Clinical trial NCT03150589
Conditions: Age-Related Macular Degeneration
Sponsor: Samsung Bioepis Co., Ltd.
Start date: 2018-03-14; Completion date: 2019-12-09
Enrollment: 705 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a randomised, double-masked, parallel group, multicentre study to evaluate the efficacy, safety, pharmacokinetics and immunogenicity of SB11 compared to Lucentis® in subjects with neovascular AMD.

Detailed description:
Subjects will be randomised in a 1:1 ratio to receive either SB11 or Lucentis® (administered via intravitreal (ITV) 0.5 mg every 4 weeks). Investigational Products (IP) (SB11 or Lucentis®) will be administered up to Week 48, and the last assessment will be done at Week 52.

Arms: arm 1: None arm 2: None
Interventions: intervention 1: SB11 (Proposed ranibizumab biosimilar) intervention 2: Lucentis (ranibizumab)
Intervention descriptions: intervention 1: SB11 (proposed ranibizumab biosimilar) 0.5mg via intravitreal injection every 4 weeks intervention 2: Lucentis (ranibizumab) 0.5mg via intravitreal injection every 4 weeks

Protocol documents:
Prot_SAP_000.pdf: 
SB11 (proposed ranibizumab biosimilar) 
SB11-G31-AMD 
Amendment 1, Sep 01, 2017 
 
Samsung Bioepis – Confidential 
Page 1 of 137 
 
 
 
Clinical Study Protocol 
 
A Phase III Randomised, Double-masked, Parallel Group, 
Multicentre Study to Compare the Efficacy, Safety, 
Pharmacokinetics and Immunogenicity between SB11 (proposed 
ranibizumab biosimilar) and Lucentis® in Subjects with Neovascular 
Age-related Macular Degeneration 
 
 
 
 
 
Product 
SB11 (proposed ranibizumab biosimilar) 
EudraCT Number 
2017-000422-36 
US pre-IND Number 
130331 
Protocol Number 
SB11-G31-AMD 
Study Phase 
Phase III 
Version and Effective Date 
Amendment 1 
Sep 01, 2017 
Sponsor 
Samsung Bioepis Co., Ltd.  
107, Cheomdan-daero, Yeonsu-gu, 
Incheon, 21987 
Republic of Korea 
 
 
 
 
 
 
This document contains confidential information belonging to Samsung Bioepis Co., Ltd. Your 
acceptance or review of this document constitutes agreement that you will not copy or disclose the 
information contained herein to others or use it for unauthorised purposes without written authorisation 
from the Sponsor. 
 


SB11 (proposed ranibizumab biosimilar) 
SB11-G31-AMD 
Amendment 1, Sep 01, 2017 
 
Samsung Bioepis – Confidential 
Page 2 of 137 
SYNOPSIS 
Name of Sponsor/Company: 
Samsung Bioepis Co., Ltd. 
Name of Finished Product: 
SB11 (proposed ranibizumab biosimilar) 
Name of Active Ingredient: 
Ranibizumab 
Title of Study: 
A Phase III Randomised, Double-masked, Parallel Group, Multicentre Study to Compare the Efficacy, 
Safety, Pharmacokinetics and Immunogenicity between SB11 (proposed ranibizumab biosimilar) and 
Lucentis® in Subjects with Neovascular Age-related Macular Degeneration 
Protocol No: 
SB11-G31-AMD 
Phase: 
III 
Indication: Neovascular Age-related Macular Degeneration (AMD) 
Objectives: 
Primary Objective: 
• 
To demonstrate the equivalence of efficacy of SB11 to Lucentis® in subjects with neovascular 
age-related macular degeneration 
 
Secondary Objectives: 
• 
To evaluate the safety of SB11 and Lucentis® 
• 
To evaluate the immunogenicity of SB11 and Lucentis® 
• 
To evaluate the systemic exposure of SB11 and Lucentis® in subjects participating in 
pharmacokinetics (PK) evaluation  
Study Design: 
This is a randomised, double-masked, parallel group, multicentre study to evaluate the efficacy, safety, 
pharmacokinetics and immunogenicity of SB11 compared to Lucentis® in subjects with neovascular 
AMD. Subjects will be randomised in a 1:1 ratio to receive either SB11 or Lucentis® (administered via 
intravitreal (ITV) 0.5 mg every 4 weeks). Investigational Products (IP) (SB11 or Lucentis®) will be 
administered up to Week 48, and the last assessment will be done at Week 52. 
Number of Subjects:  
Approximately a total of 704 subjects are planned to be randomised into this study. 
Target Population: Subjects with neovascular AMD 
Eligibility Criteria: 
Only one eye will be designated as the study eye. For subjects who meet eligibility criteria in both eyes, 
the eye with the worse Visual Acuity (VA) will be selected as the study eye. If both eyes have equal 
VA, the eye with better visual prognosis (e.g., clearer lens and ocular media and less amount of 
subfoveal scar or geographic atrophy) will be selected at the Investigator’s discretion. If there is no 
objective basis for selecting the study eye, factor such as ocular dominance, other ocular pathology and 
subject preference should be considered by the Investigator in making the selection. 
Inclusion criteria 


SB11 (proposed ranibizumab biosimilar) 
SB11-G31-AMD 
Amendment 1, Sep 01, 2017 
 
Samsung Bioepis – Confidential 
Page 3 of 137 
Name of Sponsor/Company: 
Samsung Bioepis Co., Ltd. 
Name of Finished Product: 
SB11 (proposed ranibizumab biosimilar) 
Name of Active Ingredient: 
Ranibizumab 
Subjects must meet all of the following criteria to be eligible for the study: 
1. Age ≥ 50 years at Screening 
2. Newly diagnosed, *active subfoveal Choroidal Neovascularisation (CNV) lesion secondary to 
AMD in the study eye 
* Active CNV indicates presence of leakage and intra- or sub-retinal fluid which should be 
confirmed by central reading centre during Screening 
3. The area of CNV must occupy at least 50% of total lesion in the study eye (confirmed by 
central reading centre during Screening) 
4. Total lesion area ≤ 9.0 Disc Areas (DA) in size (including blood, scars and neovascularisation) 
in the study eye (confirmed by central reading centre during Screening) 
5. Best Corrected Visual Acuity (BCVA) of 20/40 to 20/200 (letter score of 73 to 34) using 
original series Early Treatment Diabetic Retinopathy Study (ETDRS) charts or 2702 series 
Number charts in the study eye at Screening and at Week 0 (Day 1) prior to randomisation 
6. Non-childbearing potential female (e.g., permanently sterilised, postmenopausal [defined as 12 
months with no menses without an alternative medical cause prior to Screening]), OR 
Childbearing potential female subjects or male subjects with their (respectively male or 
female) partners who agree to use at least two forms of appropriate contraception method that 
can achieve a failure rate of less than 1% per year (e.g., established use of oral, injected, 
intravaginal, transdermal or implanted hormonal contraceptive, placement of an intrauterine 
device or intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised 
partner, physical barrier, sexual abstinence) from Screening until 3 months after the last ITV 
injection of IP 
7. Written informed consent form must be obtained from the subject prior to any study related 
procedure (If the subject is legal blindness or illiterate, an impartial witness should be present 
during the entire informed consent discussion) 
8. Willingness and ability to undertake all scheduled visits and assessments 
Exclusion criteria 
Subjects meeting any of the following criteria are not eligible for the study: 
1. Sub- or intra-retinal haemorrhage that comprises more than 50% of the entire lesion in the 
study eye, or presence of subfoveal blood equal to or more than one DA in size (confirmed by 
central reading centre during Screening) 


SB11 (proposed ranibizumab biosimilar) 
SB11-G31-AMD 
Amendment 1, Sep 01, 2017 
 
Samsung Bioepis – Confidential 
Page 4 of 137 
Name of Sponsor/Company: 
Samsung Bioepis Co., Ltd. 
Name of Finished Product: 
SB11 (proposed ranibizumab biosimilar) 
Name of Active Ingredient: 
Ranibizumab 
2. Scar, fibrosis or atrophy involving the centre of the fovea in the study eye (confirmed by 
central reading centre during Screening) 
3. Presence of CNV in either eye due to other causes, such as ocular histoplasmosis, trauma, 
multifocal choroiditis, angioid streaks, history of choroidal rupture or Pathologic Myopia 
(PM) (confirmed by central reading centre during Screening) 
4. Presence of retinal pigment epithelial tears or rips involving the macula in the study eye 
(confirmed by central reading centre during Screening) 
5. Presence of macular hole at any stage in the study eye (confirmed by central reading centre 
during Screening) 
6. Any concurrent macular abnormality other than AMD in the study eye which could affect the 
efficacy of IP including but not limited to epiretinal membrane, macular telangiectasia, retinal 
vascular abnormality, etc. (confirmed by central reading centre during Screening) 
7. History of vitrectomy surgery in the study eye 
8. History of trabeculectomy or other filtration surgery in the study eye 
9. History of submacular surgery or other surgical intervention for AMD in the study eye 
10. Any other intraocular surgery (including cataract surgery) or periocular surgery in the study 
eye within 90 days prior to randomisation, except for lid surgery, which may not have taken 
place within 30 days prior to randomisation 
11. Any previous ITV anti-Vascular Endothelial Growth Factor (anti-VEGF) treatment (e.g., 
bevacizumab, aflibercept, ranibizumab) to treat neovascular AMD in either eye 
12. Any previous systemic anti-VEGF treatment, within 90 days prior to randomisation, and such 
treatment will not be allowed during the study period 
13. Any systemic treatment or therapy (including prescribed herbal medication) to treat 
neovascular AMD within 30 days prior to randomisation, and such treatment or therapy will 
not be allowed during the study period. However, dietary supplements, vitamins or mineral 
will be allowed 
14. Any intravitreal injection of corticosteroid (e.g., triamcinolone acetonide) or intravitreal 
corticosteroid implant in the study eye within 180 days prior to randomisation, and such 
treatment will not be allowed during the study period 
15. Topical ocular corticosteroids administered for ≥ 30 consecutive days in the study eye within 


SB11 (proposed ranibizumab biosimilar) 
SB11-G31-AMD 
Amendment 1, Sep 01, 2017 
 
Samsung Bioepis – Confidential 
Page 5 of 137 
Name of Sponsor/Company: 
Samsung Bioepis Co., Ltd. 
Name of Finished Product: 
SB11 (proposed ranibizumab biosimilar) 
Name of Active Ingredient: 
Ranibizumab 
90 days prior to randomisation  
16. Spherical equivalent of the refractive error in the study eye demonstrating more than 8 diopters 
of myopia. For subjects who have undergone previous refractive or cataract surgery in the 
study eye, the preoperative refractive error in the study eye must not exceed 8 diopters of 
myopia 
17. Aphakia or absence of the posterior capsule in the study eye (unless it occurred as a result of a 
Yttrium Aluminium Garnet [YAG] posterior capsulotomy in association with prior posterior 
chamber Intraocular Lens [IOL] implantation) 
18. Presence of scleromalacia in either eye 
19. Current vitreous haemorrhage in the study eye 
20. Active or recent (within 28 days prior to randomisation) intraocular, extraocular and periocular 
inflammation or infection in either eye 
21. History of idiopathic or autoimmune uveitis in either eye 
22. History of retinal detachment in the study eye 
23. History of full-thickness macular hole in the study eye 
24. History of corneal transplantation surgery in the study eye 
25. Presence of advanced glaucoma or optic neuropathy that affect or threaten the central visual 
field in the study eye 
26. Uncontrolled ocular hypertension (defined as intraocular pressure ≥ 25 mmHg despite 
treatment with anti-glaucoma medication) in the study eye 
27. History of allergy to the fluorescein sodium for injection in angiography 
28. Previous participation in clinical studies of ocular investigational products to treat neovascular 
AMD in either eye or systemic investigational products to treat neovascular AMD, and such 
participation will not be allowed during the study period 
29. Previous participation in any studies of ocular or systemic investigational products (excluding 
dietary supplements, vitamins and minerals) to treat ocular or systemic disease other than 
neovascular AMD within 90 days prior to randomisation, and such participation will not be 
allowed during the study period even if the investigational product is dietary supplements, 
vitamins or minerals 


SB11 (proposed ranibizumab biosimilar) 
SB11-G31-AMD 
Amendment 1, Sep 01, 2017 
 
Samsung Bioepis – Confidential 
Page 6 of 137 
Name of Sponsor/Company: 
Samsung Bioepis Co., Ltd. 
Name of Finished Product: 
SB11 (proposed ranibizumab biosimilar) 
Name of Active Ingredient: 
Ranibizumab 
30. History or clinical evidence of diabetic retinopathy (except for mild non-proliferative diabetic 
retinopathy) or diabetic macular oedema in either eye 
31. Any concurrent ocular condition in the study eye which, in the opinion of the Investigator, 
could either increase the risk to the subject safety or which otherwise may interfere with 
evaluation of efficacy or safety including, but not limited to ocular media opacities such as 
corneal opacity or cataract that do not allow proper fundus visualisation and fundus imaging, 
and ocular surface abnormalities which prevent applanation tonometry during the study 
period after randomisation 
32. History of other disease, metabolic dysfunction, physical examination finding, or clinical 
laboratory finding that contraindicates the use of an IP in the opinion of the Investigator 
33. Pregnant or lactating women. A serum pregnancy test must be required for women of 
childbearing potential at Screening 
34. Employees of Investigational sites, individuals directly involved with the conduct of the study 
or immediate family members thereof, prisoners, and persons who are legally  
institutionalised  
35. Stroke, transient ischemic attacks, or myocardial infarction within 90 days prior to 
randomisation 
36. History of recurrent significant infections and/or current treatment for active systemic infection 
37. Known allergic reactions and/or hypersensitivity to ranibizumab or to any ingredients of the 
investigational product 
38. Prior treatment involving macula with photodynamic therapy with verteporfin, transpupillary 
thermotherapy, radiation therapy, or retinal laser treatment (e,g., focal laser photocoagulation) 
in the study eye, and such treatment will not be allowed during the study period 
39. Prior treatment with pan-retinal photocoagulation in the study eye, and such treatment will not 
be allowed during the study period 
40. Current use of systemic medications known to be toxic to the lens, retina or optic nerve, 
including deferoxamine, chloroquine/hydroxychloroquine, tamoxifen, phenothiazines, 
vigabatrin and ethambutol, and such medications will not be allowed during the study period 
Planned Study Period: 
Screening period will be 21 days. 
IPs (SB11 or Lucentis®) will be given up to Week 48, and the last assessment will be done at Week 52. 


SB11 (proposed ranibizumab biosimilar) 
SB11-G31-AMD 
Amendment 1, Sep 01, 2017 
 
Samsung Bioepis – Confidential 
Page 7 of 137 
Name of Sponsor/Company: 
Samsung Bioepis Co., Ltd. 
Name of Finished Product: 
SB11 (proposed ranibizumab biosimilar) 
Name of Active Ingredient: 
Ranibizumab 
Investigational Products: 
• 
Test IP: SB11 (proposed ranibizumab biosimilar) 
• 
Reference IP: Lucentis® (ranibizumab) 
• 
Route of administration: ITV injection 
• 
Dose: 0.5 mg every 4 weeks 
Main Criteria for Evaluation 
Primary endpoint 
For US Food and Drug Administration (FDA), Korea Ministry of Food and Drug Safety (MFDS) or 
other regulatory agency submissions for those who are in favour of the VA, the primary endpoint is: 
•  Change from baseline in BCVA at Week 8 
For European Medicines Agency (EMA) or other regulatory agency submissions for those who are in 
favour of the anatomical parameter, the primary endpoint is: 
• Change from baseline in Central Subfield Thickness (CST) at Week 4 (based on assessment by 
central reading centre) 
Secondary endpoints 
The secondary efficacy endpoints are: 
• Change from baseline in BCVA over time up to Week 24 and Week 52 
• Proportion of subjects who lost fewer than 15 letters in BCVA compared to baseline at Week 24 
and Week 52 
• Proportion of subjects who gained 15 letters or more in BCVA compared to baseline at Week 24 
and Week 52 
• Change from baseline in CST and Central Retinal Lesion Thickness (CRLT) at Week 24 and Week 
52 (based on assessment by central reading centre) 
• Change from baseline in total CNV size at Week 24 and Week 52 (based on assessment by central 
reading centre) 
• Proportion of subjects with active CNV leakage at Week 24 and Week 52 (based on assessment by 
central reading centre) 
The safety endpoints are: 


SB11 (proposed ranibizumab biosimilar) 
SB11-G31-AMD 
Amendment 1, Sep 01, 2017 
 
Samsung Bioepis – Confidential 
Page 8 of 137 
Name of Sponsor/Company: 
Samsung Bioepis Co., Ltd. 
Name of Finished Product: 
SB11 (proposed ranibizumab biosimilar) 
Name of Active Ingredient: 
Ranibizumab 
• Incidence of ocular Adverse Events (AEs) or serious ocular adverse events 
• Incidence of systemic AEs and serious systemic adverse events 
The pharmacokinetic endpoints are: 
Blood sampling for PK will be collected in approximately 40 subjects participating in PK evaluation 
(20 subjects per treatment group). 
• Systemic exposure measured pre-dose (Ctrough) and 24 to 72 hours post-dose (close to Cmax)  
The immunogenicity endpoints are: 
• Incidence of Anti-Drug Antibodies (ADAs) to ranibizumab 
• Incidence of Neutralising Antibodies (NAbs) to ranibizumab  
The exploratory endpoints are: 
• Proportion of subjects without intra- or sub-retinal fluid at Week 24 and Week 52 (based on 
assessment by central reading centre) 
The Quality of Life (QOL) is assessed using National Eye Institute 25-Item Visual Function 
Questionnaire (NEI VFQ-25). 
• Change from baseline in subscale scores and composite scores of NEI VFQ-25 at Week 24 and 
Week 52 
Statistical Methods 
Efficacy analysis 
For US FDA, Korea MFDS or other regulatory agency submissions for those who are in favour of the 
VA, the primary efficacy analysis will be performed for the Full Analysis Set (FAS) with the change 
from baseline of BCVA at Week 8 using an analysis of covariance model with the baseline BCVA as a 
covariate and region (or pooled centres) and treatment group as factors. The FAS will consist of all 
randomised subjects. The subjects will be analysed based on the treatment they were randomised to by 
intention-to-treat principle. However, subjects who do not qualify for randomisation and are 
inadvertently randomised into the study will be excluded from the FAS, provided these subjects do not 
receive any IP during the study period. The equivalence in BCVA will be declared if the two-sided 90% 
Confidence Interval (CI) of the difference of BCVA Least Squares mean (LS mean) changes from 
baseline at Week 8 between SB11 and Lucentis® lies within the pre-defined equivalence margin of [−3 
letters, 3 letters].  
For EMA or other regulatory agency submissions for those who are in favour of the anatomical 


SB11 (proposed ranibizumab biosimilar) 
SB11-G31-AMD 
Amendment 1, Sep 01, 2017 
 
Samsung Bioepis – Confidential 
Page 9 of 137 
Name of Sponsor/Company: 
Samsung Bioepis Co., Ltd. 
Name of Finished Product: 
SB11 (proposed ranibizumab biosimilar) 
Name of Active Ingredient: 
Ranibizumab 
parameter, the primary efficacy analysis will be performed for the per-protocol set (PPS-CST) with the 
change from baseline of CST at Week 4 using an analysis of covariance model with baseline CST as a 
covariate and region (or pooled centres) and treatment group as factors. The PPS-CST consists of all 
FAS subjects who have the first IP injection at Week 0 (Day 1) and complete procedures at Week 4 
without any major protocol deviations that have impact on the CST assessment. The equivalence in 
CST will be declared if the two-sided 95% CI of the difference of CST LS mean changes from baseline 
at Week 4 between SB11 and Lucentis® lies within the pre-defined equivalence margin of [−36 μm, 36 
μm]. 
There is no formal adjustment of type I error rates.  
For the primary analysis with the FAS for BCVA, missing data will be imputed for subjects who drop 
out for the study prior to the primary analysis time-point. A missing-at-random approach will assume 
that subjects who withdraw from a study had missing values similar to similar subjects who completed 
the study in that treatment group. This approach ensures that evidence of lack of equivalence is not 
diluted when there are missing data. For the components of BCVA, the missing letter will be imputed 
by multiple imputation method with the assumption of monotone missing pattern and regression 
method. For the sensitivity analyses, available case analysis and last observation carried forward 
analysis will be performed. All other efficacy measurements will be summarised descriptively by 
treatment group and visit. 
Safety analyses 
All reported terms for AEs (ocular or systemic) will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA®). AEs including ocular AEs in the study eye and/or fellow eye as 
well as systemic AEs will be summarised descriptively by treatment group.  
Changes in vital signs and clinical laboratory parameters will be summarised descriptively by treatment 
group and visit. All other safety variables will be summarised descriptively by treatment group and visit 
unless specified otherwise, and all safety variables will be listed. 
Pharmacokinetic analyses 
Blood sampling for PK will be collected in approximately 40 subjects participating in PK evaluation 
(20 subjects per treatment group). Formal PK analysis will not be performed. The systemic exposure 
will be summarised descriptively by treatment group and visit.  
Immunogenicity analyses 
The number and proportion of subjects with ADA and NAb results (e.g., “positive” or “negative”) will 
be summarised by treatment group and visit. 
NEI VFQ-25 analyses 


SB11 (proposed ranibizumab biosimilar) 
SB11-G31-AMD 
Amendment 1, Sep 01, 2017 
 
Samsung Bioepis – Confidential 
Page 10 of 137 
Name of Sponsor/Company: 
Samsung Bioepis Co., Ltd. 
Name of Finished Product: 
SB11 (proposed ranibizumab biosimilar) 
Name of Active Ingredient: 
Ranibizumab 
Subscale scores (general health, general vision, ocular pain, near activities, distance activities, vision-
specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-
specific dependency, driving, colour vision, and peripheral vision) and the composite score, which 
represent overall visual function, will be calculated, and the change from baseline will be summarised 
by treatment group and visit. 
Sample size calculation 
For the calculation of the equivalence margin for BCVA, the mean changes in VA were referred from 
two studies of Lucentis® in subjects with neovascular AMD. In MARINA study, the mean change of 
VA at Week 24 (Standard Deviation [SD]) were −6.6 (13.31) letters and 6.5 (12.00) letters for placebo 
and 0.5 mg Lucentis® treatment groups, respectively. In FOCUS study, the mean change (SD) of VA at 
Week 24 were −5.0 (16.14) letters and 4.0 (14.41) letters for placebo and 0.5 mg Lucentis® treatment 
groups, respectively. 
A fixed-effect meta-analysis of the above two studies estimates a weighted mean change in VA of 12.41 
letters with a 95% CI [10.34 letters, 14.48 letters]. The derived equivalence limit from meta-analysis is 
4.9 letters at Week 24, but by the agency recommendation the equivalence limit at Week 8 will be 3 
letters for the comparison with the 90% CI of mean difference between treatment groups. 
With the given equivalence margin of [−3 letters, 3 letters], 334 subjects per treatment group was 
calculated with the assumptions of the mean difference of 0.5 letters and pooled SD of 12.5 letters at the 
overall 5% significance level. Assuming a 5% loss from randomised subjects after 8 weeks, a sample 
size of 352 subjects per treatment group (overall sample size of 704) will give 334 completers per 
treatment group after 8 weeks, which is estimated to give 80% power to detect the equivalence of 
change from baseline in BCVA within the margin of 3 letters. 
For the calculation of the equivalence margin for CST, the mean changes in CST were referred from 
two studies of Lucentis® in subjects with neovascular AMD. In MARINA study, the mean change of 
CST at Week 4 (SD) was 8.1 (58.1) μm and −106 (122.5) μm for placebo and 0.5 mg Lucentis® 
treatment groups, respectively. In PIER study, the mean change (SD) of CST at Week 4 were 15 (94.9) 
μm and −90 (140.9) μm for placebo and 0.5 mg Lucentis® treatment groups, respectively. 
A fixed-effect meta-analysis of the above two studies estimates a weighted mean change in CST of 
109.6 μm with a 95% CI [−146.45 μm; −72.65 μm]. The derived equivalence limit from meta-analysis 
is 36 μm at Week 4. 
With the given equivalence margin of [−36 μm, 36 μm], 290 subjects per treatment group was 
calculated with the assumptions of the mean difference of 0 between treatment groups, common SD of 
133.3 μm at the overall 5% significance level. Assuming a 10% loss from FAS, a sample size of 323 per 
arm (overall sample size of 646) will give 80% power to detect the equivalence within the pre-defined 
margin. 


SB11 (proposed ranibizumab biosimilar) 
SB11-G31-AMD 
Amendment 1, Sep 01, 2017 
 
Samsung Bioepis – Confidential 
Page 11 of 137 
Name of Sponsor/Company: 
Samsung Bioepis Co., Ltd. 
Name of Finished Product: 
SB11 (proposed ranibizumab biosimilar) 
Name of Active Ingredient: 
Ranibizumab 
Therefore, the sample size of 704 allows enough power to detect the equivalence between treatment 
groups in both situations. 
 


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SB11 (proposed ranibizumab biosimilar) 
SB11-G31-AMD 
Amendment 1, Sep 01, 2017 
 
Samsung Bioepis – Confidential 
Page 13 of 137 
Table 1. Schedule of Activities 
Procedures 
Study Period 
W: Week 
Screening 
W0 
W1 
W4 
W8 
W12 
W16 
W20 
W24 
W28 
W32 
W36 
W40 
W44 
W48 
EOT24 
W52 
EOS/ 
ET25 
D: Day 
 (± visit window)  
D-21 to D-1 
D1 
D8  
(±3) 
D29 
(±7) 
D57 
(±7) 
D85 
(±7) 
D113 
(±7) 
D141 
(±7) 
D169 
(±7) 
D197 
(±7) 
D225 
(±7) 
D253 
(±7) 
D281 
(±7) 
D309 
(±7) 
D337 
(±7) 
D365 
(±7) 
V: Visit 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
V13 
V14 
V15 
V16 
Written informed consent1 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographic data2 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical/ophthalmic history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination3 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Randomisation4 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
BCVA examination6 
X 
X7 
X 
X 
X8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
OCT9 
X 
X 
X 
X10 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
FP/FA11 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
Indirect ophthalmoscopy12 
(pre- and post-dose) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Slit lamp examination13 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Intraocular pressure14 
(pre- and post-dose) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
NEI VFQ-2515 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
Clinical laboratory test16 
X 
 
 
 
 
X 
 
 
X 
 
 
X 
 
 
 
X 
Blood sampling for 
immunogenicity17 
 
X 
X 
X 
X 
 
X 
 
X 
 
 
X 
 
 
 
X 
Blood sampling for PK18 
 
X 
X 
X 
X 
 
X 
 
X 
 
 
X 
 
 
 
X 
Pregnancy test19 
X 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
IP injection20 
 
X21 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Adverse event monitoring22 
Continuously 
Prior or concomitant 
medication or therapy23 
Continuously 
EOS, End of Study; EOT, End of Treatment; ET, Early Termination; ETDRS, Early Treatment Diabetic Retinopathy Study; FA, Fluorescein Angiography; FP, Fundus Photography; IP, 
Investigational Product; NEI VFQ-25, National Eye Institute 25-item Visual Function Questionnaire; OCT, Optical Coherence Tomography; PK, Pharmacokinetics 
 


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1. 
Written informed consent must be obtained from the subject prior to any study related procedures 
2. 
Demographic data includes the date of birth (or year of birth), gender, race and ethnicity. 
3. 
Physical examination will be performed at Screening and Week 52 (EOS visit) or ET visit. The physical examination will include an assessment of the subject’s general 
appearance, skin, head, neck, throat, lymph nodes, cardiovascular, neurological, thyroid, musculoskeletal/extremities, respiratory systems and the subject’s abdomen. 
Body weight will be measured and recorded at Screening and Week 52 (EOS visit) or ET visit, but height will be measured and recorded only at Screening. 
4. 
All subjects’ eligibility should be confirmed by the central reading centre and Investigator.  
5. 
Vital signs include blood pressure, pulse rate and body temperature. Vital signs will be assessed at Screening and prior to ITV injection of IP at each visit until Week 48. 
Vital signs will also be assessed at any time during the visit at Week 52 (EOS visit) or ET visit. 
6. 
Visual acuity will be assessed in both the study eye and fellow (non-study) eye at Screening and prior to ITV injection of IP at each visit until Week 48. Visual acuity 
will also be assessed at any time during the visit at Week 52 (EOS visit) or ET visit. Subject must use either original series ETDRS charts or 2702 series Number charts 
(at a starting distance of 4 meters) consistently from Screening to Week 52 (EOS visit) or ET visit. Visual acuity testing must be performed before dilation of pupils and 
FP/FA and OCT assessment. A decrease in visual acuity of ≥ 15 letters from the last assessment of VA should be reported as AEs/Serious Adverse Events (SAEs) as 
appropriate. If there is a decrease in VA of ≥ 30 letters from the last assessment of VA or if there is a decrease in VA to the level of Light Perception or worse, it should 
be reported as SAE. 
7. 
Investigator must confirm that the subject can read between 34 letters to 73 letters using original series ETDRS charts or 2702 series Number charts at Week 0 (Day1) 
prior to randomisation  
8. 
Visit at Week 8 is the most critical as the visit is for the primary endpoint assessment for US FDA, Korea MFDS or other regulatory agency submissions for those who 
are in favour of the VA. Thus, every effort should be made to adhere to the visit schedule for the subjects. 
9. 
OCT will be performed on the study eye at Screening and prior to ITV injection of IP at each visit until Week 48.  OCT will also be performed at any time during the 
visit at Week 52 (EOS visit) or ET visit. Site staffs who will perform OCT scans in this study must be certified by the central reading centre before study starts. OCT 
devices registered in an Investigational site should be all from the same manufacture and meet the minimum software requirement, The subject should use the OCT 
device registered by the central reading centre from Screening to Week 52 (EOS visit) or ET visit. OCT images will be sent to the central reading centre. 
10. Visit at Week 4 is the most critical as the visit is for the primary endpoint assessment for EMA or other regulatory agency submissions for those who are in favour of the 
anatomical parameter. Thus, every effort should be made to adhere to the visit schedule for the subjects. 
11. FP/FA will be performed on the both eyes at Screening and those images taken from the both eyes will be sent to the central reading centre. FP/FA will also be 
performed on the study eye prior to ITV injection of IP at Week 24 and at any time during the visit at Week 52 (EOS visit) or ET visit. Those images taken from the 
study eye will be sent to the central reading centre. Site staffs who will perform FA/FP in this study must be certified by the central reading centre before study starts. 
Only FP/FA device certified by central reading centre is allowed to be used in this study. If one or more FP/FA devices are certified in an Investigational site, a subject 
must use the same FP/FA device consistently from Screening to Week 52 (EOS visit) or ET visit. If any significant change in the posterior pole (i.e., subretinal 
haemorrhage, macular hole, vitreous haemorrhage or opacity, retinal detachment, etc.) is detected with fundus examination, additional FP and/or FA can be performed at 
the Investigator’s discretion, but the images will not be sent to the central reading centre. 


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Page 15 of 137 
12. Indirect ophthalmoscopy using a standard way (i.e., usually using a head-mounted light source and a 20-30 lens) will be performed on the study eye at Screening and 
prior to ITV injection of IP and within 15 minutes after ITV injection of IP at each visit until Week 48. Indirect ophthalmoscopy will also be performed at any time 
during the visit at Week 52 (EOS visit) or ET visit. 
13. Slit lamp examination will be performed in both the study eye and fellow eye (non-study eye) at Screening and prior to ITV injection of IP at each visit until Week 48. 
Slit lamp examination will also be performed at any time during the visit at Week 52 (EOS visit) or ET visit.  
14. Intraocular Pressure (IOP) will be measured using Goldmann applanation tonometry. The same method of IOP measurement must be used in each subject from 
Screening to Week 52 (EOS visit) or ET visit. IOP will be measured on the study eye at Screening and prior to ITV injection of IP and 30-60 minutes after ITV injection 
of IP at each visit until Week 48. When IOP is measured prior to ITV injection of IP, IOP should be measured after OCT and FP/FA are completed to avoid corneal 
erosion. IOP will also be measured at any time during the visit at Week 52 (EOS visit) or ET visit.  
15. NEI VFQ-25 should be performed at Week 0 (Day1) after randomisation. Then, NEI VFQ-25 should be performed before dilation of pupil at Week 0 (Day 1), Week 24 
and Week 52 (EOS visit) or ET visit. 
16. Blood and urine sampling for clinical laboratory test will be collected at Screening and prior to ITV injection of IP at Week 12, Week 24, and Week 36. Blood and urine 
sampling for clinical laboratory test will also be collected at any time during the visit at Week 52 (EOS visit) or ET visit. Urine samples must be collected before 
performing FA to avoid false elevations in urine protein values. 
• Haematology: haemoglobin, haematocrit, platelet count, white blood cell count (total and differential) 
• Chemistry: sodium, potassium, creatinine, glucose, calcium, phosphorus, total bilirubin, albumin, alanine aminotransferase, aspartate aminotransferase, alkaline 
phosphatase, lactate dehydrogenase 
• Urinalysis (dipstick):  protein, blood, leucocytes, nitrite, glucose, ketone, pH, specific gravity, bilirubin, urobilinogen 
Blood samples will be analysed in central laboratory and urine samples will be tested in each Investigational site by using a dipstick which will be provided by Sponsor. 
17. Blood sampling for immunogenicity will be collected prior to ITV injection of IP at Week 0 (Day 1), Week 4, Week 8, Week 16, Week 24, and Week 36. Blood 
sampling for immunogenicity will also be collected at any time during the visit at Week 1 and Week 52 (EOS visit) or ET visit. 
18. Blood sampling for PK will be collected in approximately 40 subjects participating in PK evaluation (20 subjects per treatment group). Blood sampling for PK will 
be collected prior to ITV injection of IP (Ctrough) and 24-72 hours after ITV injection of IP (close to Cmax) on Week 0 (Day 1), Week 4, Week 8, Week 16, Week 24, and 
Week 36. Blood samples for PK will also be collected at any time during the visit at Week 1 and Week 52 (EOS visit). 
19. For women of childbearing potential, serum pregnancy test must be performed at Screening. The serum samples taken at Screening will be analysed in central 
laboratory. Additional serum or urine pregnancy test can be performed in each Investigational site during the study period, if necessary.  
20. Subjects will be administered SB11 or Lucentis® 0.5 mg via ITV into the study eye every 4 weeks up to Week 48. Dosing visits will be allowed within ± 7 days of the 
scheduled dosing visit date (except Week 0 (Day 1), visit window not allowed). If a dose of IP is not given within 7 days of the scheduled dosing visit date, the IP should 
be given within 20 days of the scheduled dosing visit date, but the case will be captured as protocol deviation. Dosing skip is defined when a subject does not receive the 
IP within 20 days after scheduled dosing visit date. Next scheduled dosing visit date and visit window should not be altered even though previous dosing is not 
performed on the exact scheduled dosing visit date (but, the interval between two doses injected into the study eye should be at least 14 days) or previous dosing is 
skipped.  


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21. The first ITV injection of IP and all other study procedures must be performed at the same day of randomisation or the following day after randomisation at the latest 
with a proper reason.  
22. Ocular AEs in the study eye and/or fellow eye as well as systemic AEs will be recorded after the written informed consent is obtained from the subject until Week 52 
(EOS visit) or ET visit. 
23. Any medications including prescription drug, non-prescription drugs or any therapy (except dietary supplements vitamins, minerals) received locally (in the study eye 
and/or fellow eye) or systemically within 180 days prior to Screening until Week 52 (EOS visit) or ET visit will be recorded. 
24. End of Treatment (EOT) visit is defined as the visit for the last ITV injection of SB11 or Lucentis® during the study period after randomisation. The Sponsor will not 
provide IP (SB11 or Lucentis®) to subjects after they complete the EOT visit. 
25. End of Study (EOS) visit or Early Termination (ET) visit is defined as 4 weeks (± 7 days) after the last ITV injection of SB11 or Lucentis®. 


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Page 17 of 137 
 
Table 2. Blood Sampling Schedule for PK, Immunogenicity and Clinical Laboratory Test 
Visit 
Week  
(± visit window) 
Sampling time 
PK sampling 
(Only in subjects participating 
PK evaluation) 
Immunogenicity sampling 
(in all randomised subjects) 
Clinical laboratory test 
(in all randomised subjects) 
V1 
Screening 
D-21 to D-1 
- 
- 
O* 
V2 
Week 0 
Prior to ITV injection 
O 
O 
- 
24-72 hr after ITV injection 
O 
- 
- 
V3 
Week 1 (± 3  days) 
Samples to be collected at any time during the visit 
O 
O 
- 
V4 
Week 4 (± 7 days) 
Prior to ITV injection 
O 
O 
- 
24-72 hr after ITV injection 
O 
- 
- 
V5 
Week 8 (± 7 days) 
Prior to ITV injection 
O 
O 
- 
24-72 hr after ITV injection 
O 
- 
- 
V6 
Week 12 (± 7 days) 
Prior to ITV injection 
- 
- 
O 
V7 
Week 16 (± 7 days) 
Prior to ITV injection 
O 
O 
- 
24-72 hr after ITV injection 
O 
- 
- 
V9 
Week 24 (± 7 days) 
Prior to ITV injection 
O 
O 
O 
24-72 hr after ITV injection 
O 
- 
- 
V12 
Week 36 (± 7 days) 
Prior to ITV injection 
O 
O 
O 
24-72 hr after ITV injection 
O 
- 
- 
V16 
Week 52 (EOS visit) 
 (± 7 days) 
Samples to be collected at any time during the visit 
O 
O 
O 
- 
ET visit (± 7 days) 
Samples to be collected at any time during the visit 
- 
O 
O 
* in all subjects who signed written informed consent 
 


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LIST OF ABBREVIATIONS  
ADA 
Anti-drug Antibody 
AE 
Adverse Event 
AESI 
Adverse Events of Special Interest 
AMD 
Age-related Macular Degeneration 
BCVA 
Best Corrected Visual Acuity 
CFT 
Central Foveal Thickness 
CI 
Confidence Interval 
CNV 
Choroidal Neovascularisation 
CPT 
Centre Point Thickness 
CRLT 
Central Retinal Lesion Thickness 
CRO 
Contract Research Organisation 
CSR 
Clinical Study Report 
CST 
Central Subfield Thickness 
DA 
Disc Area 
DME 
Diabetic Macular Oedema 
DR 
Diabetic Retinopathy 
DSMB 
Data and Safety Monitoring Board 
eCRF 
Electronic Case Report Form 
EMA 
European Medicines Agency 
EOS 
End of Study 
EOT 
End of Treatment 
ET 
Early Termination 


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ETDRS 
Early Treatment Diabetic Retinopathy Study 
FA  
Fluorescein Angiography 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
FP 
Fundus Photography 
GCP 
Good Clinical Practice 
HUVEC 
Human Umbilical Vein Endothelial Cells 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
ILM 
Internal Limiting Membrane 
IOL 
Intraocular Lens 
IOP 
Intraocular Pressure 
IP 
Investigational Product 
IRB 
Institutional Review Board 
ITV 
Intravitreal 
IWRS 
Interactive Web Recognition System 
LS mean 
Least Squares mean 
MedDRA 
Medical Dictionary for Regulatory Activities 
MFDS 
Ministry of Food and Drug Safety 
MoA 
Mechanism of Action 
NAb 
Neutralising Antibody 


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NEI VFQ-25 
National Eye Institute 25-Item Visual Function Questionnaire 
OCT 
Optical Coherence Tomography 
PDT 
Photodynamic Therapy 
PK 
Pharmacokinetics 
PKS 
Pharmacokinetic analysis set 
PM 
Pathologic Myopia 
PPS 
Per-protocol Set 
QOL 
Quality of Life 
RAN 
Randomised Set 
RPE 
Retinal Pigment Epithelium 
RVO 
Retinal Vein Occlusion 
SAE 
Serious Adverse Event 
SAF 
Safety Set 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SOP 
Standard Operation Procedure 
TEAE 
Treatment-Emergent Adverse Event 
US 
United States 
VA 
Visual Acuity 
VEGF 
Vascular Endothelial Growth Factor 
WHO-DDE 
World Health Organisation-Drug Dictionary Enhanced 
YAG 
Yttrium Aluminium Garnet 


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TABLE OF CONTENTS 
SYNOPSIS .................................................................................................................................. 2 
FLOW CHARTS ....................................................................................................................... 12 
LIST OF ABBREVIATIONS ................................................................................................... 18 
TABLE OF CONTENTS .......................................................................................................... 21 
LIST OF TABLES .................................................................................................................... 24 
LIST OF FIGURES .................................................................................................................. 24 
LIST OF STUDY STAFF ......................................................................................................... 25 
1. INTRODUCTION................................................................................................................. 26 
1.1. Background .................................................................................................................... 26 
1.2. Lucentis®: Ranibizumab Reference Product .................................................................. 26 
1.3. SB11: Proposed Ranibizumab Biosimilar ...................................................................... 30 
1.4. Rationale for the Study ................................................................................................... 30 
2. STUDY OBJECTIVES ......................................................................................................... 31 
2.1. Primary Objective .......................................................................................................... 31 
2.2. Secondary Objective ...................................................................................................... 31 
3. STUDY DESIGN .................................................................................................................. 31 
3.1. Overview of Study Design ............................................................................................. 31 
3.2. Rationale for the Study Design ...................................................................................... 31 
4. STUDY POPULATION ....................................................................................................... 33 
4.1. Inclusion Criteria ............................................................................................................ 33 
4.2. Exclusion Criteria........................................................................................................... 34 
4.3. Subject Discontinuation from Investigational Product .................................................. 37 
4.4. Replacement ................................................................................................................... 39 
5. TREATMENT AND INVESTIGATIONAL PRODUCT .................................................... 39 
5.1. Treatment of the Subjects ............................................................................................... 39 
5.1.1. Dosing and Treatment Schedule ......................................................................... 39 
5.1.2. Withholding Investigational Products ................................................................. 40 
5.2. Investigational Product ................................................................................................... 40 
5.2.1. Identity of Investigational Product ...................................................................... 40 
5.2.2. Assignment of Subject Number .......................................................................... 41 
5.2.3. Masking ............................................................................................................... 41 
5.2.4. Unmasking .......................................................................................................... 42 
5.2.5. Investigational Product Treatment Compliance and Accountability ................... 42 
5.2.6. Investigational Product Administration .............................................................. 43 
5.3. Prohibited Medication or Therapy ................................................................................. 43 
5.4. Fellow Eye Treatment .................................................................................................... 44 
6. STUDY VARIABLES .......................................................................................................... 45 
6.1. Study Endpoints ............................................................................................................. 45 
6.1.1. Primary Endpoint ................................................................................................ 45 
6.1.2. Secondary Endpoints ........................................................................................... 45 
6.1.3. Exploratory Endpoint .......................................................................................... 46 
6.2. Efficacy Assessments ..................................................................................................... 46 


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6.2.1. Best Corrected Visual Acuity .............................................................................. 46 
6.2.2. Anatomical Parameters ....................................................................................... 47 
6.3. Safety Assessments ........................................................................................................ 47 
6.3.1. Adverse Events .................................................................................................... 47 
6.3.2. Clinical Laboratory Test ..................................................................................... 47 
6.3.3. Pregnancy Test .................................................................................................... 48 
6.3.4. Physical Examination .......................................................................................... 49 
6.3.5. Vital Signs ........................................................................................................... 49 
6.4. Ophthalmic Assessments ............................................................................................... 49 
6.4.1. Full Ophthalmic Examinations............................................................................ 49 
6.4.2. Optical Coherence Tomography (OCT) .............................................................. 50 
6.4.3. Fundus Photography (FP) and Fluorescein Angiography (FA) .......................... 51 
6.5. Pharmacokinetic Assessment ......................................................................................... 51 
6.6. Immunogenicity Assessment ......................................................................................... 52 
6.7. NEI VFQ-25 ................................................................................................................... 52 
7. STUDY PROCEDURES ...................................................................................................... 53 
7.1. Visit 1 (Screening, D-21 to D-1) .................................................................................... 53 
7.2. Visit 2 (Week 0/Day 1) .................................................................................................. 55 
7.3. Visit 3 (Week 1 ± 3 days) .............................................................................................. 56 
7.4. Visit 4 (Week 4 ± 7 days) .............................................................................................. 57 
7.5. Visit 5 (Week 8 ± 7 days) .............................................................................................. 58 
7.6. Visit 6 (Week 12 ± 7 days) ............................................................................................ 59 
7.7. Visit 7 (Week 16 ± 7 days) ............................................................................................ 60 
7.8. Visit 8 (Week 20 ± 7 days) ............................................................................................ 61 
7.9. Visit 9 (Week 24 ± 7 days) ............................................................................................ 62 
7.10. Visit 10 (Week 28 ± 7 days)......................................................................................... 63 
7.11. Visit 11 (Week 32 ± 7 days)......................................................................................... 64 
7.12. Visit 12 (Week 36 ± 7 days)......................................................................................... 65 
7.13. Visit 13 (Week 40 ± 7 days)......................................................................................... 66 
7.14. Visit 14 (Week 44 ± 7 days)......................................................................................... 67 
7.15. End of Treatment Visit (Visit 15, Week 48 ± 7 days) .................................................. 68 
7.16. End of Study (Visit 16, Week 52 ± 7 days) or Early Termination Visit ...................... 69 
7.17. Early Termination of the Study .................................................................................... 70 
8. SAFETY MONITORING AND REPORTING .................................................................... 70 
8.1. Adverse Events............................................................................................................... 70 
8.1.1. Definition of Adverse Event ............................................................................... 70 
8.1.2. Period of Observation for Adverse Events .......................................................... 70 
8.1.3. Reporting Adverse Events ................................................................................... 71 
8.1.4. Severity Assessment ............................................................................................ 71 
8.1.5. Causality Assessment .......................................................................................... 72 
8.1.6. Emergency Unmasking for Safety Reasons ........................................................ 72 
8.1.7. Expectedness Assessment ................................................................................... 72 
8.1.8. Withdrawal due to Adverse Events ..................................................................... 73 
8.2. Serious Adverse Events.................................................................................................. 73 
8.2.1. Definition of Serious Adverse Event .................................................................. 73 
8.2.2. Reporting Serious Adverse Events ...................................................................... 75 
8.3. Adverse Events of Special Interest................................................................................. 76 
8.4. Pregnancy ....................................................................................................................... 76 


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8.5. Independent Data and Safety Monitoring Board ............................................................ 76 
9. STATISTICAL METHODS AND DATA ANALYSIS ....................................................... 77 
9.1. Analysis Sets .................................................................................................................. 77 
9.2. Statistical Methods and Analytical Plan......................................................................... 78 
9.2.1. Demographics and Baseline Characteristics ....................................................... 78 
9.2.2. Efficacy ............................................................................................................... 79 
9.2.3. Safety................................................................................................................... 79 
9.2.4. Pharmacokinetics ................................................................................................ 80 
9.2.5. Immunogenicity .................................................................................................. 80 
9.2.6. NEI VFQ-25 ........................................................................................................ 80 
9.3. Determination of Sample Size ....................................................................................... 81 
10. DATA COLLECTION AND MANAGEMENT ................................................................ 82 
10.1. Data Confidentiality ..................................................................................................... 82 
10.2. Monitoring ................................................................................................................... 82 
10.3. Data Handling and Record Keeping ............................................................................. 83 
10.4. Database Management and Coding .............................................................................. 83 
10.5. Quality Control and Quality Assurance ....................................................................... 84 
11. ETHICAL CONSIDERATIONS AND ADMINISTRATIVE PROCEDURES ................ 84 
11.1. Institutional Review Boards and Independent Ethics Committees .............................. 84 
11.2. Ethical Conduct of the Study ....................................................................................... 85 
11.3. Written Informed Consent ............................................................................................ 85 
11.4. Investigator Information ............................................................................................... 85 
11.4.1. Investigator Obligations .................................................................................... 85 
11.4.2. Coordinating Investigator .................................................................................. 86 
11.4.3. Training of Investigational Site Personnel ........................................................ 86 
11.4.4. Protocol Signatures ........................................................................................... 86 
11.5. Financing and Insurance .............................................................................................. 86 
12. PUBLICATION POLICY ................................................................................................... 87 
13. REFERENCES .................................................................................................................... 88 
APPENDIX A: Grading Scale for Anterior Chamber Flare ..................................................... 90 
APPENDIX B: Grading Scale for Anterior Chamber Cells...................................................... 91 
APPENDIX C: Grading Scale for Anterior Chamber and Vitreal Inflammatory Response ..... 92 
APPENDIX D: National Eye Institute 25-Item Visual Function Questionnaire (NEI VFQ-25 
questionnaire) .................................................................................................................... 93 
PROTOCOL SIGNATURE PAGES ...................................................................................... 104 
AMENDMENT 1: Sep 01, 2017 ............................................................................................. 107 
 


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LIST OF TABLES 
Table 1. Schedule of Activities ...................................................................................................... 13 
Table 2. Blood Sampling Schedule for PK, Immunogenicity and Clinical Laboratory Test ......... 17 
Table 3. Visual Acuity Outcomes at Month 12 and Month 24 in Studies ..................................... 28 
Table 4. Visual Acuity Outcomes at Month 6 in Studies ............................................................... 29 
Table 5. Visual Acuity Outcomes at Month 24 in Studies ............................................................. 29 
Table 6. ≥3-step and ≥2-step Improvement at Month 24 in Study D-1 and Study D-2 ................. 29 
Table 7. Investigational Products ................................................................................................... 41 
Table 8. Prohibited Medication and Therapy ................................................................................. 43 
Table 9. Parameters for Clinical Laboratory Tests ........................................................................ 48 
 
LIST OF FIGURES 
Figure 1. Graphical Study Design .................................................................................................. 12 
 


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LIST OF STUDY STAFF 
SPONSOR: 
Samsung Bioepis Co., Ltd. 
107, Cheomdan-daero, Yeonsu-gu, 
Incheon, 21987 
Republic of Korea 
Tel: +82 (32) 455 3114 
Fax: +82 (32) 455 6799  
 
Clinical Project 
Manager  
 
 
  
 
Clinical Research 
Physician  
 
 
  
 
Clinical Research 
Scientist 
 
 
 
Clinical Development 
Associate 
 
 
 
Statistician  
 
 
  
 
Project Safety Lead 
 
 
 
 
Safety Physician 
 
 
 
 


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1. INTRODUCTION 
1.1. Background 
Age-related Macular Degeneration (AMD), left untreated, is a leading cause of adult blindness 
in the developed world. Most of severe visual loss of AMD occurs from Choroidal 
Neovascularisation (CNV) or the neovascular form of AMD. Choroidal neovascularisation 
can be associated with fibrous replacement of the retinal photoreceptors and Retinal Pigment 
Epithelium (RPE), as well as atrophy of these portions of the retina in the macula, leading to 
severe visual decline with loss of reading vision, driving vision, and the ability to recognise 
faces. Vascular Endothelial Growth Factor (VEGF), a protein growth factor that both 
stimulates angiogenesis and increases vascular permeability, is a major pathogenic factor in 
CNV due to AMD. Counteracting these effects of VEGF can provide significant therapeutic 
benefit to subjects suffering from this disorder. 
In developed countries, AMD is a leading cause of severe visual loss in people 65 years of age 
and older in the US, an estimated 6% of individuals aged 65 to 74, and 20% of those older 
than 75 are affected with some stage of AMD. Also, among white people aged 40 years and 
older, AMD is the number one cause of visual impairment and blindness in the US. The 
pathogenesis of AMD is poorly understood. It is characterised by development of focal 
deposits of long –spacing collagen and phospholipid vesicles within and beneath the basement 
membrane of the RPE, called “drusen” which can be accompanied by gradual degeneration of 
photoreceptors and RPE (atrophy), which often results in slow deterioration of central Visual 
Acuity (VA). This thickening and degeneration of Bruch’s membrane can predispose to 
abnormal growth of blood vessels from the choriocapillaris, termed choroidal 
neovascularization. The occurrence of CNV heralds the onset of neovascular AMD. Leakage 
from the CNV can cause macular oedema with collection of fluid and blood beneath and 
within the macula, resulting in loss of vision. Growth of the lesions with accompanying 
fibrovascular or fibroglial tissue further destroys retinal tissue. Overtime, the CNV promotes 
scarring that damages photoreceptors and the RPE, resulting in permanent vision loss. 
Neovascular or “wet” AMD accounts for only 10% of cases of AMD yet results in 90% of the 
severe vision loss. Epidemiological studies suggest that “wet” AMD will develop in almost 1 
million persons in the US within the next 5 years [Wu EW et al., 2014, Macular 
Photocoagulation Study Group. 1991]. 
1.2. Lucentis®: Ranibizumab Reference Product 
Lucentis® is approved for indications including neovascular (wet) AMD, visual impairment 
due to Diabetic Macular Oedema (DME) and visual impairment due to macular oedema 
secondary to Retinal Vein Occlusion (branch RVO or central RVO) by both the US FDA and 
EMA. In addition, the FDA approved Lucentis® for the treatment of Diabetic Retinopathy 
(DR) in subjects with DME and the EMA approved Lucentis® for the treatment of visual 


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impairment due to CNV secondary to Pathologic Myopia (PM) [Lucentis® Prescribing 
Information. 2016, Lucentis® Summary of Product Characteristics. 2016] 
Mechanism of Action 
Ranibizumab binds to the receptor binding site of active forms of VEGF-A, including the 
biologically active, cleaved form of this molecule, VEGF110. VEGF-A has been shown to 
cause neovascularisation and leakage in models of ocular angiogenesis and vascular occlusion 
and is thought to contribute to pathophysiology of neovascular AMD, macular oedema 
following RVO, DR and DME. The binding of ranibizumab to VEGF-A prevents the 
interaction of VEGF-A with its receptors (VEGFR1 and VEGFR2) on the surface of 
endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood 
vessel formation [Lucentis® Summary of Product Characteristics. 2016]. 
Pharmacodynamics 
Increased retinal thickness (i.e., Centre Point Thickness [CPT] or Central Foveal Thickness 
[CFT]), as assessed by OCT is associated with the activity of neovascular AMD, macular 
oedema following RVO, and DME. Leakage from CNV as assessed by FA is also associated 
with the activity of neovascular AMD. Microvascular retinal changes and 
neovascularisation, as assessed by colour FP, are associated with diabetic retinopathy 
[Lucentis® Prescribing Information. 2016].  
Pharmacokinetics 
Following monthly ITV administration of Lucentis® to patients with neovascular AMD, serum 
concentrations of ranibizumab were generally low, with maximum levels (Cmax) generally 
below the ranibizumab concentration necessary to inhibit the biological activity of VEGF by 
50% (11-27 ng/ml, as assessed in an in vitro cellular proliferation assay). Cmax was dose 
proportional over the dose range of 0.05 to 1.0 mg/eye. Serum concentrations in a limited 
number of DME patients indicate that a slightly higher systemic exposure cannot be excluded 
compared to those observed in neovascular AMD patients. Serum ranibizumab concentrations 
in RVO patients were similar or slightly higher compared to those observed in neovascular 
AMD patients. 
Based on analysis of population pharmacokinetics and disappearance of ranibizumab from 
serum for patients with neovascular AMD treated with the 0.5 mg dose, the average vitreous 
elimination half-life of ranibizumab is approximately 9 days. Upon monthly ITV 
administration of Lucentis® 0.5 mg/eye, serum ranibizumab Cmax, attained approximately 1 
day after dosing, is predicted to generally range between 0.79 and 2.90 ng/ml. Serum 
ranibizumab concentrations are predicted to be approximately 90,000-fold lower than vitreal 
ranibizumab concentrations [Lucentis® Summary of Product Characteristics. 2016]. 
 


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Efficacy 
Neovascular (Wet) Age-Related Macular Degeneration 
The safety and efficacy of Lucentis® were assessed in three randomised, double or single-
masked, sham-or active-controlled studies in subjects with neovascular AMD.  
Table 3. Visual Acuity Outcomes at Month 12 and Month 24 in Studies 
Study: MARINA 
Outcome 
Month 
Sham 
(n = 229) 
Lucentis® 0.5 mg 
(n = 230) 
Loss of <15 letters in VA 
12 
60% 
91% 
24 
56% 
89% 
Gain of ≥15 letters in VA 
12 
6% 
31% 
24 
4% 
30% 
Mean change in VA (letters) 
12 
−11.0 (17.9) 
+6.3 (14.1) 
24 
−15.0  (19.7) 
+5.5 (15.9) 
Study: ANCHOR 
Outcome 
Month 
Verteporfin PDT 
(n = 141) 
Lucentis® 0.5 mg 
(n = 139) 
Loss of <15 letters in VA 
12 
66% 
98% 
24 
65% 
93% 
Gain of ≥15 letters in VA 
12 
11% 
37% 
24 
9% 
37% 
Mean change in VA (letters) 
12 
−8.5 (17.8) 
+11.0 (15.8) 
24 
−9.1 (18.7) 
+10.9 (17.3) 
Study: FOCUS 
Outcome 
Month 
Verteporfin PDT 
(n = 56) 
Lucentis® 0.5 mg+ 
Verteporfin PDT 
(n = 105) 
Loss of <15 letters in VA 
12 
68% 
91% 
24 
75% 
88% 
Gain of ≥15 letters in VA 
12 
5% 
24% 
24 
7% 
25% 
Mean change in VA (letters) 
12 
−8.2 (16.3) 
+4.9 (14.7) 
24 
−7.8 (18.0) 
+4.6 (16.7) 
Study: PIER 
Outcome 
Month 
Sham 
(n = 63) 
Lucentis® 0.5 mg 
(Quarterly dosing) 
(n = 61) 
Loss of <15 letters in VA 
12 
49% 
90% 
Mean change in VA (letters) 
12 
−16.3 
−0.2 
PDT, Photodynamic Therapy 
Source: Lucentis® Prescribing Information. U. S. Food and Drug Administration. Nov 2016.  
Am J Ophthalmol. 2006;124:1532-1542. 
Am J Ophthalmol. 2008;145:862-874. 
 


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Macular Oedema Following Retinal Vein Occlusion 
The safety and efficacy of Lucentis® were assessed in two randomised, double-masked, 1-year 
studies in subjects with macular oedema following RVO.  
Table 4. Visual Acuity Outcomes at Month 6 in Studies 
Study: BRAVO 
Outcome 
Month 
Sham 
(n = 131) 
Lucentis® 0.5 mg 
(n = 132) 
Gain of ≥15 letters in VA 
6 
29% 
61% 
Mean change in VA (letters) 
6 
+7.3 
+18.3 
Study: CRUISE 
Outcome 
Month 
Sham 
(n = 130) 
Lucentis® 0.5 mg 
(n = 130) 
Gain of ≥15 letters in VA 
6 
17% 
48% 
Mean change in VA (letters) 
6 
+0.8 
+14.9 
Source: Lucentis® Prescribing Information. U. S. Food and Drug Administration. Nov 2016. 
 
Diabetic Macular Oedema 
The safety and efficacy of Lucentis® were assessed in two randomised, double-masked, 3-
year studies. All enrolled subjects had DR and DME at baseline 
Table 5. Visual Acuity Outcomes at Month 24 in Studies 
Study: RIDE 
Outcome 
Month 
Sham 
(n = 130) 
Lucentis® 0.3 mg 
(n = 125) 
Loss of <15 letters in VA 
24 
92% 
98% 
Gain of ≥15 letters in VA 
24 
12% 
34% 
Mean change in VA (letters) 
24 
+2.3 
+10.9 
Study: RISE 
Outcome 
Month 
Sham 
(n = 127) 
Lucentis® 0.3 mg 
(n = 125) 
Loss of <15 letters in VA 
24 
90% 
98% 
Gain of ≥15 letters in VA 
24 
18% 
45% 
Mean change in VA (letters) 
24 
+2.6 
+12.5 
Source: Lucentis® Prescribing Information. U. S. Food and Drug Administration. Nov 2016. 
 
Diabetic Retinopathy in subjects with Diabetic Macular Oedema 
Efficacy and safety data of Lucentis® are derived from studies RIDE and RISE. 
Table 6. ≥3-step and ≥2-step Improvement at Month 24 in Study D-1 and Study D-2 
Study: RIDE 
Outcome 
Month 
Sham 
(n = 130) 
Lucentis® 0.3 mg 
(n = 125) 
≥3-step improvement from 
baseline in ETDRS-DRSS 
24 
2% 
17% 


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Study: RIDE 
Outcome 
Month 
Sham 
(n = 130) 
Lucentis® 0.3 mg 
(n = 125) 
≥2-step improvement from 
baseline in ETDRS-DRSS 
24 
4% 
39% 
Study: RISE 
Outcome 
Month 
Sham 
(n = 127) 
Lucentis® 0.3 mg 
(n = 125) 
≥3-step improvement from 
baseline in ETDRS-DRSS 
24 
0% 
9% 
≥2-step improvement from 
baseline in ETDRS-DRSS 
24 
7% 
37% 
ETDRS-DRSS, Early Treatment Diabetic Retinopathy Study -Diabetic Retinopathy Severity Scale 
Source: Lucentis® Prescribing Information. U. S. Food and Drug Administration. Nov 2016. 
1.3. SB11: Proposed Ranibizumab Biosimilar 
Samsung Bioepis Co., Ltd. (Incheon, Republic of Korea) has developed SB11, a proposed 
biosimilar of the ranibizumab reference product. SB11 is produced by recombinant DNA 
technology in Escherichia coli cells. Extensive characterisation studies including intact mass, 
N- and C-terminal sequencing, peptide mapping, icIEF, CE-SDS (reduced, non-reduced), SE-
HPLC, amino acid composition, disulfide bond, VEGF binding, VEGF neutralisation, and 
Human Umbilical Vein Endothelial Cells (HUVEC) anti-proliferation were performed using 
state-of-the-art techniques. Assays such as CEX-HPLC, UV absorption spectra, free thiol 
group quantification, SEC-MALS, SV-AUC, CD, DSC and FT-IR were performed for both 
non-clinical and clinical materials. 
After extensive quality similarity studies, a series of in vitro non-clinical studies including 
VEGF binding assay and cell-based assays (HUVEC anti-proliferation assay and VEGF 
neutralizing assay) were performed to demonstrate similarity in in vivo behaviour between 
SB11 and Lucentis®.  
1.4. Rationale for the Study 
A biosimilar is a biological medicinal product that is highly similar to an already authorised 
original biological medicinal product (reference medicinal product) in terms of quality, 
tolerability, and efficacy based on a comprehensive comparability exercise 
[EMA/CHMP/BMWP/403543/2010, EMEA/CHMP/437/04, U. S. Food and Drug 
Administration. 2015]. The EMA and the US FDA have developed specific guidelines for a 
biologic drug to be approved as a biosimilar [EMA/CHMP/BMWP/403543/2010, U. S. Food 
and Drug Administration. 2015, EMA/CHMP/BWP/247713/2012]. These guidelines 
recommend a stepwise approach in developing a biosimilar starting with extensive 
physicochemical and biological characterisation before initiating clinical studies for the 
comparison of the efficacy, tolerability, pharmacokinetic properties, and immunogenicity of 
the biosimilar. The purpose of this study is to demonstrate the equivalence of efficacy of SB11 


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to Lucentis® and to evaluate the safety and immunogenicity in subjects with neovascular 
AMD. In addition, systemic exposure of SB11 to Lucentis® will also be evaluated in subjects 
participating in PK evaluation. 
2. STUDY OBJECTIVES 
2.1. Primary Objective 
• 
To demonstrate the equivalence of efficacy of SB11 to Lucentis® in subjects with 
neovascular AMD 
2.2. Secondary Objective 
• 
To evaluate the safety of SB11 and Lucentis® 
• 
To evaluate the immunogenicity of SB11 and Lucentis® 
•       To evaluate the systemic exposure of SB11 and Lucentis® in subjects participating in 
PK evaluation 
3. STUDY DESIGN 
3.1. Overview of Study Design 
This is a randomised, double-masked, parallel group, multicentre study to evaluate the 
efficacy, safety, pharmacokinetics and immunogenicity of SB11 compared to Lucentis® in 
subjects with neovascular AMD. Subjects will be randomised in a 1:1 ratio to receive either 
SB11 or Lucentis® 0.5 mg via ITV into the study eye every 4 weeks.  
The screening period is 21 days. IP (SB11 or Lucentis®) will be given until 48 weeks and the 
last assessment will be done at Week 52. 
3.2. Rationale for the Study Design 
The purpose of this study is to demonstrate the equivalence of clinical efficacy of Lucentis® 
and SB11 in subjects with neovascular AMD.  
Although a Phase I comparative PK study comparing the proposed biosimilar product to 
reference product is a fundamental component in supporting a demonstration of biosimilarity 
[U. S. Food and Drug Administration. 2015], a Phase I comparative PK study has not been 
necessary to support a demonstration of biosimilarity due to negligible systemic exposure 
following ITV injection of ranibizumab. However, for supporting the assessment of overall 
systemic safety of SB11 relative to Lucentis®, systemic exposures will be collected and 
compared in the subgroup population (approximately 40 subjects, 20 subjects per treatment 
group) in Phase III comparative efficacy study.  


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Lucentis® is approved for indications including neovascular AMD, visual impairment due to 
DME and visual impairment due to macular oedema secondary to RVO by both the US FDA 
and EMA. In addition, the US FDA approved Lucentis® for the treatment of DR in subjects 
with DME and the EMA approved Lucentis® for the treatment of visual impairment due to 
CNV secondary to PM, respectively.  
Improvements of VA have been reported in the pivotal studies of the various indications. For 
example, at Month 12, the average benefit associated with Lucentis® over that of sham 
injection or PDT was approximately 13.1 to 20.8 letters, 5.9 or 11.7 letters and 6.2 or 6.6 
letters in subjects with AMD, DME and RVO, respectively. The overall difference in Best 
Corrected Visual Acuity (BCVA) between Lucentis® treated and control group was the largest 
in subjects with AMD, which indicates that neovascular AMD is the most sensitive indication 
compared to DME or RVO to show a difference between the treatments [Lee H, 2014]. In 
addition, neovascular AMD has homogeneous disease progress with fewer compounding 
factors than DME or RVO. For instance, it results in severe visual impairment with an average 
loss of around 4 lines of VA within 2 years of disease onset [Chakravarthy U et al. 2010]. 
Although this neovascular form accounts for only approximately 10% to 20% of the AMD 
cases, it is responsible for 80% to 90% of AMD-associated vision loss [Ferris FL 3rd et al. 
1984]. Therefore, Subjects with neovascular AMD are the most appropriate target population 
to evaluate the product-related difference between Lucentis® and SB11 in this study. 
This study has two different endpoints, depending on regulatory agency’s requirements for 
assessing equivalence in efficacy between SB11 and Lucentis®. 
For US FDA, Korea Ministry of Food and Drug Safety (MFDS) or other regulatory agency 
submissions for those who are in favour of the VA, the primary endpoint is the mean change 
from baseline in BCVA at Week 8. In the pivotal studies for Lucentis®, the proportion of 
subjects losing < 15 letters was used as primary endpoint to compare the efficacy between 
Lucentis® treatment group and control group. The endpoint indicates the preventive effect of 
the loss of VA, but it includes variability in individual disease progression as well as drug-
induced effect. For example, approximately 90% of the subjects who received Lucentis® lost 
VA less than 15 letters but 60% of the subjects who received sham injection (or 
PDT/verteporfin) also lost VA less than 15 letters. Thus, the proportion of subjects losing < 15 
letters could not be a sensitive primary endpoint to detect product-related effect between a 
proposed biosimilar product and reference product. On the other hand, change from baseline 
in VA, gain of letters, can reflect any change (improvement or deterioration) in the disease 
status, thus is more sensitive in detecting a difference between the two treatments. To increase 
sensitivity, evaluation of equivalence will be conducted at Week 8 before the efficacy plateau 
is reached, as requested by US FDA.  
For EMA or other regulatory agency submission for those who are in favour of the anatomical 
parameter, the primary objective is to demonstrate the equivalence of SB11 to Lucentis®, in 
terms of the mean change from baseline in CST at Week 4. The evaluation of CST is 
important as it addresses the pharmacodynamics aspects of ranibizumab. Ranibizumab binds 


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with high affinity to all active VEGF-A isoforms (e.g., VEGF110, VEGF121 and VEGF165) 
on the surface of endothelial cells, thereby preventing binding of VEGF-A to its receptors and 
reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation 
which result in reduction of CST [Lucentis® Prescribing Information 2016, Lucentis® 
Summary of Product Characteristics. 2016]. It indicates that the reduction of CST represents a 
direct effect of ranibizumab based on the Mechanism of Action (MoA). Furthermore, it has 
been reported that CST measurements and clinical outcome has a correlation. In OCT-guided, 
variable-dosing study conducted in neovascular AMD subjects, a statistically significant 
correlation between the decrease in CST at one month and the subsequent improvement in VA  
seen at two months and three months [Fung A et al. 2007]. Similarly in PrONTO study, the 
results indicated that the initial OCT response is predictor of future VA improvements 
although the strength of the correlation is affected by the fluctuations in macular fluid and the 
fact that OCT changes are detected before VA is affected. In addition, visual recovery after 
resolution of macular fluid in neovascular AMD likely depends on many variables including 
chronicity of disease, viability of photoreceptors and the RPE, progression of the underlying 
dry AMD (geographic atrophy), as well as the presence of epiretinal membranes, RPE tears, 
and fibrosis. Despite all these variables, the initial response to ranibizumab characterised by 
resolution of fluid in the macula as assessed by OCT seems to correlate with future VA 
improvement and may serve as a useful predictor of treatment efficacy [Lalwani G et al. 2009].   
The study design was consulted and agreed with both EMA and FDA prior to start of this 
study. 
4. STUDY POPULATION 
Eligibility for participation in this study will be based on the inclusion/exclusion criteria. Only 
one eye will be designated as the study eye. For subjects who meet eligibility criteria in both 
eyes, the eye with the worse VA will be selected as the study eye. If both eyes have equal VA, 
the eye with better visual prognosis (e.g., clearer lens and ocular media and less amount of 
subfoveal scar or geographic atrophy) will be selected at the Investigator’s discretion. If there 
is no objective basis for selecting the study eye, factor such as ocular dominance, other ocular 
pathology and subject preference should be considered by the Investigator in making the 
selection. 
4.1. Inclusion Criteria 
Subjects must meet all of the following criteria to be eligible for the study: 
1. Age ≥ 50 years at Screening 
2. Newly diagnosed, *active subfoveal Choroidal Neovascularisation (CNV) lesion 
secondary to AMD in the study eye 


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* Active CNV indicates presence of leakage and intra- or sub-retinal fluid which 
should be confirmed by central reading centre during Screening 
3. The area of CNV must occupy at least 50% of total lesion in the study eye (confirmed 
by central reading centre during Screening) 
4. Total lesion area ≤ 9.0 Disc Areas (DA) in size (including blood, scars and 
neovascularisation) in the study eye (confirmed by central reading centre during 
Screening) 
5. Best Corrected Visual Acuity (BCVA) of 20/40 to 20/200 (letter score of 73 to 34) 
using original series Early Treatment Diabetic Retinopathy Study (ETDRS) charts or 
2702 series Number charts in the study eye at Screening and at Week 0 (Day 1) prior 
to randomisation 
6. Non-childbearing potential female (e.g., permanently sterilised, postmenopausal 
[defined as 12 months with no menses without an alternative medical cause prior to 
Screening]), OR Childbearing potential female subjects or male subjects with their 
(respectively male or female) partners who agree to use at least two forms of 
appropriate contraception method that can achieve a failure rate of less than 1% per 
year (e.g., established use of oral, injected, intravaginal, transdermal or implanted 
hormonal contraceptive, placement of an intrauterine device or intrauterine hormone-
releasing system, bilateral tubal occlusion, vasectomised partner, physical barrier, 
sexual abstinence) from Screening until 3 months after the last ITV injection of IP 
7. Written informed consent form must be obtained from the subject prior to any study 
related procedure (If the subject is legal blindness or illiterate, an impartial witness 
should be present during the entire informed consent discussion) 
8. Willingness and ability to undertake all scheduled visits and assessments 
4.2. Exclusion Criteria 
Subjects meeting any of the following criteria are not eligible for the study: 
1. Sub- or intra-retinal haemorrhage that comprises more than 50% of the entire lesion in 
the study eye, or presence of subfoveal blood equal to or more than one DA in size 
(confirmed by central reading centre during Screening) 
2. Scar, fibrosis or atrophy involving the centre of the fovea in the study eye (confirmed 
by central reading centre during Screening) 
3. Presence of CNV in either eye due to other causes, such as ocular histoplasmosis, 
trauma, multifocal choroiditis, angioid streaks, history of choroidal rupture or 
Pathologic Myopia (PM) (confirmed by central reading centre during Screening) 


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4. Presence of retinal pigment epithelial tears or rips involving the macula in the study 
eye (confirmed by central reading centre during Screening) 
5. Presence of macular hole at any stage in the study eye (confirmed by central reading 
centre during Screening) 
6. Any concurrent macular abnormality other than AMD in the study eye which could 
affect the efficacy of IP including but not limited to epiretinal membrane, macular 
telangiectasia, retinal vascular abnormality, etc. (confirmed by central reading centre 
during Screening) 
7. History of vitrectomy surgery in the study eye 
8. History of trabeculectomy or other filtration surgery in the study eye 
9. History of submacular surgery or other surgical intervention for AMD in the study 
eye 
10. Any other intraocular surgery (including cataract surgery) or periocular surgery in the 
study eye within 90 days prior to randomisation, except for lid surgery, which may 
not have taken place within 30 days prior to randomisation 
11. Any previous ITV anti-Vascular Endothelial Growth Factor (anti-VEGF) treatment 
(e.g., bevacizumab, aflibercept, ranibizumab) to treat neovascular AMD in either eye 
12. Any previous systemic anti-VEGF treatment, within 90 days prior to randomisation, 
and such treatment will not be allowed during the study period 
13. Any systemic treatment or therapy (including prescribed herbal medication) to treat 
neovascular AMD within 30 days prior to randomisation, and such treatment or 
therapy will not be allowed during the study period. However, dietary supplements, 
vitamins or mineral will be allowed 
14. Any intravitreal injection of corticosteroid (e.g., triamcinolone acetonide) or 
intravitreal corticosteroid implant in the study eye within 180 days prior to 
randomisation, and such treatment will not be allowed during the study period 
15. Topical ocular corticosteroids administered for ≥ 30 consecutive days in the study eye 
within 90 days prior to randomisation 
16. Spherical equivalent of the refractive error in the study eye demonstrating more than 8 
diopters of myopia. For subjects who have undergone previous refractive or cataract 
surgery in the study eye, the preoperative refractive error in the study eye must not 
exceed 8 diopters of myopia 


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17. Aphakia or absence of the posterior capsule in the study eye (unless it occurred as a 
result of a Yttrium Aluminium Garnet [YAG] posterior capsulotomy in association 
with prior posterior chamber Intraocular Lens [IOL] implantation) 
18. Presence of scleromalacia in either eye 
19. Current vitreous haemorrhage in the study eye 
20. Active or recent (within 28 days prior to randomisation) intraocular, extraocular and 
periocular inflammation or infection in either eye 
21. History of idiopathic or autoimmune uveitis in either eye 
22. History of retinal detachment in the study eye 
23. History of full-thickness macular hole in the study eye 
24. History of corneal transplantation surgery in the study eye 
25. Presence of advanced glaucoma or optic neuropathy that affect or threaten the central 
visual field in the study eye 
26. Uncontrolled ocular hypertension (defined as Intraocular Pressure [IOP] ≥ 25 mmHg 
despite treatment with anti-glaucoma medication) in the study eye 
27. History of allergy to the fluorescein sodium for injection in angiography 
28. Previous participation in clinical studies of ocular investigational products to treat 
neovascular AMD in either eye or systemic investigational products to treat 
neovascular AMD, and such participation will not be allowed during the study period 
29. Previous participation in any studies of ocular or systemic investigational products 
(excluding dietary supplements, vitamins and minerals) to treat ocular or systemic 
disease other than neovascular AMD within 90 days prior to randomisation, and such 
participation will not be allowed during the study period even if the investigational 
product is dietary supplements, vitamins or minerals 
30. History or clinical evidence of diabetic retinopathy (except for mild non-proliferative 
diabetic retinopathy) or diabetic macular oedema in either eye 
31. Any concurrent ocular condition in the study eye which, in the opinion of the 
Investigator, could either increase the risk to the subject safety or which otherwise 
may interfere with evaluation of efficacy or safety including, but not limited to 
ocular media opacities such as corneal opacity or cataract that do not allow proper 


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fundus visualisation and fundus imaging, and ocular surface abnormalities which 
prevent applanation tonometry during the study period after randomisation 
32. History of other disease, metabolic dysfunction, physical examination finding, or 
clinical laboratory finding that contraindicates the use of an IP in the opinion of the 
Investigator 
33. Pregnant or lactating women. A serum pregnancy test must be required for women of 
childbearing potential at Screening 
34. Employees of Investigational sites, individuals directly involved with the conduct of 
the study or immediate family members thereof, prisoners, and persons who are 
legally institutionalised  
35. Stroke, transient ischemic attacks, or myocardial infarction within 90 days prior to 
randomisation 
36. History of recurrent significant infections and/or current treatment for active systemic 
infection 
37. Known allergic reactions and/or hypersensitivity to ranibizumab or to any ingredients 
of the investigational product 
38. Prior treatment involving macula with photodynamic therapy with verteporfin, 
transpupillary thermotherapy, radiation therapy, or retinal laser treatment (e,g., focal 
laser photocoagulation) in the study eye, and such treatment will not be allowed 
during the study period 
39. Prior treatment with pan-retinal photocoagulation in the study eye, and such treatment 
will not be allowed during the study period 
40. Current use of systemic medications known to be toxic to the lens, retina or optic 
nerve, including deferoxamine, chloroquine/hydroxychloroquine, tamoxifen, 
phenothiazines, vigabatrin and ethambutol, and such medications will not be allowed 
during the study period 
4.3. Subject Discontinuation from Investigational Product 
The subject must be discontinued from IPs in the event of any of the following: 
• 
Consent withdrawal by subject 
- 
If subjects withdraw his/her consent, Investigator must inquire the reasons for 
consent withdrawal as to whether it is related to the study (e.g., documented lack 


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of efficacy, AE or pregnancy); however, the subject could refuse to provide such 
reason 
- 
If the main reason for consent withdrawal is considered related to the study, the 
Investigator may select appropriate reason among the reasons listed below other 
than consent withdrawal 
• Rhegmatogenous retinal detachment or full-thickness macular hole in the study eye 
• 
Any newly developed or aggravated ophthalmic abnormality other than AMD in the 
study eye which could interfere with evaluation of efficacy or safety of IP including 
but not limited to retinal vascular abnormality 
• Any AEs in the study eye (e.g., intraocular inflammation, VA loss, increased IOP, 
subretinal haemorrhage, vitreous haemorrhage, local or systemic infection etc.) 
which in the opinion of the Investigator and/or subject would require IP 
discontinuation 
• Intraocular surgery in the study eye (e.g., cataract operation, vitrectomy, glaucoma 
surgery, etc.) which in the opinion of the Investigator would require IP 
discontinuation 
• Protocol deviations which may adversely affect the subject’s safety and/or integrity of 
data as agreed by the Investigator and/or upon request from the Sponsor 
• IP non-compliance 
- 
A subject  misses any of first two doses (ITV injection of IP at Week 0 (Day 1) 
and Week 4) after randomisation 
- 
A subject misses two consecutive doses during the study period after 
randomisation 
• 
Decision by the Investigator that the subject requires alternate treatment (e.g., other 
anti-VEGF agents such as bevacizumab or aflibercept, PDT, PPV etc.) to treat 
neovascular AMD in the study eye 
• 
Decision by the Sponsor that IP discontinuation is in the subject’s best medical 
interest or administrative decision for a reason (e.g., a suspicion of fraud, the subject 
enrolling in multiple clinical studies, lack of compliance, etc.) other than that of an AE 
• 
Lost to follow-up 
• 
Unmasking (except unmasking for the purpose of regulatory reporting) 


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• 
Pregnancy 
• 
Death of any cause 
Any significant change in the posterior pole (e.g., subretinal haemorrhage, macular hole, 
vitreous haemorrhage or opacity, retinal detachment, etc.) that is detected with fundus 
examination should be confirmed and documented with FP and/or FA. Investigator should 
decide IP discontinuation based on the FP and/or FA. The images taken at unscheduled visits 
will not be sent to the central reading centre. 
If a subject is prematurely discontinued from IP due to any of the above described reasons 
excluding death, the subject will complete the ET procedures (except for PK sampling) after 4 
weeks from the last ITV injection of IP and will be asked to provide continued follow-up and 
further data collection subsequent to his or her ET visit. 
If a subject agrees to continue follow-up for associated clinical outcome information until 
Week 52 irrespective of IP injection status (as long as an additional ICF e.g., withdrawal form 
is signed by the subject for this limited participation in the study), the subject’s clinical 
outcome information such as BCVA, CST, AE and concomitant medication will be collected 
through non-invasive chart review, if available. 
If a subject does not agree to continue follow-up of associated clinical outcome information, 
the subject will be terminated from the study accordingly. The data and blood samples 
collected on the subject up to ET visit remains in the study database and no further data will 
be collected. 
In all cases, the reason for IP discontinuation must be recorded in the electronic Case Report 
Form (eCRF) and in the subject’s medical record. 
4.4. Replacement 
Subjects who are discontinued from IP after randomisation will not be replaced. 
5. TREATMENT AND INVESTIGATIONAL PRODUCT 
5.1. Treatment of the Subjects 
5.1.1. Dosing and Treatment Schedule 
Subjects will be administered SB11 or Lucentis® 0.5 mg via ITV into the study eye every 4 
weeks up to Week 48 (a total of 13 administrations of IP) unless they are early discontinued 
from IP.  
IP injection will be performed by the Investigator according to delegation of study personnel 
for this study. 


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Dosing visits will be allowed within ± 7 days of the scheduled dosing visit date (except Week 
0 (Day 1), visit window not allowed). If a dose of IP is not given within 7 days of the 
scheduled dosing visit date, the IP should be given within 20 days of the scheduled dosing 
visit date, but the case will be captured as protocol deviation. Dosing skip is defined when a 
subject does not receive the IP within 20 days after scheduled dosing visit date.  
Next scheduled dosing visit date and visit window should not be altered even though previous 
dosing is not performed on the exact scheduled dosing visit date (but, the interval between two 
doses injected into the study eye should be at least 14 days) or previous dosing is skipped.  
5.1.2. Withholding Investigational Products 
If a subject experiences an AE in the study eye and the subject’s safety or well-being could be 
compromised by ITV injection of IP at the Investigator’s discretion, IPs should be withheld 
until the event has resolved. Such events in the study eye include, but are not limited to: 
• 
A decrease in BCVA of ≥30 letters compared with the last assessment of VA;  
• 
An IOP of ≥30 mmHg;  
• 
A retinal break;  
Any significant change in the posterior pole (e.g., subretinal haemorrhage, macular hole, 
vitreous haemorrhage or opacity, retinal detachment, etc.) that is detected with fundus 
examination should be confirmed and documented with FP and/or FA. Investigator should 
decide IP withholding based on the FP and/or FA. The images taken at unscheduled visits will 
not be sent to the central reading centre. 
NOTE: If a subject misses any of first two doses or two consecutive doses during the study 
period after randomisation, the subject must be discontinued from IPs according to Section 4.3.   
5.2. Investigational Product 
5.2.1. Identity of Investigational Product 
Details of the IPs are provided in Table 7. 


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Table 7. Investigational Products 
Active pharmaceutical ingredient: ranibizumab 
SB11 
 
Formulation 
Solution for ITV injection 
Contents 
One ml contains 10 mg ranibizumab 
Storage conditions 
Stored in refrigerator (2-8°C), Do not freeze 
 
 
US sourced Lucentis® 
 
Formulation 
Solution for ITV injection 
Contents 
One ml contains 10 mg ranibizumab 
Storage conditions 
Stored in refrigerator (2-8°C), Do not freeze 
The IPs will be supplied to Investigational site in one carton containing a single vial. These IP 
vials will be packed and labelled in a double-masked manner for clinical use. The labels for 
carton and vial will contain: the protocol number, unique identifier, Sponsor company name, 
expiry or retest date, storage condition and all other details according to the Good 
Manufacturing Practice (GMP) and other relevant local laws and/or regulations. 
The temperature will be monitored properly during the study period. The IPs should be 
protected from light. The IP should be stored in a secure area and clearly labelled and stored 
away from other IP or medication to prevent confusion (for example in a clearly marked box 
on a separate shelf of the refrigerator). 
A detailed guideline for IP preparation, administration, storage and destruction will be 
provided in the Pharmacy Manual.  
5.2.2. Assignment of Subject Number 
A unique subject number will be assigned to the subject by the Interactive Web Response 
System (IWRS) at Screening.  
A unique randomisation number will be assigned to the subject number by the IWRS at 
randomisation to ensure that treatment group assignment is unbiased and masked to subjects, 
Investigators, and other study personnel. The randomisation number is linked to the treatment 
group assignment, which in turn is linked to IP kit number. 
The assigned subject number(s) and randomisation number(s) will not be re-used.  
5.2.3. Masking 
This study is double-masked. Subjects, Investigators, and other study personnel will remain 
masked to the treatment group assignment throughout the study period after randomisation.  


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To ensure the masking of the treatment group assignment, one carton will contain only one IP 
vial (SB11 or Lucentis®). The carton and IP vial will be packed and labelled in identical 
appearance.  
5.2.4. Unmasking 
After all subjects complete the procedures at Week 24, or its corresponding visit, a limited 
number of identified individuals of the Sponsor and/or Contract Research Organisation (CRO) 
will be unmasked only for the reporting purpose to regulatory agency. Available efficacy and 
safety data, pharmacokinetics, and immunogenicity data will be analysed and reported in the 
Main Clinical Study Report (CSR). However, subjects, investigators, and other study 
personnel will remain masked throughout the study period 
After the last subject completes the procedures at Week 52 (EOS visit) or the corresponding 
visit and database is locked, the treatment group assignment will be unmasked and all study 
data will be analysed and reported in the Final CSR. 
Emergency unmasking is referred to Section 8.1.6. 
5.2.5. Investigational Product Treatment Compliance and Accountability 
5.2.5.1. Investigational Product Treatment Compliance 
All IP injections will be given by the Investigator to ensure compliance. The exact date and 
time of IP injection must be recorded in the source documentation and the eCRF. 
5.2.5.2. Investigational Product Accountability 
Investigator or designee should maintain the documents of IP accountability and record the IP 
kit number administered to subjects. IP accountability and dispensing records must be kept 
and contain the following information: 
• The identification of the subjects to whom the drug was dispensed. 
• The date(s) and quantity of the drug dispensed and exact package to the subject. 
• The dispensing and inventory logs must be available for inspection by the monitor. 
The used IP will be destructed at the Investigational site according to local regulation. All 
unused IPs should be returned to the Sponsor or designated vendor unless local destruction 
site is approved by the Sponsor. If destruction is authorised at the Investigational site, the 
Investigator must ensure that the materials are destroyed in compliance with all applicable 
environmental regulations, institutional policies and any instructions provided by the Sponsor. 
Destruction of the IP must be adequately documented. 


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5.2.6. Investigational Product Administration 
Using aseptic technique, all of the SB11 and Lucentis® vial contents are withdrawn through a 
blunt filter needle attached to a 1-cc syringe. The filter needle should be discarded after 
withdrawal of the vial contents and should not be used for ITV injection. The filter needle 
should be replaced with a sterile 30-gauge x 1/2-inch needle for the ITV injection of IP. The 
contents should be expelled until the plunger tip is aligned with the line that marks 0.05 mL 
on the syringe. 
The ITV injection procedure should be carried out under controlled aseptic conditions in 
accordance with local practice.  
Each vial should only be used for the treatment of a single eye.  
5.3. Prohibited Medication or Therapy  
Prohibited medication and therapy during the study period are presented in Table 8. 
Any other medications that are considered necessary for the subject’s welfare, and that are not 
expected to interfere with the evaluation of the IP may be given at the Investigator’s discretion. 
Details of any medications including both prescription, non-prescription drugs or any therapy 
(except dietary supplements, vitamins or minerals) received locally (in the study eye and/or  
fellow eye) or systemically within 180 days prior to Screening will be collected until Week 52 
(EOS visit) or ET visit. Details to be recorded include: name (generic name preferred), dose 
number and unit, frequency of administration, route of administration, start and stop dates, 
and the AE it relates to (if applicable). 
Table 8. Prohibited Medication and Therapy 
Medication or Therapy 
Time to be prohibited 
Eye to be prohibited 
ITV anti-VEGF treatment (e.g., 
bevacizumab, aflibercept, 
ranibizumab) to treat neovascular 
AMD 
• Prior to Randomisation 
• Study eye  
• Fellow eye 
ITV anti-VEGF treatment except 
IP (SB11 or Lucentis®) 
• From Randomisation to EOS/ET visit 
• Study eye  
ITV anti-VEGF treatment (e.g., 
bevacizumab, aflibercept) except 
ranibizumab 
• From Randomisation to EOS/ET visit 
• Fellow eye 
NOTE: If a subject has 
AMD in the fellow eye 
during the study period 
after randomisation, 
ONLY Lucentis® 
(ranibizumab) will be 
allowed to treat AMD. 
Systemic Anti-VEGF agents 
(e.g., bevacizumab) 
•  Within 90 days prior randomisation 
•  From Screening to EOS/ET visit 
N/A 


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Medication or Therapy 
Time to be prohibited 
Eye to be prohibited 
Systemic treatment or therapy 
(including prescribed herbal 
medication) to treat neovascular 
AMD. However, dietary 
supplements, vitamins and 
minerals are allowed. 
• Within 30 days prior randomisation 
• From Screening to EOS/ET visit 
N/A 
Systemic medications known to 
be toxic to the lens, retina or optic 
nerve including deferoxamine, 
chloroquine/hydroxychloroquine , 
tamoxifen, phenothiazines, 
vigabatrin and ethambutol 
• From Screening to EOS/ET visit 
N/A 
Intravitreal injection of 
corticosteroid (e.g., triamcinolone 
acetonide) or intravitreal 
corticosteroid implant 
• Within 180 days prior to 
randomisation 
•  From Screening to EOS/ET visit 
• Study eye 
Topical ocular corticosteroids 
• ≥ 30 consecutive days within 90 days 
prior to randomisation 
• Study eye 
Treatment involving macula with 
photodynamic therapy with 
verteporfin, transpupillary 
thermotherapy, radiation therapy, 
or retinal laser treatment (e.g., 
focal laser photocoagulation) 
• Prior to Screening 
• From Screening to EOS/ET visit 
• Study eye 
Treatment with pan-retinal 
photocoagulation 
• Prior to Screening 
• From Screening to EOS/ET visit 
• Study eye 
Ocular investigational products to 
treat neovascular AMD 
• Prior to Screening 
• From Screening to EOS/ET visit 
• Study eye  
• Fellow eye 
Systemic investigational products 
to treat neovascular AMD 
• Prior to Screening 
• From Screening to EOS/ET visit 
N/A 
Ocular investigational products to 
treat ocular diseases other than 
neovascular AMD 
• Within 90 days prior randomisation 
• From Screening to EOS/ET visit 
• Study eye  
• Fellow eye 
Systemic investigational products 
(excluding dietary supplements, 
vitamins and minerals) to treat 
systemic diseases other than 
neovascular AMD 
• Within 90 days prior randomisation 
• From Screening to EOS/ET visit 
 
NOTE:  During the study period, 
investigational products such as dietary 
supplements, vitamins and minerals 
will be prohibited. 
N/A 
N/A, Not applicable 
5.4. Fellow Eye Treatment 
The fellow eye (non-study eye) will not be considered as an additional study eye. If a subject 
has AMD in the fellow eye, the subject could receive ONLY Lucentis® and should remain in 


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the study. Lucentis® for treatment in the fellow eye will be reimbursed or provided by Sponsor 
during the study period after randomisation.  
Fellow eye injection will be performed by the Investigator for this study. However, fellow eye 
visit is not part of study, thus it will be scheduled in accordance with local practice. If a 
subject has both eyes injected on the same day, fellow eye should be injected after completion 
of ITV injection of IP on the study eye. Ocular adverse events for the fellow eye and systemic 
adverse events will be monitored and recorded after the written informed consent is obtained 
from the subject until Week 52 (EOS visit) or ET visit.  
6. STUDY VARIABLES 
6.1. Study Endpoints 
6.1.1. Primary Endpoint 
For US FDA, Korea MFDS or other regulatory agency submissions for those who are in 
favour of the VA, the primary endpoint is: 
• Change from baseline in BCVA at Week 8 
For EMA or other regulatory agency submission for those who are in favour of the anatomical 
parameter, the primary endpoint is: 
• Change from baseline in CST at Week 4 (based on assessment by central reading centre) 
6.1.2. Secondary Endpoints 
The secondary efficacy endpoints are: 
• Change from baseline in BCVA over time up to Week 24 and Week 52 
• Proportion of subjects who lost fewer than 15 letters in BCVA compared to baseline at 
Week 24 and Week 52 
• Proportion of subjects who gained 15 letters or more in BCVA compared to baseline at 
Week 24 and Week 52 
• Change from baseline in CST and Central Retinal Lesion Thickness (CRLT) at Week 24 
and Week 52 (based on assessment by central reading centre) 
• Change from baseline in total CNV size at Week 24 and Week 52 (based on assessment 
by central reading centre) 
• Proportion of subjects with active CNV leakage at Week 24 and Week 52 (based on 


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assessment by central reading centre) 
The safety endpoints are: 
• Incidence of ocular AEs or serious ocular adverse events 
• Incidence of systemic AEs or serious systemic adverse events 
The pharmacokinetic endpoints are: 
Blood sampling for PK will be collected in approximately 40 subjects participating in PK 
evaluation (20 subjects per treatment group). 
• Systemic exposure measured pre-dose (Ctrough) and 24 to 72 hours post-dose (close to 
Cmax)  
The immunogenicity endpoints are: 
• Incidence of Anti-Drug Antibodies (ADAs) to ranibizumab 
• Incidence of Neutralising Antibodies (NAbs) to ranibizumab  
6.1.3. Exploratory Endpoint 
• Proportion of subjects without intra- or sub-retinal fluid at Week 24 and Week 52 (based 
on assessment by central reading centre) 
The Quality of Life (QOL) is assessed using National Eye Institute 25-Item Visual Function 
Questionnaire (NEI VFQ-25). 
• Change from baseline in subscale scores and composite scores of NEI VFQ-25 at Week 
24 and Week 52 
6.2. Efficacy Assessments 
6.2.1. Best Corrected Visual Acuity 
VA will be assessed in both the study eye and fellow eye (non-study eye) at Screening and 
prior to ITV injection of IP at each visit until Week 48. VA will also be assessed in both the 
study eye and fellow eye (non-study eye) at any time during the visit at Week 52 (EOS visit) 
or ET visit.  
VA will be assessed using original series ETDRS charts or 2702 series Number charts at a 
starting distance of 4 meters, and then repeated at a distance of 1 meter, if necessary. Subject 


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must use the same chart consistently from Screening to Week 52 (EOS visit) or ET visit. VA 
testing must be performed before dilation of pupils and FP/FA and OCT assessment. 
VA examiners and VA lanes at Investigational sites must be certified to ensure consistent 
measurement of BCVA prior to start of study.  
A detailed protocol for conducting VA testing and refraction will be provided in the VA 
Testing Manual. 
A decrease in VA of ≥ 15 letters from the last assessment of VA should be reported as AEs/ 
Serious Adverse Events (SAEs) as appropriate. 
If the event meets one or more of the following criteria, it should be reported as SAE. 
• A decrease in VA of ≥ 30 letters from the last assessment of VA 
• A decrease in VA to the level of Light Perception or worse  
6.2.2. Anatomical Parameters 
The average retinal thickness in the central 1-mm area in the ETDRS grid (CST; central 
subfield thickness), retinal thickness between Internal Limiting Membrane (ILM) and the base 
of RPE (CRLT; central retinal lesion thickness) and other lesion characteristics will be 
evaluated using OCT on the study eye at Screening and prior to ITV injection of IP until 
Week 48. OCT will also be performed at any time during the visit at Week 52 (EOS visit) or 
ET visit.  
Lesion characteristics such as CNV size and presence of leakage or haemorrhage will also be 
evaluated using FP/FA on the study eye at Screening and prior to ITV injection of IP Week 24. 
FP/FA will also be performed at any time during the visit at Week 52 (EOS visit) or ET visit. 
6.3. Safety Assessments 
6.3.1. Adverse Events 
All AEs including ocular AEs in the study eye and/or fellow eye as well as systemic AEs will 
be recorded from the written informed consent is obtained from the subject until Week 52 
(EOS visit) or ET visit. AEs should be elicited from subjects using non-leading questions such 
as ‘How are you feeling?’. Further information on AE monitoring and reporting is presented 
in Section 8. 
6.3.2. Clinical Laboratory Test 
Blood and urine sampling for clinical laboratory test will be collected at Screening and prior 
to ITV injection of IP at Week 12, Week 24, and Week 36. Blood and urine sampling for 


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clinical laboratory test will also collected at any time during the visit at Week 52 (EOS visit) 
or ET visit (Table 2). Urine samples must be collected before performing FA to avoid false 
elevations in urine protein values. 
Blood samples will be analysed in central laboratory and urine samples will be tested in each 
Investigational site by using a dipstick which will be provided by Sponsor. A detailed process 
for clinical laboratory sampling, handling, storage and shipping will be provided in the 
Central Laboratory Manual for safety lab testing. 
The parameters for clinical laboratory tests are listed in Table 9. 
Table 9. Parameters for Clinical Laboratory Tests 
Haematology 
Chemistry 
Urinalysis1 
 
Haemoglobin 
 
Haematocrit 
 
Platelet count 
 
White blood cell count 
(total and differential) 
 
Sodium 
 
Potassium 
 
Creatinine 
 
Glucose 
 
Calcium 
 
Phosphorus 
 
Total bilirubin 
 
Albumin 
 
Alanine aminotransferase 
 
Aspartate aminotransferase 
 
Alkaline phosphatase 
 
Lactate dehydrogenase 
 
Protein 
 
Blood 
 
Leucocytes 
 
Nitrite 
 
Glucose 
 
Ketone 
 
pH 
 
Specific gravity 
 
Bilirubin, 
 
Urobilinogen 
1 Urinalysis will be tested using a dipstick which will be provided by Sponsor.  
The Investigator will check any laboratory values which have potential significance in 
subject’s safety during the study period. The Investigator will also evaluate any change in 
laboratory values. Each out of range result should be assessed as not clinically significant or 
clinically significant by Investigator. All laboratory abnormalities that require intervention 
(e.g., IP withholding, IP discontinuation, concomitant medication) should be assessed as 
clinically significant and the clinically significant abnormalities should be recorded as AEs.  
Clinical laboratory test including haematology, clinical chemistry, and urinalysis can be 
repeated during the study period at the Investigator’s discretion.  
Deleted laboratory test results with technical problems, such as handling error, sampling error, 
or tube breakage, should be followed by re-test. Result of re-test will be considered as that of 
an initial. 
6.3.3. Pregnancy Test 
For women of childbearing potential, serum pregnancy test must be performed at Screening. 
The serum samples taken at Screening will be analysed in central laboratory. 


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Additional serum or urine pregnancy test can be performed in each Investigational site during 
the study period, if necessary (at the Investigator’s discretion). 
Deleted pregnancy test result at Screening with technical problems, such as handling error, 
sampling error or tube breakage, should be followed by re-test. Result of re-test will be 
considered as that of an initial. 
6.3.4. Physical Examination 
Physical examination will be performed at Screening and Week 52 (EOS visit) or ET visit. 
The physical examination will include an assessment of the subject’s general appearance, skin, 
head, neck, throat, lymph nodes, cardiovascular, neurological, thyroid, 
musculoskeletal/extremities, respiratory systems and the subject’s abdomen. Abnormal 
findings will be documented on the source document, and any clinically significant 
abnormality or worsening of a previously noted abnormality should be recorded as an AE. 
Body weight will be recorded at Screening and Week 52 (EOS visit) or ET visit, but height 
will be measured only at Screening. 
6.3.5. Vital Signs 
Vital signs include blood pressure, heart rate and body temperature. Vital signs will be 
assessed at Screening and prior to ITV injection of IP at each visit until Week 48. Vital signs 
will also be assessed at any time during the visit at Week 52 (EOS visit) or ET visit (Table 1).  
The Investigator should assess all vital signs and any clinically significant abnormalities 
should be reported as AE. 
6.4. Ophthalmic Assessments 
6.4.1. Full Ophthalmic Examinations 
The full ophthalmic examination will consist of an external examination of the eye and adnexa 
routine screening for eyelid/pupil responsiveness (including but not limited to blepharoptosis, 
abnormal pupil shape, unequal pupils, abnormal reaction to light, and afferent pupillary 
defect), slit lamp biomicroscopy, IOP measurements and indirect ophthalmoscopy. 
The posterior segment should be examined with the slit lamp and indirect ophthalmoscopy. 
Careful evaluation of the macula, optic nerve, retinal vessels, peripheral retina and vitreous 
should be included. 
Grading scales for slit lamp biomicroscopy and indirect ophthalmoscopy are provided in 
Appendix A, B and C. 
 


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Slit lamp biomicroscopy 
The slit lamp examination (cornea, lens, iris, aqueous reaction [cells and flare]) will be 
performed in both the study eye and fellow eye at Screening and prior to ITV injection of IP at 
each visit until Week 48, irrespective of whether or not the fellow eye has AMD. Slit lamp 
examination will also be performed at any time during the visit at Week 52 (EOS visit) or ET 
visit. If the fellow eye is not diagnosed with AMD, it will be followed to determine whether or 
not AMD develops.  
Both the anterior segment and posterior segment will be assessed with the slit lamp. 
The posterior segment will be examined after dilation of pupil with 2-3 drops of 
phenylephrine-tropicamid (or any other mydriatic drug) applied topically to the eye. 
Intraocular pressure (IOP) measurement 
IOP will be measured on the study eye at Screening and prior to ITV injection of IP and 30-60 
minutes after ITV injection of IP at each visit until Week 48. When IOP is measured before 
ITV injection of IP, IOP should be measured after OCT and FP/FA are completed to avoid 
corneal erosion. IOP will also be measured at any time during the visit at Week 52 (EOS visit) 
or ET visit.  
IOP should be measured using Goldmann applanation tonometry. The same method of IOP 
measurement must be used in each subject from Screening to Week 52 (EOS visit) or ET visit.  
Indirect ophthalmoscopy 
Indirect ophthalmoscopy using in a standard way (i.e., usually using a head-mounted light 
source and a 20-30 dpt lens)will be performed on the study eye (including evaluation of 
posterior segment abnormalities of the vitreous, optic nerve, peripheral retina and retinal 
vasculature, as well as retinal pigment epithelium detachment, ischemic events including 
cotton wool spots and microaneurysms) at Screening and prior to ITV injection of IP and 0-15 
min after ITV injection of IP at each visit until Week 48. Indirect ophthalmoscopy will also be 
performed at any time during the visit at Week 52 (EOS visit) or ET visit.  
6.4.2. Optical Coherence Tomography (OCT) 
OCT will be performed on the study eye at Screening and prior to ITV injection of IP at each 
study visit until Week 48. OCT will also be performed at any time during the visit at Week 52 
(EOS visit) or ET visit. 
Site staffs who will perform OCT scans in this study must be certified by the central reading 
centre before study starts. 


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OCT devices registered in an Investigational site should be all from the same manufacture and 
meet the minimum software requirement. The subject should use the OCT devices registered 
by central reading centre during the study period.  
All original OCT images will be kept in the Investigational site and copies will be sent to the 
central reading centre for analysis and archiving. A detailed protocol for OCT image 
acquisition and transmission will be provided in the Image Handbook. 
6.4.3. Fundus Photography (FP) and Fluorescein Angiography (FA) 
FP/FA will be performed on the both eyes at Screening and those images taken from the both 
eyes will be sent to the central reading centre.   
FP/FA will also be performed on the study eye prior to ITV injection of IP at Week 24 and at 
any time during the visit at Week 52 (EOS visit) or ET visit. Those images taken from the 
study eye will be sent to the central reading centre. 
Site staffs who will perform FA/FP in this study must be certified by the central reading centre 
before study starts. 
Only FP/FA device certified by central reading centre is allowed to be used in this study. If 
one or more FP/FA devices are certified in an Investigational site, a subject must use the same 
FP/FA device consistently from Screening to Week 52 (EOS visit) or ET visit.  
All original FP/FA images will be kept in the Investigational site and copies will be sent to the 
central reading centre for analysis and archiving. A detailed protocol for FP/FA image 
acquisition and transmission will be provided in the Image Handbook. 
If any significant change in the posterior pole (e.g., subretinal haemorrhage, macular hole, 
vitreous haemorrhage or opacity, retinal detachment, etc.) is detected with fundus examination, 
additional FP and/or FA can be performed at the Investigator’s discretion, but the images will 
not be sent to the central reading centre.  
6.5. Pharmacokinetic Assessment 
Blood sampling for PK will be collected in approximately 40 subjects (20 subjects per 
treatment group) participating in PK evaluation.  
The Investigational sites which are interested in taking part in PK sub-study and are also fully 
equipped as per study requirement (e.g.,  -70 °C deep freezer for PK sample storage and 
temperature controlled centrifuge) will be selected before the study starts. The selected 
Investigational sites will be defined as PK Investigational sites which are registered in the 
IWRS.   


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Subjects screened at PK Investigational sites will be asked to participate in PK sub-study. If 
subject consents to the PK blood sampling, the subject will be enrolled in this study. Subjects 
enrolled at PK Investigational sites will be “PK subjects” participating in PK evaluation until 
the expected number of PK subjects is reached. Once the expected number of PK subjects is 
reached, the following subjects enrolled at PK Investigational sites will be “non-PK subjects” 
for whom blood sampling for PK will not be performed.  
Blood sampling for PK will be collected prior to ITV injection of IP (Ctrough) and 24-72 hours 
after ITV injection of IP (close to Cmax) at Week 0 (Day 1), Week 4, Week 8, Week 16, Week 
24, and Week 36. Blood sampling for PK will also be collected at any time during the visit at 
Week 1 and Week 52 (EOS visit) (Table 2).  
The exact date and time of sample collection must be recorded in the source documentation 
and the eCRF. A detailed process for PK sampling, handling, storage and shipping will be 
provided in the Central Laboratory Manual for PK and Immunogenicity.  
6.6. Immunogenicity Assessment 
Blood sampling for immunogenicity will be collected in all randomised subjects.  
Blood sampling for immunogenicity will be collected prior to ITV injection of IP at Week 0 
(Day 1), Week 4, Week 8, Week 16, Week 24, and Week 36. Blood sampling for 
immunogenicity will also be collected at any time during the visit at Week 1 and Week 52 
(EOS visit) or ET visit (Table 2). 
The exact date and time of sample collection must be recorded in the source documentation 
and the eCRF. A detailed process for immunogenicity sampling, handling, storage and 
shipping will be provided in the Central Laboratory Manual for PK and Immunogenicity. 
If a subject has an unresolved adverse event that is possibly related to ADA formation, he or 
she could be asked to return for immunogenicity blood sampling after Week 52 (EOS visit) or 
ET visit until the antibody titres return to baseline or stabilise at a level acceptable to the 
Investigator and Sponsor. 
6.7. NEI VFQ-25 
Vision-related QOL will be assessed using NEI VFQ-25. NEI VFQ-25 should be performed at 
Week 0 (Day 1) after randomisation. Then, NEI VFQ-25 should be performed before dilation 
of pupil at Week 0 (Day1), Week 24 and Week 52 (EOS visit) or ET visit.  
All questionnaires will be administered in the local language. Investigator or delegated site 
staff will conduct a questionnaire survey with the subject in a quiet room. The results of the 
questionnaire will be recorded in a paper questionnaire and then entered into the eCRF. 


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7. STUDY PROCEDURES 
During this study, efficacy, safety, pharmacokinetic and immunogenicity assessments will be 
performed. All results should be recorded in the source documents along with the date and 
time the procedures were performed. Such assessments must be performed at the times 
outlined in Table 1. 
7.1. Visit 1 (Screening, D-21 to D-1) 
Screening should be performed within 21 days before randomisation excluding the day of 
randomisation.  
• Written informed consent 
Investigator must discuss the study with the subject and obtain written informed consent from 
the subject prior to any study related procedures. If the subject is not randomised within 21 
days after Screening, the subject should be screen failed. Once the subject is screen failed, he 
or she should not be re-screened. 
The following procedures should be performed: 
• Demographic data 
• Medical & ophthalmic history 
• Physical examination (including body weight and height) 
• Vital signs (temperature, blood pressure and pulse rate) 
• Pregnancy test for women of childbearing potential (serum) 
• Blood and urine sampling for clinical laboratory tests  
- 
Urine samples must be collected before performing FA to avoid false elevation in 
urine protein values 
• Ocular assessments: 
• 
BCVA examination using original series ETDRS charts or 2702 series Number 
charts (before dilation of the pupils and FP/FA and OCT assessment) 
- 
Subject must use the same chart consistently from Screening to Week 52 (EOS 
visit) or ET visit 
• 
Slit lamp biomicroscopy 
• 
Indirect ophthalmoscopy 


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• 
OCT (images should be sent to central reading centre) 
• 
FP & FA (images should be sent to central reading centre) 
• 
IOP using Goldmann applanation tonometry 
• Adverse event monitoring 
• Concomitant and previous medication or therapy 
• Evaluate subject compliance with all inclusion and exclusion criteria 
Investigators are advised to send OCT and FP/FA images to central reading centre as soon as 
possible for review as this could take more time than the other procedures, in order to avoid 
exceeding the allowed 21 days. If the subject is screen failed due to any reasons before the 
Investigator send OCT and/or FP/FA images to central reading centre, the Investigator does 
not have to send the subject’s OCT and/or FP/FA images to central reading centre. 
Central reading centre will send central review results confirming the subject’s eligibility to 
the Investigational site. If a subject is confirmed as ineligible from central reading centre due 
to poor quality of images, but the investigator still considers the subject eligible for the study, 
the Investigator may be allowed to send a second set of images to the central reading centre. 
In this case, only FP/FA or OCT (and not all other screening procedures) have to be repeated 
within screening period of 21 days and the subject will retain the subject number initially 
assigned. 
Once the subject is confirmed eligible for the study, the subject will be advised on study 
restrictions such as contraception, prohibited medications and other study requirements if any. 
NOTE 
 The most critical assessment will be at Week 4 and Week 8 as these are the visits 
for primary endpoint assessment. Thus, every effort should be made to adhere 
to the visit schedule for the subjects.    
 A decrease in VA of ≥ 15 letters (compared with the last assessment of 
VA) should be reported as AEs/SAEs as appropriate. 
 Intraocular inflammation should be recorded based on the location of 
inflammation (e.g., “iritis”, “vitritis” or “iridocyclitis” rather than “uveitis”) 
 Grading scales for slit lamp biomicroscopy and indirect ophthalmoscopy are 
provided in Appendix A, B and C. 


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7.2. Visit 2 (Week 0/Day 1) 
Before randomisation 
• Evaluate subject compliance with all inclusion and exclusion criteria 
• Investigator must confirm that the subject can read between 34 letters and 73 letters 
using original series ETDRS charts or 2702 series Number charts (before dilation of 
the pupils and FP/FA or OCT assessment) prior to randomisation (Please see 
inclusion criteria #5). Subject must use the same chart consistently from Screening to 
Week 52 (EOS visit) or ET visit 
Randomisation 
• After a subject’s eligibility is confirmed by the central reading centre and Investigator, 
subject should be randomised to either SB11 or Lucentis® treatment group 
• The first ITV injection of IP and all other study procedures must be performed at the 
same day of randomisation or the following day after randomisation at the latest with 
a proper reason 
After randomisation 
 Before ITV injection of IP 
• NEI VFQ-25 (prior to dilation of pupil after randomisation) 
• Vital signs (temperature, blood pressure and pulse rate) 
• Blood sampling for immunogenicity  
• Blood sampling for pharmacokinetics for subjects participating in PK evaluation  
• Pregnancy test (serum or urine) at the Investigator’s discretion 
• Ocular assessments: 
• 
Slit lamp biomicroscopy  
• 
Indirect ophthalmoscopy  
• 
OCT (images should be sent to central reading centre) 
• 
IOP using Goldmann applanation tonometry 


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• Adverse event monitoring  
• Review of concomitant and previous medication or therapy 
 ITV injection of IP 
• IP (SB11 or Lucentis®) will be given in the study eye. 
 After ITV injection of IP 
• Ocular assessments: 
• 
Indirect ophthalmoscopy (0-15 min post-dose) 
• 
IOP using Goldmann applanation tonometry (30-60 min post-dose) 
• Blood sampling for pharmacokinetics for subjects participating in PK evaluation (24 - 
72 hours post-dose) 
• Adverse event monitoring  
7.3. Visit 3 (Week 1 ± 3 days) 
• Vital signs (temperature, blood pressure and pulse rate) 
• Blood sampling for immunogenicity 
• Blood sampling for pharmacokinetics for subjects participating in PK evaluation 
• Pregnancy test (serum or urine) at the Investigator’s discretion 
• Ocular assessments: 
• 
BCVA examination using original series ETDRS charts or 2702 series Number 
charts (before dilation  of the pupils and FP/FA or OCT assessment) 
- 
Subject must use the same chart consistently from Screening to Week 52 (EOS 
visit) or ET visit 
• 
Slit lamp biomicroscopy  
• 
Indirect ophthalmoscopy  
• 
OCT (images should be sent to central reading centre) 
• 
IOP using Goldmann applanation tonometry  


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• Adverse event monitoring  
• Review of concomitant medication or therapy 
7.4. Visit 4 (Week 4 ± 7 days) 
 Before ITV injection of IP 
• Vital signs (temperature, blood pressure and pulse rate) 
• Blood sampling for immunogenicity  
• Blood sampling for pharmacokinetics for subjects participating in PK evaluation  
• Pregnancy test (serum or urine) at the Investigator’s discretion 
• Ocular assessments: 
• 
BCVA examination using original series ETDRS charts or 2702 series Number 
charts (before dilation of the pupils and FP/FA or OCT assessment) 
- 
Subject must use the same chart consistently from Screening to Week 52 (EOS 
visit) or ET visit 
• 
Slit lamp biomicroscopy  
• 
Indirect ophthalmoscopy  
• 
OCT (images should be sent to central reading centre) 
• 
IOP using Goldmann applanation tonometry 
• Adverse event monitoring 
• Review of concomitant medication or therapy 
 ITV injection of IP 
• IP (SB11 or Lucentis®) will be given in the study eye. 
 After ITV injection of IP 
• Ocular assessments: 
• 
Indirect ophthalmoscopy (0-15 min post-dose) 
• 
IOP using Goldmann applanation tonometry (30-60 min post-dose) 


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• Blood sampling for pharmacokinetics for subjects participating in PK evaluation (24 - 
72 hours post-dose) 
• Adverse event monitoring  
7.5. Visit 5 (Week 8 ± 7 days) 
 Before ITV injection of IP 
• Vital signs (temperature, blood pressure and pulse rate) 
• Blood sampling for immunogenicity  
• Blood sampling for pharmacokinetics for subjects participating in PK evaluation  
• Pregnancy test (serum or urine) at the Investigator’s discretion 
• Ocular assessments: 
• 
BCVA examination using original series ETDRS charts or 2702 series Number 
charts (before dilation  of the pupils and FP/FA or OCT assessment) 
- 
Subject must use the same chart consistently from Screening to Week 52 (EOS 
visit) or ET visit 
• 
Slit lamp biomicroscopy  
• 
Indirect ophthalmoscopy  
• 
OCT (images should be sent to central reading centre) 
• 
IOP using Goldmann applanation tonometry 
• Adverse event monitoring 
• Review of concomitant medication or therapy 
 ITV injection of IP 
• IP (SB11 or Lucentis®) will be given in the study eye 
 After ITV injection of IP 
• Ocular assessments: 
• 
Indirect ophthalmoscopy (0-15 min post-dose) 


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• 
IOP using Goldmann applanation tonometry (30-60 min post-dose) 
• Blood sampling for pharmacokinetics for subjects participating in PK evaluation (24 - 
72 hours post-dose) 
• Adverse event monitoring  
7.6. Visit 6 (Week 12 ± 7 days) 
 Before ITV injection of IP 
• Vital signs (temperature, blood pressure and pulse rate) 
• Blood and urine sampling for clinical laboratory tests 
- 
Urine samples must be collected before performing FA to avoid false elevation in 
urine protein values 
• Pregnancy test (serum or urine) at the Investigator’s discretion 
• Ocular assessments: 
• 
BCVA examination using original series ETDRS charts or 2702 series Number 
charts (before dilation of the pupils and FP/FA or OCT assessment) 
- 
Subject must use the same chart consistently from Screening to Week 52 (EOS 
visit) or ET visit 
• 
Slit lamp biomicroscopy  
• 
Indirect ophthalmoscopy  
• 
OCT (images should be sent to central reading centre) 
• 
IOP using Goldmann applanation tonometry  
• Adverse event monitoring  
• Review of concomitant medication or therapy 
 ITV injection of IP 
• IP (SB11 or Lucentis®) will be given in the study eye. 
 After ITV injection of IP 
• Ocular assessments: 


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• 
Indirect ophthalmoscopy (0-15 min post-dose) 
• 
IOP using Goldmann applanation tonometry (30-60 min post-dose) 
• Adverse event monitoring  
7.7. Visit 7 (Week 16 ± 7 days) 
 Before ITV injection of IP 
• Vital signs (temperature, blood pressure and pulse rate) 
• Blood sampling for immunogenicity  
• Blood sampling for pharmacokinetics for subjects participating in PK evaluation  
• Pregnancy test (serum or urine) at the Investigator’s discretion 
• Ocular assessments: 
• 
BCVA examination using original series ETDRS charts or 2702 series Number 
charts (before dilation of the pupils and FP/FA or OCT assessment) 
- 
Subject must use the same chart consistently from Screening to Week 52 (EOS 
visit) or ET visit 
• 
Slit lamp biomicroscopy  
• 
Indirect ophthalmoscopy  
• 
OCT (images should be sent to central reading centre) 
• 
IOP using Goldmann applanation tonometry  
• Adverse event monitoring  
• Review of concomitant medication or therapy 
 ITV injection of IP 
• IP (SB11 or Lucentis®) will be given in the study eye. 
 After ITV injection of IP 
• Ocular assessments: 
• 
Indirect ophthalmoscopy (0-15 min post-dose) 


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• 
IOP using Goldmann applanation tonometry (30-60 min post-dose) 
• Blood sampling for pharmacokinetics for subjects participating in PK evaluation (24 - 
72 hours post-dose) 
• Adverse event monitoring  
7.8. Visit 8 (Week 20 ± 7 days) 
 Before ITV injection of IP 
• Vital signs (temperature, blood pressure and pulse rate) 
• Pregnancy test (serum or urine) at the Investigator’s discretion 
• Ocular assessments: 
• 
BCVA examination using original series ETDRS charts or 2702 series Number 
charts (before dilation of the pupils and FP/FA or OCT assessment) 
- 
Subject must use the same chart consistently from Screening to Week 52 (EOS 
visit) or ET visit 
• 
Slit lamp biomicroscopy  
• 
Indirect ophthalmoscopy  
• 
OCT (images should be sent to central reading centre) 
• 
IOP using Goldmann applanation tonometry 
• Adverse event monitoring  
• Review of concomitant medication or therapy 
 ITV injection of IP 
• IP (SB11 or Lucentis®) will be given in the study eye 
 After ITV injection of IP 
• Ocular assessments: 
• 
Indirect ophthalmoscopy (0-15 min post-dose) 
• 
IOP using Goldmann applanation tonometry (30-60 min post-dose) 


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• Adverse event monitoring  
7.9. Visit 9 (Week 24 ± 7 days) 
 Before ITV injection of IP 
• NEI VFQ-25 (before dilation of pupil) 
• Vital signs (temperature, blood pressure and pulse rate) 
• Blood and urine sampling for clinical laboratory tests  
- 
Urine samples must be collected before performing FA to avoid false elevation in 
urine protein values 
• Blood sampling for immunogenicity  
• Blood sampling for pharmacokinetics for subjects participating in PK evaluation  
• Pregnancy test (serum or urine) at the Investigator’s discretion 
• Ocular assessments: 
• 
BCVA examination using original series ETDRS charts or 2702 series Number 
charts (before dilation of the pupils and FP/FA or OCT assessment) 
- 
Subject must use the same chart consistently from Screening to Week 52 (EOS 
visit) or ET visit 
• 
Slit lamp biomicroscopy 
• 
Indirect ophthalmoscopy  
• 
FP & FA (images should be sent to central reading centre) 
• 
OCT (images should be sent to central reading centre) 
• 
IOP using Goldmann applanation tonometry  
• Adverse event monitoring  
• Review of concomitant medication or therapy 
 ITV injection of IP 
• IP (SB11 or Lucentis®) will be given in the study eye 


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 After ITV injection of IP 
• Ocular assessments: 
• 
Indirect ophthalmoscopy (0-15 min post-dose) 
• 
IOP using Goldmann applanation tonometry (30-60 min post-dose) 
• Blood sampling for pharmacokinetics for subjects participating in PK evaluation (24 - 
72 hours post-dose) 
• Adverse event monitoring  
7.10. Visit 10 (Week 28 ± 7 days) 
 Before ITV injection of IP 
• Vital signs (temperature, blood pressure and pulse rate) 
• Pregnancy test (serum or urine) at the Investigator’s discretion 
• Ocular assessments: 
• 
BCVA examination using original series ETDRS charts or 2702 series Number 
charts (before dilation of the pupils and FP/FA or OCT assessment) 
- 
Subject must use the same chart consistently from Screening to Week 52 (EOS 
visit) or ET visit 
• 
Slit lamp biomicroscopy  
• 
Indirect ophthalmoscopy  
• 
OCT (images should be sent to central reading centre) 
• 
IOP using Goldmann applanation tonometry  
• Adverse event monitoring  
• Review of concomitant medication or therapy 
 ITV injection of IP 
• IP (SB11 or Lucentis®) will be given in the study eye 
 After ITV injection of IP 


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• Ocular assessments: 
• 
Indirect ophthalmoscopy (0-15 min post-dose) 
• 
IOP using Goldmann applanation tonometry (30-60 min post-dose) 
• Adverse event monitoring  
7.11. Visit 11 (Week 32 ± 7 days) 
 Before ITV injection of IP 
• Vital signs (temperature, blood pressure and pulse rate) 
• Pregnancy test (serum or urine) at the Investigator’s discretion 
• Ocular assessments: 
• 
BCVA examination using original series ETDRS charts or 2702 series Number 
charts (before dilation of the pupils and FP/FA or OCT assessment) 
- 
Subject must use the same chart consistently from Screening to Week 52 (EOS 
visit) or ET visit 
• 
Slit lamp biomicroscopy  
• 
Indirect ophthalmoscopy  
• 
OCT (images should be sent to central reading centre) 
• 
IOP using Goldmann applanation tonometry  
• Adverse event monitoring  
• Review of concomitant medication or therapy 
 ITV injection of IP 
• IP (SB11 or Lucentis®) will be given in the study eye 
 After ITV injection of IP 
• Ocular assessments: 
• 
Indirect ophthalmoscopy (0-15 min post-dose) 
• 
IOP using Goldmann applanation tonometry (30-60 min post-dose) 


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• Adverse event monitoring  
7.12. Visit 12 (Week 36 ± 7 days) 
 Before ITV injection of IP 
• Vital signs (temperature, blood pressure and pulse rate) 
• Blood and urine sampling for clinical laboratory tests  
- 
Urine samples must be collected before performing FA to avoid false elevation in 
urine protein values 
• Blood sampling for immunogenicity 
• Blood sampling for pharmacokinetics for subjects participating in PK evaluation  
• Pregnancy test (serum or urine) at the Investigator’s discretion 
• Ocular assessments: 
• 
BCVA examination using original series ETDRS charts or 2702 series Number 
charts (before dilation of the pupils and FP/FA or OCT assessment) 
- 
Subject must use the same chart consistently from Screening to Week 52 (EOS 
visit) or ET visit 
• 
Slit lamp biomicroscopy  
• 
Indirect ophthalmoscopy  
• 
OCT (images should be sent to central reading centre) 
• 
IOP using Goldmann applanation tonometry  
• Adverse event monitoring  
• Review of concomitant medication or therapy 
 ITV injection of IP 
• IP (SB11 or Lucentis®) will be given in the study eye 
 After ITV injection of IP 
• Ocular assessments: 


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• 
Indirect ophthalmoscopy (0-15 min post-dose) 
• 
IOP using Goldmann applanation tonometry (30-60 min post-dose) 
• Blood sampling for pharmacokinetics for subjects participating in PK evaluation (24 - 
72 hours post-dose) 
• Adverse event monitoring 
7.13. Visit 13 (Week 40 ± 7 days) 
 Before ITV injection of IP 
• Vital signs (temperature, blood pressure and pulse rate) 
• Pregnancy test (serum or urine) at the Investigator’s discretion 
• Ocular assessments: 
• 
BCVA examination using original series ETDRS charts or 2702 series Number 
charts (before dilation of the pupils and FP/FA or OCT assessment) 
- 
Subject must use the same chart consistently from Screening to Week 52 (EOS 
visit) or ET visit 
• 
Slit lamp biomicroscopy  
• 
Indirect ophthalmoscopy  
• 
OCT (images should be sent to central reading centre) 
• 
IOP using Goldmann applanation tonometry  
• Adverse event monitoring 
• Review of concomitant medication or therapy 
 ITV injection of IP 
• IP (SB11 or Lucentis®) will be given in the study eye. 
 After ITV injection of IP 
• Ocular assessments: 
• 
Indirect ophthalmoscopy (0-15 min post-dose) 


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• 
IOP using Goldmann applanation tonometry (30-60 min post-dose) 
• Adverse event monitoring  
7.14. Visit 14 (Week 44 ± 7 days) 
 Before ITV injection of IP 
• Vital signs (temperature, blood pressure and pulse rate) 
• Pregnancy test (serum or urine) at the Investigator’s discretion 
• Ocular assessments: 
• 
BCVA examination using original series ETDRS charts or 2702 series Number 
charts (before dilation of the pupils and FP/FA or OCT assessment) 
- 
Subject must use the same chart consistently from Screening to Week 52 (EOS 
visit) or ET visit 
• 
Slit lamp biomicroscopy  
• 
Indirect ophthalmoscopy  
• 
OCT (images should be sent to central reading centre) 
• 
IOP using Goldmann applanation tonometry  
• Adverse event monitoring 
• Review of concomitant medication or therapy 
 ITV injection of IP 
• IP (SB11 or Lucentis®) will be given in the study eye. 
 After ITV injection of IP 
• Ocular assessments: 
• 
Indirect ophthalmoscopy (0-15 min post-dose) 
• 
IOP using Goldmann applanation tonometry (30-60 min post-dose) 
• Adverse event monitoring  


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7.15. End of Treatment Visit (Visit 15, Week 48 ± 7 days) 
End of Treatment Visit (EOT) is defined as the visit for the last ITV injection of SB11 or 
Lucentis®. The Sponsor will not provide IP (SB11 or Lucentis®) to subjects after they 
complete the EOT visit. 
 Before ITV injection of IP 
• Vital signs (temperature, blood pressure and pulse rate) 
• Pregnancy test (serum or urine) at the Investigator’s discretion 
• Ocular assessments: 
• 
BCVA examination using original series ETDRS charts or 2702 series Number 
charts (before dilation of the pupils and FP/FA or OCT assessment) 
- 
Subject must use the same chart consistently from Screening to Week 52 (EOS 
visit) or ET visit 
• 
Slit lamp biomicroscopy  
• 
Indirect ophthalmoscopy  
• 
OCT (images should be sent to central reading centre) 
• 
IOP using Goldmann applanation tonometry 
• Adverse event monitoring  
• Review of concomitant medication or therapy 
 ITV injection of IP 
• IP (SB11 or Lucentis®) will be given in the study eye 
 After ITV injection of IP 
• Ocular assessments: 
• 
Indirect ophthalmoscopy (0-15 min post-dose) 
• 
IOP using Goldmann applanation tonometry (30-60 min post-dose) 
• Adverse event monitoring  


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7.16. End of Study (Visit 16, Week 52 ± 7 days) or Early Termination Visit  
End of study (EOS) or Early Termination (ET) visit is defined as 4 weeks (± 7 days) after the 
last ITV injection of SB11 or Lucentis®. For ET visit, PK sampling will be excluded from the 
following procedures. 
• NEI VFQ-25 (before dilation of pupil) 
• Vital signs (temperature, blood pressure and pulse rate)  
• Physical examination (only body weight) 
• Blood and urine sampling for clinical laboratory tests  
- 
Urine samples must be collected before performing FA to avoid false elevation in 
urine protein values 
• Blood sampling for immunogenicity 
• Blood sampling for systemic exposure for subjects participating in PK evaluation  
• Pregnancy test (serum or urine) at the Investigator’s discretion 
• Ocular assessments: 
• 
BCVA examination using original series ETDRS charts or 2702 series Number 
charts(before dilation of the pupils and FP/FA or OCT assessment) 
- 
Subject must use the same chart consistently from Screening to Week 52 (EOS 
visit) or ET visit 
• 
Slit lamp biomicroscopy  
• 
Indirect ophthalmoscopy  
• 
FP & FA (images should be sent to central reading centre) 
• 
OCT (images should be sent to central reading centre) 
• 
IOP using Goldmann applanation tonometry  
• Adverse event monitoring  
• Review of concomitant medication or therapy 


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7.17. Early Termination of the Study 
The study can be terminated at any time for any reason by the Sponsor. Investigator may be 
informed of additional procedures to be followed in order to assure that adequate 
consideration is given to the protection of the subject’s interests. Investigator will be 
responsible for informing Independent Ethics Committees (IECs) of the early termination of 
the study. 
8. SAFETY MONITORING AND REPORTING 
8.1. Adverse Events 
8.1.1. Definition of Adverse Event 
An AE is any untoward medical occurrence in a subject or clinical investigation subject 
administered a medicinal (investigational) product or other protocol-imposed intervention and 
which does not necessarily have to have a causal relationship with this treatment or 
intervention. An AE can therefore be an unfavourable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of any 
dose of a medicinal (investigational) product or other protocol-imposed intervention, 
regardless of attribution.  
All AEs including ocular AEs in the study eye and/or fellow eye as well as systemic AEs will 
be collected from the written informed consent is obtained from the subject until Week 52 
(EOS visit) or ET visit. If the AMD is diagnosed in the fellow eye during the study period, the 
event should be also reported as an AE. 
Pre-existing conditions and any abnormal findings from assessments at the time of Screening 
which are not related to protocol-imposed intervention should not be reported as AEs, 
however pre-existing conditions which worsen (i.e., change in severity) that meets the 
definition of an AE during the study period are to be reported as AEs. 
Diagnostic and therapeutic non-invasive and invasive procedures, such as surgery, should not 
be reported as AEs. However, the medical condition for which the procedure was performed 
should be reported if it meets the definition of an AE. For example, an acute appendicitis that 
begins during the AE reporting period should be reported as an AE and the resulting 
appendectomy should be recorded as treatment of the AE.  
The AE that emerge during the treatment with an IP (i.e., Treatment-Emergent Adverse Event 
[TEAE]) will be analysed for the purposes of safety analyses. 
8.1.2. Period of Observation for Adverse Events 
All AEs (ocular or systemic) will be recorded from the written informed consent is obtained 
from the subject until Week 52 (EOS visit) or ET visit.  


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SAEs that occurred at or before Week 52 (EOS visit) or ET visit must be reported to Sponsor 
or its designated representative via eCRF SAE report form at least within 24 hours of the 
Investigator becoming aware of the event.  
SAEs that are considered to be related to the IP can be collected regardless of the study 
period. SAEs that occurred after Week 52 (EOS visit) or ET visit and that are considered to 
be related to the IP must be reported to Sponsor or its designated representative using the 
paper SAE report form at least within 24 hours of the Investigator becoming aware of the 
event (see Section 8.2.2.).  
Date and time (wherever possible) of Investigator becoming aware of the SAE will be 
recorded in the SAE form and source document properly. 
Unresolved AEs should be followed up until the Week 52 (EOS visit) or ET visit and 
follow-up information will be recorded in the eCRF. The Investigator should provide proper 
monitoring of subject’s status and related AEs for appropriate medical care of the subject 
until AE resolution or stabilisation.  
Unresolved SAE at Week 52 (EOS visit) or ET visit will be followed until event resolution or 
stabilisation (see Section 8.2.2.).  
8.1.3. Reporting Adverse Events 
AEs are to be reported and reviewed by Investigator. When reporting an AE, a diagnosis 
(when possible and appropriate) rather than each individual signs and symptoms should be 
reported. 
Each AE is to be assessed to determine if it meets the criteria of an SAE (see Section 8.2. for 
SAE definition). If an AE is classed as an SAE, it must be reported to Sponsor, or its 
designated representative, promptly according to the timeline specified in Section 8.2.2.  
For an SAE, a diagnosis with a description of signs and symptoms as well as other supporting 
information that led to the diagnosis should be described in the SAE report form and reported 
to the Sponsor, or its designated representative, according to the procedures described in 
Section 8.2.2. 
8.1.4. Severity Assessment 
Investigator is responsible for assessing and reporting the severity of AEs. The following 
classification should be used to classify AEs: 
• 
Mild events are usually transient and do not interfere with the subject’s daily activities. 
• 
Moderate events introduce a low level of inconvenience or concern to the subject and 
may interfere with daily activities. 


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• 
Severe events interrupt the subject’s usual daily activity. 
8.1.5. Causality Assessment 
Investigator is responsible for assigning a causal relationship to each AE. The causal 
relationship between the IP and the AE should be defined as not related (no) or related (yes). 
Events should be classified as “related” if there is a reasonable possibility that the IP caused 
the AE. This means that there are facts (evidence) or arguments to suggest a causal 
relationship. 
Events should be classified as “not related” if there is no reasonable possibility that the IP 
caused the AE. 
8.1.6. Emergency Unmasking for Safety Reasons 
Unmasking should be considered only when knowledge of the treatment group assigned to 
subject is deemed essential for the subject’s safety by Investigator. Emergency unmasking 
may be performed by Investigator through IWRS system if deemed necessary during the study 
period after randomisation. 
If the treatment group assigned to subject is unmasked, Investigator should promptly 
document and explain to the Sponsor about any premature unmasking (e.g., accidental 
unmasking, unmasking due to a serious adverse event) of the investigational product(s) which 
is treated to the subject.  
Pertinent information regarding the circumstances of unmasking of a subject’s treatment 
group must be documented in the subject’s source documents. This includes who performed 
the unmasking, the subject(s) affected, the reason for the unmasking, the date of the 
unmasking and the relevant IP information.  
After unmasking (except unmasking for the purpose of pre-planned regulatory reporting in 
Section 5.2.4.), subjects will be discontinued from the IP (Refer to Section 4.3.).  
8.1.7. Expectedness Assessment 
Expectedness of AEs will be assessed by referring to the safety information in the 
Investigator’s Brochure (IB) of the relevant safety section. More detailed information on 
expectedness assessment will be explained in the IB. The latest SmPC of Lucentis®, Annex I 
of EPAR Product Information posted on EMA website, will be used to assess the 
expectedness for the AEs. 


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8.1.8. Withdrawal due to Adverse Events 
Subject withdrawal from the IP due to an AE should be distinguished from withdrawal due to 
personal reasons. Subjects withdrawn due to an AE will be followed up until the time point 
specified in the protocol (refer to Section 4.3.). If subjects cannot be followed, the reasons will 
be documented by the Investigator (e.g., lost to follow-up, refusal to be followed up). When a 
subject withdraws from the IP due to an SAE, the SAE must be reported and followed in 
accordance with the requirements outlined in Section 8.2.2. 
Subjects who are discontinued from IPs because of serious or significant safety issues should 
be followed closely until the events are fully and permanently resolved or stabilised. 
8.2. Serious Adverse Events 
8.2.1. Definition of Serious Adverse Event  
An SAE is any untoward medical occurrence at any dose that: 
• Results in death  
• Is life-threatening 
• Requires inpatient hospitalisation or prolongation of existing hospitalisation 
• Results in persistent or significant disability/incapacity 
• Results in congenital anomaly/birth defects 
• Is medically important  
Life-threatening 
The term “life-threatening” in the definition of “serious” refers to an event in which the 
subject was at risk of death at the time of the event; it does not refer to an event which 
hypothetically might have caused death if it were more severe. 
Hospitalisation 
AEs reported from clinical studies associated with hospitalisation or prolongation of existing 
hospitalisation are considered serious. 
Any admission to a healthcare facility more than 24 hours meets these criteria. Admission also 
includes transfer within the hospital to an acute/intensive care unit (e.g., from the medical 
floor to a coronary care unit, neurological floor to a tuberculosis unit). Staying at the 
observation unit in the emergency room for more than 24 hours qualifies for hospitalisation. 


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Any events leading to a subsequent emergency room visit or inpatient hospitalisation for less 
than 24 hours may be regarded as medically important for its seriousness criteria, at the 
discretion of the Investigator based on medical judgement. 
Hospitalisation or prolongation of existing hospitalisation in the absence of an AE is not in 
itself an SAE. Examples include: 
• Admission for treatment of a pre-existing (prior to ICF signed) condition not 
associated with the development of a new AE or with a worsening of the pre-existing 
condition 
• Diagnostic admission (e.g., for work-up of persistent pre-treatment laboratory 
abnormality) 
• Social admission (e.g., study subject has no place to sleep) 
• Administrative admission (e.g., for a regular check-up) 
• Protocol-specified admission during a clinical study (e.g., for a procedure required by 
the study protocol) 
• Elective admission not associated with an AE (e.g., for elective cosmetic surgery) 
• Pre-planned treatments or surgical procedures 
: Pre-planned treatments or surgical procedures should be noted in the relevant source 
document for the individual subject.  
Medical and scientific judgement should be exercised in deciding whether expedited reporting 
is appropriate in other situations, such as important medical events that may not be 
immediately life-threatening or result in death or hospitalisation. However, if it is determined 
that the event may jeopardise the subject and may require intervention to prevent one of the 
other outcomes listed in the definition above, the important medical event should be reported 
as serious. Examples of such events are intensive treatment in an emergency room or at home 
for allergic bronchospasm, blood dyscrasias or convulsions that do not result in hospitalisation 
or development of drug dependency or drug abuse. 
The term “severe” is often used to describe the intensity (severity) of a specific event (as in 
mild, moderate or severe myocardial infarction); the event itself, however, may be of 
relatively minor medical significance (such as severe headache). This is not the same as 
“serious,” which is based on subject/event outcome or action criteria usually associated with 
events that pose a threat to a subject’s life or functioning. 
In addition, sight-threatening ocular adverse event will be reported as SAE if it meets one or 
more of the following criteria:   


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• A decrease in VA of ≥ 30 letters from the last assessment of VA 
• A decrease in VA to the level of Light Perception or worse  
• Requirement of surgical intervention (e.g., conventional surgery, vitreous tap or 
biopsy with ITV injection of anti-biotics, laser treatment, ITV gas injection, or retinal 
cryopexy) to prevent permanent loss of vision 
• Severe intraocular inflammation (e.g., 4+ anterior chamber cell/flare or 4+ vitritis). 
• In the investigator’s opinion, medical intervention may be required to prevent 
permanent loss of vision. 
8.2.2. Reporting Serious Adverse Events  
SAEs that occurred at or before Week 52 (EOS visit) or ET visit must be reported to Sponsor 
or its designated representative via eCRF SAE report form at least within 24 hours of the 
Investigator becoming aware of the event.  
SAEs that occurred after Week 52 (EOS visit) or ET visit and that are considered to be related 
to the IP must be reported to Sponsor or its designated representative using the paper SAE 
report form at least within 24 hours of the Investigator becoming aware of the event.  
Date and time (wherever possible) of Investigator becoming aware of the SAE will be 
recorded in the SAE form and source document properly. 
In particular, if the SAE is fatal or life-threatening, Sponsor must be notified immediately, 
irrespective of the extent of available SAE information. This timeframe also applies to 
additional (follow-up) information that becomes available on previously forwarded SAE 
reports. Sponsor will then follow expedited reporting procedures according to local and 
international regulations as appropriate. 
The Investigator is obligated to pursue and provide information to Sponsor on all SAEs in 
accordance with the timeframes for reporting specified above. In addition, Investigator may be 
requested by Sponsor to obtain specific additional follow-up information in an expedited 
fashion. In general, this will include a description of the SAE, which should be provided in 
sufficient detail so as to allow for a complete medical assessment of the case and independent 
determination of possible causality. Information on other possible causes of the event, such as 
concomitant medications and illnesses must be provided. In the case of a subject death, a 
summary of available autopsy findings must be submitted as soon as possible to Sponsor or its 
designated representative. 
All SAEs will be followed until event resolution or stabilisation (for chronic events), if 
possible, even when a subject is discontinued from IP. For chronic events that does not fully 
resolve until years later, the outcome should be reported as “resolved with sequelae” as soon 


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as the event has stabilised or returned to baseline. Follow-up information for the SAE should 
be actively sought and submitted as the information becomes available. 
8.3. Adverse Events of Special Interest 
The following AEs in the study eye will be classified as Adverse Events of Special Interests 
(AESIs) in this study: 
• Any case of new onset IOP of > 21 mm Hg that does not respond to treatment, except 
the transient pressure rise observed within an hour after ITV injection of IP 
• Any case of IOP ≥ 35 mmHg, at any time, that required treatment 
• Any case of intraocular infection such as endophthalmitis 
• Any case of intraocular inflammation such as iritis, vitritis and iridocyclitis 
• Iatrogenic traumatic cataract 
• Arterial thromboembolic events defined as nonfatal stroke, nonfatal myocardial 
infarction, or vascular death (including deaths of unknown as cause) 
8.4. Pregnancy 
Any pregnancy, including those of female partners of male subjects treated with the IP, should 
be reported to the Sponsor. If the female partner of a male subject becomes pregnant, a written 
informed consent must be obtained from the female partner before collecting any pregnancy-
related data. All pregnancies associated with the subject, from the time the subject receives the 
first ITV injection of IP until either Week 52 (EOS visit) or ET visit, should be reported to the 
Sponsor. Pregnancy reports should be submitted to the Sponsor within 24 hours from when 
the Investigator became aware of the pregnancy, using the Pregnancy Report Form. 
Although pregnancy is not an AE, all pregnancies must be followed up every 2 months until 
6-8 weeks after the outcome of the pregnancy becomes available, unless the subject is lost to 
follow-up. The pregnancy outcome should be notified to the Sponsor by submitting a follow-
up Pregnancy Report Form. If the outcome of the pregnancy meets the SAE criteria then the 
Investigator should report this case according to the SAE reporting process (Section 8.2.2.). 
8.5. Independent Data and Safety Monitoring Board 
An independent Data and Safety Monitoring Board (DSMB) will be assigned for this study. 
The DSMB will consist of external experts (e.g., physician, clinical pharmacologists or 
biostatisticians) and will review the safety and tolerability data from the study at pre-specified 
intervals. The details of the safety data and time points for review will be described in the 
DSMB Charter and in the DSMB Statistical Analysis Plan (SAP). 


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In addition, an ongoing masked review of AEs, including clinical laboratory data will be 
continuously undertaken by the Sponsor medical monitor and pharmacovigilance team. 
9. STATISTICAL METHODS AND DATA ANALYSIS  
Further information on the statistical methods to be used in this study will be provided in the 
SAP, which will be finalised prior to the database lock for reporting the main CSR. 
Statistical analysis and reporting will be performed as follows: 
• 
Interim safety analysis for independent DSMB meeting: 
A DSMB SAP, describing the methodology and presentation of results and access to 
results will be prepared as a separate document and included in the DSMB Charter. The 
safety reports for the DSMB data review meetings will be prepared according to the 
DSMB SAP.  
The statistical analysis will be performed by an independent statistical reporting team and 
the results will be communicated to the DSMB directly by an independent unmasked 
statistician. 
• 
Main CSR: 
The main analysis will take place once all subjects complete the procedures at Week 24, 
or its corresponding visit. Available efficacy and safety data, pharmacokinetics, and 
immunogenicity data will be analysed and reported. 
At the time of this reporting, a limited number of identified individuals of the Sponsor or 
CRO will be unmasked for reporting purpose. However, subjects, Investigators, and 
other study personnel will remain masked throughout the entire study period. 
• 
Final CSR: 
The final analysis will take place after the last subject completes the procedures at Week 
52 or the corresponding visit. All study data will be analysed and reported for final CSR. 
9.1. Analysis Sets 
The following sets will be used for the analyses performed in the study: 
• Randomised Set (RAN) consists of all subjects who receive a randomisation number 
at the randomisation visit.  
• Full Analysis Set (FAS) consists of all subjects who are randomised at the 
randomisation visit. Following the intent-to-treat principle, subjects will be analysed 


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according to the treatment group they are assigned to at randomisation. However, 
subjects who do not qualify for randomisation and are inadvertently randomised into 
the study will be excluded from the FAS, provided these subjects do not receive IP 
during the study period. The FAS will be the primary analysis set for BCVA 
• Per-Protocol Set for BCVA (PPS-BCVA) consists of all FAS subjects who have first 
two IP injections and complete the procedures at Week 8 without any major protocol 
deviations that have impact on the BCVA assessment. Major protocol deviations that 
will lead to exclusion from this set will be pre-defined prior to unmasking the 
treatment group assignment for analyses. 
• Per-Protocol Set for CST (PPS-CST) consists of all FAS subjects who have the first 
IP injection at Week 0 (Day 1) and complete the procedures at Week 4 without any 
major protocol deviations that have impact on the CST assessment. This PPS-CST 
will be the primary analysis set for CST. Major protocol deviations that will lead to 
exclusion from this set will be pre-defined prior to unmasking the treatment codes for 
analyses. 
• Safety Set (SAF) consists of all subjects who receive at least one IP during the study 
period after randomisation. Subjects will be analysed according to the IP received. 
• Pharmacokinetic Analysis Set (PKS) consists of all subjects in the SAF who 
participate in PK evaluation at PK Investigational sites (PK subjects) and have at least 
one PK sample analysed.  
9.2. Statistical Methods and Analytical Plan 
9.2.1. Demographics and Baseline Characteristics 
Subject demographics and baseline characteristics will be summarised by treatment group for 
the RAN and PKS. Continuous variables (e.g., age, weight, height) will be summarised with 
descriptive statistics (n, mean, SD, median, minimum, maximum) and categorical variables 
(e.g., gender, race, ethnicity) will be summarised with frequency and percentage.  
Comparison between treatment groups in baseline characteristics will be performed using the 
chi-square test or F-test as appropriate. The results of these tests will be provided including 
the p-value only for descriptive purposes and will not be used as a formal basis to determine 
the factors to be included in primary or secondary efficacy analysis models. If baseline 
imbalances are detected for any of the factors, additional analyses may be performed to adjust 
for these baseline differences. 
Relevant medical history will be summarised by treatment group for the RAN. 


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Duration of exposure to IP and number of injections will be summarised by treatment group 
with descriptive statistics for the SAF. Prior and concomitant medications and significant non-
drug therapies will be summarised by treatment group with frequency and percentage. 
9.2.2. Efficacy 
For US FDA, Korea MFDS or other regulatory agency submissions for those who are in 
favour of the VA, the primary efficacy analysis will be performed for the FAS with the 
change from baseline of BCVA at Week 8 using an analysis of covariance model with the 
baseline BCVA as a covariate and region (or pooled centres) and treatment group as factors. 
The equivalence in BCVA will be declared if the two-sided 90% Confidence Interval (CI) of 
the difference in terms of BCVA Least Squares mean (LS mean) changes from baseline at 
Week 8 between SB11 and Lucentis® lies within the pre-defined equivalence margin of [−3 
letters, 3 letters].  
For EMA or other regulatory agency submissions for those who are in favour of the 
anatomical parameter, the primary efficacy analysis will be performed for the per-protocol set 
(PPS-CST) with the change from baseline of CST at Week 4 using an analysis of covariance 
model with baseline CST as a covariate and region (or pooled centres) and treatment group as 
factors. The equivalence in CST will be declared if the two-sided 95% CI of the difference of 
the CST LS mean changes from baseline in Week 4 between SB11 and Lucentis® lies within 
the pre-defined equivalence margin of [−36 μm, 36 μm]. 
No formal adjustment of Type I error rates will be performed. 
For the primary analysis with the FAS for BCVA, missing data will be imputed for subjects 
who drop out for the study prior to the primary analysis time-point. A missing-at-random 
approach will assume that subjects who withdraw from a study had missing values similar to 
similar subjects who completed the study in that treatment group. This approach ensures that 
evidence of lack of equivalence is not diluted when there are missing data. For the 
components of BCVA, the missing letter will be imputed by multiple imputation method with 
the assumption of monotone missing pattern and regression method. For the sensitivity 
analyses, available case analysis and last observation carried forward analysis will be 
performed.  
All other secondary efficacy measurements will be summarised descriptively by treatment 
group and visit, and analysed using analysis of covariance model for continuous outcomes or 
Cochran-Mentel-Haenszel method for categorical outcomes unless otherwise specified. 
9.2.3. Safety 
All reported terms for AEs (ocular and systemic) will be coded using Medical Dictionary for 
Regulatory Activities (MedDRA®). For all AE and SAE tables, subjects will be counted once 
for each preferred term and each system organ class.  


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A TEAE will be defined as any AE with an onset date on or after the date of the first ITV 
injection of IP. AEs which are already present before the first ITV injection of IP and increase 
in severity after the first ITV injection of IP will be considered as TEAEs. Pre-existing AEs 
before the first ITV injection of IP with no increase in severity after the first ITV injection of 
IP will not be considered as TEAEs.  
All TEAEs and SAEs will be summarised respectively for study eye (ocular TEAE), fellow 
eye (ocular TEAE) and others (systemic TEAE) by the frequency and percentage of subjects 
experiencing events by system organ class, preferred term and treatment group. SAEs leading 
to IP discontinuation and TEAEs by causality and severity will be summarised similarly. All 
AEs including those pre-existing before the first ITV injection of IP will be listed by subject.  
In addition, systemic TEAEs will also be summarised without subjects who received 
Lucentis® in the fellow eye due to AMD during the study period after randomisation.  
Changes in vital signs and clinical laboratory parameters will be summarised descriptively by 
treatment group and visit. Other safety variables will be summarised unless otherwise 
specified, and all safety variables will be listed. 
All safety analyses will be performed using the SAF. 
9.2.4. Pharmacokinetics 
Blood sampling for PK will be collected in approximately 40 subjects participating in PK 
evaluation (20 subjects per treatment group). The systemic exposure will be summarised 
descriptively by treatment group and visit.  
If fellow eye received Lucentis® due to AMD during the study period after randomisation, the 
concentration measured after treatment for the fellow eye will be listed, but excluded from the 
summary statistics.  
9.2.5. Immunogenicity 
The number and proportion of subjects with ADA and NAb results (e.g., “positive” or 
“negative”) will be summarised by treatment group and visit.  
If fellow eye received Lucentis® due to AMD during the study period after randomisation, the 
ADA and NAb results obtained after treatment for the fellow eye will be listed, but excluded 
from the summary statistics. 
9.2.6. NEI VFQ-25 
Subscale scores (general health, general vision, ocular pain, near activities, distance activities, 
vision-specific social functioning, vision-specific mental health, vision-specific role 
difficulties, vision-specific dependency, driving, colour vision, and peripheral vision) and the 


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composite score, which represent overall visual function, will be calculated, and the change 
from baseline will be summarised by treatment group and visit. 
In addition, the subscale scores and composite score of NEI VFQ-25 will be also summarised 
without subjects who received Lucentis® in the fellow eye due to AMD during the study 
period after randomisation. 
9.3. Determination of Sample Size 
For the calculation of the equivalence margin for BCVA, the mean changes in VA were 
referred from two studies of Lucentis® in subjects with neovascular AMD. In MARINA study, 
the mean change of VA at Week 24 (SD) were −6.6 (13.31) letters and 6.5 (12.00) letters for 
placebo and 0.5 mg Lucentis® treatment groups, respectively. In FOCUS study, the mean 
change (SD) of VA at Week 24 were −5.0 (16.14) letters and 4.0 (14.41) letters for placebo 
and 0.5 mg Lucentis® treatment groups, respectively. 
A fixed-effect meta-analysis of the above two studies estimates a weighted mean change in 
VA of 12.41 letters with a 95% CI [10.34 letters; 14.48 letters]. The derived equivalence limit 
from meta-analysis is 4.9 letters at Week 24, but by the agency recommendation the 
equivalence limit at Week 8 will be 3 letters for the comparison with the 90% CI of mean 
difference between treatment groups. 
With the given equivalence margin of [−3 letters, 3 letters], 334 subjects per treatment groups 
was calculated with the assumptions of the mean difference of 0.5 letters and pooled standard 
deviation (SD) of 12.5 letters at the overall 5% significance level. Assuming a 5% loss from 
randomised subjects after 8 weeks, a sample size of 352 subjects per treatment groups (overall 
sample size of 704) will give 334 completers per treatment group after 8 weeks, which is 
estimated to give 80% power to detect the equivalence within the margin of 3 letters. 
For the calculation of the equivalence margin for CST, the mean changes in CST were 
referred from two studies of Lucentis® in subjects with neovascular AMD. In MARINA study, 
the mean change of CST at Week 4 (SD) was 8.1 (58.1) μm and −106 (122.5) μm for placebo 
and 0.5 mg Lucentis® treatment groups, respectively. In PIER study, the mean change (SD) of 
CST at Week 4 were 15 (94.9) μm and −90 (140.9) μm for placebo and 0.5 mg Lucentis® 
treatment groups, respectively. 
A fixed-effect meta-analysis of the above two studies estimates a weighted mean change in 
CST of −109.6 μm with a 95% CI [−146.45 μm; −72.65 μm]. The derived equivalence limit 
from meta-analysis is 36 μm at Week 4. 
With the given equivalence margin of [−36 μm, 36 μm], 290 subjects per treatment group was 
calculated with the assumptions of the mean difference of 0 between treatment groups, 
common SD of 133.3 μm at the overall 5% significance level. Assuming a 10% loss from 


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FAS, a sample size of 323 per arm (overall sample size of 646) will give 80% power to detect 
the equivalence within the pre-defined margin. 
Therefore, the sample size of 704 allows enough power to detect the equivalence between 
treatment groups in both situations. 
10. DATA COLLECTION AND MANAGEMENT 
10.1. Data Confidentiality 
Information about study subjects will be kept confidential. Subject identification information 
will be labelled with a code number, and will not include the subject’s name or other 
information that could identify them. A list linking the code and the subject’s name will be 
kept in the Investigational site files as required by International Council for Harmonisation 
(ICH) Guideline for Good Clinical Practice (GCP) to protect the subject’s confidentiality. 
The coded information will be sent to the Sponsor (or designee) who will analyse it and report 
the study results both to regulatory and ethical authorities. The Sponsor may also place data 
on public websites or publish journal articles based upon these results. Subject names or other 
directly identifiable information will not appear on any reports, publications, or other 
disclosures of clinical study outcomes. Care will be taken to prevent subjects being identified 
through these publications. In addition, data may be shared with other companies or 
researchers to aid further research into AMD. Such data sharing practices will be covered by 
confidentiality agreements. No-one outside the Investigational site will have access to subject-
identifiable information. 
10.2. Monitoring 
The Sponsor has engaged the services of a CRO to perform all monitoring functions within 
this clinical study. The monitors will work in accordance with the CRO Standard Operation 
Procedures (SOPs) and have the same rights and responsibilities as monitors from the Sponsor 
organisation. Monitors will establish and maintain regular contact between the Investigator 
and the Sponsor. 
Monitors will evaluate the competence of each Investigational site and inform the Sponsor 
about any problems relating to facilities, technical equipment or medical staff. During the 
study period, monitors will check that written informed consent has been obtained correctly 
from all subjects and that data are recorded correctly and completely. Monitors will also 
perform source data verification by comparing entries in the eCRF with corresponding source 
data and informing the Investigator of any errors or omissions. Monitors will verify adherence 
to the protocol at the Investigational site. All protocol deviations will be reported to the 
Sponsor via the Monitoring Visit Reports. Monitors will arrange for the supply of IP and 
ensure appropriate storage conditions are maintained. 


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Monitoring visits will be conducted at regular intervals according to ICH GCP. The monitor 
will provide written reports to the Sponsor on each occasion they make contact with the 
Investigator regardless of whether it is by phone or in person. 
Further details on the monitoring processes and the level of source data verification to be 
performed will be outlined in the monitoring plan. 
10.3. Data Handling and Record Keeping 
The Investigator must maintain essential study documents including protocol and protocol 
amendments, completed eCRFs, signed written ICFs and its revisions/updates, completed 
eCRFs, other relevant correspondence according to ICH GCP and other relevant study 
requirements (if applicable) until at least 2 years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or at least 2 years after the formal termination of clinical 
development of the IP or 15 years from completion of the study, or whichever longer 
according to the relevant local laws and/or regulations. These documents should be retained 
for a longer period if required by the applicable regulatory requirements or the Investigational 
site, institution or private practice in which the study is being conducted. Subject 
identification codes (subject names and corresponding study numbers) will be retained for the 
same period of time. These documents may be transferred to another responsible party, 
deemed acceptable by the Sponsor, and who agrees to abide by the retention policies. Written 
notification of transfer must be submitted to the Sponsor. The Investigator must contact the 
Sponsor prior to disposing of any study records and obtain written permission to do so. 
10.4. Database Management and Coding 
Data generated within this clinical study will be handled according to the relevant SOPs of the 
data management of the Sponsor (or an appropriate company designated by the Sponsor to 
perform these activities). The study eCRF is the primary data collection instrument for the 
study. Subject data will be captured in an eCRF and reviewed by the monitor in order to check 
adherence to the protocol and to detect any data inconsistency or discrepancy from source 
document. 
The Investigator must ensure that the clinical data required by the study protocol are carefully 
reported in the eCRF. He/she must also check that the data reported in the eCRF correspond to 
those in the medical records. The investigator will sign all collected data in eCRF. 
Forms should be available during periodic visits by study monitors to enable review for 
completeness and acceptability. Any correction to the data entered into the eCRF must be 
carried out by the Investigator or a designated member of staff. These changes may be made 
either on the initiative of the Investigational site staff or in response to monitoring or data 
queries. Any changes to written data must be made using ICH GCP corrections and any 
change to electronic data should be made in a system which can provide an audit trail. 


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Monitors and clinical data managers will review the eCRF for accuracy and can generate 
queries to the investigational staff for resolution. Corrections will be recorded in an audit trail 
that records the old information, the new information, and identification of the person making 
the changes, date of correction made and reason for change. The Investigator must sign and 
date the eCRF pages as indicated. 
Medical/surgical history and underlying diseases and AEs will be coded using MedDRA®. 
Concomitant medications will be coded using the World Health Organisation-Drug Dictionary 
Enhanced (WHO-DDE). The versions of coding dictionaries used will be stated in the clinical 
study report. 
10.5. Quality Control and Quality Assurance 
During the conduct of the study, Sponsor or its agent will conduct periodic monitoring visits 
to ensure that the protocol and ICH GCP are being followed. The monitors may review source 
documents to confirm that the data recorded on the eCRFs are accurate. The Investigator and 
institution will allow the domestic and foreign regulatory authorities, sponsor’s monitors and 
auditors’ direct access to source documents to perform this verification. The Investigational 
site may be subject to review by the IEC, and/or to quality assurance audits performed by 
Sponsor, and/or to inspection by appropriate regulatory authorities. It is important that 
Investigators and their relevant personnel are available during the monitoring visits and 
possible audits or inspections and that sufficient time is devoted to the process. 
11. ETHICAL CONSIDERATIONS AND ADMINISTRATIVE 
PROCEDURES 
11.1. Institutional Review Boards and Independent Ethics Committees 
The Investigator and the Sponsor will follow all local laws and regulations relating to contact 
with and approvals from the Institutional Review Board (IRB)/IEC. 
The Investigator must provide the Sponsor with documentation of IRB/IEC approval of the 
protocol and written informed consent before the study may begin at the Investigational site. 
The Investigator will supply documentation to the Sponsor relating to the annual renewal of 
the protocol from the IRB/IEC and any approvals of revisions to the ICF or amendments to 
the protocol.  
The Investigator will report promptly to the IRB/IEC any new information that may adversely 
affect the safety of subjects or the conduct of the study. Similarly, the Investigator will submit 
written summaries of the study status to the IRB/IEC on a regular basis and in accordance 
with the timelines required locally. Upon completion of the study, the Investigator will 
provide the ethics committee with a report on the outcome of the study if required by local 
regulations. 


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11.2. Ethical Conduct of the Study 
This study will be conducted in compliance with the protocol, the ICH GCP, the Declaration 
of Helsinki (2013) and other relevant laws and/or regulations. 
11.3. Written Informed Consent 
The written informed consent will be used to explain the risks and benefits of study 
participation to the subject in simple terms prior to any study related procedures. The written 
informed consent contains a statement that the consent is freely given, that the subject is 
aware of the risks and benefits of entering the study, and that the subject is free to withdraw 
from the study at any time. Written consent must be given by the subject after the receipt of 
detailed information on the study.  
The Investigator is responsible for ensuring that informed consent is obtained from each 
subject and for obtaining the appropriate signatures and dates on the written informed consent 
prior to the performance of any protocol procedures and prior to the first ITV injection of IP. 
The Investigator will provide each subject with a copy of the signed and dated written 
informed consent and this will be documented in the subject’s source notes.  
If the subject is legal blindness or illiterate, an impartial witness should be present during the 
entire informed consent discussion. After the written informed consent and any other written 
information to be provided to subjects is read and explained to the subject, and after the 
subject has orally consented to the subject’s participation in the study, and, if capable of doing 
so, has signed and personally dated the written informed consent, the witness should sign and 
personally date the written informed consent. By signing the written informed consent, the 
witness attests that the information in the written informed consent and any other written 
information was accurately explained to the subject and apparently understood by the subject, 
and that written informed consent was freely given by the subject. 
11.4. Investigator Information 
11.4.1. Investigator Obligations 
This study will be conducted in accordance with the ICH GCP (1997), ICH GCP E6 R2 
(2016), the ethical principles that have their origin in the Declaration of Helsinki (2013) and 
other local laws and/or regulations. 
The Investigator is the qualified physician who is responsible for ensuring that the study is 
conducted according to the signed Investigator statement, the study protocol and applicable 
regulations; for protecting the rights, safety and welfare of subjects under the Investigator’s 
care; and for the control of drugs under investigation. The Investigator must obtain the written 
informed consent of each subject to whom IP will be administered. The Investigator is also 


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responsible for supervising any individual or party who conducts study-related duties at 
Investigational site to ensure the integrity. 
11.4.2. Coordinating Investigator 
Sponsor will designate a Coordinating Investigator among the Investigators who participate in 
the study. The roles of the Coordinating Investigator are defined as following: 
• Provide scientific and medical advice and/or inputs on current medical practice, 
protocol development and Investigational site selection 
• Review ongoing study activities with Interpretation and presentation of final analyses 
• Review clinical study reports 
• Involved in development of publication strategy 
• The designated Coordinating Investigator will sign the signature page of CSR as a  
representative of other Investigators. 
11.4.3. Training of Investigational Site Personnel 
Before the first subject is enrolled into the study, a Sponsor representative will review and 
discuss the requirements of the Clinical Study Protocol and related documents with the 
investigational staff and will also train them in any study-specific procedures. 
The Investigator will ensure that appropriate training relevant to the study is given to all 
Investigational site staff and that any new information relevant to the performance of this 
study is forwarded to the staff involved. 
The Investigator will maintain a record of all individuals involved in the study (medical, 
nursing and other staff). 
11.4.4. Protocol Signatures 
The Investigator must sign the Investigator Signature Page of this protocol prior to enrolling 
subjects in the study. By signing the protocol signature page, the Investigator attests in writing 
that he or she has read, understood, and will conduct the study in accordance with the study 
protocol, ICH GCP and other relevant local laws and/or regulations. 
11.5. Financing and Insurance 
Samsung Bioepis Co., Ltd. is the Sponsor of this study and will support the financial aspects 
for the study conduct at the Investigational site.  


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Details of financial agreements are provided in the Clinical Study Agreements with the 
Investigational sites. The Sponsor has obtained suitable insurance for this study. The 
insurance details may be provided to the Investigational sites and/or the Investigators who are 
responsible for providing the IRB/IEC with these details according to local requirements if 
any.  
12. PUBLICATION POLICY 
The Sponsor supports the efforts of health authorities to increase the transparency of medical 
research conducted in human subjects. The Sponsor will register and maintain the information 
of clinical studies on a public registry program such as www.ClinicalTrials.gov. The Sponsor 
will comply with the guidelines of regulatory authorities with regards to public registration 
and disclosure of clinical study data. 
The clinical study data collected during the study are confidential and proprietary to the 
Sponsor. Sponsor shall have the right to delete any confidential or proprietary information 
contained in any proposed abstract or presentation. 
Any publications from this study should be approved by the Sponsor prior to publication or 
presentation. The rights of the Investigator with regard to publication of this study are 
described in the Clinical Study Agreement. 


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13. REFERENCES 
Chakravarthy U, Wong T, Fletcher A, et al. Clinical risk factors for age-related macular 
degeneration: a systematic review and meta-analysis. BMC Ophthalmology. 2010;10(31) 
Ferris FL 3rd, Fine SL, Hyman L. Age-related macular degeneration and blindness due to 
neovascular maculopathy. Arch Ophthalmol. 1984;102(11):1640-2. 
Fung A, Lalwani G, Rosenfeld P et al. An Optical Coherence Tomography-Guided, Variable 
Dosing Regimen with Intravitreal Ranibizumab (Lucentis) for Neovascular Age-related 
Macular Degeneration. Am J Ophthalmol. 2007;143(4):566–83. 
Guidance for industry: Scientific considerations in demonstrating biosimilarity to a reference 
product. U. S. Food and Drug Administration. (Apr 2015). Retrieved Dec 29, 2016 
from http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guid
ances/UCM291128.pdf 
Guideline on similar biological medicinal products. EMEA. (Oct 2005). 
EMEA/CHMP/437/04. Retrieved Dec 29, 2016 
from http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/
WC500003517.pdf 
Guideline on similar biological medicinal products containing biotechnology-derived proteins 
as active substance: quality issues (revision 1). EMEA. (Dec 2014). 
EMA/CHMP/BWP/247713/2012. Retrieved Dec 29, 2016 
from http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/06/
WC500167838.pdf 
Guideline on similar biological medicinal products containing monoclonal antibodies – non-
clinical and clinical issues. EMEA. (Dec 2012). EMA/CHMP/BMWP/403543/2010. Retrieved 
Dec 29, 2016 
from http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/06/
WC500128686.pdf 
Lalwani G, Rosenfeld P, Fung A et al. Variable-dosing Regimen with Intravitreal 
Ranibizumab for Neovascular Age-related Macular Degeneration: Year 2 of the PrONTO 
Study. Am J Ophthalmol. 2009;148(1):43–58. 
Lee H. Is extrapolation of the safety and efficacy data in one indication to another appropriate 
for biosimilars?. AAPS J. 2014;16(1):22-26. 
Lucentis® Prescribing Information. U. S. Food and Drug Administration. (Nov 2016). 
Retrieved Dec 29, 2016 
from http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125156s112lbl.pdf 


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Lucentis® Summary of Product Characteristics. EMEA. (Dec  2016). Retrieved Dec 29, 2016 
from http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-
_Product_Information/human/000715/WC500043546.pdf 
Macular Photocoagulation Study Group. Subfoveal neovascular lesions in age-related macular 
degeneration: guidelines for evaluation and treatment in the Macular Photocoagulation Study. 
Arch Ophthalmol. 1991;109:1242. 
Wu EW, Schaumberg DA, Park SK. Environmental cadmium and lead exposures and age-
related macular degeneration in U.S. adults: the National Health and Nutrition Examination 
Survey 2005 to 2008. Environmental research. 2014;133:178-184. 


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APPENDIX A: Grading Scale for Anterior Chamber Flare 
Grading Scale for Anterior Chamber Flare 
Flare 
 
0 
No protein is visible in the anterior chamber when viewed by an experienced 
observer using slit lamp biomicroscopy; a small, bright, focal slit-beam of 
white light; and high magnification. 
Trace 
Trace amount of protein detectable in the anterior chamber. This protein is 
visible only with careful scrutiny by an experienced observer using slit lamp 
biomicroscopy; a small, bright, focal slit-beam of white light; and high 
magnification. 
1+ 
Mild amount of protein detectable in the anterior chamber. The presence of 
protein in the anterior chamber is immediately apparent to an experienced 
observer using slit lamp biomicroscopy and high magnification, but such 
protein is detected only with careful observation with the naked eye and a 
small, bright, focal slit-beam of white light. 
2-3+ 
Moderate amount of protein detectable in the anterior chamber. These grades 
are similar to 1+ but the opacity would be readily visible to the naked eye of 
an observer using any source of a focused beam of white light, This is a 
continuum of moderate opacification, with 2+ being less apparent than 3+. 
4+ 
A large (severe) amount of protein is detectable in the anterior chamber. 
Similar to 3+, but the density of the protein approaches that of the lens. 
Additionally, frank fibrin deposition is frequently seen in acute circumstances.  
It needs to be noted that because fibrin may persist for a period of time after 
partial or complete restoration of the blood-aqueous barrier, it is possible to 
have resorbing fibrin present with lower numeric assignations for flare (e.g., 
1+ flare with fibrin). 
Reference: The Standardization of Uveitis Nomenclature (SUN) Working Group. 
Standardization of Uveitis Nomenclature for Reporting Clinical Data: Results of the First 
International Workshop. American journal of ophthalmology. 2005;140(3): 509-516. 


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APPENDIX B: Grading Scale for Anterior Chamber Cells 
Grading scale for anterior chamber cells 
The intensity of the cellular reaction in the anterior chamber is graded according to the 
number of inflammatory cells seen in a 1 x 3 mm high-powered beam at full intensity at a 
45°-60° angle. 
Cells 
 
0 
No inflammatory cells. 
Trace 
< 5 cells. 
1+ 
5 – 9 cells. 
2+ 
10 – 19 cells. 
3+ 
20 – 29 cells. 
4+ 
≥ 30 cells, cells too numerous to count. 
Reference: Bloch-Michel E., Nussenblatt RB. International Uveitis Study Group 
recommendations for the evaluation of intraocular inflammatory disease. Am J Ophthalmol. 
1987;103(2):234-5. 


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APPENDIX C: Grading Scale for Anterior Chamber and Vitreal 
Inflammatory Response 
Grading scale for anterior chamber and vitreal inflammatory response 
Cells in Retro-illuminated Field 
Description 
Grade 
0-1 
Clear 
0+ 
2-20 
Few opacities 
Trace 
21-50 
Scattered opacities 
1+ 
51-100 
Moderate opacities 
2+ 
101-250 
Many opacities 
3+ 
> 250 
Dense opacities 
4+ 
Reference: Nussenblatt RB, Palestine AG, Chan CC, Roberge F. Standardization of vitreal 
inflammatory activity in intermediate and posterior uveitis. Ophthalmology. 1985;92:467-71. 


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APPENDIX D: National Eye Institute 25-Item Visual Function 
Questionnaire (NEI VFQ-25 questionnaire) 
 
National Eye Institute  
Visual Functioning Questionnaire - 25 
(VFQ-25) 
 
version 2000 
 
 
 
(INTERVIEWER ADMINISTERED FORMAT) 
 
 
 
 
 
 
January 2000 
 
 
 
 
 
RAND hereby grants permission to use the "National Eye Institute Visual Functioning Questionnaire 25 (VFQ-25) July 1996, in 
accordance with the following conditions which shall be assumed by all to have been agreed to as a consequence of accepting and 
using this document: 
 
1.  Changes to the NEI VFQ-25 - July 1996 may be made without the written permission of RAND.  However, all such changes 
shall be clearly identified as having been made by the recipient. 
 
2.  The user of this NEI VFQ-25 - July 1996 accepts full responsibility, and agrees to hold RAND harmless, for the accuracy of 
any translations of the NEI VFQ-25 Test Version - July 1996 into another language and for any errors, omissions, 
misinterpretations, or consequences thereof. 
 
3.  The user of this NEI VFQ-25 - July 1996 accepts full responsibility, and agrees to hold RAND harmless, for any consequences 
resulting from the use of the NEI VFQ-25. 
 
4.  The user of the NEI VFQ-25 - July 1996 will provide a credit line when printing and distributing this document or in 
publications of results or analyses based on this instrument acknowledging that it was developed at RAND under the sponsorship 
of the National Eye Institute. 
 
5.  No further written permission is needed for use of this NEI VFQ-25 - July 1996.  
 
7/29/96 
 


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Instructions: 
I’m going to read you some statements about problems which involve your vision or feelings 
that you have about your vision condition.  After each question I will read you a list of 
possible answers.  Please choose the response that best describes your situation. 
Please answer all the questions as if you were wearing your glasses or contact lenses (if any). 
Please take as much time as you need to answer each question.  All your answers are 
confidential.  In order for this survey to improve our knowledge about vision problems and 
how they affect your quality of life, your answers must be as accurate as possible.  Remember, 
if you wear glasses or contact lenses for a particular activity, please answer all of the 
following questions as though you were wearing them. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Visual Functioning Questionnaire - 25 
 
 
PART 1 - GENERAL HEALTH AND VISION 
 
 
1. 
In general, would you say your overall health is*:  
 
 
(Circle One) 
READ CATEGORIES: 
Excellent ......................................   1 
 
Very Good ...................................   2 
 
Good ............................................   3 
 
Fair ...............................................   4 
 
Poor ..............................................   5 
 
 
 
 
2. 
At the present time, would you say your eyesight using both eyes (with glasses or 
contact lenses, if you wear them) is excellent, good, fair, poor, or very poor or are 
you completely blind? 
 
 
(Circle One) 
READ CATEGORIES: 
Excellent ......................................   1 
 
Good ............................................   2 
 
Fair ...............................................   3 
 
Poor ..............................................   4 
 
Very Poor .....................................   5 
 
Completely Blind .........................   6 
 
 
 
 
 
 
 
 
 
__________________________________________________________________________ 
* Skip Question 1 when the VFQ-25 is administered at the same time as the SF-36 or RAND 36-Item 
Health Survey 1.0 
 


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3. How much of the time do you worry about your eyesight? 
 
 
(Circle One) 
READ CATEGORIES: 
None of the time .......................................   1 
 
A little of the time .....................................   2 
 
Some of the time .......................................   3 
 
Most of the time ........................................   4 
 
All of the time? .........................................   5 
 
4. 
How much pain or discomfort have you had in and around your eyes (for example, 
burning, itching, or aching)?  Would you say it is: 
 
 
(Circle One) 
READ CATEGORIES: 
None .............................................   1 
 
Mild ..............................................   2 
 
Moderate ......................................   3 
 
Severe, or .....................................   4 
 
Very severe? ................................   5 
 
 
 
PART 2 - DIFFICULTY WITH ACTIVITIES 
 
The next questions are about how much difficulty, if any, you have doing certain activities 
wearing your glasses or contact lenses if you use them for that activity. 
 
5. 
How much difficulty do you have reading ordinary print in newspapers?  Would you 
say you have:  
 
(READ CATEGORIES AS NEEDED) 
 
(Circle One) 
 
No difficulty at all ......................................................................  1 
 
A little difficulty.........................................................................  2 
 
Moderate difficulty ....................................................................  3 
 
Extreme difficulty ......................................................................  4 
 
Stopped doing this because of your eyesight .............................  5 
 
Stopped doing this for other reasons or not  
interested in doing this ...............................................................  6 


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6. 
How much difficulty do you have doing work or hobbies that require you to see well up 
close, such as cooking, sewing, fixing things around the house, or using hand tools? 
Would you say: 
 
(READ CATEGORIES AS NEEDED) 
 
 (Circle One) 
 
No difficulty at all ......................................................................  1 
 
A little difficulty.........................................................................  2 
 
Moderate difficulty ....................................................................  3 
 
Extreme difficulty ......................................................................  4 
 
Stopped doing this because of your eyesight .............................  5 
 
Stopped doing this for other reasons or not  
interested in doing this ...............................................................  6 
 
 
7. 
Because of your eyesight, how much difficulty do you have finding something on a 
crowded shelf? 
 
(READ CATEGORIES AS NEEDED) 
 
(Circle One) 
 
No difficulty at all ......................................................................  1 
 
A little difficulty.........................................................................  2 
 
Moderate difficulty ....................................................................  3 
 
Extreme difficulty ......................................................................  4 
 
Stopped doing this because of your eyesight .............................  5 
 
Stopped doing this for other reasons or not  
interested in doing this ...............................................................  6 
 
 
8. 
How much difficulty do you have reading street signs or the names of stores?    
 
(READ CATEGORIES AS NEEDED) 
 
(Circle One) 
 
No difficulty at all ......................................................................  1 
 
A little difficulty.........................................................................  2 
 
Moderate difficulty ....................................................................  3 
 
Extreme difficulty ......................................................................  4 
 
Stopped doing this because of your eyesight .............................  5 
 
Stopped doing this for other reasons or not  
interested in doing this ...............................................................  6 


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9. 
Because of your eyesight, how much difficulty do you have going down steps, stairs, or 
curbs in dim light or at night?  
 
(READ CATEGORIES AS NEEDED) 
 
(Circle One) 
 
No difficulty at all ......................................................................  1 
 
A little difficulty.........................................................................  2 
 
Moderate difficulty ....................................................................  3 
 
Extreme difficulty ......................................................................  4 
 
Stopped doing this because of your eyesight .............................  5 
 
Stopped doing this for other reasons or not  
interested in doing this ...............................................................  6 
 
 
10. 
Because of your eyesight, how much difficulty do you have noticing objects off to the 
side while you are walking along? 
 
(READ CATEGORIES AS NEEDED) 
 
(Circle One) 
 
No difficulty at all ......................................................................  1 
 
A little difficulty.........................................................................  2 
 
Moderate difficulty ....................................................................  3 
 
Extreme difficulty ......................................................................  4 
 
Stopped doing this because of your eyesight .............................  5 
 
Stopped doing this for other reasons or not  
interested in doing this ...............................................................  6 
 
 
11. 
Because of your eyesight, how much difficulty do you have seeing how people react to 
things you say? 
(READ CATEGORIES AS NEEDED) 
 
(Circle One) 
 
No difficulty at all ......................................................................  1 
 
A little difficulty.........................................................................  2 
 
Moderate difficulty ....................................................................  3 
 
Extreme difficulty ......................................................................  4 
 
Stopped doing this because of your eyesight .............................  5 
 
Stopped doing this for other reasons or not  
interested in doing this ...............................................................  6 
 
 
 
 
 


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12. 
Because of your eyesight, how much difficulty do you have picking out and matching 
your own clothes? 
 
(READ CATEGORIES AS NEEDED) 
 
(Circle One) 
 
No difficulty at all ......................................................................  1 
 
A little difficulty.........................................................................  2 
 
Moderate difficulty ....................................................................  3 
 
Extreme difficulty ......................................................................  4 
 
Stopped doing this because of your eyesight .............................  5 
 
Stopped doing this for other reasons or not  
interested in doing this ...............................................................  6 
 
 
13. 
Because of your eyesight, how much difficulty do you have visiting with people in their 
homes, at parties, or in restaurants? 
(READ CATEGORIES AS NEEDED) 
 
(Circle One) 
 
No difficulty at all ......................................................................  1 
 
A little difficulty.........................................................................  2 
 
Moderate difficulty ....................................................................  3 
 
Extreme difficulty ......................................................................  4 
 
Stopped doing this because of your eyesight .............................  5 
 
Stopped doing this for other reasons or not  
interested in doing this ...............................................................  6 
 
 
14. 
Because of your eyesight, how much difficulty do you have going out to see movies, 
plays, or sports events? 
 
(READ CATEGORIES AS NEEDED) 
 
(Circle One) 
 
No difficulty at all ......................................................................  1 
 
A little difficulty.........................................................................  2 
 
Moderate difficulty ....................................................................  3 
 
Extreme difficulty ......................................................................  4 
 
Stopped doing this because of your eyesight .............................  5 
 
Stopped doing this for other reasons or not  
interested in doing this ...............................................................  6 
 
 
 
 
 


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15. 
Now, I’d like to ask about driving a car.  Are you currently driving, at least once in a 
while? 
 
 
(Circle One) 
 
 
Yes ................................. 1 Skip To Q 15c 
 
No .................................. 2 
 
15a. 
IF NO, ASK:  Have you never driven a car or have you given up driving? 
 
 
(Circle One) 
 
 
Never drove………… 1       Skip To Part 3, Q 17 
 
Gave up………………2 
 
15b. 
IF GAVE UP DRIVING:  Was that mainly because of your eyesight, mainly for 
some other reason, or because of both your eyesight and other reasons? 
 
 
(Circle One) 
 
 
Mainly eyesight ……………………..1                Skip To Part 3, Q 17 
 
Mainly other reasons………………...2                Skip To Part 3, Q 17 
 
Both eyesight and other reasons……..3               Skip To Part 3, Q 17 
 
15c. 
IF CURRENTLY DRIVING:  How much difficulty do you have driving during 
the daytime in familiar places?  Would you say you have: 
 
 
(Circle One) 
 
 
No difficulty at all ............................................  1 
 
A little difficulty ..............................................  2 
 
Moderate difficulty ..........................................  3 
 
Extreme difficulty ............................................  4 
 
 
 
 
 
 
 
 
 
 
 


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16.     How much difficulty do you have driving at night?  Would you say you have: (READ 
CATEGORIES AS NEEDED) 
 
 
(Circle One) 
 
No difficulty at all ..................................................   1 
 
A little difficulty ....................................................   2 
 
Moderate difficulty ................................................   3 
 
Extreme difficulty ..................................................   4 
 
Have you stopped doing this because 
of your eyesight .....................................................   5 
 
Have you stopped doing this for other  
reasons or are you not interested in  
doing this ................................................................  6 
 
 
 
16a. 
How much difficulty do you have driving in difficult conditions, such as in bad 
weather, during rush hour, on the freeway, or in city traffic?  Would you say 
you have:  
(READ CATEGORIES AS NEEDED) 
 
 
(Circle One) 
 
No difficulty at all ..................................................   1 
 
A little difficulty ....................................................   2 
 
Moderate difficulty ................................................   3 
 
Extreme difficulty ..................................................   4 
 
Have you stopped doing this because 
of your eyesight .....................................................   5 
 
Have you stopped doing this for other  
reasons or are you not interested in  
doing this ...............................................................   6 


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PART 3:  RESPONSES TO VISION PROBLEMS 
 
The next questions are about how things you do may be affected by your vision. For each one, 
I’d like you to tell me if this is true for you all, most, some, a little, or none of the time. 
 
 
(Circle One On Each Line) 
 
READ CATEGORIES: 
All of the 
time 
 
Most of 
the time 
 
Some of 
the time 
 
A little of 
the time 
 
None of 
the time 
 
17. Do you accomplish  
less than you would  
like because of your vision? .....  
1 
2 
3 
4 
5 
 
18. Are you limited in how long you 
can work or do other activities 
because  
of your vision?..........................  
1 
2 
3 
4 
5 
 
19. How much does pain or 
discomfort in or around your 
eyes, for example, burning, 
itching, or aching, keep you 
from doing what you’d like to 
be doing?  Would you say: .......  
1 
2 
3 
4 
5 
 


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For each of the following statements, please tell me if it is definitely true, mostly true, mostly 
false, or definitely false for you or you are not sure. 
 
 
(Circle One On Each Line) 
 
Definitely 
True 
Mostly 
True 
Not  
Sure 
Mostly 
False 
Definitely 
False 
 
 
 
 
 
20. I stay home most of the time because 
of my eyesight ...................................... 
1 
2 
3 
4 
5 
 
 
 
 
 
21. I feel frustrated a lot of the time 
because of my eyesight ...................  
1 
2 
3 
4 
5 
 
 
 
 
 
22. I have much less control over what I 
do, because of my eyesight .............  
1 
2 
3 
4 
5 
 
 
 
 
 
23. Because of my eyesight, I have 
to rely too much on what other 
people tell me ..................................  
1 
2 
3 
4 
5 
 
 
 
 
 
24. I need a lot of help from others 
because of my eyesight ...................  
1 
2 
3 
4 
5 
 
 
 
 
 
25. I worry about doing things that will 
embarrass myself or others, because 
of my eyesight .................................  
1 
2 
3 
4 
5 
 
 
That’s the end of the interview.  Thank you very much for your time and your help.  
 
 






SB11 (proposed ranibizumab biosimilar) 
SB11-G31-AMD 
Amendment 1, Sep 01, 2017 
 
Samsung Bioepis – Confidential 
Page 106 of 137 
 
SIGNATURE PAGE 
Declaration of the Principal Investigator 
Protocol Title: A Phase III Randomised, Double-masked, Parallel Group, Multicentre Study to 
Compare the Efficacy, Safety, Pharmacokinetics and Immunogenicity between SB11 
(proposed ranibizumab biosimilar) and Lucentis® in Subject with Neovascular Age-related 
Macular Degeneration 
This clinical study protocol was subjected to critical review. The information it contains is 
consistent with current knowledge of the risks and benefits of the investigational medicinal 
product, as well as with the moral, ethical and scientific principles governing clinical research 
as set out in the Declaration of Helsinki, 2013 and the guidelines on Good Clinical Practice 
applicable to this clinical study. 
Principal Investigator 
Name: 
 
Institution: 
 
Signature: 
 
Date: 
 
 
 
 
(MMM DD, YYYY) 


SB11 (proposed ranibizumab biosimilar) 
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Amendment 1, Sep 01, 2017 
 
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Page 107 of 137 
AMENDMENT 1: Sep 01, 2017 
 
Section Affected 
Original Content 
Amended/New Content 
Rationale 
Synopsis-Inclusion 
criteria 
 
4.1. Inclusion 
Criteria 
2.  
* Active CNV indicates presence of leakage as 
evidenced by Fluorescein Angiography (FA) and intra- 
or sub-retinal fluid as evidenced by Optical Coherence 
Tomography (OCT) which should be confirmed by 
central reading centre during Screening 
2.  
* Active CNV indicates presence of leakage as 
evidenced by Fluorescein Angiography (FA) and 
intra- or sub-retinal fluid as evidenced by Optical 
Coherence Tomography (OCT) which should be 
confirmed by central reading centre during Screening 
Per central reading 
centre’s practice, images 
used for assessment will 
be selected at the 
reader’s best knowledge. 
4. Total lesion area ≤ 9.0 Disc Areas (DA) in size 
(including blood, scars and neovascularisation) as 
assessed by FA in the study eye (confirmed by central 
reading centre during Screening) 
4. Total lesion area ≤ 9.0 Disc Areas (DA) in size 
(including blood, scars and neovascularisation) as 
assessed by FA in the study eye (confirmed by central 
reading centre during Screening) 
Per central reading 
centre’s practice, images 
used for assessment will 
be selected at the 
reader’s best knowledge. 
5. Best Corrected Visual Acuity (BCVA) of 20/40 to 
20/200 (letter score of 73 to 34) using Early Treatment 
Diabetic Retinopathy Study (ETDRS) chart or 2702 
Number chart in the study eye at Screening and at 
Week 0 (Day 1) prior to randomisation 
5. Best Corrected Visual Acuity (BCVA) of 20/40 to 
20/200 (letter score of 73 to 34) using original series 
Early Treatment Diabetic Retinopathy Study (ETDRS) 
charts or 2702 series Number charts in the study eye at 
Screening and at Week 0 (Day 1) prior to 
randomisation 
Clarification for charts 
used in this study 
6. Non-childbearing potential female (e.g., permanently 
sterilized, postmenopausal [defined as 12 months with 
no menses without an alternative medical cause prior to 
Screening]), OR Childbearing potential female subjects 
or male subjects with their (respectively male or 
female) partners who agree to use at least two forms of 
appropriate contraception method that can achieve a 
failure rate of less than 1% per year (e.g., established 
use of oral, injected, intravaginal, transdermal or 
implanted hormonal contraceptive, placement of an 
intrauterine device or intrauterine hormone-releasing 
6. Non-childbearing potential female (e.g., 
permanently sterilized sterilised, postmenopausal 
[defined as 12 months with no menses without an 
alternative medical cause prior to Screening]), OR 
Childbearing potential female subjects or male subjects 
with their (respectively male or female) partners who 
agree to use at least two forms of appropriate 
contraception method that can achieve a failure rate of 
less than 1% per year (e.g., established use of oral, 
injected, intravaginal, transdermal or implanted 
hormonal contraceptive, placement of an intrauterine 
Editorial change 


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SB11-G31-AMD 
Amendment 1, Sep 01, 2017 
 
Samsung Bioepis – Confidential 
Page 108 of 137 
Section Affected 
Original Content 
Amended/New Content 
Rationale 
system, bilateral tubal occlusion, vasectomised partner, 
physical barrier, sexual abstinence) from Screening 
until 3 months after the last ITV injection of IP 
device or intrauterine hormone-releasing system, 
bilateral tubal occlusion, vasectomised partner, 
physical barrier, sexual abstinence) from Screening 
until 3 months after the last ITV injection of IP 
Synopsis-Exclusion 
criteria 
 
4.2. Exclusion 
Criteria 
1. Sub- or intra-retinal haemorrhage that comprises 
more than 50% of the entire lesion in the 
study eye, or presence of subfoveal blood equal to or 
more than one DA in size as assessed by 
FA (confirmed by central reading centre during 
Screening) 
1. Sub- or intra-retinal haemorrhage that comprises 
more than 50% of the entire lesion in the 
study eye, or presence of subfoveal blood equal to or 
more than one DA in size as assessed by 
FA (confirmed by central reading centre during 
Screening) 
Per central reading 
centre’s practice, images 
used for assessment will 
be selected at the 
reader’s best knowledge. 
2. Scar, fibrosis or atrophy involving the centre of the 
fovea in the study eye as assessed by FA 
(confirmed by central reading centre during Screening) 
2. Scar, fibrosis or atrophy involving the centre of the 
fovea in the study eye as assessed by FA 
(confirmed by central reading centre during Screening) 
Per central reading 
centre’s practice, images 
used for assessment will 
be selected at the 
reader’s best knowledge. 
3. Presence of CNV in either eye due to other causes, 
such as ocular histoplasmosis, trauma, 
multifocal choroiditis, angioid streaks, history of 
choroidal rupture or Pathologic Myopia 
(PM) as assessed by FA (confirmed by central reading 
centre during Screening) 
3. Presence of CNV in either eye due to other causes, 
such as ocular histoplasmosis, trauma, 
multifocal choroiditis, angioid streaks, history of 
choroidal rupture or Pathologic Myopia 
(PM) as assessed by FA (confirmed by central reading 
centre during Screening) 
Per central reading 
centre’s practice, images 
used for assessment will 
be selected at the 
reader’s best knowledge. 
4. Presence of retinal pigment epithelial tears or rips 
involving the macula in the study eye as 
assessed by FA (confirmed by central reading centre 
during Screening) 
4. Presence of retinal pigment epithelial tears or rips 
involving the macula in the study eye as 
assessed by FA (confirmed by central reading centre 
during Screening) 
Per central reading 
centre’s practice, images 
used for assessment will 
be selected at the 
reader’s best knowledge. 
6. Any concurrent macular abnormality other than 
AMD in the study eye which, in the opinion of 
Investigator, could affect the efficacy of IP including 
but not limited to epiretinal membrane, macular 
telangiectasia, retinal vascular abnormality, etc 
6. Any concurrent macular abnormality other than 
AMD in the study eye which, in the opinion of 
Investigator, could affect the efficacy of IP including 
but not limited to epiretinal membrane, macular 
telangiectasia, retinal vascular abnormality, etc 
This criterion will be 
assessed by central 
reading centre. 


SB11 (proposed ranibizumab biosimilar) 
SB11-G31-AMD 
Amendment 1, Sep 01, 2017 
 
Samsung Bioepis – Confidential 
Page 109 of 137 
Section Affected 
Original Content 
Amended/New Content 
Rationale 
(confirmed by central reading centre) 
10. Any other intraocular surgery (including cataract 
surgery and laser photocoagulation) or periocular 
surgery in the study eye within 90 days prior to 
randomisation, except for lid surgery, which may not 
have taken place within 30 days prior to randomisation 
10. Any other intraocular surgery (including cataract 
surgery and laser photocoagulation) or periocular 
surgery in the study eye within 90 days prior to 
randomisation, except for lid surgery, which may not 
have taken place within 30 days prior to randomisation 
Error correction. Laser 
photocoagulation is not 
included in the category 
of surgery. 
13. Any systemic treatment or therapy (including 
prescribed herbal medication) to treat neovascular 
AMD within 30 days prior to randomisation, and such 
treatment or therapy will not be allowed during the 
study period. However, dietary supplementary, 
vitamins or mineral will be allowed. 
13. Any systemic treatment or therapy (including 
prescribed herbal medication) to treat neovascular 
AMD within 30 days prior to randomisation, and such 
treatment or therapy will not be allowed during the 
study period. However, 
dietary supplementary supplements, vitamins or 
mineral will be allowed. 
Editorial change 
14. Any ITV sustained drug delivery implant in the 
study eye  (e.g., intravitreal corticosteroid implant) 
within 180 days prior to randomisation, and such 
treatment will not be allowed during the study period 
14. Any ITV intravitreal injection of corticosteroid 
(e.g., triamcinolone acetonide) or sustained drug 
delivery implant in the study eye (e.g., intravitreal 
corticosteroid implant) in the study eye within 180 
days prior to randomisation, and such treatment will 
not be allowed during the study period 
Prohibited medication is 
added. 
16. Spherical equivalent of the refractive error in the 
study eye demonstrating more than 8 diopters of 
myopia 
16. Spherical equivalent of the refractive error in the 
study eye demonstrating more than 8 diopters of 
myopia. For subjects who have undergone previous 
refractive or cataract surgery in the study eye, the 
preoperative refractive error in the study eye must  
not exceed 8 diopters of myopia 
Clarification for subjects 
who have undergone 
refractive or cataract 
surgery in the study eye  
21. History of idiopathic or autoimmune-associated 
uveitis in either eye 
21. History of idiopathic or autoimmune-associated 
uveitis in either eye 
Editorial change 
24. History of corneal transplant in the study eye 
24. History of corneal transplantation surgery in the 
study eye 
Editorial change 
25. Presence of advanced glaucoma or optic 
neuropathy that involve or threaten the central visual 
25. Presence of advanced glaucoma or optic 
neuropathy that involve affect or threaten the central 
Editorial change 
 


SB11 (proposed ranibizumab biosimilar) 
SB11-G31-AMD 
Amendment 1, Sep 01, 2017 
 
Samsung Bioepis – Confidential 
Page 110 of 137 
Section Affected 
Original Content 
Amended/New Content 
Rationale 
field 
visual field in the study eye 
Target eye is specified. 
29. Previous participation in any studies of ocular or 
systemic investigational products (excluding dietary 
supplementary, vitamins and minerals) to treat ocular 
or systemic disease other than neovascular AMD 
within 90 days prior to randomisation, and such 
participation will not be allowed during the study 
period even if the investigational product is dietary 
supplementary, vitamins and minerals 
29. Previous participation in any studies of ocular or 
systemic investigational products (excluding 
dietary supplementary supplements, vitamins and 
minerals) to treat ocular or systemic disease other than 
neovascular AMD within 90 days prior to 
randomisation, and such participation will not be 
allowed during the study period even if the 
investigational product is 
dietary supplementary supplements, vitamins and 
minerals 
Editorial change 
30. History or clinical evidence of diabetic retinopathy 
(except for mild non-proliferative diabetic retinopathy), 
diabetic macular oedema or any retinal vascular disease 
other than AMD in either eye 
30. History or clinical evidence of diabetic retinopathy 
(except for mild non-proliferative diabetic retinopathy), 
or diabetic macular oedema or any retinal vascular 
disease other than AMD in either eye 
Retinal vascular disease 
that affects macula will 
be excluded from 
exclusion criterion #6. 
31. Any concurrent ocular condition in the study eye 
which, in the opinion of Investigator, could either 
increase the risk to the subject safety or which 
otherwise may interfere with evaluation of efficacy or 
safety including, but not limited to corneal opacities, 
cataract, ocular media that do not allow proper fundus 
visualisation and fundus imaging, and ocular surface 
abnormalities which prevent applanation tonometry 
during the study period after randomisation 
31. Any concurrent ocular condition in the study eye 
which, in the opinion of the Investigator, could either 
increase the risk to the subject safety or which 
otherwise may interfere with evaluation of efficacy or 
safety including, but not limited to ocular media 
opacities such as corneal opacities, opacity or 
cataract, ocular media that do not allow proper fundus 
visualisation and fundus imaging, and ocular surface 
abnormalities which prevent applanation tonometry 
during the study period after randomisation 
Editorial change 
33. Pregnant or lactating women. A serum pregnancy 
test must be required for all women at Screening 
33. Pregnant or lactating women. A serum pregnancy 
test must be required for all women of childbearing 
potential at Screening 
Pregnancy test will be 
performed only for 
childbearing potential 
female subjects. 
Not applicable 
35. Stroke, transient ischemic attacks, or 
myocardial infarction within 90 days prior to 
Exclusion criterion is 
added as per Korea 


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SB11-G31-AMD 
Amendment 1, Sep 01, 2017 
 
Samsung Bioepis – Confidential 
Page 111 of 137 
Section Affected 
Original Content 
Amended/New Content 
Rationale 
randomisation 
MFDS’s request. 
Not applicable 
36. History of recurrent significant infections and/or 
current treatment for active systemic infection 
Exclusion criterion is 
added as per Korea 
MFDS’s request. 
Not applicable 
37. Known allergic reactions and/or hypersensitivity 
to ranibizumab or to any ingredients of the 
investigational product 
Exclusion criterion is 
added as per Korea 
MFDS’s request. 
Not applicable 
38. Prior treatment involving macula with 
photodynamic therapy with verteporfin, 
transpupillary thermotherapy, radiation therapy, or 
retinal laser treatment (e,g., focal laser 
photocoagulation) in the study eye, and such 
treatment will not be allowed during the study 
period 
Exclusion criterion is 
added as per Korea 
MFDS’s request. 
Not applicable 
39. Prior treatment with pan-retinal 
photocoagulation in the study eye, and such 
treatment will not be allowed during the study 
period 
Exclusion criterion is 
added as per Korea 
MFDS’s request. 
Not applicable 
40. Current use of systemic medications known to 
be toxic to the lens, retina or optic nerve, including 
deferoxamine, chloroquine/hydroxychloroquine, 
tamoxifen, phenothiazines, vigabatrin and 
ethambutol, and such medications will not be 
allowed during the study period 
Exclusion criterion is 
added as per Korea 
MFDS’s request. 
Synopsis- 
Primary endpoints 
 
6.1.1. Primary 
Endpoint 
For US Food and Drug Administration (FDA), Korea 
Ministry of Food and Drug Safety (MFDS) or other 
regulatory agency submissions for those who are in 
favour of  VA, the primary endpoint is: 
Change from baseline in BCVA at Week 8 
For European Medicines Agency (EMA) or other 
regulatory agency submissions for those who are in 
For US Food and Drug Administration (FDA), Korea 
Ministry of Food and Drug Safety (MFDS) or other 
regulatory agency submissions for those who are in 
favour of the VA, the primary endpoint is: 
Change from baseline in BCVA at Week 8 
For European Medicines Agency (EMA) or other 
regulatory agency submissions for those who are in 
Editorial change 


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SB11-G31-AMD 
Amendment 1, Sep 01, 2017 
 
Samsung Bioepis – Confidential 
Page 112 of 137 
Section Affected 
Original Content 
Amended/New Content 
Rationale 
favour of anatomical parameter, the primary endpoint 
is: 
Change from baseline in Central Subfield Thickness 
(CST) at Week 4 (based on assessment by central 
reading centre) 
favour of the anatomical parameter, the primary 
endpoint is: 
 Change from baseline in Central Subfield Thickness 
(CST) at Week 4 (based on assessment by central 
reading centre) 
Synopsis-
Secondary 
endpoints 
 
6.1.2. Secondary 
Endpoints 
The secondary efficacy endpoints are: 
Proportion of subjects without intra- or sub-retinal fluid 
at Week 24 and Week 52 (based on assessment by 
central reading centre) 
The secondary efficacy endpoints are: 
Proportion of subjects without intra- or sub-retinal 
fluid at Week 24 and Week 52 (based on assessment 
by central reading centre) 
To move exploratory 
endpoint section. The 
endpoint has few clinical 
meaning with high 
variability. 
The pharmacokinetic endpoints are: 
PK sampling will be collected in approximately 120 
subjects participating in PK evaluation (60 subjects per 
treatment group). 
The pharmacokinetic endpoints are: 
PK sampling Blood sampling for PK will be 
collected in approximately 12040 subjects participating 
in PK evaluation (6020 subjects per treatment group). 
Number of subjects 
participating in PK 
evaluation is changed as 
per US FDA’s request. 
Synopsis-
Exploratory 
endpoint 
 
6.1.3. Exploratory 
Endpoint 
The exploratory endpoint is: 
 
The Quality of Life (QOL) is assessed using National 
Eye Institute 25-Item Visual Function Questionnaire 
(NEI VFQ-25). 
Change from baseline in subscale scores and composite 
scores of NEI-VFQ-25 at Week 24 and Week 52 
The exploratory endpoints is are : 
 
Proportion of subjects without intra- or sub-retinal 
fluid at Week 24 and Week 52 (based on assessment 
by central reading centre) 
The Quality of Life (QOL) is assessed using National 
Eye Institute 25-Item Visual Function Questionnaire 
(NEI VFQ-25). 
Change from baseline in subscale scores and composite 
scores of NEI-VFQ-25 at Week 24 and Week 52 
To move exploratory 
endpoint section. The 
endpoint has few clinical 
meaning with high 
variability. 
Synopsis- 
Statistical Methods: 
Efficacy analysis 
 
9.2.2. Efficacy 
The primary efficacy analysis will be performed for the 
FAS with the change from baseline of BCVA at Week 
8 using an analysis of covariance model with the 
baseline BCVA as a covariate and region (or pooled 
centres) and treatment group as factors. 
For US FDA, Korea MFDS or other regulatory 
agency submissions for those who are in favour of 
the VA, The the primary efficacy analysis will be 
performed for the FAS with the change from baseline 
of BCVA at Week 8 using an analysis of covariance 
model with the baseline BCVA as a covariate and 
region (or pooled centres) and treatment group as 
Clarification for primary 
efficacy endpoint 
analysis for BCVA 


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SB11-G31-AMD 
Amendment 1, Sep 01, 2017 
 
Samsung Bioepis – Confidential 
Page 113 of 137 
Section Affected 
Original Content 
Amended/New Content 
Rationale 
factors. 
The other primary efficacy analysis will be performed 
for the FAS  and Per-Protocol Set (PPS-CST) with the 
change from baseline of CST at Week 4 using an 
analysis of covariance model with baseline CST as a 
covariate and region (or pooled centres) and treatment 
group as factors. 
The other primary efficacy analysis will be 
performed for the FAS and Per-Protocol Set (PPS-
CST) For EMA or other regulatory agency 
submissions for those who are in favour of the 
anatomical parameter, the primary efficacy analysis 
will be performed for the per-protocol set (PPS-
CST) with the change from baseline of CST at Week 4 
using an analysis of covariance model with baseline 
CST as a covariate and region (or pooled centres) and 
treatment group as factors. 
Clarification for primary 
efficacy endpoint 
analysis for CST 
For the sensitivity analysis, missing data will be 
imputed using the Last Observation Carried Forward 
(LOCF) or other multiple imputation methods for the 
FAS. 
For the sensitivity analysis, missing data will be 
imputed using the Last Observation Carried 
Forward (LOCF) or other multiple imputation 
methods for the FAS. For the primary analysis with 
the FAS for BCVA, missing data will be imputed for 
subjects who drop out for the study prior to the 
primary analysis time-point. A missing-at-random 
approach will assume that subjects who withdraw 
from a study had missing values similar to similar 
subjects who completed the study in that treatment 
group. This approach ensures that evidence of lack 
of equivalence is not diluted when there are missing 
data. For the components of BCVA, the missing 
letter will be imputed by multiple imputation 
method with the assumption of monotone missing 
pattern and regression method. For the sensitivity 
analyses, available case analysis and last 
observation carried forward analysis will be 
performed. 
Clarification for missing 
imputation method 
Synopsis- 
Statistical Methods: 
Blood sampling for PK will be collected in 
approximately 120 subjects participating in PK 
Blood sampling for PK will be collected in 
approximately 12040 subjects participating in PK 
Number of subjects 
participating in PK 


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Section Affected 
Original Content 
Amended/New Content 
Rationale 
Pharmacokinetic 
analysis 
evaluation (60 subjects per treatment group). 
evaluation (6020 subjects per treatment group). 
evaluation is changed as 
per US FDA’s request. 
Synopsis- 
Statistical Methods: 
NEI VFQ-25 
analyses 
 
Subscale scores (general health, general vision, ocular 
pain, near activities, distance activities, vision-specific 
social functioning, vision-specific mental health, 
vision-specific role difficulties, vision-specific 
dependency, driving, colour vision, and peripheral 
vision) and the composite score, which represent 
overall visual function, will be calculated, and the 
change from baseline will be summarized by treatment 
group and visit. 
Subscale scores (general health, general vision, ocular 
pain, near activities, distance activities, vision-specific 
social functioning, vision-specific mental health, 
vision-specific role difficulties, vision-specific 
dependency, driving, colour vision, and peripheral 
vision) and the composite score, which represent 
overall visual function, will be calculated, and the 
change from baseline will be summarized 
summarised by treatment group and visit. 
Editorial change 
Table 1. Schedule 
of Activities 
NEI VFQ-25: 
Week 0, Week 12, Week 24, Week 36, Week 52 
(EOS/ET) 
NEI VFQ-25: 
Week 0, Week 12, Week 24, Week 36, Week 52 
(EOS/ET) 
Frequency of NEI VFQ-
25 is changed as per US 
FDA’s request. 
Table 1 
Footnote  
 
 
 
 
3. Physical examination will be performed at Screening 
and Week 52 (EOS visit) or ET visit. Body weight will 
be measured and recorded at Screening and Week 52 
(EOS visit) or ET visit, but height will be measured 
and recorded only at Screening. 
3. Physical examination will be performed at Screening 
and Week 52 (EOS visit) or ET visit. The physical 
examination will include an assessment of the 
subject’s general appearance, skin, head, neck, 
throat, lymph nodes, cardiovascular, neurological, 
thyroid, musculoskeletal/extremities, respiratory 
systems and the subject’s abdomen. Body weight 
will be measured and recorded at Screening and Week 
52 (EOS visit) or ET visit, but height will be measured 
and recorded only at Screening. 
Clarification for physical 
examination (systems 
and organs)  
6. Visual acuity will be assessed in both the study eye 
and fellow (non-study) eye at Screening and prior to 
ITV injection of IP at each visit until Week 48. Visual 
acuity will also be assessed at any time during the visit 
at Week 52 (EOS visit) or ET visit. Subject must use 
either ETDRS chart or 2702 Number chart (at a starting 
distance of 4 meters) consistently from Screening to 
6. Visual acuity will be assessed in both the study eye 
and fellow (non-study) eye at Screening and prior to 
ITV injection of IP at each visit until Week 48. Visual 
acuity will also be assessed at any time during the visit 
at Week 52 (EOS visit) or ET visit. Subject must use 
either original series ETDRS charts or 2702 series 
Number charts (at a starting distance of 4 meters) 
Clarification for charts 
used in this study 
 
 
 
 
 


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Section Affected 
Original Content 
Amended/New Content 
Rationale 
Week 52 (EOS visit) or ET visit. Visual acuity testing 
must be performed before dilation of pupils and FP/FA 
and OCT assessment. A decrease in visual acuity of > 
15 letters (compared with the last assessment of VA) 
should be reported as AEs/Serious Adverse Events 
(SAEs) as appropriate. If there is a decrease in VA of > 
30 letters (compared with the last assessment of VA) 
lasting > 1 hour or if there is a decrease in VA to the 
level of Light Perception or worse lasting > 1 hour, it 
should be reported as SAE. 
consistently from Screening to Week 52 (EOS visit) or 
ET visit. Visual acuity testing must be performed 
before dilation of pupils and FP/FA and OCT 
assessment. A decrease in visual acuity of ≥> 15 
letters (compared with from the last assessment of 
VA) should be reported as AEs/Serious Adverse 
Events (SAEs) as appropriate. If there is a decrease in 
VA of ≥> 30 letters (compared with from the last 
assessment of VA) lasting > 1 hour or if there is a 
decrease in VA to the level of Light Perception or 
worse lasting > 1 hour, it should be reported as SAE. 
 
 
 
Error correction 
 
 
 
SAE criteria are 
changed. 
7. Investigator must confirm that the subject can read 
between 34 letters to 73 letters using ETDRS chart or 
2702 Number chart at Week 0 (Day1) prior to 
randomisation 
7. Investigator must confirm that the subject can read 
between 34 letters to 73 letters using original series 
ETDRS charts or 2702 series Number charts at Week 0 
(Day1) prior to randomisation 
Clarification for charts 
used in this study 
8. Visit at Week 8 is the most critical as the visit is for 
the primary endpoint assessment for US FDA, Korea 
MFDS or other regulatory agency submissions for 
those who are in favour of VA. Thus, every effort 
should be made to adhere to the visit schedule for the 
subjects. 
8. Visit at Week 8 is the most critical as the visit is for 
the primary endpoint assessment for US FDA, Korea 
MFDS or other regulatory agency submissions for 
those who are in favour of the VA. Thus, every effort 
should be made to adhere to the visit schedule for the 
subjects. 
Editorial change 
9. OCT will be performed only in the study eye at 
Screening and prior to ITV injection of IP at each visit 
until Week 48. OCT will also be performed at any time 
during the visit at Week 52 (EOS visit) or ET visit. 
Only OCT devices registered and certified by central 
reading centre are allowed to be used in this study. If 
one or more OCT devices are registered and certified in 
an Investigational site, a subject should use the same 
OCT device consistently from Screening to Week 52 
(EOS visit) or ET visit. OCT images will be sent to the 
central reading centre. 
9. OCT will be performed only in on the study eye at 
Screening and prior to ITV injection of IP at each visit 
until Week 48. OCT will also be performed at any time 
during the visit at Week 52 (EOS visit) or ET visit.  
Site staffs who will perform OCT scans in this study 
must be certified by the central reading centre 
before study starts. OCT devices registered in an 
Investigational site should be all from the same 
manufacture and meet the minimum software 
requirement. Only OCT devices registered and 
certified by central reading centre are allowed to be 
Editorial change 


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Section Affected 
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Rationale 
used in this study. If one or more OCT devices are 
registered and certified in an Investigational site, a 
subject should use the same OCT device 
consistently The subject should use the OCT device 
registered by the central reading centre from 
Screening to Week 52 (EOS visit) or ET visit. 
10. Visit at Week 4 is the most critical as the visit is for 
the primary endpoint assessment for EMA or other 
regulatory agency submissions for those who are in 
favour of anatomical parameter. Thus, every effort 
should be made to adhere to the visit schedule for the 
subjects. 
10. Visit at Week 4 is the most critical as the visit is for 
the primary endpoint assessment for EMA or other 
regulatory agency submissions for those who are in 
favour of the anatomical parameter. Thus, every effort 
should be made to adhere to the visit schedule for the 
subjects. 
Editorial change 
11. FP/FA will be performed only in the study eye at 
Screening and prior to ITV injection of IP at Week 24. 
FP/FA will also be performed at any time during the 
visit at Week 52 (EOS visit) or ET visit. Only FP/FA 
device certified by central reading centre is allowed to 
be used in this study. If one or more FP/FA devices are 
certified in an Investigational site, a subject must use 
the same FP/FA device consistently from Screening to 
Week 52 (EOS visit) or ET visit. FP/FA images will be 
sent to the central reading centre. If any significant 
change in the posterior pole (i.e. subretinal 
haemorrhage, macular hole, vitreous haemorrhage or 
opacity, retinal detachment, etc.) is detected with 
fundus examination, additional FP and/or FA can be 
performed at Investigator’s discretion, but the images 
will not be sent to the central reading centre. 
 
11. FP/FA will be performed only in on the study both 
eyes at Screening and those images taken from the 
both eyes will be sent to the central reading centre. 
FP/FA will also be performed on the study eye prior 
to ITV injection of IP at Week 24 and. FP/FA will 
also be performed at any time during the visit at Week 
52 (EOS visit) or ET visit. Those images taken from 
the study eye will be sent to the central reading 
centre. Site staffs who will perform FA/FP in this 
study must be certified by the central reading centre 
before study starts. Only FP/FA device certified by 
central reading centre is allowed to be used in this 
study. If one or more FP/FA devices are certified in an 
Investigational site, a subject must use the same FP/FA 
device consistently from Screening to Week 52 (EOS 
visit) or ET visit. FP/FA images will be sent to the 
central reading centre. If any significant change in 
the posterior pole (i.e. subretinal haemorrhage, macular 
hole, vitreous haemorrhage or opacity, retinal 
detachment, etc.) is detected with fundus examination, 
According to exclusion 
criteria #3, FP/FA 
images taken from the 
both eyes should be sent 
to the central reading 
centre at Screening. 
 
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Rationale 
additional FP and/or FA can be performed at the 
Investigator’s discretion, but the images will not be 
sent to the central reading centre. 
12. Indirect ophthalmoscopy using a standard way (i.e., 
usually using a head-mounted light source and a 20-30 
lens) will be performed only in the study eye at 
Screening and prior to ITV injection of IP and within 
15 minutes after ITV injection of IP at each visit until 
Week 48. Indirect ophthalmoscopy will also be 
performed at any time during the visit at Week 52 
(EOS visit) or ET visit. 
12. Indirect ophthalmoscopy using a standard way (i.e., 
usually using a head-mounted light source and a 20-30 
lens) will be performed only in on the study eye at 
Screening and prior to ITV injection of IP and within 
15 minutes after ITV injection of IP at each visit until 
Week 48. Indirect ophthalmoscopy will also be 
performed at any time during the visit at Week 52 
(EOS visit) or ET visit. 
Editorial change 
 
14. Intraocular Pressure (IOP) will be measured using 
Goldmann applanation tonometry only. The same 
method of IOP measurement must be used in each 
subject from Screening to Week 52 (EOS visit) or ET 
visit. IOP will be measured only in the study eye at 
Screening and prior to ITV injection of IP and 30-60 
minutes after ITV injection of IP at each visit until 
Week 48.  
14. Intraocular Pressure (IOP) will be measured using 
Goldmann applanation tonometry only. The same 
method of IOP measurement must be used in each 
subject from Screening to Week 52 (EOS visit) or ET 
visit. IOP will be measured only in on the study eye at 
Screening and prior to ITV injection of IP and 30-60 
minutes after ITV injection of IP at each visit until 
Week 48.  
Editorial change 
 
15. NEI VFQ-25 should be performed at Week 0 
(Day1) after randomisation, but prior to starting any 
other study procedures. Then, NEI VFQ-25 should be 
performed before starting any other study procedures at 
Week 12, Week 24, Week 36 and Week 52 (EOS visit) 
or ET visit. 
15. NEI VFQ-25 should be performed at Week 0 
(Day1) after randomisation, but prior to starting any 
other study procedures. Then, NEI VFQ-25 should be 
performed before starting any other study 
procedures dilation of pupil at Week 0 (Day 
1), Week 12, Week 24, Week 36 and Week 52 (EOS 
visit) or ET visit. 
Frequency of NEI VFQ-
25 is changed as per US 
FDA’s request. 


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16. Blood and urine sampling for clinical laboratory 
test will be collected at Screening and prior to ITV 
injection of IP at Week 12, Week 24, and Week 36. 
Blood and urine sampling for clinical laboratory test 
will also be collected at any time during the visit at 
Week 52 (EOS visit) or ET visit. Urine samples must 
be collected before performing FA to avoid false 
elevations in urine protein values. 
• Haematology: haemoglobin, haematocrit, platelet 
count, white blood cell count (total and differential) 
• Chemistry: sodium, potassium, creatinine, glucose, 
calcium, phosphorus, total bilirubin, albumin, alanine 
aminotransferase, aspartate aminotransferase, alkaline 
phosphatase, lactate dehydrogenase 
• Urinalysis (dipstick):  protein, blood, leucocytes, 
nitrite, glucose, ketone, pH, specific gravity, bilirubin, 
urobilinogen 
16. Blood and urine sampling for clinical laboratory 
test will be collected at Screening and prior to ITV 
injection of IP at Week 12, Week 24, and Week 36. 
Blood and urine sampling for clinical laboratory test 
will also be collected at any time during the visit at 
Week 52 (EOS visit) or ET visit. Urine samples must 
be collected before performing FA to avoid false 
elevations in urine protein values. 
• Haematology: haemoglobin, haematocrit, platelet 
count, white blood cell count (total and differential) 
• Chemistry: sodium, potassium, creatinine, glucose, 
calcium, phosphorus, total bilirubin, albumin, alanine 
aminotransferase, aspartate aminotransferase, alkaline 
phosphatase, lactate dehydrogenase 
• Urinalysis (dipstick):  protein, blood, leucocytes, 
nitrite, glucose, ketone, pH, specific gravity, bilirubin, 
urobilinogen 
Blood samples will be analysed in central laboratory 
and urine samples will be tested in each 
Investigational site by using a dipstick which will be 
provided by Sponsor. 
Clarification for central 
laboratory test 
18. Blood sampling for PK will be collected only in 
approximately 120 subjects participating in PK 
evaluation (60 subjects per treatment group). 
18. Blood sampling for PK will be collected only in 
approximately 12040 subjects participating in PK 
evaluation (6020 subjects per treatment group). 
Number of subjects 
participating in PK 
evaluation is changed as 
per US FDA’s request. 
19. For all women, serum pregnancy test must be 
performed at Screening. Serum or urine pregnancy test 
may be performed after randomisation at Investigator’s 
discretion. 
19. For all women of childbearing potential, serum 
pregnancy test must be performed at Screening. The 
serum samples taken at Screening will be analysed 
in central laboratory. Additional Sserum or urine 
pregnancy test may can be performed after 
randomisation at Investigator’s discretion in each 
Investigational site during the study period, if 
Pregnancy test will be 
performed only for 
childbearing potential 
female subjects. 
 
Clarification for 
pregnancy test 


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necessary. 
20. Subjects will be administered SB11 or Lucentis® 
0.5 mg via ITV into the study eye every 4 weeks up to 
Week 48. Dosing visits will be allowed within ± 7 days 
of the scheduled dosing visit date (except Week 0 (Day 
1), visit window not allowed). If a dose of IP is not 
given within 7 days of the scheduled dosing visit date, 
the IP should be given within 21 days of the scheduled 
dosing visit date, but the case will be captured as 
protocol deviation. Dosing skip is defined when a 
subject does not receive the IP within 21 days (3 
weeks) after scheduled dosing visit date. Next 
scheduled dosing visit date and visit window should 
not be altered even though previous dosing is not 
performed on the exact scheduled dosing visit date 
(but, the interval between two doses injected into the 
study eye should be at least 14 days) or previous dosing 
is skipped. 
20. Subjects will be administered SB11 or Lucentis® 
0.5 mg via ITV into the study eye every 4 weeks up to 
Week 48. Dosing visits will be allowed within ± 7 days 
of the scheduled dosing visit date (except Week 0 (Day 
1), visit window not allowed). If a dose of IP is not 
given within 7 days of the scheduled dosing visit date, 
the IP should be given within 21 20 days of the 
scheduled dosing visit date, but the case will be 
captured as protocol deviation. Dosing skip is defined 
when a subject does not receive the IP within 21 20 
days (3 weeks) after scheduled dosing visit date. Next 
scheduled dosing visit date and visit window should 
not be altered even though previous dosing is not 
performed on the exact scheduled dosing visit date 
(but, the interval between two doses injected into the 
study eye should be at least 14 days) or previous dosing 
is skipped. 
Error correction 
21. The first ITV injection of IP should be performed at 
the same day of randomisation or the following day 
after randomisation at the latest with a proper reason. 
21. The first ITV injection of IP and all other study 
procedures should must be performed at the same day 
of randomisation or the following day after 
randomisation at the latest with a proper reason. 
Editorial change 
Background 
Age-related Macular Degeneration, left untreated, is a 
leading cause of adult blindness in the developed 
world. Most of severe visual loss of AMD occurs from 
CNV or the neovascular form of AMD 
 
 
…as well as atrophy of these portions of the retina in 
Age-related Macular Degeneration (AMD), left 
untreated, is a leading cause of adult blindness in the 
developed world. Most of severe visual loss of AMD 
occurs from Choroidal Neovascularisation (CNV) or 
the neovascular form of AMD 
 
… as well as atrophy of these portions of the retina in 
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the macula, leading to severe visual decline with loss of 
reading vision, driving vision, and the ability to 
recognize faces. Vascular endothelial growth factor, a 
protein growth factor that both stimulates angiogenesis 
and increases vascular permeability,… 
 
 
The pathogenesis of AMD is poorly understood. It is 
characterized by development of focal deposits of long 
–spacing collagen and phospholipid vesicles within and 
beneath the basement membrane of the RPE, called 
“drusen” which can be accompanied by gradual 
degeneration of photoreceptors and RPE (atrophy), 
which often results in slow deterioration of central 
visual acuity (VA). 
the macula, leading to severe visual decline with loss of 
reading vision, driving vision, and the ability 
to recognize recognise faces. Vascular Eendothelial 
Ggrowth Ffactor (VEGF), a protein growth factor that 
both stimulates angiogenesis and increases vascular 
permeability,… 
 
The pathogenesis of AMD is poorly understood. It 
is characterized characterised by development of 
focal deposits of long –spacing collagen and 
phospholipid vesicles within and beneath the basement 
membrane of the RPE, called “drusen” which can be 
accompanied by gradual degeneration of 
photoreceptors and RPE (atrophy), which often results 
in slow deterioration of central Visual Acuity (VA). 
1.2. Lucentis®: 
Ranibizumab 
Reference Product 
Neovascular (Wet) Age-Related Macular Degeneration 
The safety and efficacy of Lucentis® were assessed in 
three randomized, double or single-masked, sham-or 
active-controlled studies in subjects with neovascular 
AMD. 
Macular Oedema Following Retinal Vein Occlusion 
The safety and efficacy of Lucentis® were assessed in 
two randomized, double-masked, 1-year studies in 
subjects with macular oedema following RVO. 
Neovascular (Wet) Age-Related Macular Degeneration 
The safety and efficacy of Lucentis® were assessed in 
three randomized randomised, double or single-
masked, sham-or active-controlled studies in subjects 
with neovascular AMD. 
Macular Oedema Following Retinal Vein Occlusion 
The safety and efficacy of Lucentis® were assessed in 
two randomized randomised, double-masked, 1-year 
studies in subjects with macular oedema following 
RVO. 
Editorial change 
1.3. SB11: 
Proposed 
Ranibizumab 
Biosimilar 
Extensive characterization studies including intact 
mass, N- and C-terminal sequencing, peptide mapping, 
icIEF, CE-SDS (reduced, non-reduced), SE-HPLC, 
amino acid composition, disulfide bond, VEGF 
binding, VEGF neutralization, 
Extensive characterization characterisation studies 
including intact mass, N- and C-terminal sequencing, 
peptide mapping, icIEF, CE-SDS (reduced, non-
reduced), SE-HPLC, amino acid composition, disulfide 
bond, VEGF binding, VEGF neutralization 
neutralisation, 
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Rationale 
1.4. Rationale for 
the Study 
A biosimilar is a biological medicinal product that is 
highly similar to an already authorized original 
biological medicinal product … 
These guidelines recommend a stepwise approach in 
developing a biosimilar starting with extensive 
physicochemical and biological characterization before 
initiating clinical studies for the comparison of the 
efficacy,… 
A biosimilar is a biological medicinal product that is 
highly similar to an already authorized authorised 
original biological medicinal product … 
These guidelines recommend a stepwise approach in 
developing a biosimilar starting with extensive 
physicochemical and 
biological characterization characterisation before 
initiating clinical studies for the comparison of the 
efficacy,… 
Editorial change 
3.2 Rationale for 
the Study Design 
However, for supporting the assessment of overall 
systemic safety of SB11 relative to Lucentis®, systemic 
exposures will be collected and compared in the 
subgroup population (approximately 120 subjects, 60 
subjects per treatment group) in Phase III comparative 
efficacy study. 
However, for supporting the assessment of overall 
systemic safety of SB11 relative to Lucentis®, systemic 
exposures will be collected and compared in the 
subgroup population (approximately 12040 
subjects, 6020 subjects per treatment group) in Phase 
III comparative efficacy study. 
Number of subjects 
participating in PK 
evaluation is changed as 
per US FDA’s request. 
For US FDA, Korea MFDS or other regulatory agency 
submissions for those who are in favour of VA,… 
For EMA or other regulatory agency submission for 
those who are in favour of anatomical parameter,… 
Ranibizumab binds with high affinity to all active 
VEGF-A isoforms (e.g. VEGF110, VEGF121 and 
VEGF165) on the surface of endothelial cells, thereby 
preventing binding of VEGF-A to its receptors and 
reducing endothelial cell proliferation,… 
For US FDA, Korea Ministry of Food and Drug 
Safety (MFDS) or other regulatory agency submissions 
for those who are in favour of the VA,… 
For EMA or other regulatory agency submission for 
those who are in favour of the anatomical parameter,… 
Ranibizumab binds with high affinity to all active 
VEGF-A isoforms (e.g., VEGF110, VEGF121 and 
VEGF165) on the surface of endothelial cells, thereby 
preventing binding of VEGF-A to its receptors and 
reducing endothelial cell proliferation,… 
Editorial change 
4.3. Subject 
Discontinuation 
from 
Investigational 
Not applicable 
• Any newly developed or aggravated ophthalmic 
abnormality other than AMD in the study eye which 
could interfere with evaluation of efficacy or safety 
of IP including but not limited to retinal vascular 
Subject discontinuation 
from IP criterion was 
added as per India 
regulatory agency’s 


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Product  
abnormality 
request 
5.1.1. Dosing and 
Treatment 
Schedule 
Dosing visits will be allowed within ± 7 days of the 
scheduled dosing visit date (except Week 0 (Day 1), 
visit window not allowed). If a dose of IP is not given 
within 7 days of the scheduled dosing visit date, the IP 
should be given within 21 days of the scheduled dosing 
visit date, but the case will be captured as protocol 
deviation. Dosing skip is defined when a subject does 
not receive the IP within 21 days (3 weeks) after 
scheduled dosing visit date. 
Dosing visits will be allowed within ± 7 days of the 
scheduled dosing visit date (except Week 0 (Day 1), 
visit window not allowed). If a dose of IP is not given 
within 7 days of the scheduled dosing visit date, the IP 
should be given within 21 20 days of the scheduled 
dosing visit date, but the case will be captured as 
protocol deviation. Dosing skip is defined when a 
subject does not receive the IP within 21 20 days (3 
weeks) after scheduled dosing visit date. 
Error correction 
5.1.2. Withholding 
Investigational 
Products 
If a subject experiences an AE in the study eye and the 
subject’s safety or well-being could be compromised 
by ITV injection of IP at Investigator’s discretion, IPs 
could be withhold until the event has resolved. Such 
events in the study eye include, but are not limited to: 
• A decrease in BCVA of ≥30 letters compared with 
the last assessment of VA;  
• An IOP of ≥30 mmHg;  
• A retinal break;  
• A subretinal haemorrhage involving the centre of the 
fovea, or, if the size of the haemorrhage is ≥50%, of the 
total lesion area; 
If a subject experiences an AE in the study eye and the 
subject’s safety or well-being could be compromised 
by ITV injection of IP at the Investigator’s discretion, 
IPs should could be withhold withheld until the event 
has resolved. Such events in the study eye include, but 
are not limited to: 
• A decrease in BCVA of ≥30 letters compared with 
the last assessment of VA;  
• An IOP of ≥30 mmHg;  
• A retinal break;  
• A subretinal haemorrhage involving the centre of 
the fovea, or, if the size of the haemorrhage is 
≥50%, of the total lesion area; 
Editorial change 
 
 
 
 
 
 
 
 
 
As per SmPC and usual 
practice from sites 
5.2.1. Identity of 
Investigational 
Product 
The IPs will be supplied to Investigational site in one 
carton containing a single vial of 3.0 mg of 
ranibizumab in 0.3 mL solution. 
The IPs will be supplied to Investigational site in one 
carton containing a single vial. of 3.0 mg of 
ranibizumab in 0.3 mL solution. 
Editorial change 
Table 7. 
Investigational 
Products 
[Contents]  
3.0 mg of ranibizumab in 0.3 mL solution 
[Contents] 
3.0 mg of ranibizumab in 0.3 mL solution 
One ml contains 10 mg ranibizumab 
Editorial change 
5.2.6. 
Investigational 
Using aseptic technique, all of the SB11 and Lucentis® 
vial contents are withdrawn through a 19-gauge filter 
Using aseptic technique, all of the SB11 and Lucentis® 
vial contents are withdrawn through a 19-gauge blunt 
Editorial change 


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Product 
Administration 
needle attached to a 1-cc syringe. 
filter needle attached to a 1-cc syringe. 
Table 8. Prohibited 
Medication and 
Therapy 
[Medication or Therapy] 
ITV anti-VEGF treatment (e.g., bevacizumab, 
aflibercept, ranibizumab) to treat neovascular AMD 
[Time to be prohibited] 
• Prior to Screening Randomisation 
• From Screening to EOS/ET visit 
[Eye to be prohibited] 
• Study eye  
• Fellow eye 
NOTE: If a subject has AMD in the fellow eye during 
the study period after randomisation, ONLY Lucentis® 
(ranibizumab) will be allowed to treat AMD. 
 
[Medication or Therapy] 
ITV anti-VEGF treatment (e.g., bevacizumab, 
aflibercept, ranibizumab) to treat neovascular AMD 
[Time to be prohibited] 
• Prior to Screening Randomisation 
• From Screening to EOS/ET visit 
[Eye to be prohibited] 
• Study eye  
• Fellow eye 
NOTE: If a subject has AMD in the fellow eye 
during the study period after randomisation, ONLY 
Lucentis® (ranibizumab) will be allowed to treat 
AMD. 
Editorial change 
Not applicable 
 
[Medication or Therapy] 
ITV anti-VEGF treatment except IP (SB11 or 
Lucentis®)  
[Time to be prohibited] 
• From Randomisation to EOS/ET visit 
[Eye to be prohibited] 
• Study eye  
Prohibited ITV anti-
VEGF treatment is 
specified for the study 
eye. 
Not applicable 
 
[Medication or Therapy] 
ITV anti-VEGF treatment (e.g., bevacizumab, 
aflibercept) except ranibizumab  
[Time to be prohibited] 
• From Randomisation to EOS/ET visit 
[Eye to be prohibited] 
• Fellow eye 
 
NOTE: If a subject has AMD in the fellow eye 
during the study period after randomisation, ONLY 
Prohibited ITV anti-
VEGF treatment is 
specified for the fellow 
eye. 


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Rationale 
Lucentis® (ranibizumab) will be allowed to treat 
AMD. 
[Medication or Therapy] 
Systemic treatment or therapy (including prescribed 
herbal medication) to treat neovascular AMD. 
However, dietary supplementary, vitamins and 
minerals are allowed 
[Time to be prohibited] 
• Within 30days prior to randomisation 
•  From Screening to EOS/ET visit  
[Eye to be prohibited] 
• N/A 
[Medication or Therapy] 
Systemic treatment or therapy (including prescribed 
herbal medication) to treat neovascular AMD. 
However, dietary supplementary supplements, 
vitamins and minerals are allowed 
[Time to be prohibited] 
• Within 30days prior to randomisation 
•  From Screening to EOS/ET visit  
[Eye to be prohibited] 
• N/A 
Editorial change 
Not applicable 
[Medication or Therapy] 
Systemic medications known to be toxic to the lens, 
retina or optic nerve including deferoxamine, 
chloroquine/hydroxychloroquine, tamoxifen, 
phenothiazines, vigabatrin and ethambutol 
[Time to be prohibited] 
• From Screening to EOS/ET visit 
[Eye to be prohibited] 
N/A 
Prohibited medication or 
therapy is added as per 
Korea MFDS’s request. 
[Medication or Therapy] 
ITV sustained drug delivery implant (e.g., ITV 
corticosteroid implant)  
[Time to be prohibited] 
• Within 180 days prior to randomisation 
•  From Screening to EOS/ET visit  
[Eye to be prohibited] 
• Study eye 
[Medication or Therapy] 
ITV Intravitreal injection of corticosteroid (e.g., 
triamcinolone acetonide) or sustained drug delivery 
implant (e.g., ITV intravitreal corticosteroid implant) 
 [Time to be prohibited] 
• Within 180 days prior to randomisation 
• From Screening to EOS/ET visit  
[Eye to be prohibited] 
• Study eye 
Prohibited medication or 
therapy is revised 
according to updated 
exclusion criteria #15. 


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Rationale 
Not applicable 
[Medication or Therapy] 
Treatment involving macula with photodynamic 
therapy with verteporfin, transpupillary 
thermotherapy, radiation therapy, or retinal laser 
treatment (e.g., focal laser photocoagulation)  
[Time to be prohibited] 
• Prior to Screening 
• From Screening to EOS/ET visit  
[Eye to be prohibited] 
• Study eye 
Prohibited medication or 
therapy is added as per 
Korea MFDS’s request. 
Not applicable 
[Medication or Therapy] 
Treatment with pan-retinal photocoagulation  
[Time to be prohibited] 
• Prior to Screening 
• From Screening to EOS/ET visit  
[Eye to be prohibited] 
• Study eye 
Prohibited medication or 
therapy is added as per 
Korea MFDS’s request. 
[Medication or Therapy] 
Systemic investigational products (excluding dietary 
supplementary, vitamins and minerals) to treat 
systemic diseases other than neovascular AMD 
[Time to be prohibited] 
• Within 90 days prior to randomisation 
•  From Screening to EOS/ET visit  
NOTE:  During the study period, investigational 
products such as dietary supplementary, vitamins and 
minerals will be prohibited. 
[Eye to be prohibited] 
• N/A 
[Medication or Therapy] 
Systemic investigational products (excluding 
dietary supplementary supplements, vitamins and 
minerals) to treat systemic diseases other than 
neovascular AMD 
[Time to be prohibited] 
• Within 90 days prior to randomisation 
•  From Screening to EOS/ET visit  
NOTE:  During the study period, investigational 
products such as dietary supplementary supplements, 
vitamins and minerals will be prohibited. 
[Eye to be prohibited] 
• N/A 
Editorial change 
5.4. Fellow Eye 
Treatment 
Lucentis® for treatment in the fellow eye will be 
reimbursed or provided by Sponsor. 
Lucentis® for treatment in the fellow eye will be 
reimbursed or provided by Sponsor during the study 
Period of providing 
Lucentis for fellow eye 


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period after randomisation. 
treatment is specified. 
Fellow eye injection will be performed by the 
Investigator for this study. However, fellow eye visit is 
not part of study, thus it will be scheduled in 
accordance with local practice.  
Fellow eye injection will be performed by the 
Investigator for this study. However, fellow eye visit is 
not part of study, thus it will be scheduled in 
accordance with local practice. If a subject has both 
eyes injected on the same day, fellow eye should be 
injected after completion of ITV injection of IP on 
the study eye. 
To provide guideline for 
fellow eye injection  
6.2.1. Best 
Corrected Visual 
Acuity 
VA will be assessed using ETDRS chart or 2702 
Number charts (only for subjects who are not familiar 
with alphabet or subjects with illiteracy) at a starting 
distance of 4 meters, and then repeated at a distance of 
1 meter, if necessary. 
VA will be assessed using original series ETDRS 
charts or 2702 series Number charts (only for subjects 
who are not familiar with alphabet or subjects with 
illiteracy) at a starting distance of 4 meters, and then 
repeated at a distance of 1 meter, if necessary. 
Clarification for charts 
used in this study 
VA examiners and VA lanes at Investigational sites 
must be certified to ensure consistent measurement of 
BCVA prior to start of study. VA examiners should be 
masked to the subject’s treatment group and should not 
perform any other study procedures. 
VA examiners and VA lanes at Investigational sites 
must be certified to ensure consistent measurement of 
BCVA prior to start of study. VA examiners should 
be masked to the subject’s treatment group and 
should not perform any other study procedures. 
Requirement is changed. 


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Rationale 
A decrease in VA of > 15 letters (compared with the 
last assessment of VA) should be reported as AEs/ 
SAEs as appropriate. If there is a decrease in VA of > 
30 letters (compared with the last assessment of VA) or 
there is a decrease in VA to the level of Light 
Perception or worse, VA should be re-assessed after at 
least 1 hour. 
If the event meets one or more of the following criteria, 
it should be reported as SAE. 
• A decrease in VA of > 30 letters (compared with the 
last assessment of VA) lasting > 1 hour 
• A decrease in VA to the level of Light Perception or 
worse lasting > 1 hour 
A decrease in VA of > ≥15 letters (compared with 
from the last assessment of VA) should be reported as 
AEs/ Serious Adverse Events (SAEs) as 
appropriate. If there is a decrease in VA of > 30 
letters (compared with the last assessment of VA) or 
there is a decrease in VA to the level of Light 
Perception or worse, VA should be re-assessed after 
at least 1 hour. 
If the event meets one or more of the following criteria, 
it should be reported as SAE. 
• A decrease in VA of > ≥ 30 letters (compared 
with from the last assessment of VA) lasting > 1 hour 
• A decrease in VA to the level of Light Perception or 
worse lasting > 1 hour 
Error correction 
 
 
 
 
 
 
 
 
SAE criteria are 
changed. 
6.2.2. Anatomical 
Parameters 
The average retinal thickness in the central 1-mm area 
in the ETDRS grid (CST; central subfield thickness), 
retinal thickness between Internal Limiting Membrane 
(ILM) and the base of RPE (CRLT; central retinal 
lesion thickness) and other lesion characteristics will be 
evaluated using OCT only in the study eye at Screening 
and prior to ITV injection of IP until Week 48. OCT 
will also be performed at any time during the visit at 
Week 52 (EOS visit) or ET visit.  
Lesion characteristics such as CNV size and presence 
of leakage or haemorrhage will also be evaluated using 
FP/FA only in the study eye at Screening and prior to 
ITV injection of IP Week 24. FP/FA will also be 
performed at any time during the visit at Week 52 
(EOS visit) or ET visit. 
The average retinal thickness in the central 1-mm area 
in the ETDRS grid (CST; central subfield thickness), 
retinal thickness between Internal Limiting Membrane 
(ILM) and the base of RPE (CRLT; central retinal 
lesion thickness) and other lesion characteristics will be 
evaluated using OCT only in on the study eye at 
Screening and prior to ITV injection of IP until Week 
48. OCT will also be performed at any time during the 
visit at Week 52 (EOS visit) or ET visit.  
Lesion characteristics such as CNV size and presence 
of leakage or haemorrhage will also be evaluated using 
FP/FA only in on the study eye at Screening and prior 
to ITV injection of IP Week 24. FP/FA will also be 
performed at any time during the visit at Week 52 
(EOS visit) or ET visit. 
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6.3.2. Clinical 
Laboratory Test 
Clinical laboratory test including haematology, clinical 
chemistry, urinalysis and pregnancy test can be 
repeated …. 
Clinical laboratory test including haematology, clinical 
chemistry, and urinalysis and pregnancy test can be 
repeated …. 
Pregnancy test will be 
provided in the separate 
section. 
Table 9. Parameters 
for Clinical 
Laboratory Tests 
[Others] Pregnancy test2 at Screening (serum)2   
2 Serum or urine pregnancy tests may be performed after 
randomisation at Investigator’s discretion. 
[Others] Pregnancy test2 at Screening (serum)2   
2 Serum or urine pregnancy tests may be performed after 
randomisation at Investigator’s discretion. 
Pregnancy test will be 
provided in the separate 
section. 
6.3.3. Pregnancy 
Test 
Not applicable 
For women of childbearing potential, serum 
pregnancy test must be performed at Screening. 
The serum samples taken at Screening will be 
analysed in central laboratory. 
Additional serum or urine pregnancy test can be 
performed in each Investigational site during the 
study period, if necessary (at the Investigator’s 
discretion). 
Deleted pregnancy test result at Screening with 
technical problems, such as handling error, 
sampling error or tube breakage, should be 
followed by re-test. Result of re-test will be 
considered as that of an initial. 
Clarification for 
pregnancy test 
6.3.4. Physical 
Examination 
Physical examination will be performed at Screening 
and Week 52 (EOS visit) or ET visit. Abnormal 
findings will be documented on the source document, 
and any clinically significant abnormality or worsening 
of a previously noted abnormality should be recorded 
as an AE. 
Physical examination will be performed at Screening 
and Week 52 (EOS visit) or ET visit. The physical 
examination will include an assessment of the 
subject’s general appearance, skin, head, neck, 
throat, lymph nodes, cardiovascular, neurological, 
thyroid, musculoskeletal/extremities, respiratory 
systems and the subject’s abdomen. Abnormal 
findings will be documented on the source document, 
and any clinically significant abnormality or worsening 
of a previously noted abnormality should be recorded 
as an AE. 
Clarification for physical 
examination (systems 
and organs) 
6.4.1. Full 
The examination of the anterior segment is performed 
The examination of the anterior segment is 
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Ophthalmic 
Examinations 
- Slit lamp 
biomicroscopy 
only with the slit lamp without any additive drugs or 
lenses. 
 
The posterior segment should be examined with the slit 
lamp and the appropriate lens. For this examination the 
pupil of the eye must be dilated with 2-3 drops of 
phenylephrine-tropicamid (or any other mydriatic) 
applied topically to the eye. 
performed only with the slit lamp without any 
additive drugs or lenses. Both the anterior segment 
and posterior segment will be assessed with the slit 
lamp. 
The posterior segment should will be examined after 
dilation of pupil with the slit lamp and the 
appropriate lens. For this examination the pupil of 
the eye must be dilated with 2-3 drops of 
phenylephrine-tropicamid (or any other mydriatic 
drug) applied topically to the eye. 
6.4.1. Full 
Ophthalmic 
Examinations 
- Intraocular 
pressure (IOP) 
measurement 
IOP will be measured only in the study eye at 
Screening and prior to ITV injection of IP and 30-60 
minutes after ITV injection of IP at each visit until 
Week 48. 
IOP will be measured only in on the study eye at 
Screening and prior to ITV injection of IP and 30-60 
minutes after ITV injection of IP at each visit until 
Week 48. 
Editorial change 
IOP should be measured using Goldmann applanation 
tonometry only. 
IOP should be measured using Goldmann applanation 
tonometry only. 
Editorial change 
6.4.1. Full 
Ophthalmic 
Examinations 
- Indirect 
ophthalmoscopy 
Indirect ophthalmoscopy using in a standard way (i.e., 
usually using a head-mounted light source and a 20-30 
dpt lens)will be performed only in the study eye 
(including evaluation of posterior segment 
abnormalities of the vitreous, optic nerve, peripheral 
retina and retinal vasculature, as well as retinal pigment 
epithelium detachment, ischemic events including 
cotton wool spots and microaneurysms) at Screening 
and prior to ITV injection of IP and 0-15 min after ITV 
injection of IP at each visit until Week 48. 
Indirect ophthalmoscopy using in a standard way (i.e., 
usually using a head-mounted light source and a 20-30 
dpt lens)will be performed only in on the study eye 
(including evaluation of posterior segment 
abnormalities of the vitreous, optic nerve, peripheral 
retina and retinal vasculature, as well as retinal pigment 
epithelium detachment, ischemic events including 
cotton wool spots and microaneurysms) at Screening 
and prior to ITV injection of IP and 0-15 min after ITV 
injection of IP at each visit until Week 48. 
Editorial change 
6.4.2. Optical 
Coherence 
Tomography 
(OCT) 
OCT will be performed only in the study eye at 
Screening and prior to ITV injection of IP at each study 
visit until Week 48. OCT will also be performed at any 
time during the visit at Week 52 (EOS visit) or ET 
visit. 
OCT will be performed only in on the study eye at 
Screening and prior to ITV injection of IP at each study 
visit until Week 48. OCT will also be performed at any 
time during the visit at Week 52 (EOS visit) or ET 
visit. 
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Only OCT devices registered and certified by central 
reading centre are allowed to be used in this study. If 
one or more OCT devices are registered and certified in 
an Investigational site, a subject should use the same 
OCT device consistently during the study period. If 
OCT devices registered and certified in an 
Investigational site are all from the same manufacturer 
and they use the same imaging system and the same 
version of software, the subject could use either of 
them during the study period. 
Site staffs who will perform OCT scans in this study 
must be certified by the central reading centre 
before study starts. 
Only OCT devices registered and certified by 
central reading centre are allowed to be used in this 
study. If one or more OCT devices are registered 
and certified in an Investigational site, a subject 
should use the same OCT device consistently OCT 
devices registered in an Investigational site should 
be all from the same manufacture and meet the 
minimum software requirement. The subject should 
use the OCT devices registered by central reading 
centre during the study period. If OCT devices 
registered and certified in an Investigational site are 
all from the same manufacturer and they use the 
same imaging system and the same version of 
software, the subject could use either of them 
during the study period. 
Editorial change 
6.4.3. Fundus 
Photography (FP) 
and Fluorescein 
Angiography (FA) 
FP/FA will be performed only in the study eye at 
Screening and prior to ITV injection of IP at Week 24. 
FP/FA will also be performed at any time during the 
visit at Week 52 (EOS visit) or ET visit. 
FP/FA will be performed only in on the study both 
eyes at Screening and those images taken from the 
both eyes will be sent to the central reading centre.  
FP/FA will also be performed on the study eye prior 
to ITV injection of IP at Week 24 and. FP/FA will 
also be performed at any time during the visit at Week 
52 (EOS visit) or ET visit. Those images taken from 
the study eye will be sent to the central reading 
centre. 
Site staffs who will perform FA/FP in this study 
must be certified by the central reading centre 
before study starts. 
According to exclusion 
criteria #3, FP/FA 
images taken from the 
both eyes should be sent 
to the central reading 
centre at Screening. 
 
Editorial change 
6.5. 
Pharmacokinetic 
Blood samples for PK will be collected in 
approximately 120 subjects (60 subjects per treatment 
Blood samplessampling for PK will be collected in 
approximately 12040 subjects (6020 subjects per 
Number of subjects 
participating in PK 


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Assessment 
group) participating in PK evaluation. 
treatment group) participating in PK evaluation. 
evaluation is changed as 
per US FDA’s request. 
6.6. 
Immunogenicity 
Assessment 
…he or she could be asked to return for 
immunogenicity blood sampling after Week 52 (EOS 
visit) or ET visit until the antibody titres return to 
baseline or stabilize at a level acceptable to the 
Investigator and Sponsor. 
…he or she could be asked to return for 
immunogenicity blood sampling after Week 52 (EOS 
visit) or ET visit until the antibody titres return to 
baseline or stabilize stabilise at a level acceptable to 
the Investigator and Sponsor. 
Editorial change 
6.7. NEI VFQ-25 
Vision-related QOL will be assessed using NEI VFQ-
25. NEI VFQ-25 should be performed at Week 0 (Day 
1) after randomisation, but prior to starting any other 
study procedures. Then, NEI VFQ-25 should be 
performed before starting any other study procedures at 
Week 12, Week 24, Week 36 and Week 52 (EOS visit) 
or ET visit. All questionnaires will be administered in 
the local language. A certified person will conduct a 
questionnaire survey with the subject in a quiet room. 
Vision-related QOL will be assessed using NEI VFQ-
25. NEI VFQ-25 should be performed at Week 0 (Day 
1) after randomisation, but prior to starting any other 
study procedures. Then, NEI VFQ-25 should be 
performed before starting any other study 
procedures dilation of pupil at Week 0 (Day 
1), Week 12, Week 24, Week 36 and Week 52 (EOS 
visit) or ET visit. All questionnaires will be 
administered in the local language. A certified person 
Investigator or delegated site staff will conduct a 
questionnaire survey with the subject in a quiet room. 
Frequency of NEI VFQ-
25 is changed as per US 
FDA’s request. 
 
 
 
 
 
Certification for the 
interviewer is not 
required for this study. 
7. Study 
Procedures-all 
pages 
• Ocular assessments: 
• BCVA examination using ETDRS chart or 2702 
Number chart (before dilation of the pupils and FP/FA 
and OCT assessment) 
 
• IOP using Goldmann applanation tonometry only 
• Ocular assessments: 
• BCVA examination using original series ETDRS 
charts or 2702 series Number charts (before dilation of 
the pupils and FP/FA and OCT assessment) 
 
• IOP using Goldmann applanation tonometry only 
Clarification for charts 
used in this study 
 
 
 
Editorial change 
7.1. Visit 1 
(Screening , D-21 
to D-1) 
If the subject is not randomized within 21 days after 
Screening, 
If the subject is not randomized randomised within 
21 days after Screening, 
Editorial change 
• Pregnancy test (serum, all female) 
• Pregnancy test for women of childbearing potential 
(serum, all female) 
Pregnancy test will be 
performed only for 
childbearing potential 
female subjects. 


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If the subject is screen failed due to any reasons other 
than central review results, OCT and FP/FA images 
may not be transferred to central reading centre. 
If the subject is screen failed due to any reasons  
before the Investigator send OCT and/or FP/FA 
images to central reading centre, the Investigator 
does not have to send the subject’s OCT and/or 
FP/FA images to central reading centre. other than 
central review results, OCT and FP/FA images may 
not be transferred to central reading centre. 
Editorial change 
NOTE 
A decrease in VA of > 15 letters (compared with the 
last assessment of VA) should be reported as 
AEs/SAEs as appropriate. 
NOTE 
A decrease in VA of > ≥15 letters (compared with the 
last assessment of VA) should be reported as 
AEs/SAEs as appropriate. 
Error correction 
7.2. Visit 2 (Week 
0/Day 1) 
Before randomisation 
• Investigator must confirm that the subject can read 
between 34 letters and 73 letters using ETDRS chart or 
2702 Number chart (before dilation of the pupils and 
FP/FA or OCT assessment) prior to randomisation 
(Please see inclusion criteria #5). 
Before randomisation 
•  Investigator must confirm that the subject can read 
between 34 letters and 73 letters using original series 
ETDRS charts or 2702 series Number charts (before 
dilation of the pupils and FP/FA or OCT assessment) 
prior to randomisation (Please see inclusion criteria 
#5). 
Clarification for charts 
used in this study 
Randomisation 
• After a subject’s eligibility is confirmed by the central 
reading centre and Investigator, subject should be 
randomized to either SB11 or Lucentis® treatment 
group. 
• IP injection and study procedures which should be 
performed before ITV injection of IP must be 
performed must be performed at the same day of 
randomisation or the following day after randomisation 
at the latest with a proper reason. 
Randomisation 
• After a subject’s eligibility is confirmed by the central 
reading centre and Investigator, subject should be 
randomized randomised to either SB11 or Lucentis® 
treatment group. 
• The first ITV injection of IP injection and all other 
study procedures which should be performed before 
ITV injection of IP must be performed must be 
performed at the same day of randomisation or the 
following day after randomisation at the latest with a 
proper reason. 
Editorial change 
After randomisation 
Before ITV injection of IP 
After randomisation 
Before ITV injection of IP 
Requirement is changed. 


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Rationale 
• NEI VFQ-25 (prior to starting any other study 
procedures after randomisation) 
• NEI VFQ-25 (prior to starting any other study 
procedures dilation of pupil after randomisation) 
7.6. Visit 6 (Week 
12 ± 7 days) 
7.12. Visit 12 
(Week 36 ± 7 days) 
Before ITV injection of IP 
• NEI VFQ-25 (before starting any other study 
procedures) 
Before ITV injection of IP 
• NEI VFQ-25 (before starting any other study 
procedures) 
Frequency of NEI VFQ-
25 is changed as per US 
FDA’s request. 
7.9. Visit 9 (Week 
24 ± 7 days) 
7.16. End of Study 
(Visit 16, Week 52 
± 7 days) or Early 
Termination Visit 
Before ITV injection of IP 
• NEI VFQ-25 (before starting any other study 
procedures) 
Before ITV injection of IP 
• NEI VFQ-25 (before starting any other study 
procedures dilation of pupil) 
Requirement is changed. 
8.1.1. Definition of 
Adverse Event 
All AEs including ocular AEs in the study eye and/or 
fellow eye as well as systemic AEs will be collected 
from the written informed consent is obtained from the 
subject until Week 52 (EOS visit) or ET visit. 
All AEs including ocular AEs in the study eye and/or 
fellow eye as well as systemic AEs will be collected 
from the written informed consent is obtained from the 
subject until Week 52 (EOS visit) or ET visit. If the 
AMD is diagnosed in the fellow eye during the study 
period, the event should be also reported as AE. 
To provide guideline for 
AE reporting  for AMD 
in the fellow eye 
8.2.1. Definition of 
Serious Adverse 
Event 
Not applicable 
Life-threatening 
The term “life-threatening” in the definition of 
“serious” refers to an event in which the subject was 
at risk of death at the time of the event; it does not 
refer to an event which hypothetically might have 
caused death if it were more severe. 
Hospitalisation 
AEs reported from clinical studies associated with 
hospitalisation or prolongation of existing 
hospitalisation are considered serious. 
Any admission to a healthcare facility more than 24 
hours meets these criteria. Admission also includes 
transfer within the hospital to an acute/intensive 
Clarification for “Life-
threatening” and 
“Hospitalisation” 


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Amended/New Content 
Rationale 
care unit (e.g., from the medical floor to a coronary 
care unit, neurological floor to a tuberculosis unit). 
Staying at the observation unit in the emergency 
room for more than 24 hours qualifies for 
hospitalisation. 
Any events leading to a subsequent emergency room 
visit or inpatient hospitalisation for less than 24 
hours may be regarded as medically important for 
its seriousness criteria, at the discretion of 
Investigator based on medical judgement.  
Hospitalisation or prolongation of existing 
hospitalisation in the absence of an AE is not in 
itself an SAE. Examples include: 
• Admission for treatment of a pre-existing (prior to 
ICF signed) condition not associated with the 
development of a new AE or with a worsening of the 
pre-existing condition 
• Diagnostic admission (e.g., for work-up of 
persistent pre-treatment laboratory abnormality) 
• Social admission (e.g., study subject has no place 
to sleep) 
• Administrative admission (e.g., for a regular 
check-up) 
• Protocol-specified admission during a clinical 
study (e.g., for a procedure required by the study 
protocol) 
• Elective admission not associated with an AE (e.g., 
for elective cosmetic surgery) 
• Pre-planned treatments or surgical procedures 
: Pre-planned treatments or surgical procedures 
should be noted in the relevant source document for 
the individual subject.  


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• A decrease in VA of > 30 letters (compared with the 
last assessment of VA) lasting > 1 hour (confirmed by 
re-assessment) 
• A decrease in VA to the level of Light Perception or 
worse lasting > 1 hour (confirmed by re-assessment) 
• A decrease in VA of > ≥ 30 letters (compared with 
from the last assessment of VA) lasting > 1 hour 
(confirmed by re-assessment) 
• A decrease in VA to the level of Light Perception or 
worse lasting > 1 hour (confirmed by re-assessment) 
Error correction 
 
SAE criteria are 
changed. 
8.2.2. Reporting 
Serious Adverse 
Events 
In addition, an Investigator may be requested by 
Sponsor to obtain specific additional follow-up 
information in an expedited fashion. 
In addition, an Investigator may be requested by 
Sponsor to obtain specific additional follow-up 
information in an expedited fashion. 
Editorial change 
8.3. Adverse 
Events of Special 
Interest 
• Any case of ocular infection such as endophthalmitis 
• Any case of intraocular infection such as 
endophthalmitis 
Editorial change 
Not applicable 
• Iatrogenic traumatic cataract 
• Arterial thromboembolic events defined as 
nonfatal stroke, nonfatal myocardial infarction, or 
vascular death (including deaths of unknowns 
cause) 
Events are added as 
AESI as per EMA SmPC 
and FDA Prescribing 
Information. 
9.1. Analysis Sets 
• Per-Protocol Set for CST (PPS-CST) consists of all 
FAS subjects who have the first IP injection at Week 0 
(Day 1) and complete the procedures at Week 4 
without any major protocol deviations that have impact 
on the CST assessment. This PPS-CST will be the 
primary analysis set for CST in addition to FAS. Major 
protocol deviations that will lead to exclusion from this 
set will be pre-defined prior to unmasking the treatment 
codes for analyses. 
• Per-Protocol Set for CST (PPS-CST) consists of all 
FAS subjects who have the first IP injection at Week 0 
(Day 1) and complete the procedures at Week 4 
without any major protocol deviations that have impact 
on the CST assessment. This PPS-CST will be the 
primary analysis set for CST in addition to FAS. 
Major protocol deviations that will lead to exclusion 
from this set will be pre-defined prior to unmasking the 
treatment codes for analyses. 
Clarification analysis set 
for CST 
9.2.4. 
Pharmacokinetics 
Blood sampling for PK will be collected in 120 
subjects participating in PK evaluation (60 per 
treatment group). 
Blood sampling for PK will be collected in 
approximately 12040 subjects participating in PK 
evaluation (6020 subjects per treatment group). 
Number of subjects 
participating in PK 
evaluation is changed as 
per US FDA’s request. 
10.1. Data 
Confidentiality 
A list linking the code and the subject’s name will be 
kept in the Investigational site files as required by 
International Conference on Harmonisation’s (ICH) 
A list linking the code and the subject’s name will be 
kept in the Investigational site files as required by 
International Conference on Council for 
Error correction 


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Guideline for Good Clinical Practice (GCP) to protect 
the subject’s confidentiality. 
Harmonisation’s (ICH) Guideline for Good Clinical 
Practice (GCP) to protect the subject’s confidentiality. 
LIST OF 
ABBREVIATION
S 
ICH: International Council on Harmonisation 
ICH: International Council onfor Harmonisation 
Error correction 
LOCF: Last Observation Carried Forward 
LOCF: Last Observation Carried Forward 
RPE: Retinal Pigment Epithelial 
RPE: Retinal Pigment Epithelial Epithelium 
LIST OF STUDY 
STAFF 
Clinical Project Manager 
 
 
Clinical Project Manager 
 
 
Responsible person is 
changed. 
Clinical Research Physician 
 
 
Clinical Research Physician 
 
Responsible person is 
changed. 
Statistician 
  
Statistician 
 
 
 
 
Responsible person is 
changed 
Project Safety Lead 
 
Project Safety Lead 
 
 
Responsible person is 
changed 
Appendix D: 
National Eye 
Institute 25-Item 
Visual Function 
Questionnaire (NEI 
VFQ-25 
Not applicable 
National Eye Institute 25-Item Visual Function 
Questionnaire is added. 
NEI VFQ-25 
questionnaire is added. 


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questionnaire) 
All pages 
at Investigator’s discretion 
at the Investigator’s discretion 
Editorial change 
in the opinion of Investigator 
in the opinion of the Investigator 
Editorial change