasian: Afghan, Caucasian, 
Egypt, Egyptian, El Salvadore, Greek, 
Hispanic, Israeli, Italian, Maltese, 
Middle East, Middle Eastern, South 
American, Turkish, Yugoslavian 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Black African 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Asian: Asian and Indian 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Aboriginal and Torres Strait Islander 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Pacific Islander 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Not Sure 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Ethnicity n(%) 
 
 
 
Anglo Saxon 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Northern European 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Southern European 
x (xx.x) 
x (xx.x) 
x (xx.x) 

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Asian Indian 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Other 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Not Sure 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Do you have a family history of AMD? 
 
 
 
Yes 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
No 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Is there any history of arterial thromboembolic events? 
 
 
Yes 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
No 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Has the participant ever smoked cigarettes, pipes or cigars? 
 
 
Yes 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
No 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
*Age calculated at date of informed consent 
SD: Standard Deviation 
 
 

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Table 14.1-10 
Baseline characteristics by Treatment Group 
Randomised Set 
 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
P Value 
Total 
(N=X) 
Age (years)* 
     - 
 
 
x.xxxx 
 
     n 
xxx 
xxx 
 
xxx 
     Mean 
xx.x 
xx.x 
 
xx.x 
     Median 
xx.x 
xx.x 
 
xx.x 
     SD 
x.x 
x.x 
 
x.x 
     Minimum 
xx 
xx 
 
xx 
     Maximum 
xx 
xx 
 
xx 
Gender 
     - 
 
 
x.xxxx 
 
     Female 
xxx (xx.x%) 
xxx (xx.x%) 
 
xxx (xx.x%) 
     Male 
xxx (xx.x%) 
xxx (xx.x%) 
 
xxx (xx.x%) 
Race 
     - 
 
 
0.5840 
 
     AFGHAN 
1 (0.4%) 
 
 
xxx (xx.x%) 
     ……………… 
1 (0.4%) 
 
 
xxx (xx.x%) 
 
Race (Grouped) 
     - 
 
 
x.xxxx 
 
Caucasian: Afghan, Caucasian, 
Egypt, Egyptian, El Salvadore, 
Greek, Hispanic, Israeli, Italian, 
Maltese, Middle East, Middle 
Eastern, South American, Turkish, 
Yugoslavian 
xxx (xx.x%) 
xxx (xx.x%) 
 
xxx (xx.x%) 
Black African 
xxx (xx.x%) 
xxx (xx.x%) 
 
xxx (xx.x%) 
Asian: Asian and Indian 
xxx (xx.x%) 
xxx (xx.x%) 
 
xxx (xx.x%) 
Aboriginal and Torres Strait 
Islander 
xxx (xx.x%) 
xxx (xx.x%) 
 
xxx (xx.x%) 
Pacific Islander 
xxx (xx.x%) 
xxx (xx.x%) 
 
xxx (xx.x%) 
Not Sure 
xxx (xx.x%) 
xxx (xx.x%) 
 
xxx (xx.x%) 

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Intensive  
(N=X) 
 Relaxed  
(N=X) 
P Value 
Total 
(N=X) 
Ethnicity 
     - 
  
 
x.xxxx 
  
     ABORIGINAL 
xxx (xx.x%) 
 
 
xxx (xx.x%) 
     ……………… 
 
 
     WELSH 
xxx (xx.x%) 
 
 
xxx (xx.x%) 
 
 
Family history of AMD 
     - 
  
 
x.xxxx 
  
     No 
xxx (xx.x%) 
xxx (xx.x%) 
 
xxx (xx.x%) 
     Yes 
xxx (xx.x%) 
xxx (xx.x%) 
 
xxx (xx.x%) 
 
 
 
History of arterial thromboembolic events 
     - 
  
 
0.2342 
  
     No 
216 (85.7%) 
86 (90.5%) 
 
302 (87.0%) 
     Yes 
36 (14.3%) 
9 (9.5%) 
 
45 (13.0%) 
Smoking History 
 
 
     - 
  
 
0.2612 
  
     Current smoker 
24 (9.5%) 
8 (8.4%) 
 
32 (9.2%) 
     Never smoked 
108 (42.9%) 
50 (52.6%) 
 
158 (45.5%) 
     Smoked in the past 
120 (47.6%) 
37 (38.9%) 
 
157 (45.2%) 
Smoking History (Grouped) 
 
 
     - 
  
 
0.7516 
  
     Current smoker 
24 (9.5%) 
8 (8.4%) 
 
32 (9.2%) 
     Non-Smoker 
228 (90.5%) 
87 (91.6%) 
 
315 (90.8%) 
Previous exposure of non-study eye 
 
 
     - 
  
 
0.0246 
  
     No 
183 (72.6%) 
80 (84.2%) 
 
263 (75.8%) 
     Yes 
69 (27.4%) 
15 (15.8%) 
 
84 (24.2%) 
Previous exposure - treatment 
 
 
     - 
  
 
0.3904 
  
     Avastin 
10 (14.5%) 
3 (20.0%) 
 
13 (15.5%) 
     Eylea 
15 (21.7%) 
5 (33.3%) 
 
20 (23.8%) 
     Lucentis 
50 (72.5%) 
7 (46.7%) 
 
57 (67.9%) 
     Visudyne 
7 (10.1%) 
 
 
7 (8.3%) 
     Other 
2 (2.9%) 
 
 
2 (2.4%) 

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Intensive  
(N=X) 
 Relaxed  
(N=X) 
P Value 
Total 
(N=X) 
Study Eye 
 
 
     - 
  
 
0.0149 
  
     Left eye 
109 (43.3%) 
55 (57.9%) 
 
164 (47.3%) 
     Right eye 
143 (56.7%) 
40 (42.1%) 
 
183 (52.7%) 
Best Corrective Visual Acuity 
 
 
     - 
  
 
0.2503 
  
     n 
252 
95 
 
347 
     Mean 
63.8 
61.8 
 
63.2 
     Median 
67.0 
63.0 
 
66.0 
     SD 
13.7 
14.7 
 
14.0 
     Minimum 
23 
23 
 
23 
     Maximum 
90 
85 
 
90 
BCVA (Categorical) 
     - 
  
 
0.1910 
  
     <70 
145 (57.5%) 
62 (65.3%) 
  
207 (59.7%) 
     >=70 
107 (42.5%) 
33 (34.7%) 
  
140 (40.3%) 
Central Subfield Foveal Thickness 
 
 
     - 
  
 
0.4227 
  
     n 
252 
95 
  
347 
     Mean 
445.0 
461.6 
  
449.5 
     Median 
405.0 
409.0 
  
406.0 
     SD 
175.6 
162.6 
 
172.1 
     Minimum 
169 
256 
  
169 
     Maximum 
1309 
1123 
 
1309 
Central Subfield Foveal Volume 
 
 
 
     - 
  
 
0.3304 
  
     n 
252 
95 
  
347 
     Mean 
0.4 
0.4 
 
0.4 
     Median 
0.3 
0.3 
 
0.3 
     SD 
0.2 
0.3 
 
0.2 
     Minimum 
0 
0 
  
0 
     Maximum 
3 
3 
 
3 
Intraretinal Fluid 
 
 
 
     - 
  
  
0.7260 
  
     Absent 
159 (63.1%) 
58 (61.1%) 
 
217 (62.5%) 
     Present 
93 (36.9%) 
37 (38.9%) 
 
130 (37.5%) 

Novartis 
Confidential 
Page 52 
MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
P Value 
Total 
(N=X) 
Intraretinal Fluid - Center Involvement 
 
 
     - 
  
 
0.6946 
  
     Absent 
8 (3.2%) 
4 (4.2%) 
 
12 (3.5%) 
     Present 
85 (33.7%) 
33 (34.7%) 
 
118 (34.0%) 
Intraretinal Cysts 
     - 
  
 
0.8995 
  
     Absent 
108 (42.9%) 
40 (42.1%) 
  
148 (42.7%) 
     Definite 
144 (57.1%) 
55 (57.9%) 
  
199 (57.3%) 
Intraretinal Cysts - Center Involvement 
 
 
     - 
  
 
0.3667 
  
     Absent 
8 (3.2%) 
5 (5.3%) 
  
13 (3.7%) 
     Definite 
136 (54.0%) 
50 (52.6%) 
  
186 (53.6%) 
Any Subretinal Fluid 
 
 
 
 
     - 
  
 
0.0341 
  
     Absent 
51 (20.2%) 
10 (10.5%) 
 
61 (17.6%) 
     Present 
201 (79.8%) 
85 (89.5%) 
 
286 (82.4%) 
Any Subretinal Fluid - Center Involvement 
 
 
 
 
     - 
  
 
0.1079 
  
     Absent 
18 (7.1%) 
3 (3.2%) 
 
21 (6.1%) 
     Present 
183 (72.6%) 
82 (86.3%) 
 
265 (76.4%) 
Morphological Changes 
 
 
 
 
     - 
  
 
0.3693 
  
     Absent 
176 (69.8%) 
71 (74.7%) 
  
247 (71.2%) 
     Definite 
76 (30.2%) 
24 (25.3%) 
 
100 (28.8%) 
Morphological Change - Epiretinal Membrane 
     - 
  
  
0.4748 
  
     No 
48 (19.0%) 
13 (13.7%) 
 
61 (17.6%) 
     Yes 
29 (11.5%) 
11 (11.6%) 
 
40 (11.5%) 
 
 

Novartis 
Confidential 
Page 53 
MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
P Value 
Total 
(N=X) 
No Intraretinal Fluid or Cysts (derived) 
 
 
     - 
  
 
0.7266 
  
     IRF or IR Cyst or both (IRF and Cyst) 
154 (61.1%) 
60 (63.2%) 
 
214 (61.7%) 
     No IRF nor IR Cyst 
98 (38.9%) 
35 (36.8%) 
 
133 (38.3%) 
 
 
 
Morphological Change - Vitreo-Retinal Traction 
 
     - 
  
  
0.7219 
  
     No 
38 (15.1%) 
13 (13.7%) 
 
51 (14.7%) 
     Yes 
38 (15.1%) 
11 (11.6%) 
 
49 (14.1%) 
Morphological Change - Macular Hole 
 
 
 
     - 
  
  
- 
  
     No 
76 (30.2%) 
24 (25.3%) 
 
100 (28.8%) 
 
 
 
Morphological Change - Atrophy 
 
 
 
     - 
  
  
0.0990 
  
     No 
36 (14.3%) 
16 (16.8%) 
 
52 (15.0%) 
     Yes 
40 (15.9%) 
8 (8.4%) 
 
48 (13.8%) 
Morphological Change - Other 
 
 
 
     - 
  
  
0.5722 
  
     No 
75 (29.8%) 
24 (25.3%) 
 
99 (28.5%) 
     Yes 
1 (0.4%) 
  
 
1 (0.3%) 
Subfoveal Fluid Center Point 
 
 
 
     - 
  
  
0.7931 
  
     Absent 
27 (10.7%) 
7 (7.4%) 
 
34 (9.8%) 
     Not Applicable 
10 (4.0%) 
2 (2.1%) 
 
12 (3.5%) 
     Present 
17 (6.7%) 
6 (6.3%) 
 
23 (6.6%) 
Subfoveal Fluid - Height at Center Point 
 
 
 
     - 
  
  
0.2698 
  
     <=200um 
14 (5.6%) 
6 (6.3%) 
 
20 (5.8%) 
     >200um 
3 (1.2%) 
 
 
3 (0.9%) 
Evidence of CNV Complex 
 
 
     - 
  
 
0.0460 
  
     Absent 
9 (3.6%) 
 
 
9 (2.6%) 
     Can't Grade 
1 (0.4%) 
 
 
1 (0.3%) 
     Definite 
232 (92.1%) 
95 (100.0%) 
 
327 (94.2%) 
     Questionable 
10 (4.0%) 
 
 
10 (2.9%) 

Novartis 
Confidential 
Page 54 
MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
P Value 
Total 
(N=X) 
Location of CNV Complex, by centre involvement* (derived) 
 
     - 
  
 
- 
  
CNV Leakage 
 
 
 
     - 
  
 
0.1795 
  
     Absent 
2 (0.8%) 
 
 
2 (0.6%) 
     Can't Grade 
1 (0.4%) 
1 (1.1%) 
 
2 (0.6%) 
     Definite 
230 (91.3%) 
94 (98.9%) 
 
324 (93.4%) 
     Questionable 
9 (3.6%) 
 
 
9 (2.6%) 
Area of CNV 
 
 
 
     - 
  
 
0.1179 
  
     n 
228 
92 
 
320 
     Mean 
5.589 
4.688 
 
5.330 
     Median 
4.045 
3.500 
 
3.715 
     SD 
4.899 
3.954 
 
4.659 
     Minimum 
0.30 
0.43 
 
0.30 
     Maximum 
30.09 
22.72 
 
30.09 
CNV Location 
 
 
 
     - 
  
 
0.2412 
  
     Can't Grade 
3 (1.2%) 
1 (1.1%) 
 
4 (1.2%) 
     Extrafoveal 
16 (6.3%) 
3 (3.2%) 
 
19 (5.5%) 
     Juxtafoveal 
23 (9.1%) 
9 (9.5%) 
 
32 (9.2%) 
     No CNV complex 
10 (4.0%) 
 
 
10 (2.9%) 
     Subfoveal 
200 (79.4%) 
82 (86.3%) 
 
282 (81.3%) 
CNV Location, by centre involvement* (derived) 
 
 
     - 
  
 
0.3611 
 
     Can't Grade 
3 (1.2%) 
1 (1.1%) 
 
4 (1.2%) 
     Extrafoveal 
x (x.x%) 
x (x.x%) 
 
x (x.x%) 
     Extrafoveal with centre involvement 
16 (6.3%) 
3 (3.2%) 
 
19 (5.5%) 
     Juxtafoveal 
2 (0.8%) 
2 (2.1%) 
 
4 (1.2%) 
     Juxtafoveal with centre involvement 
21 (8.3%) 
7 (7.4%) 
 
28 (8.1%) 
     No CNV complex 
2 (0.8%) 
 
 
2 (0.6%) 
     Subfoveal 
200 (79.4%) 
82 (86.3%) 
 
282 (81.3%) 

Novartis 
Confidential 
Page 55 
MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
P Value 
Total 
(N=X) 
Type of CNV 
 
 
 
 
     - 
  
 
0.5981 
 
     Can't Grade 
7 (2.8%) 
1 (1.1%) 
 
8 (2.3%) 
     Occult (fibrovascular PED) 
178 (70.6%) 
72 (75.8%) 
 
250 (72.0%) 
     Occult (late leakage) 
4 (1.6%) 
 
 
4 (1.2%) 
     Occult with serious PED 
10 (4.0%) 
6 (6.3%) 
 
16 (4.6%) 
     Other 
5 (2.0%) 
1 (1.1%) 
 
6 (1.7%) 
     Predominant classic 
38 (15.1%) 
15 (15.8%) 
 
53 (15.3%) 
Type of CNV (Grouping 1) 
 
 
 
 
     - 
  
 
0.6981 
 
     Can't Grade 
7 (2.8%) 
1 (1.1%) 
 
8 (2.3%) 
     Occult 
192 (76.2%) 
78 (82.1%) 
 
270 (77.8%) 
     Other 
5 (2.0%) 
1 (1.1%) 
 
6 (1.7%) 
     Predominant classic 
38 (15.1%) 
15 (15.8%) 
 
53 (15.3%) 
Type of CNV (Grouping 2) 
 
 
 
 
     - 
  
 
0.6069 
 
     Can't Grade 
7 (2.8%) 
1 (1.1%) 
 
8 (2.3%) 
     Other 
197 (78.2%) 
79 (83.2%) 
 
276 (79.5%) 
     Predominant classic 
38 (15.1%) 
15 (15.8%) 
 
53 (15.3%) 
Type of CNV (Grouping 3) 
 
 
 
 
     - 
  
 
0.5005 
 
     Can't Grade 
7 (2.8%) 
1 (1.1%) 
 
8 (2.3%) 
     Non-PED 
47 (18.7%) 
16 (16.8%) 
 
63 (18.2%) 
     PED 
188 (74.6%) 
78 (82.1%) 
 
266 (76.7%) 
CNV Center Involvement 
 
 
 
 
     - 
  
  
0.1731 
  
     Absent 
6 (2.4%) 
  
  
6 (1.7%) 
     Definite 
231 (91.7%) 
91 (95.8%) 
  
322 (92.8%) 
     Questionable 
3 (1.2%) 
  
  
3 (0.9%) 
Lesion Components - CNV 
 
 
 
 
     - 
  
  
- 
  
     CNV 
239 (94.8%) 
95 (100.0%) 
  
334 (96.3%) 
Lesion Components - Blood 
 
 
 
 
     - 
  
  
0.8264 
  
     Blood 
95 (37.7%) 
39 (41.1%) 
  
134 (38.6%) 
     No 
144 (57.1%) 
56 (58.9%) 
  
200 (57.6%) 

Novartis 
Confidential 
Page 56 
MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
P Value 
Total 
(N=X) 
Lesion Components - Serious PED 
 
 
 
 
     - 
  
  
0.6364 
  
     No 
227 (90.1%) 
89 (93.7%) 
  
316 (91.1%) 
     Serious PED 
12 (4.8%) 
6 (6.3%) 
  
18 (5.2%) 
Lesion Components - RPE rip/tear 
 
 
 
 
     - 
  
  
- 
  
     No 
239 (94.8%) 
95 (100.0%) 
  
334 (96.3%) 
Lesion Components - Can't Grade 
 
 
 
 
     - 
  
  
0.0240 
  
     Can't Grade 
13 (5.2%) 
  
  
13 (3.7%) 
     No 
239 (94.8%) 
95 (100.0%) 
  
334 (96.3%) 
Lesion Components - Others 
 
 
 
 
     - 
  
  
0.7288 
  
     No 
178 (70.6%) 
69 (72.6%) 
  
247 (71.2%) 
     Others 
61 (24.2%) 
26 (27.4%) 
  
87 (25.1%) 
Area of Lesion 
 
 
 
 
     - 
  
  
0.3695 
  
     n 
232 
94 
  
326 
     Mean 
6.332 
5.724 
  
6.157 
     Median 
4.400 
4.000 
  
4.335 
     SD 
5.642 
5.259 
  
5.533 
     Minimum 
0.30 
0.43 
  
0.30 
     Maximum 
35.06 
25.15 
  
35.06 
Geographic Atrophy  
 
 
 
 
     - 
  
  
0.0064 
  
     Absent 
203 (80.6%) 
88 (92.6%) 
  
291 (83.9%) 
     Definite 
49 (19.4%) 
7 (7.4%) 
  
56 (16.1%) 
Location of Geographic Atrophy - Central Subfield 
 
 
 
     - 
  
  
0.9125 
  
     No 
34 (13.5%) 
5 (5.3%) 
  
39 (11.2%) 
     Yes 
15 (6.0%) 
2 (2.1%) 
  
17 (4.9%) 
Location of Geographic Atrophy - Inner Subfield 
 
 
 
     - 
  
  
0.2850 
  
     No 
7 (2.8%) 
  
  
7 (2.0%) 
     Yes 
42 (16.7%) 
7 (7.4%) 
  
49 (14.1%) 

Novartis 
Confidential 
Page 57 
MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
P Value 
Total 
(N=X) 
Location of Geographic Atrophy - Other Subfield 
 
 
 
     - 
  
  
0.2795 
  
     No 
17 (6.7%) 
1 (1.1%) 
  
18 (5.2%) 
     Yes 
32 (12.7%) 
6 (6.3%) 
  
38 (11.0%) 
Location of Geographic Atrophy - Can't Grade 
 
 
 
     - 
  
  
- 
  
     No 
49 (19.4%) 
7 (7.4%) 
  
56 (16.1%) 
Geographic Atrophy - Area 
 
 
 
 
     - 
  
  
0.7834 
  
     n 
46 
7 
  
53 
     Mean 
3.207 
2.617 
  
3.129 
     Median 
1.470 
0.850 
  
1.440 
     SD 
5.397 
4.123 
  
5.216 
     Minimum 
0.06 
0.33 
  
0.06 
     Maximum 
30.69 
11.69 
  
30.69 
Retinal Abnormalities 
 
 
 
 
     - 
  
  
0.4664 
  
     Absent 
3 (1.2%) 
  
  
3 (0.9%) 
     Definite 
248 (98.4%) 
95 (100.0%) 
  
343 (98.8%) 
     Not Applicable 
1 (0.4%) 
  
  
1 (0.3%) 
Retinal Abnormalities - Drusen 
 
 
 
 
     - 
  
  
0.9035 
  
     No 
3 (1.2%) 
1 (1.1%) 
  
4 (1.2%) 
     Yes 
245 (97.2%) 
94 (98.9%) 
  
339 (97.7%) 
Retinal Abnormalities - Atrophy 
 
 
 
 
     - 
  
  
0.0076 
  
     No 
208 (82.5%) 
90 (94.7%) 
  
298 (85.9%) 
     Yes 
40 (15.9%) 
5 (5.3%) 
  
45 (13.0%) 
Retinal Abnormalities - Fibrosis 
 
 
 
 
     - 
  
  
0.9937 
  
     No 
235 (93.3%) 
90 (94.7%) 
  
325 (93.7%) 
     Yes 
13 (5.2%) 
5 (5.3%) 
  
18 (5.2%) 
Retinal Abnormalities - Hemorrhage (old format CF data) 
 
 
 
     - 
  
  
0.9897 
  
     No 
146 (57.9%) 
56 (58.9%) 
  
202 (58.2%) 
     Yes 
102 (40.5%) 
39 (41.1%) 
  
141 (40.6%) 

Novartis 
Confidential 
Page 58 
MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
P Value 
Total 
(N=X) 
Retinal Abnormalities - PED 
 
 
 
 
     - 
  
  
0.6179 
  
     No 
238 (94.4%) 
90 (94.7%) 
  
328 (94.5%) 
     Yes 
10 (4.0%) 
5 (5.3%) 
  
15 (4.3%) 
Retinal Abnormalities - Other 
 
 
 
 
     - 
  
  
0.5250 
  
     No 
158 (62.7%) 
57 (60.0%) 
  
215 (62.0%) 
     Yes 
90 (35.7%) 
38 (40.0%) 
  
128 (36.9%) 
Retinal Abnormalities Location Central 
 
 
 
 
     - 
  
  
0.2937 
  
     No 
2 (0.8%) 
3 (3.2%) 
  
5 (1.4%) 
     Yes 
3 (1.2%) 
1 (1.1%) 
  
1 (0.3%) 
Retinal Abnormalities Location Peripheral 
 
 
 
 
     - 
  
  
0.2937 
  
     No 
2 (0.8%) 
3 (3.2%) 
  
5 (1.4%) 
     Yes 
3 (1.2%) 
1 (1.1%) 
  
1 (0.3%) 
Hemorrhage (new format CF data) 
 
 
 
 
     - 
  
  
0.7765 
  
     Absent 
148 (58.7%) 
54 (56.8%) 
  
202 (58.2%) 
     Definite 
103 (40.9%) 
41 (43.2%) 
  
144 (41.5%) 
     Not Applicable 
1 (0.4%) 
  
  
1 (0.3%) 
Hemorrhage Location Central Subfield 
 
 
 
 
     - 
  
  
0.0730 
  
     No 
5 (2.0%) 
2 (2.1%) 
  
4 (1.2%) 
     Yes 
  
2 (2.1%) 
  
2 (0.6%) 
Hemorrhage Location Inner Subfield 
 
 
 
 
     - 
  
  
0.2937 
  
     No 
2 (0.8%) 
3 (3.2%) 
  
4 (1.2%) 
     Yes 
3 (1.2%) 
1 (1.1%) 
  
2 (0.6%) 
Hemorrhage Location Outer Subfield 
 
 
 
 
     - 
  
  
0.6353 
  
     No 
3 (1.2%) 
3 (3.2%) 
  
5 (1.4%) 
     Yes 
 
2 (0.8%) 
1 (1.1%) 
  
1 (0.3%) 

Novartis 
Confidential 
Page 59 
MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
P Value 
Total 
(N=X) 
CNV Location (CRF DATA) 
 
 
 
 
     - 
  
  
0.2168 
  
     Juxtafoveal 
4 (1.6%) 
  
  
4 (1.2%) 
     Subfoveal 
248 (98.4%) 
95 (100.0%) 
  
343 (98.8%) 
     Extrafoveal 
xx (x.x%) 
xx (x.x%) 
 
xx (x.x%) 
IRF (CRF DATA) 
 
 
 
 
     - 
  
  
0.4505 
  
     Absent 
60 (23.8%) 
19 (20.0%) 
  
79 (22.8%) 
     Present 
192 (76.2%) 
76 (80.0%) 
  
268 (77.2%) 
     Can’t Grade 
xx (x.x%) 
xx (x.x%) 
 
xx (x.x%) 
SRF (CRF DATA) 
 
 
 
 
     - 
  
  
0.0258 
  
     Absent 
62 (24.6%) 
13 (13.7%) 
  
75 (21.6%) 
     Can't grade 
  
1 (1.1%) 
  
1 (0.3%) 
     Present 
190 (75.4%) 
81 (85.3%) 
  
271 (78.1%) 
 
 
*: Centre involvement is concluded when 'Intraretinal Fluid - Center Involvement'='Present', 'Intraretinal Cysts - Center 
Involvement'='Definite' or 'Any Subretinal Fluid - Center Involvement'='Present'. 
 
 
 

Novartis 
Confidential 
Page 60 
MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
Table 14.1-11 
Baseline characteristics by genotyping status 
Randomised Set 
 
 
Genotype Sample 
(N=X) 
NO Genotype Sample 
(N=X) 
P Value 
Total 
(N=X) 
Age (years)* 
     - 
 
 
x.xxxx 
 
     n 
xxx 
xxx 
 
xxx 
     Mean 
xx.x 
xx.x 
 
xx.x 
     Median 
xx.x 
xx.x 
 
xx.x 
     SD 
x.x 
x.x 
 
x.x 
     Minimum 
xx 
xx 
 
xx 
     Maximum 
xx 
xx 
 
xx 
Gender 
     - 
 
 
x.xxxx 
 
     Female 
xxx (xx.x%) 
xxx (xx.x%) 
 
xxx (xx.x%) 
     Male 
xxx (xx.x%) 
xxx (xx.x%) 
 
xxx (xx.x%) 
Race 
     - 
 
 
0.5840 
 
     AFGHAN 
1 (0.4%) 
 
 
xxx (xx.x%) 
     ……………… 
1 (0.4%) 
 
 
xxx (xx.x%) 
 
Race (Grouped) 
     - 
 
 
x.xxxx 
 
Caucasian: Afghan, Caucasian, Egypt, 
Egyptian, El Salvadore, Greek, Hispanic, 
Israeli, Italian, Maltese, Middle East, 
Middle Eastern, South American, Turkish, 
Yugoslavian 
xxx (xx.x%) 
xxx (xx.x%) 
 
xxx (xx.x%) 
Black African 
xxx (xx.x%) 
xxx (xx.x%) 
 
xxx (xx.x%) 
Asian: Asian and Indian 
xxx (xx.x%) 
xxx (xx.x%) 
 
xxx (xx.x%) 
Aboriginal and Torres Strait Islander 
xxx (xx.x%) 
xxx (xx.x%) 
 
xxx (xx.x%) 
Pacific Islander 
xxx (xx.x%) 
xxx (xx.x%) 
 
xxx (xx.x%) 
Not Sure 
xxx (xx.x%) 
xxx (xx.x%) 
 
xxx (xx.x%) 
Ethnicity 
     - 
  
 
x.xxxx 
  
     ABORIGINAL 
xxx (xx.x%) 
 
 
xxx (xx.x%) 
     ……………… 
 
 
     WELSH 
xxx (xx.x%) 
 
 
xxx (xx.x%) 

Novartis 
Confidential 
Page 61 
MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
 
Genotype Sample 
(N=X) 
NO Genotype Sample 
(N=X) 
P Value 
Total 
(N=X) 
 
 
Family history of AMD 
     - 
  
 
x.xxxx 
  
     No 
xxx (xx.x%) 
xxx (xx.x%) 
 
xxx (xx.x%) 
     Yes 
xxx (xx.x%) 
xxx (xx.x%) 
 
xxx (xx.x%) 
History of arterial thromboembolic events 
     - 
  
 
0.2342 
  
     No 
216 (85.7%) 
86 (90.5%) 
 
302 (87.0%) 
     Yes 
36 (14.3%) 
9 (9.5%) 
 
45 (13.0%) 
Smoking History 
 
 
     - 
  
 
0.2612 
  
     Current smoker 
24 (9.5%) 
8 (8.4%) 
 
32 (9.2%) 
     Never smoked 
108 (42.9%) 
50 (52.6%) 
 
158 (45.5%) 
     Smoked in the past 
120 (47.6%) 
37 (38.9%) 
 
157 (45.2%) 
Smoking History (Grouped) 
 
 
     - 
  
 
0.7516 
  
     Current smoker 
24 (9.5%) 
8 (8.4%) 
 
32 (9.2%) 
     Non-Smoker 
228 (90.5%) 
87 (91.6%) 
 
315 (90.8%) 
Previous exposure of non-study eye 
 
 
     - 
  
 
0.0246 
  
     No 
183 (72.6%) 
80 (84.2%) 
 
263 (75.8%) 
     Yes 
69 (27.4%) 
15 (15.8%) 
 
84 (24.2%) 
Previous exposure - treatment 
 
 
     - 
  
 
0.3904 
  
     Avastin 
10 (14.5%) 
3 (20.0%) 
 
13 (15.5%) 
     Eylea 
15 (21.7%) 
5 (33.3%) 
 
20 (23.8%) 
     Lucentis 
50 (72.5%) 
7 (46.7%) 
 
57 (67.9%) 
     Visudyne 
7 (10.1%) 
 
 
7 (8.3%) 
     Other 
2 (2.9%) 
 
 
2 (2.4%) 
Study Eye 
 
 
     - 
  
 
0.0149 
  
     Left eye 
109 (43.3%) 
55 (57.9%) 
 
164 (47.3%) 
     Right eye 
143 (56.7%) 
40 (42.1%) 
 
183 (52.7%) 

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MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
 
Genotype Sample 
(N=X) 
NO Genotype Sample 
(N=X) 
P Value 
Total 
(N=X) 
Best Corrective Visual Acuity 
 
 
     - 
  
 
0.2503 
  
     n 
252 
95 
 
347 
     Mean 
63.8 
61.8 
 
63.2 
     Median 
67.0 
63.0 
 
66.0 
     SD 
13.7 
14.7 
 
14.0 
     Minimum 
23 
23 
 
23 
     Maximum 
90 
85 
 
90 
BCVA (Categorical) 
     - 
  
 
0.1910 
  
     <70 
145 (57.5%) 
62 (65.3%) 
  
207 (59.7%) 
     >=70 
107 (42.5%) 
33 (34.7%) 
  
140 (40.3%) 
Central Subfield Foveal Thickness 
 
 
     - 
  
 
0.4227 
  
     n 
252 
95 
  
347 
     Mean 
445.0 
461.6 
  
449.5 
     Median 
405.0 
409.0 
  
406.0 
     SD 
175.6 
162.6 
 
172.1 
     Minimum 
169 
256 
  
169 
     Maximum 
1309 
1123 
 
1309 
Central Subfield Foveal Volume 
 
 
 
     - 
  
 
0.3304 
  
     n 
252 
95 
  
347 
     Mean 
0.4 
0.4 
 
0.4 
     Median 
0.3 
0.3 
 
0.3 
     SD 
0.2 
0.3 
 
0.2 
     Minimum 
0 
0 
  
0 
     Maximum 
3 
3 
 
3 
Intraretinal Fluid 
 
 
 
     - 
  
  
0.7260 
  
     Absent 
159 (63.1%) 
58 (61.1%) 
 
217 (62.5%) 
     Present 
93 (36.9%) 
37 (38.9%) 
 
130 (37.5%) 
Intraretinal Fluid - Center Involvement 
 
 
     - 
  
 
0.6946 
  
     Absent 
8 (3.2%) 
4 (4.2%) 
 
12 (3.5%) 
     Present 
85 (33.7%) 
33 (34.7%) 
 
118 (34.0%) 

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MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
 
Genotype Sample 
(N=X) 
NO Genotype Sample 
(N=X) 
P Value 
Total 
(N=X) 
Intraretinal Cysts 
     - 
  
 
0.8995 
  
     Absent 
108 (42.9%) 
40 (42.1%) 
  
148 (42.7%) 
     Definite 
144 (57.1%) 
55 (57.9%) 
  
199 (57.3%) 
Intraretinal Cysts - Center Involvement 
 
 
     - 
  
 
0.3667 
  
     Absent 
8 (3.2%) 
5 (5.3%) 
  
13 (3.7%) 
     Definite 
136 (54.0%) 
50 (52.6%) 
  
186 (53.6%) 
Any Subretinal Fluid 
 
 
 
 
     - 
  
 
0.0341 
  
     Absent 
51 (20.2%) 
10 (10.5%) 
 
61 (17.6%) 
     Present 
201 (79.8%) 
85 (89.5%) 
 
286 (82.4%) 
Any Subretinal Fluid - Center Involvement 
 
 
 
 
     - 
  
 
0.1079 
  
     Absent 
18 (7.1%) 
3 (3.2%) 
 
21 (6.1%) 
     Present 
183 (72.6%) 
82 (86.3%) 
 
265 (76.4%) 
Morphological Changes 
 
 
 
 
     - 
  
 
0.3693 
  
     Absent 
176 (69.8%) 
71 (74.7%) 
  
247 (71.2%) 
     Definite 
76 (30.2%) 
24 (25.3%) 
 
100 (28.8%) 
Morphological Change - Epiretinal Membrane 
     - 
  
  
0.4748 
  
     No 
48 (19.0%) 
13 (13.7%) 
 
61 (17.6%) 
     Yes 
29 (11.5%) 
11 (11.6%) 
 
40 (11.5%) 
No Intraretinal Fluid or Cysts (derived) 
 
 
     - 
  
 
0.7266 
  
     IRF or IR Cyst or both (IRF and Cyst) 
154 (61.1%) 
60 (63.2%) 
 
214 (61.7%) 
     No IRF nor IR Cyst 
98 (38.9%) 
35 (36.8%) 
 
133 (38.3%) 
 
 
 

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MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
 
Genotype Sample 
(N=X) 
NO Genotype Sample 
(N=X) 
P Value 
Total 
(N=X) 
Morphological Change - Vitreo-Retinal Traction 
 
     - 
  
  
0.7219 
  
     No 
38 (15.1%) 
13 (13.7%) 
 
51 (14.7%) 
     Yes 
38 (15.1%) 
11 (11.6%) 
 
49 (14.1%) 
Morphological Change - Macular Hole 
 
 
 
     - 
  
  
- 
  
     No 
76 (30.2%) 
24 (25.3%) 
 
100 (28.8%) 
Morphological Change - Atrophy 
 
 
 
     - 
  
  
0.0990 
  
     No 
36 (14.3%) 
16 (16.8%) 
 
52 (15.0%) 
     Yes 
40 (15.9%) 
8 (8.4%) 
 
48 (13.8%) 
Morphological Change - Other 
 
 
 
     - 
  
  
0.5722 
  
     No 
75 (29.8%) 
24 (25.3%) 
 
99 (28.5%) 
     Yes 
1 (0.4%) 
  
 
1 (0.3%) 
Subfoveal Fluid Center Point 
 
 
 
     - 
  
  
0.7931 
  
     Absent 
27 (10.7%) 
7 (7.4%) 
 
34 (9.8%) 
     Not Applicable 
10 (4.0%) 
2 (2.1%) 
 
12 (3.5%) 
     Present 
17 (6.7%) 
6 (6.3%) 
 
23 (6.6%) 
Subfoveal Fluid - Height at Center Point 
 
 
 
     - 
  
  
0.2698 
  
     <=200um 
14 (5.6%) 
6 (6.3%) 
 
20 (5.8%) 
     >200um 
3 (1.2%) 
 
 
3 (0.9%) 
Evidence of CNV Complex 
 
 
     - 
  
 
0.0460 
  
     Absent 
9 (3.6%) 
 
 
9 (2.6%) 
     Can't Grade 
1 (0.4%) 
 
 
1 (0.3%) 
     Definite 
232 (92.1%) 
95 (100.0%) 
 
327 (94.2%) 
     Questionable 
10 (4.0%) 
 
 
10 (2.9%) 
Location of CNV Complex, by centre involvement* (derived) 
 
     - 
  
 
- 
  

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MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
 
Genotype Sample 
(N=X) 
NO Genotype Sample 
(N=X) 
P Value 
Total 
(N=X) 
CNV Leakage 
 
 
 
     - 
  
 
0.1795 
  
     Absent 
2 (0.8%) 
 
 
2 (0.6%) 
     Can't Grade 
1 (0.4%) 
1 (1.1%) 
 
2 (0.6%) 
     Definite 
230 (91.3%) 
94 (98.9%) 
 
324 (93.4%) 
     Questionable 
9 (3.6%) 
 
 
9 (2.6%) 
Area of CNV 
 
 
 
     - 
  
 
0.1179 
  
     n 
228 
92 
 
320 
     Mean 
5.589 
4.688 
 
5.330 
     Median 
4.045 
3.500 
 
3.715 
     SD 
4.899 
3.954 
 
4.659 
     Minimum 
0.30 
0.43 
 
0.30 
     Maximum 
30.09 
22.72 
 
30.09 
CNV Location 
 
 
 
     - 
  
 
0.2412 
  
     Can't Grade 
3 (1.2%) 
1 (1.1%) 
 
4 (1.2%) 
     Extrafoveal 
16 (6.3%) 
3 (3.2%) 
 
19 (5.5%) 
     Juxtafoveal 
23 (9.1%) 
9 (9.5%) 
 
32 (9.2%) 
     No CNV complex 
10 (4.0%) 
 
 
10 (2.9%) 
     Subfoveal 
200 (79.4%) 
82 (86.3%) 
 
282 (81.3%) 
CNV Location, by centre involvement* (derived) 
 
 
     - 
  
 
0.3611 
 
     Can't Grade 
3 (1.2%) 
1 (1.1%) 
 
4 (1.2%) 
     Extrafoveal 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
     Extrafoveal with centre involvement 
16 (6.3%) 
3 (3.2%) 
 
19 (5.5%) 
     Juxtafoveal 
2 (0.8%) 
2 (2.1%) 
 
4 (1.2%) 
     Juxtafoveal with centre involvement 
21 (8.3%) 
7 (7.4%) 
 
28 (8.1%) 
     No CNV complex 
2 (0.8%) 
 
 
2 (0.6%) 
     Subfoveal 
200 (79.4%) 
82 (86.3%) 
 
282 (81.3%) 
Type of CNV 
 
 
 
 
     - 
  
 
0.5981 
 
     Can't Grade 
7 (2.8%) 
1 (1.1%) 
 
8 (2.3%) 
     Occult (fibrovascular PED) 
178 (70.6%) 
72 (75.8%) 
 
250 (72.0%) 
     Occult (late leakage) 
4 (1.6%) 
 
 
4 (1.2%) 
     Occult with serious PED 
10 (4.0%) 
6 (6.3%) 
 
16 (4.6%) 
     Other 
5 (2.0%) 
1 (1.1%) 
 
6 (1.7%) 
     Predominant classic 
38 (15.1%) 
15 (15.8%) 
 
53 (15.3%) 

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MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
 
Genotype Sample 
(N=X) 
NO Genotype Sample 
(N=X) 
P Value 
Total 
(N=X) 
Type of CNV (Grouping 1) 
 
 
 
 
     - 
  
 
0.6981 
 
     Can't Grade 
7 (2.8%) 
1 (1.1%) 
 
8 (2.3%) 
     Occult 
192 (76.2%) 
78 (82.1%) 
 
270 (77.8%) 
     Other 
5 (2.0%) 
1 (1.1%) 
 
6 (1.7%) 
     Predominant classic 
38 (15.1%) 
15 (15.8%) 
 
53 (15.3%) 
Type of CNV (Grouping 2) 
 
 
 
 
     - 
  
 
0.6069 
 
     Can't Grade 
7 (2.8%) 
1 (1.1%) 
 
8 (2.3%) 
     Other 
197 (78.2%) 
79 (83.2%) 
 
276 (79.5%) 
     Predominant classic 
38 (15.1%) 
15 (15.8%) 
 
53 (15.3%) 
Type of CNV (Grouping 3) 
 
 
 
 
     - 
  
 
0.5005 
 
     Can't Grade 
7 (2.8%) 
1 (1.1%) 
 
8 (2.3%) 
     Non-PED 
47 (18.7%) 
16 (16.8%) 
 
63 (18.2%) 
     PED 
188 (74.6%) 
78 (82.1%) 
 
266 (76.7%) 
CNV Center Involvement 
 
 
 
 
     - 
  
  
0.1731 
  
     Absent 
6 (2.4%) 
  
  
6 (1.7%) 
     Definite 
231 (91.7%) 
91 (95.8%) 
  
322 (92.8%) 
     Questionable 
3 (1.2%) 
  
  
3 (0.9%) 
Lesion Components - CNV 
 
 
 
 
     - 
  
  
- 
  
     CNV 
239 (94.8%) 
95 (100.0%) 
  
334 (96.3%) 
Lesion Components - Blood 
 
 
 
 
     - 
  
  
0.8264 
  
     Blood 
95 (37.7%) 
39 (41.1%) 
  
134 (38.6%) 
     No 
144 (57.1%) 
56 (58.9%) 
  
200 (57.6%) 
Lesion Components - Serious PED 
 
 
 
 
     - 
  
  
0.6364 
  
     No 
227 (90.1%) 
89 (93.7%) 
  
316 (91.1%) 
     Serious PED 
12 (4.8%) 
6 (6.3%) 
  
18 (5.2%) 
Lesion Components - RPE rip/tear 
 
 
 
 
     - 
  
  
- 
  
     No 
239 (94.8%) 
95 (100.0%) 
  
334 (96.3%) 

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MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
 
Genotype Sample 
(N=X) 
NO Genotype Sample 
(N=X) 
P Value 
Total 
(N=X) 
Lesion Components - Can't Grade 
 
 
 
 
     - 
  
  
0.0240 
  
     Can't Grade 
13 (5.2%) 
  
  
13 (3.7%) 
     No 
239 (94.8%) 
95 (100.0%) 
  
334 (96.3%) 
 
 
 
 
Lesion Components - Others 
 
 
 
 
     - 
  
  
0.7288 
  
     No 
178 (70.6%) 
69 (72.6%) 
  
247 (71.2%) 
     Others 
61 (24.2%) 
26 (27.4%) 
  
87 (25.1%) 
Area of Lesion 
 
 
 
 
     - 
  
  
0.3695 
  
     n 
232 
94 
  
326 
     Mean 
6.332 
5.724 
  
6.157 
     Median 
4.400 
4.000 
  
4.335 
     SD 
5.642 
5.259 
  
5.533 
     Minimum 
0.30 
0.43 
  
0.30 
     Maximum 
35.06 
25.15 
  
35.06 
Geographic Atrophy 
 
 
 
 
     - 
  
  
0.0064 
  
     Absent 
203 (80.6%) 
88 (92.6%) 
  
291 (83.9%) 
     Definite 
49 (19.4%) 
7 (7.4%) 
  
56 (16.1%) 
Location of Geographic Atrophy - Central Subfield 
 
 
 
     - 
  
  
0.9125 
  
     No 
34 (13.5%) 
5 (5.3%) 
  
39 (11.2%) 
     Yes 
15 (6.0%) 
2 (2.1%) 
  
17 (4.9%) 
Location of Geographic Atrophy - Inner Subfield 
 
 
 
     - 
  
  
0.2850 
  
     No 
7 (2.8%) 
  
  
7 (2.0%) 
     Yes 
42 (16.7%) 
7 (7.4%) 
  
49 (14.1%) 
Location of Geographic Atrophy - Other Subfield 
 
 
 
     - 
  
  
0.2795 
  
     No 
17 (6.7%) 
1 (1.1%) 
  
18 (5.2%) 
     Yes 
32 (12.7%) 
6 (6.3%) 
  
38 (11.0%) 
Location of Geographic Atrophy - Can't Grade 
 
 
 
     - 
  
  
- 
  
     No 
49 (19.4%) 
7 (7.4%) 
  
56 (16.1%) 

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MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
 
Genotype Sample 
(N=X) 
NO Genotype Sample 
(N=X) 
P Value 
Total 
(N=X) 
Geographic Atrophy - Area 
 
 
 
 
     - 
  
  
0.7834 
  
     n 
46 
7 
  
53 
     Mean 
3.207 
2.617 
  
3.129 
     Median 
1.470 
0.850 
  
1.440 
     SD 
5.397 
4.123 
  
5.216 
     Minimum 
0.06 
0.33 
  
0.06 
     Maximum 
30.69 
11.69 
  
30.69 
Retinal Abnormalities 
 
 
 
 
     - 
  
  
0.4664 
  
     Absent 
3 (1.2%) 
  
  
3 (0.9%) 
     Definite 
248 (98.4%) 
95 (100.0%) 
  
343 (98.8%) 
     Not Applicable 
1 (0.4%) 
  
  
1 (0.3%) 
Retinal Abnormalities - Drusen 
 
 
 
 
     - 
  
  
0.9035 
  
     No 
3 (1.2%) 
1 (1.1%) 
  
4 (1.2%) 
     Yes 
245 (97.2%) 
94 (98.9%) 
  
339 (97.7%) 
Retinal Abnormalities - Atrophy 
 
 
 
 
     - 
  
  
0.0076 
  
     No 
208 (82.5%) 
90 (94.7%) 
  
298 (85.9%) 
     Yes 
40 (15.9%) 
5 (5.3%) 
  
45 (13.0%) 
Retinal Abnormalities - Fibrosis 
 
 
 
 
     - 
  
  
0.9937 
  
     No 
235 (93.3%) 
90 (94.7%) 
  
325 (93.7%) 
     Yes 
13 (5.2%) 
5 (5.3%) 
  
18 (5.2%) 
Retinal Abnormalities - Hemorrhage (old format CF data) 
 
 
 
     - 
  
  
0.9897 
  
     No 
146 (57.9%) 
56 (58.9%) 
  
202 (58.2%) 
     Yes 
102 (40.5%) 
39 (41.1%) 
  
141 (40.6%) 
Retinal Abnormalities - PED 
 
 
 
 
     - 
  
  
0.6179 
  
     No 
238 (94.4%) 
90 (94.7%) 
  
328 (94.5%) 
     Yes 
10 (4.0%) 
5 (5.3%) 
  
15 (4.3%) 
 
 
 
 

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MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
 
Genotype Sample 
(N=X) 
NO Genotype Sample 
(N=X) 
P Value 
Total 
(N=X) 
Retinal Abnormalities - Other 
 
 
 
 
     - 
  
  
0.5250 
  
     No 
158 (62.7%) 
57 (60.0%) 
  
215 (62.0%) 
     Yes 
90 (35.7%) 
38 (40.0%) 
  
128 (36.9%) 
Retinal Abnormalities Location Central 
 
 
 
 
     - 
  
  
0.2937 
  
     No 
2 (0.8%) 
3 (3.2%) 
  
5 (1.4%) 
     Yes 
3 (1.2%) 
1 (1.1%) 
  
1 (0.3%) 
Retinal Abnormalities Location Peripheral 
 
 
 
 
     - 
  
  
0.2937 
  
     No 
2 (0.8%) 
3 (3.2%) 
  
5 (1.4%) 
     Yes 
3 (1.2%) 
1 (1.1%) 
  
1 (0.3%) 
Hemorrhage (new format CF data) 
 
 
 
 
     - 
  
  
0.7765 
  
     Absent 
148 (58.7%) 
54 (56.8%) 
  
202 (58.2%) 
     Definite 
103 (40.9%) 
41 (43.2%) 
  
144 (41.5%) 
     Not Applicable 
1 (0.4%) 
  
  
1 (0.3%) 
Hemorrhage Location Central Subfield 
 
 
 
 
     - 
  
  
0.0730 
  
     No 
5 (2.0%) 
2 (2.1%) 
  
4 (1.2%) 
     Yes 
  
2 (2.1%) 
  
2 (0.6%) 
Hemorrhage Location Inner Subfield 
 
 
 
 
     - 
  
  
0.2937 
  
     No 
2 (0.8%) 
3 (3.2%) 
  
4 (1.2%) 
     Yes 
3 (1.2%) 
1 (1.1%) 
  
2 (0.6%) 
Hemorrhage Location Outer Subfield 
 
 
 
 
     - 
  
  
0.6353 
  
     No 
3 (1.2%) 
3 (3.2%) 
  
5 (1.4%) 
     Yes 
2 (0.8%) 
1 (1.1%) 
  
1 (0.3%) 
CNV Location (CRF DATA) 
 
 
 
 
     - 
  
  
0.2168 
  
     Juxtafoveal 
4 (1.6%) 
  
  
4 (1.2%) 
     Subfoveal 
248 (98.4%) 
95 (100.0%) 
  
343 (98.8%) 
     Extrafoveal 
xx (x.x%) 
xx (x.x%) 
 
xx (x.x%) 
 
 
 
 

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MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
 
Genotype Sample 
(N=X) 
NO Genotype Sample 
(N=X) 
P Value 
Total 
(N=X) 
IRF (CRF DATA) 
 
 
 
 
     - 
  
  
0.4505 
  
     Absent 
60 (23.8%) 
19 (20.0%) 
  
79 (22.8%) 
     Present 
192 (76.2%) 
76 (80.0%) 
  
268 (77.2%) 
     Can’t Grade 
xx (x.x%) 
xx (x.x%) 
 
xx (x.x%) 
SRF (CRF DATA) 
 
 
 
 
     - 
  
  
0.0258 
  
     Absent 
62 (24.6%) 
13 (13.7%) 
  
75 (21.6%) 
     Can't grade 
  
1 (1.1%) 
  
1 (0.3%) 
     Present 
190 (75.4%) 
81 (85.3%) 
  
271 (78.1%) 
 
 
*: Centre involvement is concluded when 'Intraretinal Fluid - Center Involvement'='Present', 'Intraretinal Cysts - Center 
Involvement'='Definite' or 'Any Subretinal Fluid - Center Involvement'='Present'. 
 
 
 

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MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
Table 14.1-12 
Baseline Medical History Questions by treatment group  
Randomised Set 
 
 
 
Intensive  
(N=X) 
n (%) 
 Relaxed  
(N=X) 
n (%) 
Total 
(N=X) 
n (%) 
 
 
 
 
 
Are there any relevant Medical history/Current medical conditions to be reported?* 
 
 
Yes 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
No 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
Table 14.1-13 
Medical History, by primary system organ class, preferred terms and treatment 
Randomised Set 
 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
System Organ Class (SOC) 
           Preferred Term (PT) 
Nr (%) of  
Subjects 
Nr (%) of  
Subjects 
Nr (%) of  
Subjects 
 
 
 
 
 
All Body Systems 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
SOC1 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
PT1 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
PT2 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
SOC2 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
PT1 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
PT2 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x) 
x (xx.x) 
x (xx.x) 
……….. 
 
 
 
 

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MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
Table 14.1-14 
Ocular Medical History, by primary system organ class, preferred terms 
Randomised Set 
 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
System Organ Class (SOC) 
           Preferred Term (PT) 
Nr (%) of  
Subjects 
Nr (%) of  
Subjects 
Nr (%) of  
Subjects 
 
 
 
 
 
Eye disorders 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
PT1 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
PT2 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 

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MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
Table 14.1-15 Medical History - Arterial Thomboembolic Events 
Randomised Set 
 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
 
 
 
 
 
 
 
 
Arterial Thomboembolic Events (ATEs)* 
xx.x 
x 
xx.x 
x 
xx.x 
x 
Nonfatal myocardial infarction 
xx.x 
x 
xx.x 
x 
xx.x 
x 
Nonfatal stroke 
xx.x 
x 
xx.x 
x 
xx.x 
x 
 
 
 
 
 
 
 
* ATEs defined as nonfatal myocardial infarction, nonfatal stroke, vascular death and death of unknown cause 
AE: Adverse Event 
Note: Some patients may have experienced multiple events 
 

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MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
Table 14.1-16  
Baseline AMD characteristics (STUDY EYE) by treatment group 
Randomised Set 
 
 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
 
 
 
 
 
Was any treatment ever given to the fellow eye prior to Screening? 
 
 
No 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Yes 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Lucentis 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Eylea 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Visudyne 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Avastin 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Steroids 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Other 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Total BCVA Score (ETDRS letters) 
 
 
 
 
n 
x 
x 
x 
 
Mean 
x.x 
x.x 
x.x 
 
Median 
x.x 
x.x 
x.x 
 
SD 
x.x 
x.x 
x.x 
 
Minimum 
x 
x 
x 
 
Maximum 
x 
x 
x 
 
 
 
 
 
Visual Acuity - Categorical (20/40) 
 
 
 
 
>=70 letters 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
<70 letters 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
 
 
 
 

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Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
 
Central Subfield Foveal  Thickness (µm)* 
 
 
 
 
n 
x 
x 
x 
 
Mean 
x.x 
x.x 
x.x 
 
Median 
x.x 
x.x 
x.x 
 
SD 
x.x 
x.x 
x.x 
 
Minimum 
x 
x 
x 
 
Maximum 
x 
x 
x 
 
 
 
 
 
Central Subfield Volume (mm3)* 
 
 
 
 
n 
x 
x 
x 
 
Mean 
x.x 
x.x 
x.x 
 
Median 
x.x 
x.x 
x.x 
 
SD 
x.x 
x.x 
x.x 
 
Minimum 
x 
x 
x 
 
Maximum 
x 
x 
x 
 
 
 
 
 
Area of Lesion (mm2)* 
 
 
 
 
n 
x 
x 
x 
 
Mean 
x.x 
x.x 
x.x 
 
Median 
x.x 
x.x 
x.x 
 
SD 
x.x 
x.x 
x.x 
 
Minimum 
x 
x 
x 
 
Maximum 
x 
x 
x 
 
 
 
 
 
Intra-Retinal Fluid Status 
 
 
 
 
Absent 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Present 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Can’t Grade 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
 

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Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
 
Intra-Retinal Fluid Status* 
 
 
 
 
Absent 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Present 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Can’t Grade 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Intra-Retinal Fluid Centre Involvement* 
 
 
 
 
Absent 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Present 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Can’t Grade 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Intra-Retinal Cysts* 
 
 
 
 
Absent 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Present 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Intra-Retinal Cysts Centre Involvement* 
 
 
 
 
Absent 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Present 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Sub-Retinal Fluid Status 
 
 
 
 
Absent 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Present 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Can’t Grade 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Sub-Retinal Fluid Status* 
 
 
 
 
Absent 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Present 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Can’t Grade 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
 
 

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Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
 
Sub-Retinal Fluid Centre Involvement* 
 
 
 
 
Absent 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Present 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Can’t Grade 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Sub-Retinal Fluid at Centrepoint* 
 
 
 
 
Absent 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Present 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Can’t Grade 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Sub-Retinal Fluid Height at Centrepoint 
 
 
 
 
<=200μm 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
>200 μm 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Not Applicable 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Sub-Retinal Fluid Height at Centrepoint* 
 
 
 
 
<=200μm 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
>200 μm 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Not Applicable 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Morphologic Changes* 
 
 
 
 
Epiretinal Membrane 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Vitreoretinal Traction 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Macular Hole 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Atrophy 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Other 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
 
 
 

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Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
 
Area of CNV (mm2)* 
 
 
 
 
n 
x 
x 
x 
 
Mean 
x.x 
x.x 
x.x 
 
Median 
x.x 
x.x 
x.x 
 
SD 
x.x 
x.x 
x.x 
 
Minimum 
x 
x 
x 
 
Maximum 
x 
x 
x 
 
 
 
 
CNV Complex (lesion) 
 
 
 
 
Absent 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Definite 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Questionable 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
…… 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
CNV Complex (lesion)* 
 
 
 
 
Absent 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Definite 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Questionable 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
…… 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
CNV Complex (lesion) Location 
 
 
 
 
Subfoveal 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Juxtafoveal 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Juxtafoveal with centre 
involvement 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Extrafoveal 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Extrafoveal with centre 
involvement 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Can’t grade 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
 

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Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
 
CNV Location 
 
 
 
 
Subfoveal 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Juxtafoveal 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Extrafoveal 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Can’t grade 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
CNV Location* 
 
 
 
 
Subfoveal 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Juxtafoveal 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Juxtafoveal with centre 
involvement 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Extrafoveal 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Extrafoveal with centre 
involvement 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Can’t grade 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
CNV Secondary to …..* 
 
 
 
 
AMD 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Angioid Streaks 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Idiopathic 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Pathologic Myopia 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Macular telangiectasis 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Other 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Type of CNV* 
 
 
 
 
Predominantly classic 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Occult 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Fibrovascular PED 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Serous PED 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Other 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 

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Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
 
CNV Leakage* 
 
 
 
 
Absent 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Present 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Lesion Components* 
 
 
 
 
Blood 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
CNV 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Serous PED 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
RPE Tear 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Other 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Can’t Grade 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Geographic Atrophy (Status)* 
 
 
 
 
Absent 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Definite 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Can’t Grade 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Not Applicable 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Geographic Atrophy Location* 
 
 
 
 
Central Subfield 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Inner Subfield 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Outer Subfield 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Geographic Atrophy Area (mm2)* 
 
 
 
 
n 
x 
x 
x 
 
Mean 
x.x 
x.x 
x.x 
 
Median 
x.x 
x.x 
x.x 
 
SD 
x.x 
x.x 
x.x 
 
Minimum 
x 
x 
x 
 
Maximum 
x 
x 
x 

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Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
 
 
 
 
 
Haemorrhage* 
 
 
 
 
Yes 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
No 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Haemorrhage Location* 
 
 
 
 
Central Subfield 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Inner Subfield  
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Outer Subfield 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Retinal Abnormality* 
 
 
 
 
Drusen 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Atrophy 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Fibrosis 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
PED 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Other 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Retinal Abnormality Location* 
 
 
 
 
Central 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Periphery 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
* Source: 
 
Note: Geographic Atrophy not assessed by all sites. 

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Table 14.1-17 
Baseline AMD characteristics (FELLOW EYE) by treatment group 
Randomised Set 
 
 
 
Intensive  
(N=X) 
n (%) 
 Relaxed  
(N=X) 
n (%) 
Total 
(N=X) 
n (%) 
 
 
 
 
 
Fellow Eye 
 
 
Left 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Right 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Was any treatment ever given to the fellow eye prior to Screening? 
 
 
No 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Yes 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Lucentis 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Eylea 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Visudyne 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Avastin 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Steroids 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Other 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
 
 

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Section 14.2 – Efficacy and other non-safety data (e.g. PK, PK/PD, health economics, QoL) 
Figures (Section 14.2) 

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Figure 14.2-1 
Absolute BCVA over time by treatment  
Full Analysis Set 
 
 
 
Note: Locally weighted scatterplot smooth (loess) curves 

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Figure 14.2-2 
Absolute change in BCVA over time by treatment  
Per Protocol Set 
 
 
 
 
 

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Figure 14.2-3 
Visual Acuity over time, stratified by baseline acuity 
Full Analysis Set 
 
Example:  
 
 
 
 

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Figure 14.2-4 
Visual Acuity over time, stratified by baseline acuity 
Per Protocol Set 
 
Example:  
 
 
 
 

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Figure 14.2-5 
Change in BCVA from baseline stratified by visual acuity  
Full Analysis Set 
 
 
Example:  
 
 
 
 
 

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Figure 14.2-6 
Change in BCVA from baseline stratified by visual acuity  
Per Protocol Set 
 
 
Example:  
 
 
 
 
 

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Figure 14.2-7 
Proportion of Patients with >= 15 letter increase in BCVA from baseline, over time by treatment  
Full Analysis Set 
 
 
 
 

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Figure 14.2-8 
Proportion of Patients with >= 15 letter increase in BCVA from baseline at Month 12 and 24 
Full Analysis Set 
 
Bar graph with p-values 
 
 
 
p = x.xxxx 
p = x.xxxx 

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Figure 14.2-9 
Proportion of patients achieving >=6/12 vision, over time by treatment  
Full Analysis Set 
 
 
 
Time series graph as per Figure 14.2-7. 
 
 

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Figure 14.2-10 Proportion of of patients achieving >=6/12 vision at Month 12 and 24 
Full Analysis Set 
 
 
Column graph as per Figure 14.2-8. 
 
 

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Figure 14.2-11 Proportion of patients showing worse than 6/60 vision, over time by treatment  
Full Analysis Set 
 
Time series graph as per Figure 14.2-7. 
 
 
 

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Figure 14.2-12 Proportion of of patients showing worse than 6/60 vision at Month 12 and 24 
Full Analysis Set 
 
 
Column graph as per Figure 14.2-8. 
 
 

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Figure 14.2-13 Proportion of patients with IRF and BCVA, over time by treatment  
Full Analysis Set 
 
 
 
 
 
 
Note to Programmer: “IRF” refers to IRF and IRC (cysts) grouped together 

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Figure 14.2-14 Proportion of patients with SRF and BCVA, over time by treatment 
Full Analysis Set 
 
As per Figure 14.2-13. 
 
 

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Figure 14.2-15 Proportion of patients with IRF and SRF, and BCVA, over time by treatment 
 
Full Analysis Set 
 
As per Figure 14.2-13. 
 
 
 
Note to Programmer: “IRF” refers to IRF and IRC (cysts) grouped together 

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Figure 14.2-16 Proportion of patients with neither IRF or SRF, and BCVA, over time by treatment 
 
Full Analysis Set 
 
 
 
 
Note to Programmer: “IRF” refers to IRF and IRC (cysts) grouped together 

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Figure 14.2-17 Proportion of patients with Geographic Atrophy and BCVA, over time by treatment 
 
Full Analysis Set 
 
As per Figure 14.2-13. 
 

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Figure 14.2-18 Proportion of Patients with IRF over time by treatment  
Full Analysis Set 
 
Time series graph as per Figure 14.2-7. 
 
 
 
Note to Programmer: “IRF” refers to IRF and IRC (cysts) grouped together 

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Figure 14.2-19 Proportion of Patients with SRF over time by treatment  
Full Analysis Set 
 
Time series graph as per Figure 14.2-7. 
 
 
 

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Figure 14.2-20 Proportion of Patients with IRF and SRF over time by treatment  
Full Analysis Set 
 
Time series graph as per Figure 14.2-7. 
 
 
 
Note to Programmer: “IRF” refers to IRF and IRC (cysts) grouped together 

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Figure 14.2-21 Proportion of Patients with neither IRF or SRF over time by treatment  
Full Analysis Set 
 
Time series graph as per Figure 14.2-7. 
 
 
 
Note to Programmer: “IRF” refers to IRF and IRC (cysts) grouped together 

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Figure 14.2-22 Proportion of Patients with Geographic Atrophy over time by treatment  
Full Analysis Set 
 
Time series graph as per Figure 14.2-7. 
 

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Figure 14.2-23 Change in geographic atrophy area from baseline over time by treatment  
Full Analysis Set 
 
 
Time series graph as per Figure 14.2-5. 
 

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Figure 14.2-24 Change in Central Subfield Foveal Thickness from baseline, over time by treatment  
Full Analysis Set 
 
Time series graph as per Figure 14.2-5. 
 

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Figure 14.2-25 Number of injections by treatment at 12 and 24 months 
Full Analysis Set 
 
 
 
 
 
 
 
Baseline to <Month 12 
Month 12 to Month 24 
Baseline to Month 24 

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Tables (Section 14.2) 
Table 14.2-1 
Visual Acuity – Summary and Change from Baseline 
Full Analysis Set and Per-Protocol Set 
 
Visit 
Statistic 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
Actual Value 
Absolute 
Change from 
Baseline* 
Actual Value 
Absolute 
Change from 
Baseline 
Actual Value 
Absolute 
Change from 
Baseline 
 
 
 
 
 
 
 
 
Screening 
n 
x 
- 
x 
- 
x 
- 
 
Mean 
x.x 
 
 - 
x.x 
- 
x.x 
- 
 
Median 
x.x 
- 
x.x 
- 
x.x 
- 
 
SD 
x.x 
- 
x.x 
- 
x.x 
- 
 
Minimum 
x 
- 
x 
- 
x 
- 
 
Maximum 
x 
- 
x 
- 
x 
- 
 
 
 
 
 
 
 
 
Baseline* 
n 
x 
- 
x 
- 
x 
- 
 
Mean 
x.x 
- 
x.x 
- 
x.x 
- 
 
Median 
x.x 
- 
x.x 
- 
x.x 
- 
 
SD 
x.x 
- 
x.x 
- 
x.x 
- 
 
Minimum 
x 
- 
x 
- 
x 
- 
 
Maximum 
x 
- 
x 
- 
x 
- 
 
 
 
 
 
 
 
 
Week n 
……. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Continued through to Month 24 
 
*Baseline: The last available non-missing value collected just prior to the start of treatment in the study eye 
SD: Standard Deviation 
 
 

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CRFB002AAU15/RFB002/Ranibizumab 
 
 
Table 14.2-2 
Visual Acuity – Mixed Model Analysis 
Full Analysis Set 
 
Random Effects Mixed Model* 
Treatment Effects 
Num d.f. Den d.f. 
F-stat 
p-value 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
 Baseline Effect 
x 
xx 
x.xx 
x.xxxx 
 
 
 
 Treatment  
x 
xx 
x.xx 
x.xxxx 
 
 
 
 Visit 
x 
xx 
x.xx 
x.xxxx 
 
 
 
 
 
 
 
 
 
 
 Treatment*Visit 
x 
xx 
x.xx 
x.xxxx 
 
 
 
 
 
 
 
 
 
 
Least Squares Means 
 Month 2 (95% CI) 
 
 
 
 
 
x.xx (x.xx, x.xx) 
x.xx (x.xx, x.xx) 
 Month 12 (95% CI) 
 
 
 
 
 
x.xx (x.xx, x.xx) 
x.xx (x.xx, x.xx) 
 Month 24 (95% CI) 
 
 
 
 
 
x.xx (x.xx, x.xx) 
x.xx (x.xx, x.xx) 
Treatment Effect 
 Month 2, Treatment Effect (95%CI) 
 
 
 
 
 
x.xx (x.xx,x.xx) 
 Month 2, p-value 
 
 
 
 
 
x.xxxx 
 Month 12, Treatment Effect (95%CI) 
 
 
 
 
 
x.xx (x.xx,x.xx) 
 Month 12, p-value 
 
 
 
 
 
x.xxxx 
 Month 24, Treatment Effect (95%CI) 
 
 
 
 
 
x.xx (x.xx,x.xx) 
 Month 24, p-value 
 
 
 
 
 
x.xxxx 
 
 
 
 
 
 
 
*Mixed Model: Change from Baseline (BCVA) = Baseline (BCVA) + Treatment + Visit (weeks) + Treatment * Visit + Subject (random effect) 
CI: Confidence Interval;  
 
Note to Programmer: The above table is an example only. Output to be updated to reflect aspects of the final 
model as appropriate. 

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Table 14.2-3 Visual Acuity – Mixed Model Analysis 
Per Protocol Set 
 
Mixed Model* 
Treatment Effects 
Num d.f. Den d.f. 
F-stat 
p-value 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
 Treatment Main Effects 
x 
xx 
x.xx 
x.xxxx 
 
 
 
 Visits 
x 
xx 
x.xx 
x.xxxx 
 
 
 
 Baseline Effect 
x 
xx 
x.xx 
x.xxxx 
 
 
 
 Class variable 
x 
xx 
x.xx 
x.xxxx 
 
 
 
 Treatment * Visit 
x 
xx 
x.xx 
x.xxxx 
 
 
 
Least Squares Means 
 Month 2 (95% CI) 
 
 
 
 
 
x.xx (x.xx, x.xx) 
x.xx (x.xx, x.xx) 
 Month 12 (95% CI) 
 
 
 
 
 
x.xx (x.xx, x.xx) 
x.xx (x.xx, x.xx) 
 Month 24 (95% CI) 
 
 
 
 
 
x.xx (x.xx, x.xx) 
x.xx (x.xx, x.xx) 
Treatment Effect 
 Month 2, Treatment Effect (95%CI) 
 
 
 
 
 
x.xx (x.xx,x.xx) 
 Month 2, p-value 
 
 
 
 
 
x.xxxx 
 Month 12, Treatment Effect (95%CI) 
 
 
 
 
 
x.xx (x.xx,x.xx) 
 Month 12, p-value 
 
 
 
 
 
x.xxxx 
 Month 24, Treatment Effect (95%CI) 
 
 
 
 
 
x.xx (x.xx,x.xx) 
 Month 24, p-value 
 
 
 
 
 
x.xxxx 
 
 
 
 
 
 
 
*Mixed Model: Change from Baseline (BCVA) = Baseline (BCVA) + Treatment + Visit (weeks) + Treatment * Visit + Subject (random effect) 
CI: Confidence Interval 
Note to Programmer: The above table is an example only. Output to be updated to reflect aspects of the final 
model as appropriate. 

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Table 14.2-4 Proportion of Patients with >=15 letters change from baseline – Logistic Regression 
Full Analysis Set 
 
Intensive  
(N=X) 
 
Relaxed  
(N=X) 
 
 
 
Letters change from baseline to Month 12 
 
 
 
>= 15 letters                  YES 
xx (xx.x%) 
 
xx (xx.x%) 
 
 
 
NO 
xx (xx.x%) 
 
xx (xx.x%) 
 
 
 
Odds Ratio* 
 
 
 
 Odds Ratio (95% CI) 
 
x.xx (x.xx,x.xx) 
 
 p-value 
 
x.xxxx 
 
 
 
 
Letters change from baseline to Month 24 
 
 
 
>= 15 letters                  YES 
xx (xx.x%) 
 
xx (xx.x%) 
 
 
 
NO 
xx (xx.x%) 
 
xx (xx.x%) 
 
 
 
Odds Ratio* 
 
 
 
 Odds Ratio (95% CI) 
 
x.xx (x.xx,x.xx) 
 
 p-value 
 
x.xxxx 
 
 
 
 
*Logistic regression model includes treatment as factor and baseline BCVA as covariate 
 
 

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Table 14.2-4 Proportion of Patients with less than 15 letters lost change from baseline – Logistic Regression 
Full Analysis Set 
 
Intensive  
(N=X) 
 
Relaxed  
(N=X) 
 
 
 
Letters change from baseline to Month 12 
 
 
 
<15 letters lost               YES 
xx (xx.x%) 
 
xx (xx.x%) 
 
 
 
NO 
xx (xx.x%) 
 
xx (xx.x%) 
 
 
 
Odds Ratio* 
 
 
 
 Odds Ratio (95% CI) 
 
x.xx (x.xx,x.xx) 
 
 p-value 
 
x.xxxx 
 
 
 
 
Letters change from baseline to Month 24 
 
 
 
<15 letters lost               YES 
xx (xx.x%) 
 
xx (xx.x%) 
 
 
 
NO 
xx (xx.x%) 
 
xx (xx.x%) 
 
 
 
Odds Ratio* 
 
 
 
 Odds Ratio (95% CI) 
 
x.xx (x.xx,x.xx) 
 
 p-value 
 
x.xxxx 
 
 
 
 
*Logistic regression model includes treatment as factor and baseline BCVA as covariate 
 
 

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Table 14.2-5 Proportion of Patients who achieve >=6/12 visual acuity – Logistic Regression 
Full Analysis Set 
 
Intensive  
(N=X) 
 
Relaxed  
(N=X) 
 
 
 
Baseline 
 
 
 
>= 6/12 visual acuity 
xx (xx.x%) 
 
xx (xx.x%) 
<6/12 visual acuity  
xx (xx.x%) 
 
xx (xx.x%) 
 
 
 
Month 12 
 
 
 
>= 6/12 visual acuity 
xx (xx.x%) 
 
xx (xx.x%) 
<6/12 visual acuity  
xx (xx.x%) 
 
xx (xx.x%) 
 
 
 
Odds Ratio* 
 
 
 
 Odds Ratio (95% CI) 
 
x.xx (x.xx,x.xx) 
 
 p-value 
 
x.xxxx 
 
 
 
 
Month 24 
 
 
 
>= 6/12 visual acuity 
xx (xx.x%) 
 
xx (xx.x%) 
<6/12 visual acuity  
xx (xx.x%) 
 
xx (xx.x%) 
 
 
 
Odds Ratio* 
 
 
 
 Odds Ratio (95% CI) 
 
x.xx (x.xx,x.xx) 
 
 p-value 
 
x.xxxx 
 
 
 
 
*Logistic regression model includes treatment as factor and baseline BCVA as covariate 
 
 

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Table 14.2-6 Proportion of Patients who achieve <=6/60 visual acuity – Logistic Regression 
Full Analysis Set 
 
Intensive  
(N=X) 
 
Relaxed  
(N=X) 
 
 
 
Baseline 
 
 
 
<= 6/60 visual acuity 
xx (xx.x%) 
 
xx (xx.x%) 
>6/60 visual acuity  
xx (xx.x%) 
 
xx (xx.x%) 
 
 
 
Month 2 
 
 
 
<= 6/60 visual acuity 
xx (xx.x%) 
 
xx (xx.x%) 
>6/60 visual acuity  
xx (xx.x%) 
 
xx (xx.x%) 
 
 
 
Odds Ratio* 
 
 
 
 
Odds Ratio (95% CI) 
 
x.xx (x.xx,x.xx) 
 
 
p-value 
 
x.xxxx 
 
 
 
 
Month 12 
 
 
 
<= 6/60 visual acuity 
xx (xx.x%) 
 
xx (xx.x%) 
>6/60 visual acuity  
xx (xx.x%) 
 
xx (xx.x%) 
 
 
 
Odds Ratio* 
 
 
 
 Odds Ratio (95% CI) 
 
x.xx (x.xx,x.xx) 
 
 p-value 
 
x.xxxx 
 
 
 
 
Month 24 
 
 
 
<= 6/60 visual acuity 
xx (xx.x%) 
 
xx (xx.x%) 
>6/60 visual acuity  
xx (xx.x%) 
 
xx (xx.x%) 
 
 
 
Odds Ratio* 
 
 
 
 Odds Ratio (95% CI) 
 
x.xx (x.xx,x.xx) 
 
 p-value 
 
x.xxxx 
 
 
 
 
*Logistic regression model includes treatment as factor and baseline BCVA as covariate 
 
 

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Table 14.2-7 
Interval Decision Summary Table 
Full Analysis Set 
 
Visit 
Interval Decision* 
Intensive 
(N=X) 
Relaxed 
(N=X) 
Total 
(N=X) 
 
 
 
 
 
Week 8 
 
 
 
 
 
Loss in VA 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Haemorrhage 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
IRF/SRF 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Loss in VA AND Haemorrhage 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Loss in VA AND IRF/SRF 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Loss in VA AND Haemorrhage AND IRF/SRF 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
Haemorrhage AND IRF/SRF 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
Week n 
……………. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Interval Decisions: 
Loss in VA:  
A loss of VA of >=5 letters or more than the best VA recorded since treatment started (Where VA loss is considered, by the 
investigator, to be due to disease activity); 
Haemorrhage: 
New retinal haemorrhage; 
IRF/SRF: 
Intensive Arm: The presence of any intra-retinal fluid or sub-retinal fluid on OCT 
   Relaxed Arm: The presence of any intra-retinal fluid or sub-retinal fluid >200 μm in height at foveal centre? 
 
 

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Table 14.2-8 
Number of Injections  
 
Visit 
 
Intensive 
(N=X)  
 Relaxed 
(N=X)  
Total 
(N=X) 
 
 
 
 
 
Number of Injections 
n 
x 
x 
x 
 
Mean (SD) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
 
Min; Max 
x;x 
x;x 
x;x 
 
 
 
 
 
Exposure (year) 
n 
x 
x 
x 
 
Mean (SD) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
 
Min; Max 
x;x 
x;x 
x;x 
 
 
 
 
 
Injections per year* 
 
xx 
xx 
xx 
 
 
 
 
 
* Injections per year = Total number of injections / total exposure to treatment (years) 
 
Visit 
 
Intensive 
(N=X)  
 Relaxed 
(N=X)  
Total 
(N=X) 
 
 
 
 
 
Number of Injections 
n 
x 
x 
x 
 
Mean (SD) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
 
Min; Max 
x;x 
x;x 
x;x 
 
 
 
 
 
Exposure (year) 
n 
x 
x 
x 
 
Mean (SD) 
x.x (x.x) 
x.x (x.x) 
x.x (x.x) 
 
Min; Max 
x;x 
x;x 
x;x 
 
 
 
 
 
Injections per year* 
 
xx 
xx 
xx 
 
 
 
 
 
* Injections per year = Total number of injections / total exposure to treatment (years) 
 
 

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Table 14.2-9 
Number of Injections from Baseline to Months 12 and 24 – Negative Binomial Regression  
Full Analysis Set 
 
 
Negative Binomial Regression* 
 
Treatment Effects 
 
Estimate 
Standard 
Error 
Chi-square 
p-value 
 
Intensive  
(N=X) 
 
 Relaxed  
(N=X) 
Parameter Estimates 
 
 
 
 
 
 
 
 
Intercept 
x.xx 
x.xxxx 
x.xx 
x.xxxx 
 
 
 
 
Treatment 
x.xx 
x.xxxx 
x.xx 
x.xxxx 
 
 
 
 
Disperson 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Least Squares Means 
 
 
 
 
 
 
 
 
Least Squares Means (95% CI) 
 
 
 
 
 
x.xx (x.xx, x.xx) 
 
x.xx (x.xx, x.xx) 
Treatment Effect 
 
 
 
 
 
 
 
 
Treatment Effect (95% CI) 
 
 
 
 
 
 
x.xx (x.xx, x.xx) 
p-value 
 
 
 
 
 
 
x.xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* number of injections will be the outcome variable, and treatment and BL BCVA as a predictor. The logarithm of length of time (year) each subject is in 
the study up to their 24 month visit will be used as an offset variable.   
 
 

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Table 14.2-10 
Treatment Interval Summary (Based on Interval Decision) 
Full Analysis Set and Per-Protocol Set 
 
Statistic 
Intensive 
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
 
 
 
 
n 
x 
x 
x 
Mean 
x.x 
x.x 
x.x 
Median 
x.x 
x.x 
x.x 
SD 
x.x 
x.x 
x.x 
Minimum 
x 
x 
x 
Maximum 
x 
x 
x 
 
 
 
 
SD: Standard Deviation 
 
 
 
  
 
 
Average treatment interval for each group - need to average it out for patient then average out for the treatment arm 

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Table 14.2-11 
Treatment Interval Summary (Based on Actual Intervals between Visits) 
Full Analysis Set and Per-Protocol Set 
 
Statistic 
Intensive 
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
 
 
 
 
n 
x 
x 
x 
Mean 
x.x 
x.x 
x.x 
Median 
x.x 
x.x 
x.x 
SD 
x.x 
x.x 
x.x 
Minimum 
x 
x 
x 
Maximum 
x 
x 
x 
 
 
 
 
SD: Standard Deviation 
 
 
 
  
 
 
Average treatment interval for each group - need to average it out for patient then average out for the treatment arm 

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Table 14.2-12 
Treatment Interval Visit Summary (Based on Interval Decision) 
Full Analysis Set 
 
Visit 
Interval 
Intensive  
(N=x) 
 Relaxed  
(N=x) 
Total 
(N=x) 
 
 
 
 
 
Week 4 
4 Weeks 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
Week 8 
4 Weeks 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
Week 12  
4 Weeks 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
6 Weeks 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
8 Weeks 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
10 Weeks 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
12 Weeks 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
Week n  
4 Weeks 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
6 Weeks 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
8 Weeks 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
10 Weeks 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
12 Weeks 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table 14.2-13 
Treatment Interval Visit Summary (Based on Actual Intervals between Visits) 
Full Analysis Set 
 
Visit 
Interval 
Intensive  
(N=x) 
 Relaxed  
(N=x) 
Total 
(N=x) 
 
 
 
 
 
Week 4 
4 Weeks 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
Week 8 
4 Weeks 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
Week 12  
4 Weeks 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
6 Weeks 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
8 Weeks 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
10 Weeks 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
12 Weeks 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
Week n  
4 Weeks 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
6 Weeks 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
8 Weeks 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
10 Weeks 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
12 Weeks 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table 14.2-14 Breakpoint Set Interval - Summary  
Full Analysis Set 
 
Visit 
Interval 
Intensive  
(N=x) 
 Relaxed  
(N=x) 
Total 
(N=x) 
 
 
 
 
 
Week 52  
4 Weeks 
x (x.xx%) 
x (x.xx%) 
x (x.xx%) 
 
6 Weeks 
x (x.xx%) 
x (x.xx%) 
x (x.xx%) 
 
8 Weeks 
x (x.xx%) 
x (x.xx%) 
x (x.xx%) 
 
10 Weeks 
x (x.xx%) 
x (x.xx%) 
x (x.xx%) 
 
12 Weeks 
x (x.xx%) 
x (x.xx%) 
x (x.xx%) 
 
Has not reached 
breakpoint 
x (x.xx%) 
x (x.xx%) 
x (x.xx%) 
 
 
 
 
 
Week 104  
4 Weeks 
x (x.xx%) 
x (x.xx%) 
x (x.xx%) 
 
6 Weeks 
x (x.xx%) 
x (x.xx%) 
x (x.xx%) 
 
8 Weeks 
x (x.xx%) 
x (x.xx%) 
x (x.xx%) 
 
10 Weeks 
x (x.xx%) 
x (x.xx%) 
x (x.xx%) 
 
12 Weeks 
x (x.xx%) 
x (x.xx%) 
x (x.xx%) 
 
Has not reached 
breakpoint 
x (x.xx%) 
x (x.xx%) 
x (x.xx%) 
 
 
 
 
 
 
 
 
Note to Programmer: Use assigned interval (Interval Decision)  

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Table 14.2-15 Post-Breakpoint Maximum Inteval - Summary  
Full Analysis Set 
 
Visit 
Interval 
Intensive  
(N=x) 
 Relaxed  
(N=x) 
Total 
(N=x) 
 
 
 
 
 
Week 52  
4 Weeks 
x (x.xx%) 
x (x.xx%) 
x (x.xx%) 
 
6 Weeks 
x (x.xx%) 
x (x.xx%) 
x (x.xx%) 
 
8 Weeks 
x (x.xx%) 
x (x.xx%) 
x (x.xx%) 
 
10 Weeks 
x (x.xx%) 
x (x.xx%) 
x (x.xx%) 
 
Has not reached 
breakpoint 
x (x.xx%) 
x (x.xx%) 
x (x.xx%) 
 
 
 
 
 
Week 104  
4 Weeks 
x (x.xx%) 
x (x.xx%) 
x (x.xx%) 
 
6 Weeks 
x (x.xx%) 
x (x.xx%) 
x (x.xx%) 
 
8 Weeks 
x (x.xx%) 
x (x.xx%) 
x (x.xx%) 
 
10 Weeks 
x (x.xx%) 
x (x.xx%) 
x (x.xx%) 
 
Has not reached 
breakpoint 
x (x.xx%) 
x (x.xx%) 
x (x.xx%) 
 
 
 
 
 
 
 
 
Note to Programmer: Use assigned interval (Interval Decision)  

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Table 14.2-16 
Time to Breakpoint - Summary  
Full Analysis Set 
 
 
Intensive  
(N=x) 
 Relaxed  
(N=x) 
Total 
(N=x) 
 
 
 
 
Time to Meet Breakpoint Criteria (weeks) 
n 
x 
x 
x 
Mean 
x.x 
x.x 
x.x 
Median 
x.x 
x.x 
x.x 
SD 
x.x 
x.x 
x.x 
Minimum 
x 
x 
x 
Maximum 
x 
x 
x 
 
 
 
 
SD: Standard Deviation 
 

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Table 14.2-17 
Time to Breakpoint – Survival Analysis 
Full Analysis Set 
 
 
 
Intensive  
(N=x) 
 Relaxed  
(N=x) 
Total 
(N=x) 
 
 
 
 
 
Total Subjects 
x 
x 
X 
 
Event n(%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
Censored n(%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
Time to Events (Weeks) 
 
 
 
 
25 Percentile (95% CI) 
x (xx,xx) 
x (xx,xx) 
x (xx,xx) 
 
Median (95% CI) 
x (xx,xx) 
x (xx,xx) 
x (xx,xx) 
 
75 Percentile (95% CI) 
x (xx,xx) 
x (xx,xx) 
x (xx,xx) 
 
Range 
xx;xx 
xx;xx 
xx;xx 
 
 
 
 
 
 
 

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Table 14.2-18 
Geographic Atrophy Area – Summary and Change from Baseline (Central Reading Center Data) 
Full Analysis Set 
 
Visit 
Statistic 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
Actual Value 
Absolute 
Change from 
Baseline* 
Actual Value 
Absolute 
Change from 
Baseline 
Actual Value 
Absolute 
Change from 
Baseline 
 
 
 
 
 
 
 
 
Screening 
n 
x 
- 
x 
- 
x 
- 
 
Mean 
x.x 
- 
x.x 
- 
x.x 
- 
 
Median 
x.x 
- 
x.x 
- 
x.x 
- 
 
SD 
x.x 
- 
x.x 
- 
x.x 
- 
 
Minimum 
x 
- 
x 
- 
x 
- 
 
Maximum 
x 
- 
x 
- 
x 
- 
 
 
 
 
 
 
 
 
Baseline* 
n 
x 
- 
x 
- 
x 
- 
 
Mean 
x.x 
- 
x.x 
- 
x.x 
- 
 
Median 
x.x 
- 
x.x 
- 
x.x 
- 
 
SD 
x.x 
- 
x.x 
- 
x.x 
- 
 
Minimum 
x 
- 
x 
- 
x 
- 
 
Maximum 
x 
- 
x 
- 
x 
- 
 
 
 
 
 
 
 
 
Week n 
……. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Continued through to Month 24 
 
*Baseline: The last available non-missing value collected just prior to the start of treatment in the study eye 
SD: Standard Deviation 

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Table 14.2-19 
Geographic Atrophy – Categorical Summary 
Full Analysis Set 
 
Visit 
 
Intensive  
 Relaxed  
Total 
 
 
 
 
 
Baseline* 
Present 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
Absent 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
Week 4 
Present 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
Absent 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
Week 8 
Present 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
Absent 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
Week n 
Present 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
Absent 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
*Baseline: The last available non-missing value collected just prior to the start of treatment in the study eye 
SD: Standard Deviation 
 
 

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Table 14.2-20 
Geographic Atrophy – Survival Analysis 
Full Analysis Set 
 
 
 
Intensive  
(N=x) 
 Relaxed  
(N=x) 
Total 
(N=x) 
 
 
 
 
 
Total Subjects 
x 
x 
X 
 
Event n(%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
Censored n(%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
Time to Events (Weeks) 
 
 
 
 
25 Percentile (95% CI) 
x (xx,xx) 
x (xx,xx) 
x (xx,xx) 
 
Median (95% CI) 
x (xx,xx) 
x (xx,xx) 
x (xx,xx) 
 
75 Percentile (95% CI) 
x (xx,xx) 
x (xx,xx) 
x (xx,xx) 
 
Range 
xx;xx 
xx;xx 
xx;xx 
 
 
 
 
 
 
 
Intensive  
(N=x) 
 Relaxed  
(N=x) 
Total 
(N=x) 
 
 
 
 
 
Total Subjects 
x 
x 
X 
 
Event n(%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
Censored n(%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
Time to Events (Weeks) 
 
 
 
 
25 Percentile (95% CI) 
x (xx,xx) 
x (xx,xx) 
x (xx,xx) 
 
Median (95% CI) 
x (xx,xx) 
x (xx,xx) 
x (xx,xx) 
 
75 Percentile (95% CI) 
x (xx,xx) 
x (xx,xx) 
x (xx,xx) 
 
Range 
xx;xx 
xx;xx 
xx;xx 
 
 
 
 
 
 
 
 

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Table 14.2-21 
Geographic Atrophy – Mixed Model Analysis 
Full Analysis Set 
 
Mixed Model* 
Treatment Effects 
Num d.f. Den d.f. 
F-stat 
p-value 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
 Treatment Main Effects 
x 
xx 
x.xx 
x.xxxx 
 
 
 
 Visits 
x 
xx 
x.xx 
x.xxxx 
 
 
 
 Baseline Effect 
x 
xx 
x.xx 
x.xxxx 
 
 
 
 Class variable 
x 
xx 
x.xx 
x.xxxx 
 
 
 
 Class variable 
x 
xx 
x.xx 
x.xxxx 
 
 
 
Least Squares Means 
 Month 2 
 
 
 
 
 
x.xx (x.xx) 
x.xx (x.xx) 
 Month 12 
 
 
 
 
 
x.xx (x.xx) 
x.xx (x.xx) 
 Month 24 
 
 
 
 
 
x.xx (x.xx) 
x.xx (x.xx) 
Treatment Effect 
 Month 2, Treatment Effect (95%CI) 
 
 
 
 
 
 
x.xx (x.xx,x.xx) 
 Month 2, p-value 
 
 
 
 
 
 
x.xxxx 
 Month 12, Treatment Effect (95%CI) 
 
 
 
 
 
 
x.xx (x.xx,x.xx) 
 Month 12, p-value 
 
 
 
 
 
 
x.xxxx 
 Month 24, Treatment Effect (95%CI) 
 
 
 
 
 
 
x.xx (x.xx,x.xx) 
 Month 24, p-value 
 
 
 
 
 
 
x.xxxx 
 
 
 
 
 
 
 
*Mixed Model: Change from Baseline (Geographic Atrophy Area) = Baseline (Geographic Atrophy Area) + Treatment + Visit (weeks)  
CI: Confidence Interval; SE: Standard Error 
 
 
 
Note to Programmer: The above table is an example only. Output to be updated to reflect aspects of the final 
model as appropriate. 

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Table 14.2-22 
Geographic Atrophy – Mixed Model Analysis 
Per Protocol Set 
 
Mixed Model* 
Treatment Effects 
Num d.f. Den d.f. 
F-stat 
p-value 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
 Treatment Main Effects 
x 
xx 
x.xx 
x.xxxx 
 
 
 
 Visits 
x 
xx 
x.xx 
x.xxxx 
 
 
 
 Baseline Effect 
x 
xx 
x.xx 
x.xxxx 
 
 
 
 Class variable 
x 
xx 
x.xx 
x.xxxx 
 
 
 
 Class variable 
x 
xx 
x.xx 
x.xxxx 
 
 
 
Least Squares Means 
 Month 2 
 
 
 
 
 
x.xx (x.xx) 
x.xx (x.xx) 
 Month 12 
 
 
 
 
 
x.xx (x.xx) 
x.xx (x.xx) 
 Month 24 
 
 
 
 
 
x.xx (x.xx) 
x.xx (x.xx) 
Treatment Effect 
 Month 2, Treatment Effect (95%CI) 
 
 
 
 
 
 
x.xx (x.xx,x.xx) 
 Month 2, p-value 
 
 
 
 
 
 
x.xxxx 
 Month 12, Treatment Effect (95%CI) 
 
 
 
 
 
 
x.xx (x.xx,x.xx) 
 Month 12, p-value 
 
 
 
 
 
 
x.xxxx 
 Month 24, Treatment Effect (95%CI) 
 
 
 
 
 
 
x.xx (x.xx,x.xx) 
 Month 24, p-value 
 
 
 
 
 
 
x.xxxx 
 
 
 
 
 
 
 
*Mixed Model: Change from Baseline (Geographic Atrophy Area) = Baseline (Geographic Atrophy Area) + Treatment + Visit (weeks)  
CI: Confidence Interval; SE: Standard Error 
 
 
 
Note to Programmer: The above table is an example only. Output to be updated to reflect aspects of the final 
model as appropriate. 

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Table 14.2-23 
Proportion of Patients with Geographic Atrophy from Baseline to Month 24 – Logistic Regression 
Full Analysis Set 
 
Intensive  
(N=X) 
 
Relaxed  
(N=X) 
 
 
 
Status of Geographic Atrophy 
 
 
 
Baseline 
 
 
 
 
Absent 
xx (xx.x%) 
 
xx (xx.x%) 
 
Present 
xx (xx.x%) 
 
xx (xx.x%) 
 
 
 
Month 24 
 
 
 
 
 
Absent 
xx (xx.x%) 
 
xx (xx.x%) 
 
Present 
xx (xx.x%) 
 
xx (xx.x%) 
                                     Newly developed geographic atrophy only 
xx (xx.x%) 
 
xx (xx.x%) 
 
 
 
Odds Ratios* 
 
 
 
 
 
 
 
Odds Ratio (95% CI) 
 
x.xx (x.xx,x.xx) 
 
 
 
 
 
p-value 
 
x.xxxx 
 
 
 
 
*Logistic regression model (proportion of newly developed geographic atrophy at Month 24) includes treatment as factor 
  

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Table 14.2-24 
Proportion of Patients showing intra-retinal /  sub-retinal fluid, by visit 
Full Analysis Set 
 
 
 
 
 
Intensive  
(N=X) 
n (%) 
 Relaxed  
(N=X) 
n (%) 
p-value 
(Logistic Regression) 
Total 
(N=X) 
n (%) 
 
 
 
 
 
 
Screening 
Intra-retinal Fluid 
x (xx.x) 
x (xx.x) 
x.xxx 
x (xx.x) 
 
No Intra-retinal Fluid 
x (xx.x) 
x (xx.x) 
x.xxx 
x (xx.x) 
 
Intra-retinal Fluid – Center Involvement  
x (xx.x) 
x (xx.x) 
x.xxx 
x (xx.x) 
 
No Intra-retinal Fluid – Center Involvement 
x (xx.x) 
x (xx.x) 
x.xxx 
x (xx.x) 
 
Sub-retinal Fluid 
x (xx.x) 
x (xx.x) 
x.xxx 
x (xx.x) 
 
No Sub-retinal Fluid 
x (xx.x) 
x (xx.x) 
x.xxx 
x (xx.x) 
 
No Intra-retinal Fluid or Sub-retinal Fluid 
x (xx.x) 
x (xx.x) 
x.xxx 
x (xx.x) 
 
Intra-retinal Fluid OR Sub-retinal Fluid 
x (xx.x) 
x (xx.x) 
x.xxx 
x (xx.x) 
 
Intra-retinal Fluid AND Sub-retinal Fluid 
x (xx.x) 
x (xx.x) 
x.xxx 
x (xx.x) 
 
 
 
 
 
 
Baseline 
Intra-retinal Fluid 
x (xx.x) 
x (xx.x) 
x.xxx 
x (xx.x) 
 
No Intra-retinal Fluid 
x (xx.x) 
x (xx.x) 
x.xxx 
x (xx.x) 
 
Intra-retinal Fluid – Center Involvement  
x (xx.x) 
x (xx.x) 
x.xxx 
x (xx.x) 
 
No Intra-retinal Fluid – Center Involvement 
x (xx.x) 
x (xx.x) 
x.xxx 
x (xx.x) 
 
Sub-retinal Fluid 
x (xx.x) 
x (xx.x) 
x.xxx 
x (xx.x) 
 
No Sub-retinal Fluid 
x (xx.x) 
x (xx.x) 
x.xxx 
x (xx.x) 
 
No Intra-retinal Fluid or Sub-retinal Fluid 
x (xx.x) 
x (xx.x) 
x.xxx 
x (xx.x) 
 
Intra-retinal Fluid OR Sub-retinal Fluid 
x (xx.x) 
x (xx.x) 
x.xxx 
x (xx.x) 
 
Intra-retinal Fluid AND Sub-retinal Fluid 
x (xx.x) 
x (xx.x) 
x.xxx 
x (xx.x) 
 
 
 
 
 
 
Week n 
Intra-retinal Fluid 
x (xx.x) 
x (xx.x) 
x.xxx 
x (xx.x) 
 
No Intra-retinal Fluid 
x (xx.x) 
x (xx.x) 
x.xxx 
x (xx.x) 
 
Sub-retinal Fluid 
x (xx.x) 
x (xx.x) 
x.xxx 
x (xx.x) 
 
………… 
 
 
 
 

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Table 14.2-25 Proportion of patients with SRF at baseline who never resolve their SRF (irrespective of their IRF) – Logistic 
Regression 
Full Analysis Set 
 
Intensive  
(N=X) 
 
Relaxed  
(N=X) 
 
 
 
Month 2 
xx (xx.x%) 
 
xx (xx.x%) 
 
Odds Ratio* 
 
 
 
 
 
Odds Ratio (95% CI) 
 
x.xx (x.xx,x.xx) 
 
 
 
p-value 
 
x.xxxx 
 
 
 
 
Month 12 
xx (xx.x%) 
 
xx (xx.x%) 
 
Odds Ratio* 
 
 
 
 
 
Odds Ratio (95% CI) 
 
x.xx (x.xx,x.xx) 
 
 
 
p-value 
 
x.xxxx 
 
 
 
 
Month 24 
xx (xx.x%) 
 
xx (xx.x%) 
 
Odds Ratio* 
 
 
 
 
 
Odds Ratio (95% CI) 
 
x.xx (x.xx,x.xx) 
 
 
 
p-value 
 
x.xxxx 
 
 
 
 
 
 
 
 
*Logistic regression model includes treatment as factor and baseline BCVA as covariate 
 
 

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Table 14.2-26 Proportion of patients with IRF at baseline who never resolve their IRF (irrespective of their SRF) – Logistic 
Regression 
Full Analysis Set 
 
Intensive  
(N=X) 
 
Relaxed  
(N=X) 
 
 
 
Month 2 
xx (xx.x%) 
 
xx (xx.x%) 
 
Odds Ratio* 
 
 
 
 
 
Odds Ratio (95% CI) 
 
x.xx (x.xx,x.xx) 
 
 
 
p-value 
 
x.xxxx 
 
 
 
 
Month 12 
xx (xx.x%) 
 
xx (xx.x%) 
 
Odds Ratio* 
 
 
 
 
 
Odds Ratio (95% CI) 
 
x.xx (x.xx,x.xx) 
 
 
 
p-value 
 
x.xxxx 
 
 
 
 
Month 24 
xx (xx.x%) 
 
xx (xx.x%) 
 
Odds Ratio* 
 
 
 
 
 
Odds Ratio (95% CI) 
 
x.xx (x.xx,x.xx) 
 
 
 
p-value 
 
x.xxxx 
 
 
 
 
 
 
 
 
*Logistic regression model includes treatment as factor and baseline BCVA as covariate 
 
 

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Table 14.2-27 Proportion of patients with IRF and SRF at baseline who never resolve either their IRF or SRF – Logistic Regression 
Full Analysis Set 
 
Intensive  
(N=X) 
 
Relaxed  
(N=X) 
 
 
 
Month 2 
xx (xx.x%) 
 
xx (xx.x%) 
 
Odds Ratio* 
 
 
 
 
 
Odds Ratio (95% CI) 
 
x.xx (x.xx,x.xx) 
 
 
 
p-value 
 
x.xxxx 
 
 
 
 
Month 12 
xx (xx.x%) 
 
xx (xx.x%) 
 
Odds Ratio* 
 
 
 
 
 
Odds Ratio (95% CI) 
 
x.xx (x.xx,x.xx) 
 
 
 
p-value 
 
x.xxxx 
 
 
 
 
Month 24 
xx (xx.x%) 
 
xx (xx.x%) 
 
Odds Ratio* 
 
 
 
 
 
Odds Ratio (95% CI) 
 
x.xx (x.xx,x.xx) 
 
 
 
p-value 
 
x.xxxx 
 
 
 
 
 
 
 
 
*Logistic regression model includes treatment as factor and baseline BCVA as covariate 
 
 

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Table 14.2-28 
Intra-Retinal and Sub-Retinal Fluid – Generalized Estimating Equation  
Full Analysis Set 
 
Generalised Estimating Equation* 
 
Treatment Effects 
Odds 
Ratio 
95% CI 
Lower 
95% CI 
Upper 
p-value 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Intra-Retinal Fluid 
 
 
 
 
 
 
 
Parameter Estimates 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Visit  
x.xx 
x.xx 
x.xx 
x.xxxx 
 
 
 
Least Squares Means 
  
Month n 
 
 
 
 
 
x.xx (x.xx) 
x.xx (x.xx) 
  
Month n 
 
 
 
 
 
x.xx (x.xx) 
x.xx (x.xx) 
 
 
 
 
 
 
 
Sub-Retinal Fluid 
 
 
 
 
 
 
 
Parameter Estimates 
 
 
 
 
 
 
 
Intercept 
x.xx 
x.xx 
x.xx 
x.xxxx 
 
 
 
Treatment 
x.xx 
x.xx 
x.xx 
x.xxxx 
 
 
 
Month  
x.xx 
x.xx 
x.xx 
x.xxxx 
 
 
 
Least Squares Means 
 
 
 
 
 
 
 
  
Month n 
 
 
 
 
 
x.xx (x.xx) 
x.xx (x.xx) 
  
Month n 
 
 
 
 
 
x.xx (x.xx) 
x.xx (x.xx) 
 
 
 
 
 
 
*Generalised Estimating Equation (GEE) 
 

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Table 14.2-29 Central Retinal Thickness – Summary and Change from Baseline, by treatment 
Full Analysis Set 
 
Visit 
Statistic 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
Actual Value 
Absolute 
Change from 
Baseline* 
Actual Value 
Absolute 
Change from 
Baseline 
Actual Value 
Absolute 
Change from 
Baseline 
 
 
 
 
 
 
 
 
Screening 
n 
x 
- 
x 
- 
x 
- 
 
Mean 
x.x 
- 
x.x 
- 
x.x 
- 
 
Median 
x.x 
- 
x.x 
- 
x.x 
- 
 
SD 
x.x 
- 
x.x 
- 
x.x 
- 
 
Minimum 
x 
- 
x 
- 
x 
- 
 
Maximum 
x 
- 
x 
- 
x 
- 
 
 
 
 
 
 
 
 
Baseline 
n 
x 
- 
x 
- 
x 
- 
 
Mean 
x.x 
- 
x.x 
- 
x.x 
- 
 
Median 
x.x 
- 
x.x 
- 
x.x 
- 
 
SD 
x.x 
- 
x.x 
- 
x.x 
- 
 
Minimum 
x 
- 
x 
- 
x 
- 
 
Maximum 
x 
- 
x 
- 
x 
- 
 
 
 
 
 
 
 
 
Week n 
……. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Continued through to Month 24 
 
 
 
 
 
 
*Baseline: The last available non-missing value collected just prior to the start of treatment in the study eye 
SD: Standard Deviation 
 
 

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Table 14.2-30 
Central Retinal Thickness – Mixed Model Analysis 
Full Analysis Set 
 
 
Random effect Mixed Model * 
 
Treatment Effects 
Num 
d.f. 
Den d.f. 
F-stat 
p-value 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
 Treatment Main Effects 
x 
xx 
x.xx 
x.xxxx 
 
 
 
 Visits 
x 
xx 
x.xx 
x.xxxx 
 
 
 
 Baseline Effect 
x 
xx 
x.xx 
x.xxxx 
 
 
 
 Class variable 
x 
xx 
x.xx 
x.xxxx 
 
 
 
 Class variable 
x 
xx 
x.xx 
x.xxxx 
 
 
 
Least Squares Means 
 Month 2 (95%CI) 
 
 
 
 
 
x.xx (x.xx,x.xx) 
x.xx (x.xx,x.xx) 
 Month 12 (95%CI) 
 
 
 
 
 
x.xx (x.xx,x.xx) 
x.xx (x.xx,x.xx) 
 Month 24 (95%CI) 
 
 
 
 
 
 
 
Treatment Effect 
 Month 2, Treatment Effect (95%CI) 
 
 
 
 
 
 
x.xx (x.xx,x.xx) 
 Month 2, p-value 
 
 
 
 
 
 
x.xxxx 
 Month 12, Treatment Effect (95%CI) 
 
 
 
 
 
 
x.xx (x.xx,x.xx) 
 Month 12, p-value 
 
 
 
 
 
 
x.xxxx 
 Month 24, Treatment Effect (95%CI) 
 
 
 
 
 
 
x.xx (x.xx,x.xx) 
 Month 24, p-value 
 
 
 
 
 
 
x.xxxx 
 
 
 
 
 
 
 
*Mixed Model: Change from Baseline (CRT) = Baseline (CRT) + Treatment + Visit (weeks) + Treatment * Visit + Subject (random effect) 
CI: Confidence Interval; CRT: Central Retinal Thickness; SE: Standard Error 
 
 

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Table 14.2-31 
Genotyping by Treatment 
Full Analysis Set 
 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
P Value 
Total 
(N=X) 
rsXXXXXXXX 
     - 
x.xxxx 
     GG 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     GT 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     TT 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
rsXXXXXXXX 
     - 
x.xxxx 
     CC 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     CT 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     TT 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
rsXXXXXXXX 
     - 
x.xxxx 
     CC 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     CT 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
…….. 
 
 
 
 
 
 
 
 
 
 
* Fisher Analysis 
 
 
 

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Table 14.2-32 
Genotyping by Race 
Full Analysis Set 
 
 
Asian 
(N=X) 
 Caucasian  
(N=X) 
P Value* 
Total 
(N=X) 
rsXXXXXXXX 
     - 
x.xxxx 
     GG 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     GT 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     TT 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
rsXXXXXXXX 
     - 
x.xxxx 
     CC 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     CT 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     TT 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
rsXXXXXXXX 
     - 
x.xxxx 
     CC 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     CT 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
…….. 
 
 
 
 
 
 
 
 
 
 
* Fisher Analysis 
 
 

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Listings (Section 14.2) 
Not applicable. 

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Section 14.3 – Safety data 
Tables (Section 14.3) 
Table 14.3-1 
Number (%) of patients receiving each dose and regimen of study medication by treatment and visit 
Safety Set 
 
Visit 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
 
 
 
 
Baseline 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Week 4 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Week 8 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Week n 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Week n 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Week n 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Week n 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Week n 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Week n 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Week n 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Week n 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Week n 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Month n 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Month n 
x (xx.x) 
x (xx.x) 
x (xx.x) 
Month 24 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 

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Table 14.3-2 
Duration of exposure to study drug, by treatment 
Safety Set 
 
 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
 
 
 
 
 
Duration of Exposure (days)* 
 
 
 
 
n 
x 
x 
x 
 
Mean 
x.x 
x.x 
x.x 
 
Median 
x.x 
x.x 
x.x 
 
SD 
x.x 
x.x 
x.x 
 
Minimum 
x 
x 
x 
 
Maximum 
x 
x 
x 
 
 
 
 
 
SD: Standard Deviation 
*Duration of Exposure = Date of first treatment to date of End of Treatment 
 
 

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Table 14.3-3 
Medications and significant non-drug therapies taken prior to the start of study drug by ATC class, preferred 
term and treatment 
Safety Set 
 
Anatomic Therapeutic Classification (ATC) 
              Preferred Term (PT) 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
 
 
 
 
 
Any ATC Class with medication/surgery 
 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
 
Nr of concomitant medications reported 
 
x 
x 
x 
 
 
 
 
 
 
ATC1 
 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
PT1 
 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
PT2 
 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
…. 
 
…. 
…. 
…. 
 
PTx 
 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
 
ATC1 
 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
PT1 
 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
PT2 
 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
…. 
 
…. 
…. 
…. 
 
PTx 
 
x (xx.x) 
x (xx.x) 
x (xx.x) 
……….. 
 
 
 
 
Note: Patients who take the same medication (in terms of the preferred term) more than once will be counted only once for that medication. 
 

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Table 14.3-4 
Forbidden concomitant medications and significant non-drug therapies after start of study drug by ATC class, 
preferred term and treatment 
Safety Set 
 
Anatomic Therapeutic Classification (ATC) 
              Preferred Term (PT) 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
 
 
 
 
 
Any ATC Class with medication/surgery 
 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
 
Nr of concomitant medications reported 
 
x 
x 
x 
 
 
 
 
 
 
ATC1 
 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
PT1 
 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
PT2 
 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
…. 
 
…. 
…. 
…. 
 
PTx 
 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
 
 
 
 
 
ATC1 
 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
PT1 
 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
PT2 
 
x (xx.x) 
x (xx.x) 
x (xx.x) 
 
…. 
 
…. 
…. 
…. 
 
PTx 
 
x (xx.x) 
x (xx.x) 
x (xx.x) 
……….. 
 
 
 
 
Note: Patients who take the same medication (in terms of the preferred term) more than once will be counted only once for that medication. 
 
 

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Table 14.3-5 
Vital signs by visit and treatment 
Safety Set 
 
Visit 
Statistic 
Intensive 
(N=X) 
 Relaxed 
(N=X)  
Total 
(N=X) 
 
 
 
 
 
Systolic Blood Pressure  (SBP) (mmHg) 
 
 
Screening 
n 
x 
x 
x 
 
Mean 
x.x 
x.x 
x.x 
 
Median 
x.x 
x.x 
x.x 
 
SD 
x.x 
x.x 
x.x 
 
Minimum 
x 
x 
x 
 
Maximum 
x 
x 
x 
 
 
 
 
 
Baseline 
n 
x 
x 
x 
 
Mean 
x.x 
x.x 
x.x 
 
Median 
x.x 
x.x 
x.x 
 
SD 
x.x 
x.x 
x.x 
 
Minimum 
x 
x 
x 
 
Maximum 
x 
x 
x 
 
 
 
 
 
Diastolic Blood Pressure  (DBP) (mmHg) 
 
 
………… 
 
 
 
 
*Baseline: The last available non-missing value collected just prior to the start of treatment in the study eye 
SD: Standard Deviation 

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Table 14.3-6 
Ophthalmic Examination – Intraocular Pressure (IOP) by treatment 
Safety Set 
 
Visit 
Statistic 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
Actual Value 
Absolute 
Change from 
Baseline* 
Actual Value 
Absolute 
Change from 
Baseline 
Actual Value 
Absolute 
Change from 
Baseline 
 
 
 
 
 
 
 
 
Screening 
n 
x 
- 
x 
- 
x 
- 
 
Mean 
x.x 
- 
x.x 
- 
x.x 
- 
 
Median 
x.x 
- 
x.x 
- 
x.x 
- 
 
SD 
x.x 
- 
x.x 
- 
x.x 
- 
 
Minimum 
x 
- 
x 
- 
x 
- 
 
Maximum 
x 
- 
x 
- 
x 
- 
 
 
 
 
 
 
 
 
Baseline 
n 
x 
- 
x 
- 
x 
- 
 
Mean 
x.x 
- 
x.x 
- 
x.x 
- 
 
Median 
x.x 
- 
x.x 
- 
x.x 
- 
 
SD 
x.x 
- 
x.x 
- 
x.x 
- 
 
Minimum 
x 
- 
x 
- 
x 
- 
 
Maximum 
x 
- 
x 
- 
x 
- 
 
 
 
 
 
 
 
 
Week n 
……. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Continued through to Month 24 
 
 
 
 
 
 
*Baseline: The last available non-missing value collected just prior to the start of treatment in the study eye 
SD: Standard Deviation 

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Listings (Section 14.3) 
Listing 14.3-1 
Patients with notably abnormal vital signs 
Safety Set 
 
Subject 
Number 
Visit 
Were Vital Signs 
Performed? 
Date of Vital Signs 
Assessment 
(YYYY-MM-DD) 
Systolic Blood 
Pressure 
 (mmHg)* 
Diastolic Blood 
Pressure 
 (mmHg)* 
 
 
 
 
 
 
XXX-XX 
ABCD 
Yes/No 
YYYY-MM-DD 
XXXH 
XXXH 
 
ABCD 
Yes/No 
YYYY-MM-DD 
XXXH 
XXXH 
 
ABCD 
Yes/No 
YYYY-MM-DD 
XXXL 
XXXL 
 
ABCD 
Yes/No 
YYYY-MM-DD 
XXXL 
XXXL 
………….. 
 
 
 
 
 
 
 
 
 
 
 
XXX-XX 
ABCD 
Yes/No 
YYYY-MM-DD 
XXXH 
XXXH 
 
ABCD 
Yes/No 
YYYY-MM-DD 
XXXH 
XXXH 
 
ABCD 
Yes/No 
YYYY-MM-DD 
XXXL 
XXXL 
 
ABCD 
Yes/No 
YYYY-MM-DD 
XXXL 
XXXL 
………….. 
 
 
 
 
 
*Flags: H=High (Systolic - >180 and increase from baseline of >20, Diastolic - >105 and increase from baseline of >15) 
L=Low (Systolic - <90 and decrease from baseline of >20, Diastolic - <50 and decrease from baseline of >15)  

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Section 14.3.1 – Displays of adverse events 
Figures (Section 14.3.1) 
No Output 

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Tables (Section 14.3.1) 
Table 14.3.1-1 
Incidence of adverse events, regardless of study drug relationship, by primary system organ class, 
preferred term and treatment 
Safety Set 
 
System Organ Class (SOC) 
           Preferred Term (PT) 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
 
 
 
 
 
 
 
 
All Body Systems 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
 
 
 
 
 
 
 
SOC1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
…. 
…. 
…. 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
 
 
 
 
 
 
 
SOC2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
…. 
…. 
…. 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
……….. 
 
 
 
 
 
 
AE: Adverse Event 
Note: Multiple records from the same subject are only counted once within the same category 

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Table 14.3.1-2 
Incidence of ocular adverse events, regardless of study drug relationship, by primary system organ class, 
preferred term and treatment 
Safety Set 
 
System Organ Class (SOC) 
           Preferred Term (PT) 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
 
 
 
 
 
 
 
 
All Ocular 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
 
 
 
 
 
 
 
SOC1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
…. 
…. 
…. 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
 
 
 
 
 
 
 
SOC2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
…. 
…. 
…. 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
……….. 
 
 
 
 
 
 
AE: Adverse Event 
Note: Multiple records from the same subject are only counted once within the same category 

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Table 14.3.1-3 
Incidence of adverse events, regardless of study drug relationship by primary system organ class, preferred 
term, maximum severity and treatment 
Safety Set 
 
System Organ Class (SOC) 
           Preferred Term (PT) 
Intensive 
(N=X) 
 
Relaxed 
(N=X) 
 
Total 
(N=X) 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
 
 
 
 
 
 
 
 
 
 
 
 
All Body Systems 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
SOC1 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
           PT1 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
           PT2 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
           …. 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
           PTx 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
SOC2 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
           PT1 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
           PT2 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
           …. 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
           PTx 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Subjects are counted once at maximum severity within each sub grouping.                                                              

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Table 14.3.1-4 
Incidence of ocular adverse events, regardless of study drug relationship by primary system organ class, 
preferred term, maximum severity and treatment 
Safety Set 
 
System Organ Class (SOC) 
           Preferred Term (PT) 
Intensive 
(N=X) 
 
Relaxed 
(N=X) 
 
Total 
(N=X) 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
 
 
 
 
 
 
 
 
 
 
 
 
All Body Systems 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
SOC1 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
           PT1 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
           PT2 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
           …. 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
           PTx 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
SOC2 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
           PT1 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
           PT2 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
           …. 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
           PTx 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Subjects are counted once at maximum severity within each sub grouping.                                                              

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Table 14.3.1-5 
Incidence of adverse events, by primary system organ class, preferred term, maximum relationship to study drug 
and treatment 
Safety Set 
 
System Organ Class (SOC) 
           Preferred Term (PT) 
Intensive  
(N=X) 
 
Relaxed  
(N=X) 
 
Total 
(N=X) 
Not Suspected 
Suspected 
 
Not Suspected 
Suspected 
 
Not Related 
Related* 
 
 
 
 
 
 
 
 
 
All Body Systems 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
 
 
SOC1 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
           PT1 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
           PT2 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
           …. 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
           PTx 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
 
 
SOC2 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
           PT1 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
           PT2 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
           …. 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
           PTx 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
 
 
*Related: includes possibly, probably and definitely related 
Note: Percentages are based on the number of subjects in each group. 

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Table 14.3.1-6 
Incidence of adverse events suspected to be related to study drug, by primary system organ class, preferred 
term and treatment 
Safety Set 
 
System Organ Class (SOC) 
           Preferred Term (PT) 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
 
 
 
 
 
 
 
 
All Body Systems 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
 
 
 
 
 
 
 
SOC1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
…. 
…. 
…. 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
 
 
 
 
 
 
 
SOC2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
…. 
…. 
…. 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
……….. 
 
 
 
 
 
 
AE: Adverse Event 
Note: Multiple records from the same subject are only counted once within the same category 
 
 

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Table 14.3.1-7 
Incidence of ocular adverse events suspected to be related to study drug, by primary system organ class, 
preferred term and treatment 
Safety Set 
 
System Organ Class (SOC) 
           Preferred Term (PT) 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
 
 
 
 
 
 
 
 
All Body Systems 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
 
 
 
 
 
 
 
SOC1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
…. 
…. 
…. 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
 
 
 
 
 
 
 
SOC2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
…. 
…. 
…. 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
……….. 
 
 
 
 
 
 
AE: Adverse Event 
Note: Multiple records from the same subject are only counted once within the same category 

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Table 14.3.1-8 
Incidence of serious adverse events, regardless of study drug relationship, by primary system organ class, 
preferred term and treatment 
Safety Set 
 
System Organ Class (SOC) 
           Preferred Term (PT) 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
 
 
 
 
 
 
 
 
All Body Systems 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
 
 
 
 
 
 
 
SOC1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
…. 
…. 
…. 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
 
 
 
 
 
 
 
SOC2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
…. 
…. 
…. 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
……….. 
 
 
 
 
 
 
AE: Adverse Event 
Note: Multiple records from the same subject are only counted once within the same category 

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Table 14.3.1-9 
Incidence of ocular serious adverse events, regardless of study drug relationship, by primary system organ 
class, preferred term and treatment 
Safety Set 
 
System Organ Class (SOC) 
           Preferred Term (PT) 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
 
 
 
 
 
 
 
 
All Body Systems 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
 
 
 
 
 
 
 
SOC1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
…. 
…. 
…. 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
 
 
 
 
 
 
 
SOC2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
…. 
…. 
…. 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
……….. 
 
 
 
 
 
 
AE: Adverse Event 
Note: Multiple records from the same subject are only counted once within the same category 
 
 

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Table 14.3.1-10 
Incidence of adverse events leading to treatment withdrawal, regardless of study drug relationship, by 
primary system organ class, preferred term and treatment 
Safety Set 
 
System Organ Class (SOC) 
           Preferred Term (PT) 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
 
 
 
 
 
 
 
 
All Body Systems 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
 
 
 
 
 
 
 
SOC1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
…. 
…. 
…. 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
 
 
 
 
 
 
 
SOC2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
…. 
…. 
…. 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
……….. 
 
 
 
 
 
 
AE: Adverse Event 
Note: Multiple records from the same subject are only counted once within the same category 

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Table 14.3.1-11 
Incidence of ocular adverse events leading to treatment withdrawal, regardless of study drug relationship, 
by primary system organ class, preferred term and treatment 
Safety Set 
 
System Organ Class (SOC) 
           Preferred Term (PT) 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
 
 
 
 
 
 
 
 
All Body Systems 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
 
 
 
 
 
 
 
SOC1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
…. 
…. 
…. 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
 
 
 
 
 
 
 
SOC2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
…. 
…. 
…. 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
……….. 
 
 
 
 
 
 
AE: Adverse Event 
Note: Multiple records from the same subject are only counted once within the same category 

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Table 14.3.1-12 Incidence of adverse events leading to study drug interruption, regardless of study drug relationship, by primary 
system organ class, preferred term and treatment 
Safety Set 
 
System Organ Class (SOC) 
           Preferred Term (PT) 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
 
 
 
 
 
 
 
 
All Body Systems 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
 
 
 
 
 
 
 
SOC1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
…. 
…. 
…. 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
 
 
 
 
 
 
 
SOC2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
…. 
…. 
…. 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
……….. 
 
 
 
 
 
 
AE: Adverse Event 
Note: Multiple records from the same subject are only counted once within the same category 

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Table 14.3.1-13 Incidence of ocular adverse events leading to study drug interruption, regardless of study drug relationship, by 
primary system organ class, preferred term and treatment 
Safety Set 
 
System Organ Class (SOC) 
           Preferred Term (PT) 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
 
 
 
 
 
 
 
 
All Body Systems 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
 
 
 
 
 
 
 
SOC1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
…. 
…. 
…. 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
 
 
 
 
 
 
 
SOC2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
…. 
…. 
…. 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
……….. 
 
 
 
 
 
 
AE: Adverse Event 
Note: Multiple records from the same subject are only counted once within the same category 
 

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Table 14.3.1-14 Incidence of adverse events requiring significant additional therapy, regardless of study drug relationship, by 
primary system organ class, preferred term and treatment 
Safety Set 
 
System Organ Class (SOC) 
           Preferred Term (PT) 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
 
 
 
 
 
 
 
 
All Body Systems 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
 
 
 
 
 
 
 
SOC1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
…. 
…. 
…. 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
 
 
 
 
 
 
 
SOC2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
…. 
…. 
…. 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
……….. 
 
 
 
 
 
 
AE: Adverse Event 
Note: Multiple records from the same subject are only counted once within the same category 

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Table 14.3.1-15 Incidence of ocular adverse events requiring significant additional therapy, regardless of study drug 
relationship, by primary system organ class, preferred term and treatment 
Safety Set 
 
System Organ Class (SOC) 
           Preferred Term (PT) 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
 
 
 
 
 
 
 
 
All Body Systems 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
 
 
 
 
 
 
 
SOC1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
…. 
…. 
…. 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
 
 
 
 
 
 
 
SOC2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
…. 
…. 
…. 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
……….. 
 
 
 
 
 
 
AE: Adverse Event 
Note: Multiple records from the same subject are only counted once within the same category 
 

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Table 14.3.1-16 
Deaths, by primary system organ class, preferred term and treatment 
Safety Set 
 
Principal Cause of Death 
 
System Organ Class (SOC) 
           Preferred Term (PT) 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
 
 
 
 
 
 
 
 
All Body Systems 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
 
 
 
 
 
 
 
SOC1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
…. 
…. 
…. 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
 
 
 
 
 
 
 
SOC2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT1 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
PT2 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
 
…. 
…. 
…. 
…. 
…. 
…. 
…. 
 
PTx 
x (xx.x%) 
x 
x (xx.x%) 
x 
x (xx.x%) 
x 
……….. 
 
 
 
 
 
 
AE: Adverse Event 
Note: Multiple records from the same subject are only counted once within the same category 

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Table 14.3.1-17 
Arterial Thomboembolic Events 
Safety Set 
 
 
Intensive  
(N=X) 
 Relaxed  
(N=X) 
Total 
(N=X) 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
Nr (%) of 
Subjects 
Nr of  
AEs 
 
 
 
 
 
 
 
 
Arterial Thomboembolic Events (ATEs)* 
xx.x 
x 
xx.x 
x 
xx.x 
x 
Nonfatal myocardial infarction 
xx.x 
x 
xx.x 
x 
xx.x 
x 
Nonfatal stroke 
xx.x 
x 
xx.x 
x 
xx.x 
x 
Vascular death and death of unknown 
cause 
xx.x 
x 
xx.x 
x 
xx.x 
x 
 
 
 
 
 
 
 
* ATEs defined as nonfatal myocardial infarction, nonfatal stroke, vascular death and death of unknown cause 
AE: Adverse Event 
Note: Some patients may have experienced multiple events 

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Section 14.3.2 – Listings of deaths, other serious and significant adverse events 
Listings (Section 14.3.2) 
Listing 14.3.2-1 Deaths, by treatment 
Safety Set 
 
Site / Subject 
Number 
Age 
Sex 
Race 
Date of Last Dose 
(YYYY-MM-DD) 
Date of Death 
(YYYY-MM-DD) 
Study 
Day* 
Principal cause reported 
 
 
 
 
 
 
 
 
XXX / XXX-XX 
XX 
Male 
Caucasian 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
ABCD 
XXX / XXX-XX 
XX 
Female 
Asian 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
ABCD 
XXX / XXX-XX 
XX 
XX 
XX 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
ABCD 
XXX / XXX-XX 
XX 
XX 
XX 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
ABCD 
XXX / XXX-XX 
XX 
XX 
XX 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
ABCD 
XXX / XXX-XX 
XX 
XX 
XX 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
ABCD 
XXX / XXX-XX 
XX 
XX 
XX 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
ABCD 
XXX / XXX-XX 
XX 
XX 
XX 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
ABCD 
……. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Relative to the first day of treatment (Baseline) 

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Listing 14.3.2-2 Serious adverse events, by treatment 
Safety Set 
 
Site / Subject 
Number 
Age /  
Sex /  
Race 
Adverse Event (REPORTED/  
Preferred /  
System Organ Class) 
Start Date 
(YYYY-MM-DD) / 
Study day 
End Date 
(YYYY-MM-DD) / 
Study day 
Duration 
(Days) 
Severity 
Relationship 
to Study 
Medication 
Action 
Taken 
 
 
 
 
 
 
 
 
 
XXX / XXX-XX 
55/M/Ca 
ABCD / abcd / abcd 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
Mild 
Not susp 
X 
XXX / XXX-XX 
76/F/As 
ABCD / abcd / abcd 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
Mod 
susp 
X 
XXX / XXX-XX 
55/M/Ca 
ABCD / abcd / abcd 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
Sev 
Not susp 
X 
XXX / XXX-XX 
76/F/As 
ABCD / abcd / abcd 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
Mild 
susp 
X 
XXX / XXX-XX 
55/M/Ca 
ABCD / abcd / abcd 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
Mod 
Not susp 
X 
XXX / XXX-XX 
76/F/As 
ABCD / abcd / abcd 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
Sev 
susp 
X 
XXX / XXX-XX 
55/M/Ca 
ABCD / abcd / abcd 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
Mild 
Not susp 
X 
XXX / XXX-XX 
76/F/As 
ABCD / abcd / abcd 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
Mod 
susp 
X 
……. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severity: Mild=Mild, Mod=Moderate, Sev=Severe 
Relationship to study drug: Not susp=Not suspected, Susp=Suspected 
Action taken: 1=Study drug dosage adjusted/temporarily interrupted, 2=Study drug permanently discontinued due to this AE 
                      3=Concomitant medication taken, 4=Non-drug therapy given, 5=Hospitalization/Prolonged hospitalization 
Note: Study day is relative to the first day of treatment (Baseline) 

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Listing 14.3.2-3 Adverse events causing study drug discontinuation by treatment 
Safety Set 
 
Site / Subject 
Number 
Age /  
Sex /  
Race 
Adverse Event (REPORTED/  
Preferred /  
System Organ Class) 
Start Date 
(YYYY-MM-DD) / 
Study day 
End Date 
(YYYY-MM-DD) / 
Study day 
Duration 
(Days) 
Severity 
Relationship 
to Study 
Medication 
Action 
Taken 
 
 
 
 
 
 
 
 
 
XXX / XXX-XX 
55/M/Ca 
ABCD / abcd / abcd 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
Mild 
Not susp 
X 
XXX / XXX-XX 
76/F/As 
ABCD / abcd / abcd 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
Mod 
susp 
X 
XXX / XXX-XX 
55/M/Ca 
ABCD / abcd / abcd 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
Sev 
Not susp 
X 
XXX / XXX-XX 
76/F/As 
ABCD / abcd / abcd 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
Mild 
susp 
X 
XXX / XXX-XX 
55/M/Ca 
ABCD / abcd / abcd 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
Mod 
Not susp 
X 
XXX / XXX-XX 
76/F/As 
ABCD / abcd / abcd 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
Sev 
susp 
X 
XXX / XXX-XX 
55/M/Ca 
ABCD / abcd / abcd 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
Mild 
Not susp 
X 
XXX / XXX-XX 
76/F/As 
ABCD / abcd / abcd 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
Mod 
susp 
X 
……. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severity: Mild=Mild, Mod=Moderate, Sev=Severe 
Relationship to study drug: Not susp=Not suspected, Susp=Suspected 
Action taken: 1=Study drug dosage adjusted/temporarily interrupted, 2=Study drug permanently discontinued due to this AE 
                      3=Concomitant medication taken, 4=Non-drug therapy given, 5=Hospitalization/Prolonged hospitalization 
Note: Study day is relative to the first day of treatment (Baseline) 

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Listing 14.3.2-4 Adverse events requiring interruption by treatment 
Safety Set 
 
Site / Subject 
Number 
Age /  
Sex /  
Race 
Adverse Event (REPORTED/  
Preferred /  
System Organ Class) 
Start Date 
(YYYY-MM-DD) / 
Study day 
End Date 
(YYYY-MM-DD) / 
Study day 
Duration 
(Days) 
Severity 
Relationship 
to Study 
Medication 
Action 
Taken 
 
 
 
 
 
 
 
 
 
XXX / XXX-XX 
55/M/Ca 
ABCD / abcd / abcd 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
Mild 
Not susp 
X 
XXX / XXX-XX 
76/F/As 
ABCD / abcd / abcd 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
Mod 
susp 
X 
XXX / XXX-XX 
55/M/Ca 
ABCD / abcd / abcd 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
Sev 
Not susp 
X 
XXX / XXX-XX 
76/F/As 
ABCD / abcd / abcd 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
Mild 
susp 
X 
XXX / XXX-XX 
55/M/Ca 
ABCD / abcd / abcd 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
Mod 
Not susp 
X 
XXX / XXX-XX 
76/F/As 
ABCD / abcd / abcd 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
Sev 
susp 
X 
XXX / XXX-XX 
55/M/Ca 
ABCD / abcd / abcd 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
Mild 
Not susp 
X 
XXX / XXX-XX 
76/F/As 
ABCD / abcd / abcd 
YYYY-MM-DD 
YYYY-MM-DD 
XX 
Mod 
susp 
X 
……. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severity: Mild=Mild, Mod=Moderate, Sev=Severe 
Relationship to study drug: Not susp=Not suspected, Susp=Suspected 
Action taken: 1=Study drug dosage adjusted/temporarily interrupted, 2=Study drug permanently discontinued due to this AE 
                      3=Concomitant medication taken, 4=Non-drug therapy given, 5=Hospitalization/Prolonged hospitalization 
Note: Study day is relative to the first day of treatment (Baseline) 
 

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Listing 14.3.2-5 Adverse events requiring significant additional therapy 
Safety Set 
 
Site / Subject 
Number 
Age /  
Sex /  
Race 
Adverse Event (REPORTED/  
Preferred /  
System Organ Class) 
Start Date 
(YYYY-MM-DD) / 
Study day 
End Date 
(YYYY-MM-DD) / 
Study day 
Duration 
(Days) 
Severity 
Relationship 
to Study 
Medication 
Action 
Taken 
 
 
 
 
 
 
 
 
 
XXX / XXX-XX 
55/M/Ca 
ABCD / abcd / abcd 
YYYY-MM-DD / 
X 
YYYY-MM-DD / 
X 
XX 
Mild 
Not susp 
X 
XXX / XXX-XX 
76/F/As 
ABCD / abcd / abcd 
YYYY-MM-DD / 
X 
YYYY-MM-DD / 
X 
XX 
Mod 
susp 
X 
XXX / XXX-XX 
55/M/Ca 
ABCD / abcd / abcd 
YYYY-MM-DD / 
X 
YYYY-MM-DD / 
X 
XX 
Sev 
Not susp 
X 
XXX / XXX-XX 
76/F/As 
ABCD / abcd / abcd 
YYYY-MM-DD / 
X 
YYYY-MM-DD / 
X 
XX 
Mild 
susp 
X 
XXX / XXX-XX 
55/M/Ca 
ABCD / abcd / abcd 
YYYY-MM-DD / 
X 
YYYY-MM-DD / 
X 
XX 
Mod 
Not susp 
X 
XXX / XXX-XX 
76/F/As 
ABCD / abcd / abcd 
YYYY-MM-DD / 
X 
YYYY-MM-DD / 
X 
XX 
Sev 
susp 
X 
XXX / XXX-XX 
55/M/Ca 
ABCD / abcd / abcd 
YYYY-MM-DD / 
X 
YYYY-MM-DD / 
X 
XX 
Mild 
Not susp 
X 
XXX / XXX-XX 
76/F/As 
ABCD / abcd / abcd 
YYYY-MM-DD / 
X 
YYYY-MM-DD / 
X 
XX 
Mod 
susp 
X 
……. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severity: Mild=Mild, Mod=Moderate, Sev=Severe 
Relationship to study drug: Not susp=Not suspected, Susp=Suspected 
Action taken: 1=Study drug dosage adjusted/temporarily interrupted, 2=Study drug permanently discontinued due to this AE 
                      3=Concomitant medication taken, 4=Non-drug therapy given, 5=Hospitalization/Prolonged hospitalization 
Note: Study day is relative to the first day of treatment (Baseline) 
 

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Section 14.3.3 – Narratives of deaths, other serious and significant adverse events (non Biometric deliverables) 
No output 
Section 14.3.4 – Abnormal laboratory value listings 
Listings (Section 14.3.4) 
No output 

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Listings (Section 16.1.7) 
Listing 16.1.7-1 Randomized allocation to treatment 
All Enrolled 
 
Site 
Subject 
Number 
Age /  
Sex /  
Race 
Randomisation 
Number 
Treatment 
Randomisation Date  
(YYYY-MM-DD) /  
Study Day 
 
 
 
 
 
 
XXX 
XXX-XX 
55/M/Ca 
XXXX 
Intensive 
YYYY-MM-DD / X 
XXX 
XXX-XX 
76/F/As 
XXXX 
Relaxed 
YYYY-MM-DD / X 
XXX 
XXX-XX 
55/M/Ca 
XXXX 
Relaxed 
YYYY-MM-DD / X 
XXX 
XXX-XX 
76/F/As 
XXXX 
Intensive 
YYYY-MM-DD / X 
XXX 
XXX-XX 
55/M/Ca 
XXXX 
Intensive 
YYYY-MM-DD / X 
XXX 
XXX-XX 
76/F/As 
XXXX 
Intensive 
YYYY-MM-DD / X 
XXX 
XXX-XX 
55/M/Ca 
XXXX 
Relaxed 
YYYY-MM-DD / X 
XXX 
XXX-XX 
76/F/As 
XXXX 
Relaxed 
YYYY-MM-DD / X 
……. 
 
 
 
 
 
 
 
 
 
 
 
Note: Study day is relative to the first day of treatment (Baseline) 
 

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Section 16.1.9 – Documentation of statistical methods 
Tables (Section 16.1.9) 
No output 

Novartis 
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MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
Section 16.2 – Patient data listings 
Section 16.2.1 – Discontinued patients 
Listing 16.2.1-1 Study phase completion by treatment 
Full Analysis Set 
 
Site / Subject 
Number 
Age / 
Sex / 
Race 
Study phase 
Last known date on study 
drug 
(YYYY-MM-DD) /  
Study Day 
Completed 
Primary 
reason  
Was 
treatment 
code 
revealed 
Date 
Revealed 
 
 
 
 
 
 
 
 
XXX / XXX-XX 
55/M/Ca 
Comparative 
YYYY-MM-DD / X 
Yes 
- 
No 
- 
XXX / XXX-XX 
76/F/As 
Comparative 
YYYY-MM-DD / X 
Yes 
- 
No 
- 
XXX / XXX-XX 
55/M/Ca 
Comparative 
YYYY-MM-DD / X 
No 
Abcd 
No 
- 
XXX / XXX-XX 
76/F/As 
Comparative 
YYYY-MM-DD / X 
Yes 
- 
No 
- 
XXX / XXX-XX 
55/M/Ca 
Comparative 
YYYY-MM-DD / X 
Yes 
- 
No 
- 
XXX / XXX-XX 
76/F/As 
Comparative 
YYYY-MM-DD / X 
Yes 
- 
No 
- 
XXX / XXX-XX 
55/M/Ca 
Comparative 
YYYY-MM-DD / X 
Yes 
- 
No 
- 
XXX / XXX-XX 
76/F/As 
Comparative 
YYYY-MM-DD / X 
Yes 
- 
No 
- 
……. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Study day is relative to the first day of treatment (Baseline) 

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Listing 16.2.1-2 Screened subjects discontinued from study prior to randomization 
All subjects 
 
Site / Subject 
Number 
Age / 
Sex / 
Race 
Date of Discontinuation 
(YYYY-MM-DD) 
Primary reason for 
discontinuation 
 
 
 
 
XXX / XXX-XX 
55/M/Ca 
YYYY-MM-DD 
Adverse Event 
XXX / XXX-XX 
76/F/As 
YYYY-MM-DD 
Lost to follow-up 
XXX / XXX-XX 
55/M/Ca 
YYYY-MM-DD 
Physician decision 
XXX / XXX-XX 
76/F/As 
YYYY-MM-DD 
Pregnancy 
XXX / XXX-XX 
55/M/Ca 
YYYY-MM-DD 
Screen failure 
XXX / XXX-XX 
76/F/As 
YYYY-MM-DD 
Study terminated by sponsor 
XXX / XXX-XX 
55/M/Ca 
YYYY-MM-DD 
Technical problems 
XXX / XXX-XX 
76/F/As 
YYYY-MM-DD 
Subject/guardian decision 
XXX / XXX-XX 
55/M/Ca 
YYYY-MM-DD 
Death 
……. 
 
 
 
 
 
 
 

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Section 16.2.2 – Protocol deviations 
Listing 16.2.2-1.1 
Protocol deviations by treatment 
Full Analysis Set 
 
 
Subject Number 
 
Any Protocol 
Deviation? 
 
Type of Deviation 
 
Date of 
Deviation 
(YYYY-MM-
DD) 
 
Visit 
 
Specify Deviation Details 
 
 
 
 
 
 
 
 
Intensive 
 
 
 
 
XXX-XX 
Yes 
Inclusion criteria 
YYYY-MM-DD 
- 
ABCD 
XXX-XX 
Yes 
Exclusion criteria 
YYYY-MM-DD 
ABCD 
ABCD 
XXX-XX 
Yes 
Discontinuation of Treatment 
YYYY-MM-DD 
ABCD 
ABCD 
XXX-XX 
Yes 
Medication (includes excluded meds) 
YYYY-MM-DD 
ABCD 
ABCD 
XXX-XX 
Yes 
Others 
YYYY-MM-DD 
ABCD 
ABCD 
XXX-XX 
No 
- 
- 
- 
- 
 
 
 
 
 
 
Relaxed 
 
 
 
 
XXX-XX 
Yes 
Exclusion criteria 
YYYY-MM-DD 
- 
ABCD 
XXX-XX 
Yes 
Discontinuation of Treatment 
YYYY-MM-DD 
ABCD 
ABCD 
XXX-XX 
Yes 
Medication (includes excluded meds) 
YYYY-MM-DD 
ABCD 
ABCD 
 
 
 
 
 
 
 
 
 
 
 
 

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Section 16.2.3 – Patients excluded from the efficacy analysis 
Listing 16.2.3-1 Patients excluded from Per-Protocol efficacy analysis by treatment 
Full Analysis Set 
 
 
Subject Number 
Reason for Exclusion from Per-Protocol 
Efficacy Analysis 
 
 
Intensive 
 
XXX-XX 
xxxxxxxxxxxxxxxxx 
XXX-XX 
xxxxxxxxxxxxxxxxx 
XXX-XX 
xxxxxxxxxxxxxxxxx 
XXX-XX 
xxxxxxxxxxxxxxxxx 
XXX-XX 
xxxxxxxxxxxxxxxxx 
XXX-XX 
xxxxxxxxxxxxxxxxx 
 
 
Relaxed 
 
XXX-XX 
xxxxxxxxxxxxxxxxx 
XXX-XX 
xxxxxxxxxxxxxxxxx 
XXX-XX 
xxxxxxxxxxxxxxxxx 
 
 
 
 

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Section 16.2.4 – Demographic data 
Listing 16.2.4-1 Patient Disposition 
Randomised Set 
 
Subject Number 
Informed 
Consent Date 
(YYYY-MM-DD) 
Did the patient 
complete the 
study? 
Date of 
Withdrawal  
(YYYY-MM-DD) 
Date of 
Completion 
(YYYY-MM-DD) 
Reason for Treatment Termination 
 
 
 
 
 
 
Intensive 
 
 
 
 
 
XXX-XX 
YYYY-MM-DD 
Yes 
YYYY-MM-DD 
YYYY-MM-DD 
ABCD 
XXX-XX 
YYYY-MM-DD 
No 
YYYY-MM-DD 
- 
ABCD 
XXX-XX 
YYYY-MM-DD 
Yes 
YYYY-MM-DD 
YYYY-MM-DD 
ABCD 
XXX-XX 
YYYY-MM-DD 
Yes 
YYYY-MM-DD 
YYYY-MM-DD 
ABCD 
 
 
 
 
 
 
Relaxed 
 
 
 
 
 
XXX-XX 
YYYY-MM-DD 
Yes 
YYYY-MM-DD 
YYYY-MM-DD 
ABCD 
XXX-XX 
YYYY-MM-DD 
No 
YYYY-MM-DD 
YYYY-MM-DD 
ABCD 
XXX-XX 
YYYY-MM-DD 
Yes 
YYYY-MM-DD 
YYYY-MM-DD 
ABCD 
XXX-XX 
YYYY-MM-DD 
Yes 
YYYY-MM-DD 
YYYY-MM-DD 
ABCD 
 
 
 
 
 
 
  

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Listing 16.2.4-2 Eligibility Criteria 
Randomised Set 
 
Subject Number 
Has the patient met all 
Inclusion Criteria? 
Has the patient met all Exclusion 
Criteria? 
 
 
 
Intensive 
 
 
XXX-XX 
Yes 
Yes 
XXX-XX 
No: Inc 1 
No: Exc 1 
XXX-XX 
Yes 
Yes 
XXX-XX 
No: Inc 2 
No: Exc 2 
 
 
 
Relaxed 
 
 
XXX-XX 
Yes 
Yes 
XXX-XX 
No: Inc 3 
No: Exc 3 
XXX-XX 
Yes 
Yes 
XXX-XX 
No: Inc 4 
No: Exc 4 
 
 
 
  

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Listing 16.2.4-3 Patient demographics by treatment 
Randomised Set 
 
 
Subject Number 
 
 
Gender 
Child-bearing 
Potential 
 
Date of Birth 
 
Age* 
 
Predominant Race 
 
Ethnicity 
 
 
 
 
 
 
 
Intensive 
 
 
 
XXX-XX 
Female 
Able to bear children 
YYYY-MM-DD 
XX 
Caucasian 
Anglo Saxon 
XXX-XX 
Male 
- 
YYYY-MM-DD 
XX 
Black African 
Northern European 
XXX-XX 
Female 
Post Menopausal 
YYYY-MM-DD 
XX 
Asian 
Southern European 
XXX-XX 
Female 
Sterile - of child 
bearing age 
YYYY-MM-DD 
XX 
Caucasian 
Asian Indian 
XXX-XX 
Male 
- 
YYYY-MM-DD 
XX 
Other: xxxxxx 
Other: xxxxxx 
………. 
 
 
 
 
 
 
 
 
 
 
 
 
 
Relaxed 
 
 
 
XXX-XX 
Female 
 
YYYY-MM-DD 
XX 
Caucasian 
Anglo Saxon 
XXX-XX 
Male 
 
YYYY-MM-DD 
XX 
Black African 
Northern European 
XXX-XX 
Female 
 
YYYY-MM-DD 
XX 
Asian 
Southern European 
XXX-XX 
Female 
 
YYYY-MM-DD 
XX 
Caucasian 
Asian Indian 
XXX-XX 
Male 
 
YYYY-MM-DD 
XX 
Black African 
Other: xxxxxx 
………. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Listing 16.2.4-4 Patient demographic questions by treatment 
Randomised Set 
 
 
Subject 
Number 
 
Family 
History of 
AMD 
Is yes, was it a first 
degree relative? 
Ever smoked 
cigarettes, pipes or 
cigars 
If the participant smoked in 
the past, when did the 
participant stop smoking? 
 
 
 
 
 
Intensive 
 
 
 
 
XXX-XX 
Yes 
Yes 
Never smoked 
- 
XXX-XX 
Yes 
No 
Smoked in the past 
One year ago or less 
XXX-XX 
Yes 
Yes 
Current smoker 
- 
XXX-XX 
Yes 
No 
Never smoked 
- 
XXX-XX 
Yes 
Yes 
Smoked in the past 
More than one year ago 
………. 
 
 
 
 
 
 
 
 
 
Relaxed 
 
 
 
 
XXX-XX 
No 
- 
Never smoked 
- 
XXX-XX 
No 
- 
Smoked in the past 
One year ago or less 
XXX-XX 
No 
- 
Current smoker 
- 
XXX-XX 
No 
- 
Never smoked 
- 
XXX-XX 
No 
- 
Smoked in the past 
More than one year ago 
………. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Listing 16.2.4-5 Relevant medical history and current medical conditions by treatment 
Randomised Set 
 
 
Subject 
Number 
 
MH 
No 
History Condition 
(REPORTED / Preferred / System 
Organ Class) 
Site 
 
Date of Diagnosis 
(YYYY-MM-DD) 
 
Ongoing? 
 
 
 
 
 
 
Intensive 
 
 
 
XXX-XX 
1 
ABCD  / Acbd / Acbd 
Left eye 
YYYY-MM-DD 
Yes/No 
 
2 
ABCD  / Acbd / Acbd 
Non-ocular 
YYYY-MM-DD 
Yes/No 
 
3 
ABCD  / Acbd / Acbd 
Right eye 
YYYY-MM-DD 
Yes/No 
 
4 
ABCD  / Acbd / Acbd 
Non-ocular 
YYYY-MM-DD 
Yes/No 
XXX-XX 
1 
ABCD  / Acbd / Acbd 
Both eyes 
YYYY-MM-DD 
Yes/No 
……… 
 
 
 
 
 
 
 
 
 
 
 
Relaxed 
 
 
 
XXX-XX 
1 
ABCD  / Acbd / Acbd 
Left eye 
YYYY-MM-DD 
Yes/No 
 
2 
ABCD  / Acbd / Acbd 
Non-ocular 
YYYY-MM-DD 
Yes/No 
 
3 
ABCD  / Acbd / Acbd 
Right eye 
YYYY-MM-DD 
Yes/No 
 
4 
ABCD  / Acbd / Acbd 
Non-ocular 
YYYY-MM-DD 
Yes/No 
XXX-XX 
1 
ABCD  / Acbd / Acbd 
Both eyes 
YYYY-MM-DD 
Yes/No 
……… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NK: Not Known; MH No: Medical History Number 
 

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Listing 16.2.4-6 AMD Treatment History (STUDY eye) 
Randomised Set 
 
 
Subject 
Number 
 
FELLOW 
Eye 
Was any treatment 
ever given to the 
fellow eye prior to 
Screening? 
Treatment 
Dose 
Start date of 
treatment 
(YYYY-MM-DD) 
Stop date of 
treatment 
(YYYY-MM-DD) 
Ongoing 
 
 
 
 
 
 
 
 
Intensive 
 
 
 
 
 
 
 
XXX-XX 
Left 
Yes 
Lucentis 
XX unit 
YYYY-MM-DD 
YYYY-MM-DD 
- 
XXX-XX 
Right 
Yes 
Eylea 
XX unit 
YYYY-MM-DD 
- 
Yes 
XXX-XX 
Left 
Yes 
Visudyne 
XX unit 
YYYY-MM-DD 
YYYY-MM-DD 
- 
 
 
 
Avastin 
XX unit 
YYYY-MM-DD 
YYYY-MM-DD 
- 
XXX-XX 
Left 
No 
- 
- 
- 
- 
- 
……… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Relaxed 
 
 
 
 
 
 
 
XXX-XX 
Left 
Yes 
Lucentis 
XX unit 
YYYY-MM-DD 
YYYY-MM-DD 
- 
XXX-XX 
Right 
Yes 
Eylea 
XX unit 
YYYY-MM-DD 
- 
Yes 
XXX-XX 
Left 
Yes 
Steroids 
XX unit 
YYYY-MM-DD 
YYYY-MM-DD 
- 
 
 
 
Other 
XX unit 
YYYY-MM-DD 
YYYY-MM-DD 
- 
XXX-XX 
Left 
No 
- 
- 
- 
- 
- 
……… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NK: Not Known; MH No: Medical History Number 

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MAP Module 7.1 
 
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Listing 16.2.4-7 AMD Treatment History (FELLOW eye) 
Randomised Set 
 
 
Subject 
Number 
 
FELLOW 
Eye 
Was any treatment 
ever given to the 
fellow eye prior to 
Screening? 
Treatment 
Dose 
Start date of 
treatment 
(YYYY-MM-DD) 
Stop date of 
treatment 
(YYYY-MM-DD) 
Ongoing 
 
 
 
 
 
 
 
 
Intensive 
 
 
 
 
 
 
 
XXX-XX 
Left 
Yes 
Lucentis 
XX unit 
YYYY-MM-DD 
YYYY-MM-DD 
- 
XXX-XX 
Right 
Yes 
Eylea 
XX unit 
YYYY-MM-DD 
- 
Yes 
XXX-XX 
Left 
Yes 
Visudyne 
XX unit 
YYYY-MM-DD 
YYYY-MM-DD 
- 
 
 
 
Avastin 
XX unit 
YYYY-MM-DD 
YYYY-MM-DD 
- 
XXX-XX 
Left 
No 
- 
- 
- 
- 
- 
……… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Relaxed 
 
 
 
 
 
 
 
XXX-XX 
Left 
Yes 
Lucentis 
XX unit 
YYYY-MM-DD 
YYYY-MM-DD 
- 
XXX-XX 
Right 
Yes 
Eylea 
XX unit 
YYYY-MM-DD 
- 
Yes 
XXX-XX 
Left 
Yes 
Steroids 
XX unit 
YYYY-MM-DD 
YYYY-MM-DD 
- 
 
 
 
Other 
XX unit 
YYYY-MM-DD 
YYYY-MM-DD 
- 
XXX-XX 
Left 
No 
- 
- 
- 
- 
- 
……… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NK: Not Known; MH No: Medical History Number 

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MAP Module 7.1 
 
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Listing 16.2.4-8 AMD Treatment at Baseline 
Randomised Set 
 
 
Subject 
Number 
 
Treatment at Baseline 
EYE 
Date of diagnosis of active CNV 
due to wet AMD (YYYY-MM-DD) 
Type of CNV 
Location 
CNV 
classification 
 
 
 
 
 
 
Intensive 
 
 
 
 
 
XXX-XX 
Two treatment naïve eyes 
STUDY – Right 
YYYY-MM-DD 
Subfoveal 
Occult 
 
 
FELLOW - Left 
YYYY-MM-DD 
Juxtafoveal 
Predominantly 
classic 
XXX-XX 
One eye (fellow eye) being treated 
with ranibizumab 
STUDY – Right 
YYYY-MM-DD 
Extrafoveal 
Minimally classic 
 
 
FELLOW - Left 
YYYY-MM-DD 
Note evaluable 
PCV 
XXX-XX 
One eye (fellow eye) being treated 
with anti-VEGF other than 
ranibizumab 
STUDY – Right 
YYYY-MM-DD 
Subfoveal 
RAP 
 
 
FELLOW - Left 
YYYY-MM-DD 
Juxtafoveal 
Note evaluable 
XXX-XX 
Two treatment naïve eyes 
STUDY – Right 
YYYY-MM-DD 
Extrafoveal 
Occult 
 
 
FELLOW - Left 
YYYY-MM-DD 
Note evaluable 
Predominantly 
classic 
……… 
 
 
 
 
 
 
 
 
 
 
 
Relaxed 
 
 
 
 
 
XXX-XX 
Two treatment naïve eyes 
STUDY – Right 
YYYY-MM-DD 
Subfoveal 
Occult 
 
 
FELLOW - Left 
YYYY-MM-DD 
Juxtafoveal 
Predominantly 
classic 
XXX-XX 
One eye (fellow eye) being treated 
with ranibizumab 
STUDY – Right 
YYYY-MM-DD 
Extrafoveal 
Minimally classic 
 
 
FELLOW - Left 
YYYY-MM-DD 
Note evaluable 
PCV 
……… 
 
 
 
 
 
 
 
 
 
 
 
NK: Not Known; MH No: Medical History Number 

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Section 16.2.5  
Compliance and/or drug concentration data  
Listing 16.2.5-1 Dose administration record by treatment (STUDY eye) 
Safety Set 
 
 
Subject 
Number 
 
Visit 
Was Study Drug 
Administered? 
Date of dosing  
(YYYY-MM-DD) 
Total dose 
administered 
(mg) 
STUDY eye 
treated 
Batch number 
 
 
 
 
 
 
 
XXX-XX 
Baseline 
Yes 
YYYY-MM-DD 
XX 
Left eye 
XXXXXXX 
 
Week n 
Yes 
YYYY-MM-DD 
XX 
Left eye 
Not available 
 
…… 
 
 
 
 
 
 
 
 
 
 
 
 
XXX-XX 
Baseline 
Yes 
YYYY-MM-DD 
XX 
Right eye 
XXXXXXX 
 
Week n 
No: xxxxxxx 
- 
- 
- 
 
 
…… 
 
 
 
 
 
 
 
 
 
 
 
 
                                                                                           

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Listing 16.2.5-2 Dose administration record by treatment (FELLOW eye) 
Safety Set 
 
 
Subject 
Number 
 
Visit 
Was treatment 
for FELLOW 
eye given? 
FELLOW eye 
treated 
Date of dosing  
(YYYY-MM-DD) 
Treatment for wet AMD to 
fellow eye 
Total dose 
administered  
 
 
 
 
 
 
 
XXX-XX 
Baseline 
Yes 
Left eye 
YYYY-MM-DD 
xxxxxxxxxxxxx 
XX units 
 
Week n 
Yes 
Left eye 
YYYY-MM-DD 
Not xxxxxxxxxxxxx 
XX units 
 
…… 
 
 
 
 
 
 
 
 
 
 
 
 
XXX-XX 
Baseline 
Yes 
Right eye 
YYYY-MM-DD 
xxxxxxxxxxxxx 
XX units 
 
Week n 
No 
- 
- 
 
- 
 
…… 
 
 
 
 
 
 
 
 
 
 
 
 
                                                                                           
 

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Listing 16.2.5-3 Medications and significant non-drug therapies prior to start of study drug by treatment 
Randomised Set 
 
 
Subject 
Number 
 
CM 
No 
Concomitant Medication 
(REPORTED / Preferred) 
Reason 
 
 
 
 
Intensive 
 
XXX-XX 
1 
ABCD  / Acbd 
xxxxxxxxxxxxxxxx 
 
2 
ABCD  / Acbd 
xxxxxxxxxxxxxxxx 
 
3 
ABCD  / Acbd 
xxxxxxxxxxxxxxxx 
 
4 
ABCD  / Acbd 
xxxxxxxxxxxxxxxx 
XXX-XX 
1 
ABCD  / Acbd 
xxxxxxxxxxxxxxxx 
……… 
 
 
 
 
 
 
 
Relaxed 
 
XXX-XX 
1 
ABCD  / Acbd 
xxxxxxxxxxxxxxxx 
 
2 
ABCD  / Acbd 
xxxxxxxxxxxxxxxx 
 
3 
ABCD  / Acbd 
xxxxxxxxxxxxxxxx 
 
4 
ABCD  / Acbd 
xxxxxxxxxxxxxxxx 
XXX-XX 
1 
ABCD  / Acbd 
xxxxxxxxxxxxxxxx 
……… 
 
 
 
 
 
 
 
 
 
 
 
 

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MAP Module 7.1 
 
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Listing 16.2.5-4 Medications and significant non-drug therapies after start of study drug by treatment 
Full Analysis Set 
 
 
Subject 
Number 
 
CM 
No 
Concomitant Medication 
(REPORTED / Preferred) 
Start Date 
(YYYY-MM-DD) 
Stop Date 
(YYYY-MM-DD) 
Reason 
 
 
 
 
 
 
Intensive 
 
 
 
XXX-XX 
1 
ABCD  / Acbd 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxx 
 
2 
ABCD  / Acbd 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxx 
 
3 
ABCD  / Acbd 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxx 
 
4 
ABCD  / Acbd 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxx 
XXX-XX 
1 
ABCD  / Acbd 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxx 
……… 
 
 
 
 
 
 
 
 
 
 
 
Relaxed 
 
 
 
XXX-XX 
1 
ABCD  / Acbd 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxx 
 
2 
ABCD  / Acbd 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxx 
 
3 
ABCD  / Acbd 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxx 
 
4 
ABCD  / Acbd 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxx 
XXX-XX 
1 
ABCD  / Acbd 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxx 
……… 
 
 
 
 
 
 
 
 
 
 
 
 

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Listing 16.2.5-5 Medications and significant non-drug therapies after start of study drug by treatment (STUDY EYE) 
Full Analysis Set 
 
 
Subject 
Number 
 
CM 
No 
Concomitant Medication 
(REPORTED / Preferred) 
Start Date 
(YYYY-MM-DD) 
Stop Date 
(YYYY-MM-DD) 
Reason 
 
 
 
 
 
 
Intensive 
 
 
 
XXX-XX 
1 
ABCD  / Acbd 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxx 
 
2 
ABCD  / Acbd 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxx 
 
3 
ABCD  / Acbd 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxx 
 
4 
ABCD  / Acbd 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxx 
XXX-XX 
1 
ABCD  / Acbd 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxx 
……… 
 
 
 
 
 
 
 
 
 
 
 
Relaxed 
 
 
 
XXX-XX 
1 
ABCD  / Acbd 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxx 
 
2 
ABCD  / Acbd 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxx 
 
3 
ABCD  / Acbd 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxx 
 
4 
ABCD  / Acbd 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxx 
XXX-XX 
1 
ABCD  / Acbd 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxx 
……… 
 
 
 
 
 
 
 
 
 
 
 
NOTE: Includes all ocular medications administered to the STUDY eye only. 
 

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Listing 16.2.5-6 Medications and significant non-drug therapies after start of study drug by treatment (FELLOW EYE) 
Full Analysis Set 
 
 
Subject 
Number 
 
CM 
No 
Concomitant Medication 
(REPORTED / Preferred) 
Start Date 
(YYYY-MM-DD) 
Stop Date 
(YYYY-MM-DD) 
Reason 
 
 
 
 
 
 
Intensive 
 
 
 
XXX-XX 
1 
ABCD  / Acbd 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxx 
 
2 
ABCD  / Acbd 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxx 
 
3 
ABCD  / Acbd 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxx 
 
4 
ABCD  / Acbd 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxx 
XXX-XX 
1 
ABCD  / Acbd 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxx 
……… 
 
 
 
 
 
 
 
 
 
 
 
Relaxed 
 
 
 
XXX-XX 
1 
ABCD  / Acbd 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxx 
 
2 
ABCD  / Acbd 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxx 
 
3 
ABCD  / Acbd 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxx 
 
4 
ABCD  / Acbd 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxx 
XXX-XX 
1 
ABCD  / Acbd 
YYYY-MM-DD 
YYYY-MM-DD 
xxxxxxxxxxxxxxxx 
……… 
 
 
 
 
 
 
 
 
 
 
 
NOTE: Includes all ocular medications administered to the FELLOW eye only. 
 

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Section 16.2.6 – Individual efficacy response data and other non-safety data  
Listing 16.2.6-1 CF/FA/AF by treatment (STUDY EYE) (CRF Data) 
Full Analysis Set 
 
Subject 
Number 
Visit 
STUDY 
eye 
assessed 
Was CF 
Performed? 
Date CF 
performed 
(YYYY-MM-DD) 
Was FA 
Performed? 
Date FA 
performed 
(YYYY-MM-
DD) 
Presence of 
Retinal 
Haemorrhage 
Was AF 
Performed? 
Date AF 
performed 
(YYYY-MM-
DD) 
 
 
 
 
 
 
 
 
 
 
Intensive 
 
 
 
 
 
 
 
 
 
XXX-XX 
ABCD 
Left 
Yes 
YYYY-MM-DD 
Yes 
YYYY-MM-DD 
Yes 
Yes 
YYYY-MM-DD 
 
ABCD 
Left 
Yes 
YYYY-MM-DD 
Yes 
YYYY-MM-DD 
No 
Yes 
YYYY-MM-DD 
 
ABCD 
Left 
Yes 
YYYY-MM-DD 
Yes 
YYYY-MM-DD 
Evaluable 
Yes 
YYYY-MM-DD 
 
ABCD 
Left 
Yes 
YYYY-MM-DD 
Yes 
YYYY-MM-DD 
Yes 
Yes 
YYYY-MM-DD 
………….. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXX-XX 
ABCD 
Right 
Yes 
YYYY-MM-DD 
Yes 
YYYY-MM-DD 
Yes 
Yes 
YYYY-MM-DD 
 
ABCD 
Right 
Yes 
YYYY-MM-DD 
Yes 
YYYY-MM-DD 
No 
Yes 
YYYY-MM-DD 
 
ABCD 
Right 
Yes 
YYYY-MM-DD 
Yes 
YYYY-MM-DD 
Evaluable 
Yes 
YYYY-MM-DD 
 
ABCD 
Right 
No 
YYYY-MM-DD 
No 
YYYY-MM-DD 
Yes 
No 
YYYY-MM-DD 
………….. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Relaxed 
 
 
 
 
 
 
 
 
 
………….. 
 
 
 
 
 
 
 
 
 
AF: Autofluorescence, CF: Colour Fundus Photography, FA: Fluorescein Angiography 

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Confidential 
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Listing 16.2.6-2 CF/FA/AF by treatment (FELLOW EYE) 
Full Analysis Set 
 
Subject 
Number 
Visit 
FELLOW 
eye 
assessed 
Was CF 
Performed? 
Date CF 
performed 
(YYYY-MM-DD) 
Was FA 
Performed? 
Date FA 
performed 
(YYYY-MM-
DD) 
Presence of 
Retinal 
Haemorrhage 
Was AF 
Performed? 
Date AF 
performed 
(YYYY-MM-
DD) 
 
 
 
 
 
 
 
 
 
 
Intensive 
 
 
 
 
 
 
 
 
 
XXX-XX 
ABCD 
Left 
Yes 
YYYY-MM-DD 
Yes 
YYYY-MM-DD 
Yes 
Yes 
YYYY-MM-DD 
 
ABCD 
Left 
Yes 
YYYY-MM-DD 
Yes 
YYYY-MM-DD 
No 
Yes 
YYYY-MM-DD 
 
ABCD 
Left 
Yes 
YYYY-MM-DD 
Yes 
YYYY-MM-DD 
Evaluable 
Yes 
YYYY-MM-DD 
 
ABCD 
Left 
Yes 
YYYY-MM-DD 
Yes 
YYYY-MM-DD 
Yes 
Yes 
YYYY-MM-DD 
………….. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXX-XX 
ABCD 
Right 
Yes 
YYYY-MM-DD 
Yes 
YYYY-MM-DD 
Yes 
Yes 
YYYY-MM-DD 
 
ABCD 
Right 
Yes 
YYYY-MM-DD 
Yes 
YYYY-MM-DD 
No 
Yes 
YYYY-MM-DD 
 
ABCD 
Right 
Yes 
YYYY-MM-DD 
Yes 
YYYY-MM-DD 
Evaluable 
Yes 
YYYY-MM-DD 
 
ABCD 
Right 
No 
YYYY-MM-DD 
No 
YYYY-MM-DD 
Yes 
No 
YYYY-MM-DD 
………….. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Relaxed 
 
 
 
 
 
 
 
 
 
………….. 
 
 
 
 
 
 
 
 
 
AF: Autofluorescence, CF: Colour Fundus Photography, FA: Fluorescein Angiography 

Novartis 
Confidential 
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Listing 16.2.6-3 Fluorescein Angiography Assessments by treatment (STUDY EYE) (Central Reading Center Data) 
Full Analysis Set 
 
Subject 
Number 
Visit 
STUDY eye 
assessed 
Parameter 
Result 
 
 
 
 
 
Intensive 
 
 
 
 
XXX-XX 
ABCD 
Left 
Lesion leakage present 
Yes 
 
 
 
Lesions components* 
CNV, blood 
 
 
 
Type of lesion 
Occult 
 
 
 
Location of lesion 
Subfoveal 
 
 
 
CNV present 
Yes 
 
 
 
CNV Location 
Subfoveal 
 
 
 
CNV leakage present 
Yes 
 
 
 
Area of lesion (mm2) 
xx 
 
 
 
Area of CNV (mm2) 
xx 
 
 
 
Geographic Atrophy present 
Yes 
………….. 
 
 
Location of Geographic Atrophy 
Outer Subfield 
 
 
 
Total area of Geographic Atrophy within ETDRS grid 
xx 
Relaxed 
 
 
 
 
………….. 
 
 
 
 

Novartis 
Confidential 
Page 199 
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CRFB002AAU15/RFB002/Ranibizumab 
 
 
Listing 16.2.6-4 Colour Fundus Assessments by treatment (STUDY EYE) (Central Reading Center Data) 
Full Analysis Set 
 
Subject 
Number 
Visit 
STUDY eye 
assessed 
Parameter 
Result 
 
 
 
 
 
Intensive 
 
 
 
 
XXX-XX 
ABCD 
Left 
Haemorrhage present 
Yes 
 
 
 
Haemorrhage location 
Central subfield 
 
 
 
Retinal Abnormalities present 
Yes: Drusen 
 
 
 
Retinal Abnormalities Location 
Central 
 
 
 
Retinal Abnormalities Type 
Inflammation 
 
 
 
 
 
 
…….. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
………….. 
 
 
 
 
 
 
 
 
 
Relaxed 
 
 
 
 
………….. 
 
 
 
 

Novartis 
Confidential 
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CRFB002AAU15/RFB002/Ranibizumab 
 
 
Listing 16.2.6-5 Visual Acuity by Treatment (STUDY EYE) 
Full Analysis Set and Per-Protocol 
 
Subject 
Number 
Visit 
Was VA 
Performed? 
Date VA 
performed 
(YYYY-MM-DD) 
Was 
Refraction 
Performed? 
STUDY Eye 
Assessed 
EDTRS chart 
used for 3 
metres lane? 
Total BCVA 
score 
 
 
 
 
 
 
 
 
Intensive 
 
 
 
 
 
XXX-XX 
ABCD 
Yes 
YYYY-MM-DD 
Yes/No 
Left eye 
Yes/No 
XX 
 
ABCD 
Yes 
YYYY-MM-DD 
Yes/No 
Left eye 
Yes/No 
XX 
 
ABCD 
Yes 
YYYY-MM-DD 
Yes/No 
Left eye 
Yes/No 
XX 
 
ABCD 
Yes 
YYYY-MM-DD 
Yes/No 
Left eye 
Yes/No 
XX 
………….. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXX-XX 
ABCD 
Yes 
YYYY-MM-DD 
Yes/No 
Right eye 
Yes/No 
XX 
 
ABCD 
Yes 
YYYY-MM-DD 
Yes/No 
Right eye 
Yes/No 
XX 
 
ABCD 
Yes 
YYYY-MM-DD 
Yes/No 
Right eye 
Yes/No 
XX 
 
ABCD 
Not Done: 
specify 
- 
- 
- 
- 
- 
………….. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Relaxed 
 
 
 
 
 
 
 
………….. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
VA: Visual Acuity, BCVA: Best Corrective Visual Acuity 

Novartis 
Confidential 
Page 201 
MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
Listing 16.2.6-6 Visual Acuity by Treatment (FELLOW EYE) 
Full Analysis Set 
 
Subject 
Number 
Visit 
Was VA 
Performed? 
Date VA 
performed 
(YYYY-MM-DD) 
Was 
Refraction 
Performed? 
FELLOW 
Eye 
Assessed 
EDTRS chart 
used for 3 
metres lane? 
Total BCVA 
score 
 
 
 
 
 
 
 
 
Intensive 
 
 
 
 
 
XXX-XX 
ABCD 
Yes 
YYYY-MM-DD 
Yes/No 
Left eye 
Yes/No 
XX 
 
ABCD 
Yes 
YYYY-MM-DD 
Yes/No 
Left eye 
Yes/No 
XX 
 
ABCD 
Yes 
YYYY-MM-DD 
Yes/No 
Left eye 
Yes/No 
XX 
 
ABCD 
Yes 
YYYY-MM-DD 
Yes/No 
Left eye 
Yes/No 
XX 
………….. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXX-XX 
ABCD 
Yes 
YYYY-MM-DD 
Yes/No 
Right eye 
Yes/No 
XX 
 
ABCD 
Yes 
YYYY-MM-DD 
Yes/No 
Right eye 
Yes/No 
XX 
 
ABCD 
Yes 
YYYY-MM-DD 
Yes/No 
Right eye 
Yes/No 
XX 
 
ABCD 
Not Done: 
specify 
- 
- 
- 
- 
- 
………….. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Relaxed 
 
 
 
 
 
 
 
………….. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
VA: Visual Acuity, BCVA: Best Corrective Visual Acuity 

Novartis 
Confidential 
Page 202 
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CRFB002AAU15/RFB002/Ranibizumab 
 
 
Listing 16.2.6-7 Optical Coherence Tomography (OCT) by Treatment (STUDY EYE) (CRF Data) 
Full Analysis Set 
 
Subject 
Number 
Visit 
Was 
OCT 
Performe
d? 
Date OCT 
performed 
(YYYY-MM-
DD) 
STUDY 
Eye 
Type of OCT 
(Including subtype if 
high 
definition/spectral 
domain OCT) 
Presence 
of intra-
retinal fluid 
Compared 
to previous 
intra-retinal 
assessment 
Presence of 
sub-retinal 
fluid 
Compared 
to previous 
sub-retinal 
assessmen
t 
>200μm 
height or 
SRF at 
foveal centre 
 
 
 
 
 
 
 
 
 
 
 
Intensive 
 
 
 
 
 
 
 
 
 
 
XXX-XX 
ABCD 
Yes 
YYYY-MM-DD 
Left 
eye 
Other: Time domain 
Present 
- 
Present 
- 
Yes 
 
ABCD 
Yes 
YYYY-MM-DD 
Left 
eye 
Other: Time domain 
Present 
No change 
Present 
No change 
No 
 
ABCD 
Yes 
YYYY-MM-DD 
Left 
eye 
Other: Time domain 
Absence 
Improved  
Absence 
Improved  
Yes 
 
ABCD 
Yes 
YYYY-MM-DD 
Left 
eye 
Other: Time domain 
Present 
Worse 
Present 
Worse 
No 
………….. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Relaxed 
 
 
 
 
 
 
 
 
 
 
XXX-XX 
ABCD 
Yes 
YYYY-MM-DD 
Right 
eye 
High definition / 
spectral domain: 
Cirrus 
Present 
- 
Present 
- 
Yes 
 
ABCD 
Yes 
YYYY-MM-DD 
Right 
eye 
High definition / 
spectral domain: 
Cirrus 
Absent 
Improved 
Absent 
Improved 
No 
 
ABCD 
Yes 
YYYY-MM-DD 
Right 
eye 
High definition / 
spectral domain: 
Cirrus 
Can’t 
grade 
- 
Can’t grade 
- 
Yes 
 
ABCD 
Not 
Done: 
specify 
- 
- 
- 
- 
- 
- 
- 
- 
………….. 
 
 
 
 
 
 
 
 
 
 
OCT: Optical Coherence Tomography, SRF: Sub-retinal fluid 

Novartis 
Confidential 
Page 203 
MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
Listing 16.2.6-8 Optical Coherence Tomography (OCT) by Treatment (FELLOW EYE) (CRF Data) 
Full Analysis Set 
 
Subject 
Number 
Visit 
Was 
OCT 
Performe
d? 
Date OCT 
performed 
(YYYY-MM-
DD) 
FELLO
W 
 Eye 
Type of OCT 
(Including subtype if 
high 
definition/spectral 
domain OCT) 
Presence 
of intra-
retinal fluid 
Compared 
to previous 
intra-retinal 
assessment 
Presence of 
sub-retinal 
fluid 
Compared 
to previous 
sub-retinal 
assessmen
t 
>200μm 
height or 
SRF at 
foveal centre 
 
 
 
 
 
 
 
 
 
 
 
Intensive 
 
 
 
 
 
 
 
 
 
 
XXX-XX 
ABCD 
Yes 
YYYY-MM-DD 
Left 
eye 
Other: Time domain 
Present 
- 
Present 
- 
Yes 
 
ABCD 
Yes 
YYYY-MM-DD 
Left 
eye 
Other: Time domain 
Present 
No change 
Present 
No change 
No 
 
ABCD 
Yes 
YYYY-MM-DD 
Left 
eye 
Other: Time domain 
Absence 
Improved  
Absence 
Improved  
Yes 
 
ABCD 
Yes 
YYYY-MM-DD 
Left 
eye 
Other: Time domain 
Present 
Worse 
Present 
Worse 
No 
………….. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Relaxed 
 
 
 
 
 
 
 
 
 
 
XXX-XX 
ABCD 
Yes 
YYYY-MM-DD 
Right 
eye 
High definition / 
spectral domain: 
Cirrus 
Present 
- 
Present 
- 
Yes 
 
ABCD 
Yes 
YYYY-MM-DD 
Right 
eye 
High definition / 
spectral domain: 
Cirrus 
Absent 
Improved 
Absent 
Improved 
No 
 
ABCD 
Yes 
YYYY-MM-DD 
Right 
eye 
High definition / 
spectral domain: 
Cirrus 
Can’t 
grade 
- 
Can’t grade 
- 
Yes 
 
ABCD 
Not 
Done: 
specify 
- 
- 
- 
- 
- 
- 
- 
- 
………….. 
 
 
 
 
 
 
 
 
 
 
OCT: Optical Coherence Tomography, SRF: Sub-retinal fluid 

Novartis 
Confidential 
Page 204 
MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
Listing 16.2.6-9 Optical Coherence Tomography (OCT) by treatment (STUDY EYE) (Central Reading Center Data) 
Full Analysis Set 
 
Subject 
Number 
Visit 
STUDY eye 
assessed 
Parameter 
Result 
Comments 
 
 
 
 
 
 
Intensive 
 
 
 
 
 
XXX-XX 
ABCD 
Left 
Central Subfield Foveal Thickness 
xx 
ABCD 
 
 
 
Central Subfield Volume 
xx 
 
 
 
 
Cysts Present? 
Yes 
 
 
 
 
Cyst(s) involving central macula 
Yes 
 
 
 
 
Cysts: Thickness at Center Point 
xx 
 
 
 
 
Vitreomacular traction present 
Yes 
 
 
…….. 
 
Subretinal fluid (within 6x6mm scan) present 
Yes 
 
 
 
 
Intraretinal fluid present 
No 
 
 
 
 
Vitreoretinal Abnormalities 
No 
 
 
 
 
Type of OCT 
HD 
 
 
 
 
GA Measurement* 
xx 
 
 
 
 
Subfoveal SRF (at centrepoint) present** 
Yes 
 
 
 
 
 
 
 
………….. 
 
 
 
 
 
 
 
 
 
 
 
Relaxed 
 
 
 
 
 
………….. 
 
 
 
 
 
* Where allowable by imaging equipment at site 
** For the relaxed arm, if “Yes”, height “> 200um” or “= or <200um” 

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Confidential 
Page 205 
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Listing 16.2.6-10 
Genotyping Sampling 
Full Analysis Set 
 
Subject 
Number 
Consent 
provided for 
genotyping 
sample 
collection? 
Date of consent 
specific to 
genotyping 
(YYYY-MM-DD) 
Was genotyping 
sample taken? 
Date genotyping 
sample collected 
(YYYY-MM-DD) 
Sample 
Number 
 
 
 
 
 
 
Intensive 
 
 
 
 
 
XXX-XX 
Yes  
YYYY-MM-DD 
Yes  
YYYY-MM-DD 
XXXXXX 
XXX-XX 
Yes 
YYYY-MM-DD 
Yes 
YYYY-MM-DD 
XXXXXX 
XXX-XX 
Yes 
YYYY-MM-DD 
Yes 
YYYY-MM-DD 
XXXXXX 
XXX-XX 
Yes 
YYYY-MM-DD 
Yes 
YYYY-MM-DD 
XXXXXX 
XXX-XX 
Yes 
YYYY-MM-DD 
Yes 
YYYY-MM-DD 
XXXXXX 
XXX-XX 
Yes 
YYYY-MM-DD 
No 
- 
- 
XXX-XX 
Yes 
YYYY-MM-DD 
Yes 
YYYY-MM-DD 
XXXXXX 
………….. 
 
 
 
 
 
 
 
 
 
 
 
Relaxed 
 
 
 
 
 
………….. 
 
 
 
 
 
 
 
 
 
 
 

Novartis 
Confidential 
Page 206 
MAP Module 7.1 
 
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Listing 16.2.6-11 
Genotyping SNPs 
Full Analysis Set 
 
Subject 
Number 
rsXXXXXXXX 
rsXXXXXXXX 
rsXXXXXXXX 
rsXXXXXXXX 
rsXXXXXXXX 
rsXXXXXXXX 
rsXXXXXXXX 
rsXXXXXXXX 
rsXXXXXXXX 
 
 
 
 
 
 
 
 
 
 
Intensive 
 
 
 
 
 
 
 
 
 
XXX-XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XXX-XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XXX-XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XXX-XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XXX-XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XXX-XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XXX-XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
………….. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Relaxed 
 
 
 
 
 
 
 
 
 
………….. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Novartis 
Confidential 
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CRFB002AAU15/RFB002/Ranibizumab 
 
 
Section 16.2.7 – Adverse event listings 
Listing 16.2.7-1 Adverse events 
Safety Set 
 
Subject 
Number 
AE 
No 
Adverse Event 
(REPORTED / 
Preferred / System 
Organ Class) 
Start Date 
(YYYY-MM-DD) / 
Study Day 
Stop Date 
(YYYY-MM-DD) / 
Study Day 
Duration 
(Days) 
Site 
Severity 
Action Taken 
Relation to 
Study Drug 
 
 
 
 
 
 
 
 
 
 
Intensive 
 
 
 
 
 
 
 
 
 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Left 
Mild 
ABCD 
Susp 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Right 
Mod 
ABCD 
Not susp 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Both 
Sev 
ABCD 
Susp 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Non-
Ocular 
Mild 
ABCD 
Not susp 
 
 
 
 
 
 
 
 
 
 
Intensive 
 
 
 
 
 
 
 
 
 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Left 
Mild 
ABCD 
Susp 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Right 
Mod 
ABCD 
Not susp 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Both 
Sev 
ABCD 
Susp 
 
 
 
 
 
 
 
 
 
 
NK: Not Known; AE No = Adverse Number                                                                                           
Severity: Mild=Mild, Mod=Moderate, Sev=Severe 
Relationship to study drug: Not susp=Not suspected, Susp=Suspected 
Action taken: 1=Study drug dosage adjusted/temporarily interrupted, 2=Study drug permanently discontinued due to this AE 
                      3=Concomitant medication taken, 4=Non-drug therapy given, 5=Hospitalization/Prolonged hospitalization 
Note: Day is relative to the first day of treatment (day 1) 

Novartis 
Confidential 
Page 208 
MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
Listing 16.2.7-2 Ocular adverse events 
Safety Set 
 
Subject 
Number 
AE 
No 
Adverse Event 
(REPORTED / 
Preferred / System 
Organ Class) 
Start Date 
(YYYY-MM-DD) / 
Study Day 
Stop Date 
(YYYY-MM-DD) / 
Study Day 
Duration 
Site 
Severity 
Action Taken 
Relation to 
Study Drug 
 
 
 
 
 
 
 
 
 
 
Intensive 
 
 
 
 
 
 
 
 
 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Left 
Mild 
ABCD 
Susp 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Right 
Mod 
ABCD 
Not susp 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Both 
Sev 
ABCD 
Susp 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Non-
Ocular 
Mild 
ABCD 
Not susp 
 
 
 
 
 
 
 
 
 
 
Intensive 
 
 
 
 
 
 
 
 
 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Left 
Mild 
ABCD 
Susp 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Right 
Mod 
ABCD 
Not susp 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Both 
Sev 
ABCD 
Susp 
 
 
 
 
 
 
 
 
 
 
NK: Not Known; AE No = Adverse Number                                                                                           
Severity: Mild=Mild, Mod=Moderate, Sev=Severe 
Relationship to study drug: Not susp=Not suspected, Susp=Suspected 
Action taken: 1=Study drug dosage adjusted/temporarily interrupted, 2=Study drug permanently discontinued due to this AE 
                      3=Concomitant medication taken, 4=Non-drug therapy given, 5=Hospitalization/Prolonged hospitalization 
Note: Day is relative to the first day of treatment (day 1) 

Novartis 
Confidential 
Page 209 
MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
Listing 16.2.7-3 Adverse events suspect to be related to study drug and/or ocular injection 
Safety Set 
 
Subject 
Number 
AE 
No 
Adverse Event 
(REPORTED / 
Preferred / System 
Organ Class) 
Start Date 
(YYYY-MM-DD) / 
Study Day 
Stop Date 
(YYYY-MM-DD) / 
Study Day 
Duration 
Site 
Severity 
Action Taken 
 
 
 
 
 
 
 
 
 
Intensive 
 
 
 
 
 
 
 
 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Left 
Mild 
ABCD 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Right 
Mod 
ABCD 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Both 
Sev 
ABCD 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Non-
Ocular 
Mild 
ABCD 
 
 
 
 
 
 
 
 
 
Intensive 
 
 
 
 
 
 
 
 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Left 
Mild 
ABCD 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Right 
Mod 
ABCD 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Both 
Sev 
ABCD 
 
 
 
 
 
 
 
 
 
NK: Not Known; AE No = Adverse Number                                                                                           
Severity: Mild=Mild, Mod=Moderate, Sev=Severe 
Action taken: 1=Study drug dosage adjusted/temporarily interrupted, 2=Study drug permanently discontinued due to this AE 
                      3=Concomitant medication taken, 4=Non-drug therapy given, 5=Hospitalization/Prolonged hospitalization 
Note: Day is relative to the first day of treatment (day 1) 

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Confidential 
Page 210 
MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
Listing 16.2.7-4 Serious adverse events 
Safety Set 
 
Subject 
Number 
AE 
No 
Adverse Event 
(REPORTED / 
Preferred / System 
Organ Class) 
Start Date 
(YYYY-MM-DD) / 
Study Day 
Stop Date 
(YYYY-MM-DD) / 
Study Day 
Duration 
Site 
Severity 
Action Taken 
Relation to 
Study Drug 
 
 
 
 
 
 
 
 
 
 
Intensive 
 
 
 
 
 
 
 
 
 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Left 
Mild 
ABCD 
Susp 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Right 
Mod 
ABCD 
Not susp 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Both 
Sev 
ABCD 
Susp 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Non-
Ocular 
Mild 
ABCD 
Not susp 
 
 
 
 
 
 
 
 
 
 
Intensive 
 
 
 
 
 
 
 
 
 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Left 
Mild 
ABCD 
Susp 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Right 
Mod 
ABCD 
Not susp 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Both 
Sev 
ABCD 
Susp 
 
 
 
 
 
 
 
 
 
 
NK: Not Known; AE No = Adverse Number                                                                                           
Severity: Mild=Mild, Mod=Moderate, Sev=Severe 
Relationship to study drug: Not susp=Not suspected, Susp=Suspected 
Action taken: 1=Study drug dosage adjusted/temporarily interrupted, 2=Study drug permanently discontinued due to this AE 
                      3=Concomitant medication taken, 4=Non-drug therapy given, 5=Hospitalization/Prolonged hospitalization 
Note: Day is relative to the first day of treatment (day 1) 

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Confidential 
Page 211 
MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
Listing 16.2.7-5 Adverse events leading to treatment withdrawal 
Safety Set 
 
Subject 
Number 
AE 
No 
Adverse Event 
(REPORTED / 
Preferred / System 
Organ Class) 
Start Date 
(YYYY-MM-DD) / 
Study Day 
Stop Date 
(YYYY-MM-DD) / 
Study Day 
Duration 
Site 
Severity 
Action Taken 
Relation to 
Study Drug 
 
 
 
 
 
 
 
 
 
 
Intensive 
 
 
 
 
 
 
 
 
 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Left 
Mild 
ABCD 
Susp 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Right 
Mod 
ABCD 
Not susp 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Both 
Sev 
ABCD 
Susp 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Non-
Ocular 
Mild 
ABCD 
Not susp 
 
 
 
 
 
 
 
 
 
 
Intensive 
 
 
 
 
 
 
 
 
 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Left 
Mild 
ABCD 
Susp 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Right 
Mod 
ABCD 
Not susp 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Both 
Sev 
ABCD 
Susp 
 
 
 
 
 
 
 
 
 
 
NK: Not Known; AE No = Adverse Number                                                                                           
Severity: Mild=Mild, Mod=Moderate, Sev=Severe 
Relationship to study drug: Not susp=Not suspected, Susp=Suspected 
Action taken: 1=Study drug dosage adjusted/temporarily interrupted, 2=Study drug permanently discontinued due to this AE 
                      3=Concomitant medication taken, 4=Non-drug therapy given, 5=Hospitalization/Prolonged hospitalization 
Note: Day is relative to the first day of treatment (day 1) 

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Confidential 
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MAP Module 7.1 
 
CRFB002AAU15/RFB002/Ranibizumab 
 
 
Listing 16.2.7-6 Adverse events leading to treatment interruption 
Safety Set 
 
Subject 
Number 
AE 
No 
Adverse Event 
(REPORTED / 
Preferred / System 
Organ Class) 
Start Date 
(YYYY-MM-DD) / 
Study Day 
Stop Date 
(YYYY-MM-DD) / 
Study Day 
Duration 
Site 
Severity 
Action Taken 
Relation to 
Study Drug 
 
 
 
 
 
 
 
 
 
 
Intensive 
 
 
 
 
 
 
 
 
 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Left 
Mild 
ABCD 
Susp 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Right 
Mod 
ABCD 
Not susp 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Both 
Sev 
ABCD 
Susp 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Non-
Ocular 
Mild 
ABCD 
Not susp 
 
 
 
 
 
 
 
 
 
 
Intensive 
 
 
 
 
 
 
 
 
 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Left 
Mild 
ABCD 
Susp 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Right 
Mod 
ABCD 
Not susp 
XXX-XX 
X 
ABCD 
YYYY-MM-DD / X 
YYYY-MM-DD / X 
X 
Both 
Sev 
ABCD 
Susp 
 
 
 
 
 
 
 
 
 
 
NK: Not Known; AE No = Adverse Number                                                                                           
Severity: Mild=Mild, Mod=Moderate, Sev=Severe 
Relationship to study drug: Not susp=Not suspected, Susp=Suspected 
Action taken: 1=Study drug dosage adjusted/temporarily interrupted, 2=Study drug permanently discontinued due to this AE 
                      3=Concomitant medication taken, 4=Non-drug therapy given, 5=Hospitalization/Prolonged hospitalization 
Note: Day is relative to the first day of treatment (day 1) 

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Section 16.2.8 – Laboratory measurements 
 
No output 

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Section 16.2.9 – Vital signs, physical findings and other observations related to safety listings 
Listing 16.2.9-1 Vital signs by treatment 
Safety Set 
 
Subject 
Number 
Visit 
Were Vital Signs 
Performed? 
Date of Vital Signs 
Assessment 
(YYYY-MM-DD) 
Systolic Blood 
Pressure 
 (mmHg)* 
Diastolic Blood 
Pressure 
 (mmHg)* 
 
 
 
 
 
 
XXX-XX 
ABCD 
Yes/No 
YYYY-MM-DD 
XXXH 
XXX 
 
ABCD 
Yes/No 
YYYY-MM-DD 
XXX 
XXX 
 
ABCD 
Yes/No 
YYYY-MM-DD 
XXXL 
XXX 
 
ABCD 
Yes/No 
YYYY-MM-DD 
XXX 
XXX 
………….. 
 
 
 
 
 
 
 
 
 
 
 
XXX-XX 
ABCD 
Yes/No 
YYYY-MM-DD 
XXX 
XXX 
 
ABCD 
Yes/No 
YYYY-MM-DD 
XXX 
XXX 
 
ABCD 
Yes/No 
YYYY-MM-DD 
XXX 
XXX 
 
ABCD 
Yes/No 
YYYY-MM-DD 
XXX 
XXX 
………….. 
 
 
 
 
 
*Flags: H=High (Systolic - >180 and increase from baseline of >20, Diastolic - >105 and increase from baseline of >15) 
L=Low (Systolic - <90 and decrease from baseline of >20, Diastolic - <50 and decrease from baseline of >15)  

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Listing 16.2.9-2 Ophthalmic Examinations by treatment (STUDY EYE) 
Safety Set 
 
Subject 
Number 
Visit 
Was OE 
Performed? 
Date OE 
performed 
(YYYY-MM-DD) 
STUDY 
Eye 
assessed 
IOP 
(mmHg) 
Examination 
Result 
 
 
 
 
 
 
 
 
XXX-XX 
Screening 
Yes 
YYYY-MM-DD 
Left eye 
XX 
Cornea 
Iris 
Vitreous 
Disc 
Retina other than AMD 
Lens 
  
Normal 
Abnormal 
Abnormal 
Normal 
Abnormal  
Phakic 
 
 
Baseline 
Yes 
YYYY-MM-DD 
Left eye 
XX 
Changes since previous assessment?  
Cornea 
Iris 
Vitreous 
Disc 
Retina other than AMD 
Lens 
AREDS – Nuclear Sclerosis 
AREDS – Cortical 
AREDS – PSC  
Yes: xxxxxxxx 
Normal 
Abnormal 
Abnormal 
Normal 
Abnormal  
Aphakic 
<2 
>2 
>2 
 
Week n 
Yes 
YYYY-MM-DD 
Left eye 
XX 
…………. 
…………. 
 
Week n 
Yes 
YYYY-MM-DD 
Left eye 
XX 
…………. 
…………. 
………….. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXX-XX 
………….. 
 
 
 
 
 
 
………….. 
 
 
 
 
 
 
 
OE: Ophthalmic Examination, IOP: Intra Ocular Pressure 

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Listing 16.2.9-3 Ophthalmic Examinations by treatment (FELLOW EYE) 
Safety Set 
 
Subject 
Number 
Visit 
Was OE 
Performed? 
Date OE 
performed 
(YYYY-MM-DD) 
FELLOW 
Eye 
assessed 
IOP 
(mmHg) 
Examination 
Result 
 
 
 
 
 
 
 
 
XXX-XX 
Screening 
Yes 
YYYY-MM-DD 
Left eye 
XX 
Cornea 
Iris 
Vitreous 
Disc 
Retina other than AMD 
Lens 
  
Normal 
Not done 
Abnormal 
Normal 
Abnormal  
Normal 
 
 
Baseline 
Yes 
YYYY-MM-DD 
Left eye 
XX 
Changes since previous assessment?  
Cornea 
Iris 
Vitreous 
Disc 
Retina other than AMD 
Lens 
AREDS – Nuclear Sclerosis 
AREDS – Cortical 
AREDS – PSC  
Yes: xxxxxxxx 
Normal 
Not done 
Abnormal 
Normal 
Abnormal 
Normal 
<2 
>2 
>2 
 
Week n 
Yes 
YYYY-MM-DD 
Left eye 
XX 
…………. 
…………. 
 
Week n 
Yes 
YYYY-MM-DD 
Left eye 
XX 
…………. 
…………. 
………….. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXX-XX 
………….. 
 
 
 
 
 
 
………….. 
 
 
 
 
 
 
 
OE: Ophthalmic Examination, IOP: Intra Ocular Pressure 

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Listing 16.2.9-4 Pregnancy test data by treatment 
Safety Set 
 
Subject 
Number 
Was pregnancy test 
done? 
Type of sample 
taken 
Date of sample  
(YYYY-MM-DD) 
Result of Test 
 
 
 
 
 
Intensive 
 
 
 
 
XXX-XX 
Yes 
Urine sample 
YYYY-MM-DD 
Negative 
XXX-XX 
Yes 
Serum sample 
YYYY-MM-DD 
Negative 
XXX-XX 
Yes 
Urine sample 
YYYY-MM-DD 
Negative 
XXX-XX 
Yes 
Serum sample 
YYYY-MM-DD 
Negative 
………….. 
 
 
 
 
 
 
 
 
 
Relaxed 
 
 
 
 
XXX-XX 
Yes 
Urine sample 
YYYY-MM-DD 
Negative 
XXX-XX 
Yes 
Serum sample 
YYYY-MM-DD 
Negative 
XXX-XX 
Yes 
Urine sample 
YYYY-MM-DD 
Negative 
XXX-XX 
No 
- 
- 
- 
………….. 
 
 
 
 
*Flags: H=High (Systolic - >180 and increase from baseline of >20, Diastolic - >105 and increase from baseline of >15) 
L=Low (Systolic - <90 and decrease from baseline of >20, Diastolic - <50 and decrease from baseline of >15)  

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Section 16.2.10 – Listing of subject numbers who reported at least one safety event of special interest by event and 
treatment 
No output 
 
Section 16.2.11 – Case retrieval strategy listing 
No output