Clinical trial NCT03539549
Conditions: Macular Degeneration
Sponsor: Allergan
Start date: 2018-05-25; Completion date: 2019-02-27
Enrollment: 124 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The objective of this study is to evaluate abicipar pegol for safety and treatment effects in participants with neovascular age-related macular degeneration (AMD).

Detailed description:

Arms: arm 1: Abicipar pegol 2 mg administered to the study eye by intravitreal injection on Day 1 and Weeks 4, 8, 16, and 24.
Interventions: intervention 1: Abicipar pegol
Intervention descriptions: intervention 1: Abicipar pegol 2 mg administered to the study eye by intravitreal injection on Day 1 and Weeks 4, 8, 16, and 24.

Protocol documents:
Prot_000.pdf: 
NCT03539549 
 
Study ID: 1771‐201‐008 
 
 
 
Title: Evaluation of Abicipar Pegol in Patients with Neovascular Age‐Related Macular Degeneration 
 
Protocol Amendment 1 Date: 16 Oct 2018 
 
 


 
 
Approval Date: 
 
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Allergan Confidential 
Protocol 1771-201-008
 
 
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Title Page 
ALLERGAN – CONFIDENTIAL 
The following contains confidential, proprietary information  
which is the property of Allergan 
EVALUATION OF ABICIPAR PEGOL IN PATIENTS WITH NEOVASCULAR 
AGE-RELATED MACULAR DEGENERATION 
Protocol Number:   
1771-201-008 
Phase: 
2 
Name of Investigational Product: 
Abicipar pegol 
Sponsor: 
Allergan (North America) 
2525 Dupont Drive 
Irvine, California USA 92612 
 
 
Emergency Telephone Number(s): 
Refer to the Study Contacts Page. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Refer to the final page of this protocol for electronic signature 
and date of approval. 
The following information can be found on FDA Form 1572 and/or study contacts page:  Name and 
contact information of Allergan study personnel and Emergency Telephone Numbers; name, address, 
and statement of qualifications of each investigator; name of each subinvestigator working under the 
supervision of the investigator; name and address of the research facilities to be used; name and 
address of each reviewing IRB; US 21 CFR 312.23 section 6(iii)b. 
 


 
 
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INVESTIGATOR SIGNATURE PAGE 
INVESTIGATOR: 
 
 
 
 
I agree to: 
• Implement and conduct this study diligently and in strict compliance with the protocol, 
good clinical practices and all applicable laws and regulations. 
• Maintain all information supplied by Allergan in confidence and, when this 
information is submitted to an Institutional Review Board (IRB), Independent Ethics 
Committee (IEC) or another group, it will be submitted with a designation that the 
material is confidential. 
• Ensure that all persons assisting with the trial are adequately informed about the 
protocol, the investigational product(s), and their trial-related duties and functions. 
I have read this protocol in its entirety and I agree to all aspects. 
 
 
 
 
 
Investigator Printed Name 
 
Signature 
 
Date 
 
 


 
 
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Table of Contents 
Table of Contents ...................................................................................................................... 3 
List of Tables ............................................................................................................................. 6 
List of Figures ........................................................................................................................... 6 
Protocol Summary .................................................................................................................... 7 
1. 
Background and Clinical Rationale ................................................................................. 13 
2. 
Study Objectives .............................................................................................................. 15 
3. 
Study Design .................................................................................................................... 16 
4. 
Study Population and Entry Criteria ................................................................................ 16 
4.1 
Number of Patients ................................................................................................. 16 
4.2 
Study Population Characteristics ........................................................................... 16 
4.3 
Inclusion Criteria .................................................................................................... 16 
4.4 
Exclusion Criteria................................................................................................... 17 
4.5 
Permissible and Prohibited Medications/Treatments ............................................. 20 
4.5.1  Permissible Medications/Treatments ......................................................... 20 
4.5.1.1 
Definition of Females of (Non-)Childbearing Potential and/or 
Acceptable Contraceptive Methods .......................................... 21 
4.5.2  Prohibited Medications/Treatments ........................................................... 21 
4.5.3  Special Diet or Activities ........................................................................... 22 
5. 
Study Treatments ............................................................................................................. 22 
5.1 
Study Treatments and Formulations ....................................................................... 22 
5.2 
Control Treatment(s) .............................................................................................. 22 
5.3 
Methods for Masking ............................................................................................. 22 
5.4 
Treatment Allocation Ratio and Stratification........................................................ 22 
5.5 
Method for Assignment to Treatment Groups/Randomization .............................. 23 
5.6 
Treatment Regimen and Dosing ............................................................................. 23 
5.6.1  Treatment Regimen/Dosage Adjustments/Dose Discontinuation .............. 23 
5.7 
Storage of Study Medications/Treatments ............................................................. 24 
5.8 
Preparation of Study Medications/Treatments ....................................................... 24 
5.9 
Treatment Administration ...................................................................................... 24 
6. 
Response Measures and Summary of Data Collection Methods ..................................... 24 
6.1 
Efficacy Measures .................................................................................................. 24 


 
 
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6.4 
Examination Procedures, Tests, Equipment, and Techniques ................................ 26 
6.4.1  Disease Characterization ............................................................................ 26 
6.4.1.1 
Dilated Color Fundus Photography ........................................... 26 
6.4.1.2 
Fluorescein Angiography .......................................................... 26 
6.4.2  Efficacy ...................................................................................................... 26 
6.4.2.1 
Best-corrected Visual Acuity ..................................................... 26 
6.4.2.2 
Optical Coherence Tomography ................................................ 27 
 
 
 
 
 
 
 
 
 
 
6.4.3.5 
Best-corrected Visual Acuity ..................................................... 29 
6.4.3.6 
Pregnancy Test .......................................................................... 29 
6.4.3.7 
Adverse Events .......................................................................... 29 
6.5 
Other Study Supplies .............................................................................................. 30 
6.6 
Summary of Methods of Data Collection .............................................................. 30 
7. 
Statistical Procedures ....................................................................................................... 30 
7.1 
Analysis Populations .............................................................................................. 30 
7.2 
Methods of Analysis ............................................................................................... 30 
7.2.1  Efficacy Analyses ....................................................................................... 30 
 
 
 
 
 
 
7.3 
Subgroup Analyses ................................................................................................. 31 
7.4 
Sample Size Calculation ........................................................................................ 31 
7.5 
Interim Analyses..................................................................................................... 32 
 
 
8.1 
Patient Entry Procedures ........................................................................................ 32 
8.1.1  Overview of Entry Procedures ................................................................... 32 
8.1.2  Informed Consent and Patient Privacy ....................................................... 32 
8.2 
Procedures for Final Study Entry ........................................................................... 32 


 
 
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8.4 
Instructions for the Patients .................................................................................... 38 
8.5 
Unscheduled Visits ................................................................................................. 38 
8.6 
Compliance with Protocol ...................................................................................... 38 
8.7 
Early Discontinuation of Patients .......................................................................... 39 
8.8 
Study Termination .................................................................................................. 39 
9. 
Adverse Events ................................................................................................................ 39 
9.1 
Definitions .............................................................................................................. 39 
9.1.1  Adverse Event ............................................................................................ 39 
9.1.2  Serious Adverse Event ............................................................................... 40 
9.1.3  Severity ...................................................................................................... 40 
9.1.4  Relationship to Study Drug or Study Procedure ........................................ 41 
9.2 
Procedures for Reporting Adverse Events ............................................................. 41 
9.3 
Procedures for Reporting a Serious Adverse Event ............................................... 41 
9.4 
Procedures for Unmasking of Study Medication ................................................... 42 
10.  Administrative Items ....................................................................................................... 42 
10.1  Protection of Human Patients ................................................................................ 43 
10.1.1  Compliance with Informed Consent Regulations (US 21 CFR Part 50) and 
Relevant Country Regulations ................................................................... 43 
10.1.2  Compliance With IRB or IEC Regulations ................................................ 43 
10.1.3  Compliance With Good Clinical Practice .................................................. 43 
10.1.4  Compliance With Electronic Records; Electronic Signatures Regulations 
(US 21CFR Part 11) ................................................................................... 43 
10.2  Changes to the Protocol ......................................................................................... 43 
10.3  Patient Confidentiality ........................................................................................... 44 
10.3.1  Patient Privacy ........................................................................................... 44 
10.4  Documentation ....................................................................................................... 44 


 
 
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10.4.1  Source Documents ..................................................................................... 44 
10.4.2  Case Report Form Completion................................................................... 46 
10.4.3  Study Summary .......................................................................................... 46 
10.4.4  Retention of Documentation ...................................................................... 46 
10.5  Labeling, Packaging, and Return or Disposal of Study Medications/Treatments .. 47 
10.5.1  Labeling/Packaging .................................................................................... 47 
10.5.2  Clinical Supply Inventory .......................................................................... 47 
10.5.3  Return or Disposal of Study Medications/Treatments and/or Supplies ..... 47 
10.6  Monitoring by the Sponsor .................................................................................... 47 
10.7  Handling of Biological Specimens......................................................................... 48 
10.8  Publications ............................................................................................................ 48 
10.9  Coordinating Investigator ...................................................................................... 48 
11.  References ........................................................................................................................ 49 
12.  Attachments ..................................................................................................................... 51 
12.1  Glossary of Abbreviations ...................................................................................... 51 
12.2  Protocol Amendment Summary Amendment 1 ..................................................... 54 
 
List of Tables 
 
 
 
 
 
List of Figures 
 
 
 
 


 
 
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Protocol Summary 
 
Study Compound(s):  Abicipar pegol (hereafter referred to as abicipar) 
Phase:  2 
Study Objective(s):  The primary objective is to evaluate abicipar for safety and treatment effect in patients 
with neovascular age-related macular degeneration (AMD). 
Study Design 
Structure:  multicenter, open-label, single-arm study  
Duration:  28 weeks 
Study Treatment Groups:  2 mg abicipar  
Controls:  not applicable 
Dosage/Dose Regimen:  intravitreal injections of 2 mg abicipar administered at baseline (Day 1) and Weeks 4, 
8, 16, and 24 
Randomization/Stratification:  None 
Visit Schedule:  There will be 9 scheduled visits during the study. These include screening (Days -21 to -2); 
baseline (Day 1); Weeks 4, 8, 12, 16, 20, 24, and 28/Early Exit. For patients at selected sites who participate in 
pharmacokinetic (PK) blood sampling, there will be 1 additional visit:  Day 3. 
Study Population Characteristics 
Number of Patients:  Approximately 100 patients will be enrolled at approximately 40 sites in the US. 
Condition/Disease:  Patients with neovascular AMD 
Key Inclusion Criteria: 
 
 
 
Key General Inclusion Criteria: 
• 
Male or female patients, 50 years of age or older at the time of informed consent   
Key Ocular Inclusion Criteria (study eye): 
 
 
 
 
  
 
 
  
• 
BCVA ≤ 78 and ≥ 24 letters (20/32 to 20/320 Snellen equivalents, respectively) at screening and 
baseline (Day 1, prior to treatment)  
Key Ocular Inclusion Criterion (Non-study Eye): 
• 
BCVA of 34 letters (Snellen equivalent 20/200) or better at baseline (Day 1, prior to treatment) 


 
 
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Key Exclusion Criteria:   
Key Ocular Exclusion Criteria (Either Eye) 
• 
Active periocular, ocular, or intraocular infection at baseline (Day 1) 
 
 
 
Key Ocular Exclusion Criteria (Study Eye): 
 
 
  
 
 
 
 
 
 
 
• 
Previous or concurrent macular laser treatment  
 
 
  
 
 
  
 
 
 
  
 
  
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
o 
Cataract or refractive surgery (excluding yttrium aluminum garnet [YAG] laser posterior 
capsulotomy) within the last 3 months prior to baseline (Day 1) 
Response Measures 
Efficacy:  
• 
BCVA assessed by Early Treatment of Diabetic Retinopathy Study (ETDRS) letters 
• 
Central retinal thickness (CRT) assessed with spectral-domain optical coherence tomography 
(SD-OCT) 


 
 
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General Statistical Methods and Types of Analyses:   
The safety population, consisting of patients who received at least 1 study treatment, will be used for all 
analyses. Statistical analysis will be primarily descriptive. 
Efficacy: Summary statistics of the following efficacy variables will be provided: 
• 
Proportion of patients with stable vision (ie, patients who lose fewer than 15 letters in BCVA) from 
baseline  
• 
Mean change from baseline in BCVA 
• 
Proportion of patients with a gain of 15 or more ETDRS letters in BCVA from baseline  
• 
Mean change from baseline in CRT as assessed with SD-OCT 
  
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
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Sample Size Calculation:  The study will enroll approximately 100 patients. This sample size is determined 
empirically and is considered appropriate for the planned assessments. 


 
 
 
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1. 
Background and Clinical Rationale  
Age-related macular degeneration (AMD) is the leading cause of severe vision loss in 
industrialized countries worldwide (World Health Organization 2013). AMD is a macular 
disorder characterized by drusen deposits, retinal pigment epithelium (RPE) abnormalities, 
geographic atrophy, and neovascular maculopathy (Pieramici 2006). The advanced stages of 
AMD, which are associated with severe loss of vision, consist of either choroidal 
neovascularization (neovascular AMD) or central geographic atrophy. The majority of severe 
vision loss due to advanced AMD is attributable to the development of choroidal 
neovascularization (CNV) (Ferris 1983, Sommer 1991). Neovascular AMD is characterized 
by the growth of choroidal vessels into the subretinal space. These newly formed vessels 
have a tendency to leak blood and fluid, causing retinal edema, which is accompanied by 
metamorphopsia. The new vessels are accompanied by proliferation of fibrous tissue, and the 
continued growth of this lesion into the macula results in progressive, severe, and irreversible 
central vision loss (Shah 2007, Shah 2009). Left untreated, neovascular AMD results in 
severe visual impairment with an average loss of around 4 lines of visual acuity within 
2 years of disease onset (Blinder 2003, Wong 2008). 
Vascular endothelial growth factor-A (VEGF-A) is implicated in the development and 
maintenance of neovascularization that characterizes the neovascular form of AMD 
(Ding 2009). Studies have shown elevated VEGF-A levels in areas of laser-induced CNV in 
primates, and clinically in patients with AMD. VEGF-A is a potent mitogen for endothelial 
cells, which causes increased vascular permeability and promotes leukocyte-induced damage 
to retinal endothelial cells (Grisanti 2008). Degenerated tissues produce and release 
VEGF-A, which binds to specific receptors located on the endothelial cells of nearby 
preexisting blood vessels. These endothelial cells then proliferate and migrate out through the 
diseased tissue. Pericytes, smooth muscle-like cells, provide structural support to these newly 
formed blood vessel loops and blood flow begins in these vessels. Thus, VEGF-A serves as a 
rate-limiting step in angiogenesis (Ciulla 2009). It also increases vascular permeability by 
leukocyte-mediated endothelial cell injury, formation of fenestrae, and the dissolution of tight 
junctions. This leads to intraretinal fluid accumulation and subsequent distortion of the 
macula, resulting in decreased visual acuity (Cheung 2013). 
The discovery of VEGF-A’s role in the pathogenesis of neovascular ocular disease provided a 
strong rationale for the development of highly specific and targeted anti-vascular endothelial 
growth factor (VEGF)-based therapies (Ciulla 2009). Three anti-VEGF agents, pegaptanib 
sodium, ranibizumab, and aflibercept are currently approved in many countries for the 
treatment of neovascular AMD. In addition, off-label use of a fourth anti-VEGF agent, 


 
 
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bevacizumab, as a treatment option for neovascular AMD, has become common worldwide. 
These agents are delivered to the vitreal cavity by intravitreal injection. This method is now 
widely accepted as a safe and effective means of delivering anti-VEGF compounds to the 
back of the eye. 
One drawback with currently approved anti-VEGF treatments is the need to frequently 
administer intravitreal injections. It would be highly desirable to develop an agent that 
requires less frequent injections. Not only would this remove a significant treatment burden 
on patients and their health care providers, but it would decrease the risk of complications 
associated with frequent intravitreal injections.  
Abicipar pegol (hereafter referred to as abicipar) is a pegylated designed ankyrin repeat 
protein (DARPin) therapeutic with an overall molecular weight of approximately 34 kDa. 
DARPin therapeutics are a novel class of small, single domain proteins. The protein moiety 
consists of an alternative scaffold domain to antigen receptors based on ankyrin repeats 
targeted against human VEGF-A. The targeting sequence is covalently linked to a single 
molecule of maleimide polyethylene glycol of 20 kDa (mPEG20) through a polypeptide 
linker and a carboxy-terminal cysteine. 
Abicipar binds to and inhibits the biological activity of human VEGF-A. Results of in vitro 
assays show that abicipar inhibits VEGF-mediated cellular responses in several different 
assays, generally in the low picomolar range. In vivo pharmacodynamic data demonstrate 
marked efficacy in 2 ocular animal models relevant to the target indication of neovascular 
AMD. Abicipar has demonstrated a pharmacodynamic profile that is appropriate for a 
product being developed for use in the treatment of exudative or ischemic retinal diseases. 
In addition, in vivo rabbit ocular studies have been conducted to assess the ocular 
pharmacokinetics (PK) of abicipar. Data from these studies indicate that abicipar has a vitreal 
half-life that ranges from approximately 3.9 to 7.5 days, indicating a potential for a longer 
duration of action compared to marketed anti-VEGF therapies when considering dissociation 
constant, half-life, and dose. 
The abicipar clinical development program for neovascular AMD consists of a completed 
Phase 1 study (MP0112-CP01), an ongoing Phase 1 clinical pharmacokinetics study 
(150998-012) and an ongoing Phase 1 clinical pharmacokinetics study (1771-101-008 [to be 
conducted in Japan]), 3 completed Phase 2 studies (150998-001 [in 3 stages], 150998-002 
[conducted in Japan], and 150998-003 [conducted in the United States]), and 2 ongoing 
global Phase 3 safety and efficacy studies (150998-005 and 150998-006). Abicipar 
intravitreal injection has been shown to be safe and effective for the treatment of neovascular 


 
 
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AMD in 1 Phase 1 and 3 Phase 2 clinical studies. One Phase 1 study (MP0112-CP01) and 3 
Phase 2 studies (150998-001, 150998-002, and 150998-003) have been completed in the 
neovascular AMD program. Study MP0112-CP01 was a single-ascending-dose study 
evaluating intravitreal doses of abicipar ranging from 0.04 to 2 mg/eye in patients with 
neovascular AMD. Study 150998-001 was conducted in 3 stages. Stage 1 was an open-label, 
single-dose, dose-escalation study to evaluate the safety of abicipar and establish the highest 
tolerable dose. Stage 1 dose cohorts included 1 mg, 2 mg, 3 mg, and 4.2 mg abicipar given as 
a single intravitreal injection. Stage 2 was a randomized, double-masked study to assess the 
safety and efficacy of 3 mg and 4.2 mg abicipar versus ranibizumab 0.5 mg in up to 2 
intravitreal injections. Stage 3 was a randomized, double-masked study to evaluate the safety 
and efficacy of repeat administration of abicipar 1 mg and 2 mg (1 injection at baseline and 
then every 4 weeks; total 3 injections) versus ranibizumab 0.5 mg (1 injection at baseline and 
then every 4 weeks; total 5 injections).  
Studies 150998-002 and 150998-003 were similarly designed randomized and 
double-masked studies to evaluate the safety and efficacy of 1 and 2 mg of abicipar following 
repeat administration (1 injection at baseline and then every 4 weeks; total 3 injections) 
versus ranibizumab 0.5 mg (1 injection at baseline and then every 4 weeks; total 5 injections) 
in treatment-naïve Japanese and non-Japanese patients with neovascular AMD, respectively, 
to support the clinical development in Japan.  
Following administration of a 2-mg dose, abicipar was measurable in human serum between 
baseline (Day 1) and Week 1 postdose, with concentrations falling below the lower limit of 
quantitation (BLQ) by Week 4. Peak serum concentration after dosing (Cmax) was observed 
between 1 and 3 days postdose and ranged from 1.05 to 2.66 nM. These concentrations are 
7-fold and 35-fold lower than those observed at the no-observed-adverse-effect level in 
rabbits and dogs, respectively. Concentrations of abicipar were BLQ by 4 weeks following a 
single injection (Studies MP0112-CP01 and 150998-001, Stage 1) or 3 repeat injections 
(Study 150998-001, Stage 3, Study 150988-002, Study 150998-003). The latter data suggest 
that abicipar does not accumulate in the systemic circulation following 3 monthly injections.  
Study 1771-201-008, which follows a new protocol numbering system, is designed to 
evaluate the safety and treatment effect of abicipar produced using a modified manufacturing 
process.  
2. 
Study Objectives  
The primary objective is to evaluate abicipar for safety and treatment effect in patients with 
neovascular AMD. 


 
 
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3. 
Study Design 
This is a multicenter, open-label, 28-week study to evaluate abicipar for safety and treatment 
effect in patients with neovascular AMD. Approximately 100 patients will be enrolled to 
receive 2 mg abicipar administered at baseline (Day 1) and Weeks 4, 8, 16, and 24. 
There will be a total of 9 scheduled visits during the study. These include screening 
(Days -21 to -2); baseline (Day 1); Weeks 4, 8, 12, 16, 20, 24, and 28/Early Exit. For patients 
at selected sites who participate in PK blood sampling, there will be 1 additional visit:  
Day 3. 
4. 
Study Population and Entry Criteria 
4.1 
Number of Patients  
Approximately 100 patients will be enrolled at approximately 40 sites. 
4.2 
Study Population Characteristics 
This study will enroll patients with neovascular AMD. 
One eye will be selected as the study eye for the duration of the study. If both eyes are 
eligible, the eye with the worse best-corrected visual acuity (BCVA), assessed at screening 
and confirmed at baseline (Day 1), will be selected as the study eye. If both eyes meet all the 
inclusion/exclusion criteria and BCVA values are identical for both eyes, the patient may 
choose to select their non-dominant eye for treatment, or else the right eye will be selected as 
the study eye. 
4.3 
Inclusion Criteria 
The following are requirements for entry into the study: 
General Inclusion Criteria 
 
1. Male or female patients, 50 years of age or older at the time of informed consent 
2. Patient has completed/signed an informed consent prior to conduct of any study-
related procedures or examinations, is able to follow study instructions, and is likely to 
complete all required visits 


 
 
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3. Patient has provided, at screening, written documentation in accordance with the 
relevant country and local privacy requirements (eg, Written Authorization for Use 
and Release of Health and Research Study Information and written Data Protection 
consent) 
 
Ocular Inclusion Criteria (Study Eye) 
 
 
 
 
 
 
 
  
6. BCVA ≤ 78 and ≥ 24 letters (20/32 to 20/320 Snellen equivalents, respectively) at 
screening and at baseline (Day 1, prior to treatment) visits 
 
 
 
Ocular Inclusion Criteria (Non-study Eye) 
8. BCVA of 34 letters (Snellen equivalent 20/200) or better at baseline (Day 1, prior to 
treatment) 
4.4 
Exclusion Criteria 
The following are criteria for exclusion from participating in the study: 
General Exclusion Criteria 
 
 
 
 
 
 


 
 
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Ocular Exclusion Criteria (Either Eye) 
8. Active periocular, ocular, or intraocular infection at baseline (Day 1) 
 
 
 
 
Ocular Exclusion Criteria (Study Eye) 
 
 


 
 
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17. Previous or concurrent macular laser treatment 
 
 
 
 
 
  
  
 
 
  
 
 
 
 
 
 
 


 
 
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• Cataract or refractive surgery (excluding yttrium aluminum garnet [YAG] laser 
posterior capsulotomy) within the last 3 months prior to baseline (Day 1) 
 
 
 
 
 
 
 
 
 
 
4.5 
Permissible and Prohibited Medications/Treatments 
4.5.1 
Permissible Medications/Treatments 
Therapy considered necessary for the patient’s welfare may be given at the discretion of the 
investigator. All medications must be recorded in the electronic case report form (eCRF). If 
the permissibility of a specific medication/treatment is in question, please contact Allergan. 
• Non-investigational therapies for the non-study eye are permissible at any time, at the 
investigator’s discretion 
• Corticosteroids administered via intra-nasal, inhaled, intra-articular, or ocular topical 
routes are permitted during the study 
• If cataract surgery is necessary, attempt to schedule cataract surgery ≥ 7 days after the 
most recent study treatment. Study treatment may be resumed ≥ 14 days after cataract 
surgery, assuming an absence of surgical-related complications 


 
 
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4.5.1.1 
Definition of Females of (Non-)Childbearing Potential and/or 
Acceptable Contraceptive Methods 
For purposes of this study, females will be considered of childbearing potential unless they 
are naturally postmenopausal or permanently sterilized (ie, hysterectomy). Natural 
menopause is defined as the permanent cessation of menstrual periods, determined 
retrospectively after a woman has experienced 12 months of amenorrhea without any other 
obvious pathological or physiological cause. For women of childbearing potential who may 
participate in the study, the following methods of contraception, if properly used, are 
generally considered reliable: hormonal contraceptives (ie, oral, patch, injection, implant), 
male condom with intravaginal spermicide, diaphragm or cervical cap with spermicide, 
vaginal contraceptive ring, intrauterine device, surgical sterilization (bilateral tubal ligation, 
bilateral salpingectomy), vasectomized partner, or sexual abstinence. For male patients who 
participate in the study, condoms should be used as method of contraception. 
The investigator and each patient will determine the appropriate method of contraception for 
the patient during the participation in the study. 
If a female becomes pregnant during the study, the investigator will notify the sponsor 
immediately after the pregnancy is confirmed and the patient will be exited from the study 
after appropriate safety follow-up. The investigator will (1) notify the patient’s physician that 
the patient was being treated with an investigational drug (abicipar), and (2) follow the 
progress of the pregnancy. The investigator must document the outcome of the pregnancy 
and provide a copy of the documentation to Allergan. 
If a female partner of a male study patient becomes pregnant during the study, the 
investigator will notify Allergan immediately after the pregnancy is confirmed. The 
investigator will (1) obtain a consent from the female partner for pregnancy follow-up, and 
(2) follow the progress of the pregnancy to term. The investigator must document the 
outcome of the pregnancy and provide a copy of the documentation to Allergan. 
4.5.2 
Prohibited Medications/Treatments 
The decision to administer a prohibited medication/treatment is done with the safety of the 
study patient as the primary consideration. When possible, it is recommended to notify 
Allergan before the prohibited medication/treatment is administered. 
Use of the following medications are prohibited during the study: 


 
 
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• Any periocular injection or intravitreally administered therapy other than study 
medication in the study eye 
• Verteporfin PDT for treatment of neovascular AMD in the study eye 
• Systemic (eg, oral, intravenous, intramuscular) corticosteroids taken within 5 days 
prior to any study visit 
• Systemic (eg, intravenous, oral) anti-VEGF medications (eg, bevacizumab, 
ziv-aflibercept) or VEGF-receptor inhibitor (eg, sunitinib, sorafenib, pazopanib)  
4.5.3 
Special Diet or Activities 
Patients are not required to fast prior to blood and urine collections for laboratory tests. 
5. 
Study Treatments  
5.1 
Study Treatments and Formulations 
Abicipar is a solution at a concentration of 40 mg/mL provided in sterile single-use glass 
vial. Abicipar produced using a modified manufacturing process will be utilized in this trial. 
One single-dose vial will be packaged in a box for each injection. Materials for preparing 
abicipar for intravitreal injection will also be provided. These include a filter needle, an 
injection needle, and an injection syringe. 
5.2 
Control Treatment(s)  
Not applicable. 
5.3 
Methods for Masking 
Not applicable. 
5.4 
Treatment Allocation Ratio and Stratification 
Not applicable. 


 
 
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5.5 
Method for Assignment to Treatment Groups/Randomization 
Prior to initiation of study treatment, each patient who provides informed consent and/or 
assent will be assigned a patient number that will serve as the patient identification number 
on all study documents. 
This is an open-label, single arm study. No randomization will be performed. Study 
medication will be labeled with medication kit numbers.  
5.6 
Treatment Regimen and Dosing 
Enrolled patients will receive 2 mg abicipar administered by intravitreal injections at baseline 
(Day 1) and Weeks 4, 8, 16, and 24. 
5.6.1 
Treatment Regimen/Dosage Adjustments/Dose Discontinuation 
If the study eye develops a treatment-related adverse event at any time during the study, 
treatment dose may be temporarily held or discontinued and the reason for dose holding or 
discontinuation will be recorded on the eCRF. 
The treatment regimen will be adjusted based on the following criteria: 
• Intraocular inflammation: discontinue the dose and exit the patient when the event of 
intraocular inflammation has been resolved. For more information, refer to 
Section 6.3.2. 
• IOP: hold dose if IOP is ≥ 30 mm Hg in the study eye. Treatment may resume when 
IOP is < 30 mm Hg, either spontaneously or by treatment, as determined by the 
evaluating physician. 
• New retinal break or retinal detachment: hold dose for the study eye. Treatment may 
resume after the retinal break/detachment has been successfully treated. 
• Ocular and/or periocular infection: hold dose until the infection is resolved in both 
eyes 
The investigator may hold or discontinue study treatment for other safety reasons at his/her 
discretion. 


 
 
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5.7 
Storage of Study Medications/Treatments 
The study medication must be stored in a secure area and administered only to patients 
entered into the clinical study, at no cost to the patient, in accordance with the conditions 
specified on the study medication kit label and in the procedure manual. 
Only assigned individuals authorized by the investigator may have access to study 
medication. 
5.8 
Preparation of Study Medications/Treatments 
Abicipar must be prepared in a hospital pharmacy or by an investigator or trained assistant in 
the clinic using aseptic technique. The instructions for preparation of the individual doses are 
provided in the procedure manual. 
5.9 
Treatment Administration 
Abicipar will be administered by intravitreal injection as specified in the procedure manual. 
The injection volume is 0.05 mL (50 µL). 
Prior to study treatment, the study eye of each patient will be anesthetized with topical 
anesthetic and prepared according to the standard protocol detailed in the Procedure Manual. 
Medication will be injected into the vitreous of the study eye through the pars plana. 
6. 
Response Measures and Summary of Data Collection Methods 
6.1 
Efficacy Measures 
• BCVA assessed using the Early Treatment of Diabetic Retinopathy Study (ETDRS) 
letters (Age-Related Eye Disease Study [AREDS] Research Group, 2001) 
• Central retinal thickness (CRT) assessed with spectral-domain optical coherence 
tomography (SD-OCT) 
 
 
 
 
 
 


 
 
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Any adverse events potentially
 
 
 
 
 
6.4 
Examination Procedures, Tests, Equipment, and Techniques 
Details for all examination procedures and tests are provided in the corresponding procedure 
manuals. 
6.4.1 
Disease Characterization 
6.4.1.1 
Dilated Color Fundus Photography 
A standardized procedure for the collection of fundus digital photographic images of the 
retina, optic disc, and macula will be followed. Color fundus images are required to be sent 
to Allergan for evaluation, as necessary. 
6.4.1.2 
Fluorescein Angiography 
A standardized procedure for examining the retinal circulation and vessel permeability using 
a dye tracing method will be followed. It involves injection of sodium fluorescein into the 
systemic circulation, and then an angiogram is obtained by digitally photographing the 
fluorescence emitted after illumination of the retina with blue light at a wavelength of 
490 nanometers. Fluorescein angiograms are required to be sent to Allergan for evaluation, as 
necessary. 
6.4.2 
Efficacy 
6.4.2.1 
Best-corrected Visual Acuity 
BCVA measures will be quantified using the ETDRS method (AREDS Research Group, 
2001). BCVA testing must precede any examination requiring contact with the study eye. 
BCVA must be performed following manifest refraction and completed according to the 
procedures outlined in the procedure manual. Certification of the examiners at each 
investigative site will occur prior to screening any study patients. 


 
 
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6.4.2.2 
Optical Coherence Tomography 
OCT is a laser-based, non-invasive, diagnostic system providing high-resolution imaging 
optical sections of the retina. The CRT in the study eye (defined as the central 1000 microns 
from the center of the fovea) will be captured using SD-OCT. 
Electronic OCT images will be assessed at the site and will be used to confirm patient 
eligibility for study enrollment as well as to monitor disease progression for safety. Images 
are required to be sent to Allergan. The same OCT system (eg, Spectralis or Cirrus) must be 
used throughout the study for a given patient. See the procedure manual for further details. 


 
 
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6.4.3.5 
Best-corrected Visual Acuity 
All BCVA measures will be used as safety measures to evaluate vision loss over time. BCVA 
is also used as a measure of efficacy as described in Section 6.4.2.1. 
6.4.3.6 
Pregnancy Test 
Females of childbearing potential will have urine pregnancy tests performed at baseline 
(Day 1, prior to treatment administration) and study exit. Urine pregnancy test kits will be 
provided by the site and will be administered at the site according to the instructions 
provided with the tests. The pregnancy test must be negative for the patient to receive study 
medication. Additional pregnancy tests may be performed at any time during the study, at the 
investigator’s discretion. 
6.4.3.7 
Adverse Events 
All adverse events will be monitored and reported on an adverse event eCRF, including 
seriousness, severity, action taken, and relationship to study drug. If adverse events occur, the 
first concern will be the safety of the study patient. 


 
 
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6.5 
Other Study Supplies 
Allergan will make provisions (directly or indirectly) to supply the study sites with standard 
photographs for grading of cataracts, ETDRS supplies (if needed), medications or supplies 
(anti-infective ophthalmic solution, local anesthetic eyedrop, dilating eyedrop, povidone 
iodine, syringe, needles, cotton tip swabs, sterile fields, and cellulose sponges), PK blood 
sampling kits, and immunogenicity (anti-abicipar antibody) blood sampling kits. Tubes for 
collection of clinical laboratory analysis will be provided by a central laboratory. 
6.6 
Summary of Methods of Data Collection 
Clinical data will be entered into the eCRF using an electronic data capture system. Data 
entered into the eCRF will correspond to and be supported by source documentation 
maintained at the sites. 
7. 
Statistical Procedures 
This section is a summary of the planned statistical analyses. A detailed statistical analysis 
plan (SAP) will be developed and finalized before database lock. 
7.1 
Analysis Populations 
The safety population, consisting of patients who received at least 1 study treatment, will be 
used for all analyses. 
7.2 
Methods of Analysis 
7.2.1 
Efficacy Analyses 
Efficacy measures will be based on BCVA and CRT measured in the study eye. Efficacy 
variables include the following: 
• Proportion of patients with stable vision (ie, patients who lose fewer than 15 letters in 
BCVA) from baseline 
• Mean change from baseline in BCVA 
• Proportion of patients with a gain of 15 or more ETDRS letters in BCVA from 
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• Mean change from baseline in CRT as assessed with SD-OCT 
Efficacy variables will be summarized using descriptive statistics as appropriate. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
7.3 
Subgroup Analyses 
Not applicable. 
7.4 
Sample Size Calculation 
The study will enroll approximately 100 patients. This sample size is determined empirically 
and is considered appropriate for the planned assessments. 


 
 
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7.5 
Interim Analyses 
An interim analysis is planned when all patients have completed the Week 12 visit or have 
exited early from the study.  
 
 
 
 
 
 
 
8.1 
Patient Entry Procedures 
8.1.1 
Overview of Entry Procedures 
Prospective patients as defined by the criteria in Sections 4.3 and 4.4 (inclusion/exclusion 
criteria) will be considered for entry into this study. 
8.1.2 
Informed Consent and Patient Privacy 
The study will be discussed with the patient and a patient wishing to participate must give 
informed consent prior to any study-related procedures or change in treatment. The patient 
must also give authorization and other written documentation in accordance with the relevant 
country and local privacy requirements (where applicable) prior to any study-related 
procedures or change in treatment. 
Each patient that provides informed consent and/or assent will be assigned a patient number 
that will be used on patient documentation throughout the study. 
8.2 
Procedures for Final Study Entry 
All screening laboratory tests must be performed, and the results must be evaluated and 
determined to be acceptable to the investigator prior to patient entry into the study. Screening 
laboratory tests may be repeated once at the discretion of the investigator or Allergan. 
A urine pregnancy test administered to women of childbearing potential at the baseline 
(Day 1) visit must be negative prior to treatment administration. 


 
 
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A patient is considered to have entered the study at the time of assignment to treatment at the 
baseline (Day 1) visit. See Section 5.5 for the method for assignment to treatment. 


 
 
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8.4 
Instructions for the Patients 
Patients are instructed that they do not need to fast before visits. 
Patients are instructed to strictly follow the study visit schedule and to report all changes in 
condition to the investigative site. 
8.5 
Unscheduled Visits 
Additional examinations may be performed as necessary to ensure the safety and well-being 
of patients during the study. The eCRFs should be completed for each unscheduled visit. 
8.6 
Compliance with Protocol 
Allergan must be informed of any patients who are inadvertently enrolled despite significant 
deviation from protocol-specified criteria. A decision regarding the patient’s continued 
participation will be made on a case-by-case basis. 


 
 
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8.7 
Early Discontinuation of Patients 
Patients may voluntarily withdraw from the study at any time. A patient’s participation in the 
study may be terminated if it is deemed by the investigator or Allergan that it is unsafe for the 
patient to continue in the study. 
Notification of early patient discontinuation from the study and the reason for discontinuation 
will be made to the sponsor and will be clearly documented on the appropriate eCRF.  
For patients who discontinue from the study early due to other reasons, every effort must be 
made to have these patients return to the clinical center for completion of the Early Exit visit. 
8.8 
Study Termination 
The study may be stopped at his/her study site at any time by the site investigator. Allergan 
may stop the study (and/or the study site) for any reason with appropriate notification. 
9. 
Adverse Events 
Adverse events occurring during the study will be recorded on an adverse event eCRF. If 
adverse events occur, the first concern will be the safety of the study participants. 
9.1 
Definitions 
9.1.1 
Adverse Event 
An adverse event is any untoward medical occurrence in a patient or clinical investigation 
patient administered a pharmaceutical product and that does not necessarily have a causal 
relationship with this treatment. An adverse event can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom, or disease temporally 
associated with the use of a medicinal (investigational) product, whether or not related to the 
medicinal (investigational) product. In addition, during the screening period, adverse events 
will be assessed regardless of the administration of a pharmaceutical product. 
Note:  Adverse events must be collected once informed consent has been obtained, regardless 
of whether or not the patient has been administered study drug. 
Progression of treatment indication including new or worsening of anticipated clinical signs 
or symptoms, which are collected as clinical efficacy variables and assessed as unequivocally 
associated with the disease progression and/or lack of efficacy, should NOT be reported as 


 
 
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adverse events unless the disease progression is greater than anticipated in the natural course 
of the disease. 
Adverse events will be assessed, documented, and recorded in the eCRF throughout the study 
(ie, after informed consent has been obtained). At each visit, the investigator will begin by 
querying for adverse events by asking each patient a general, non-directed question such as 
“How have you been feeling since the last visit?”  Directed questioning and examination will 
then be done as appropriate. All reported adverse events will be documented on the 
appropriate eCRF. 
9.1.2 
Serious Adverse Event 
A serious adverse event is any adverse event occurring at any dose that results in any of the 
following outcomes:  death, a life-threatening adverse event, inpatient hospitalization or 
prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a 
congenital anomaly/birth defect. Important medical events that may not result in death, be 
life-threatening, or require hospitalization may be considered a serious adverse event when, 
based upon appropriate medical judgment, they may jeopardize the patient and may require 
medical or surgical intervention to prevent one of the outcomes listed in this definition. (See 
Section 9.3 for procedures for reporting a serious adverse event.) 
Allergan considers all cancer adverse events as serious adverse events. In addition, Allergan 
considers any abortion (spontaneous or nonspontaneous) as a serious adverse event. 
Pre-planned surgeries or procedures for pre-existing, known medical conditions for which a 
patient requires hospitalization is not reportable as a serious adverse event. 
Any pre-planned surgery or procedure should be clearly documented in the site source 
documents by the medically qualified investigator at the time of the patient’s entry into the 
study. If it has not been documented at the time of the patient’s entry into the study, then it 
should be documented as a serious adverse event and reported to Allergan. 
9.1.3 
Severity 
A clinical determination will be made of the intensity of an adverse event. The severity 
assessment for a clinical adverse event must be completed using the following definitions as 
guidelines: 


 
 
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Mild 
Awareness of sign or symptom, but easily tolerated. 
Moderate 
Discomfort enough to cause interference with usual activity. 
Severe 
Incapacitating with inability to work or do usual activity. 
Not applicable 
In some cases, an adverse event may be an ‘all or nothing’ finding 
which cannot be graded. 
 
9.1.4 
Relationship to Study Drug or Study Procedure 
A determination will be made of the relationship (if any) between an adverse event and the 
study drug or study procedure, as applicable. A causal relationship is present if a 
determination is made that there is a reasonable possibility that the adverse event may have 
been caused by the drug or study procedure. 
A study procedure occurring during the screening/baseline period can include a study 
required diagnostic procedure. 
For treatment-related adverse events, the investigator will note on the eCRF whether the 
event is related to the study medication, and/or the injection procedure. 
9.2 
Procedures for Reporting Adverse Events 
Any adverse event must be recorded on the appropriate eCRF. 
All adverse events that are drug-related and unexpected (not listed as treatment-related in the 
current Investigator’s Brochure) must be reported to the governing Institutional Review 
Board/Independent Ethics Committee (IRB/IEC) as required by the IRB/IEC, local 
regulations, and the governing health authorities. Any adverse event that is marked ‘ongoing’ 
at the exit visit must be followed-up as appropriate. 
9.3 
Procedures for Reporting a Serious Adverse Event 
Any serious adverse event occurring during the study period (beginning with informed 
consent) and for at least 12 weeks after the last dose of study drug must be immediately 
reported but no later than 24 hours after learning of a serious adverse event. Serious adverse 
events must be reported to Allergan (or Agent of Allergan) as listed on the Allergan Study 
Contacts Page and recorded on the serious adverse event form. All patients with a serious 
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the sponsor and the IRB/IEC with any additional requested information (eg, autopsy reports 
and discharge summaries). 
In the event of a serious adverse event, the investigator must: 
1. Notify Allergan immediately by fax or email using the serious adverse event form 
(contact details can be found on page 1 of the serious adverse event form); phone 
numbers and relevant Allergan personnel contacts are also on the front page of 
protocol and Study Contacts Page. 
2. Obtain and maintain in his/her files all pertinent medical records, information, and 
medical judgments from colleagues who assisted in the treatment and follow-up of the 
patient. 
3. Provide Allergan with a complete, written description of the adverse event(s) on the 
serious adverse event form describing the event chronologically, including any 
treatment given (eg, medications administered, procedures performed) for the adverse 
event(s). Summarize relevant clinical information about the event:  signs, symptoms, 
diagnosis, clinical course and relevant clinical laboratory tests, etc. Include any 
additional or alternative explanation(s) for the causality which includes a statement as 
to whether the event was or was not related to the use of the investigational drug. 
4. Promptly inform the governing IRB/IEC of the serious adverse event as required by 
the IRB/IEC, local regulations, and the governing health authorities. 
9.4 
Procedures for Unmasking of Study Medication 
This is an open-label study. 
10. 
Administrative Items 
This protocol is to be conducted in accordance with the applicable Good Clinical Practice 
(GCP) regulations and guidelines, eg, the International Conference on Harmonisation (ICH) 
Guideline on GCP. 


 
 
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10.1 
Protection of Human Patients 
10.1.1 
Compliance with Informed Consent Regulations (US 21 CFR 
Part 50) and Relevant Country Regulations 
Written informed consent is to be obtained from each patient prior to any study-related 
activities or procedures in the study, and/or from the patient’s legally authorized 
representative.  
10.1.2 
Compliance With IRB or IEC Regulations 
This study is to be conducted in accordance with IRB regulations (US 21 CFR Part 56.103) 
or applicable IEC regulations. The investigator must obtain approval from a properly 
constituted IRB/IEC prior to initiating the study and re-approval or review at least annually. 
Allergan is to be notified immediately if the responsible IRB/IEC has been disqualified or if 
proceedings leading to disqualification have begun. Copies of all IRB/IEC correspondence 
with the investigator should be provided to Allergan. 
10.1.3 
Compliance With Good Clinical Practice 
This protocol is to be conducted in accordance with the applicable GCP regulations and 
guidelines. 
10.1.4 
Compliance With Electronic Records; Electronic Signatures 
Regulations (US 21CFR Part 11) 
This study is to be conducted in compliance with the regulations on electronic records and 
electronic signature. 
10.2 
Changes to the Protocol 
The investigator must not implement any deviation from or changes of the protocol without 
approval by Allergan and prior review and documented approval/favorable opinion from the 
IRB/IEC of a protocol amendment, except where necessary to eliminate immediate hazards 
to study patients, or when the changes involve only logistical or administrative aspects of the 
study (eg, change in monitors, change of telephone numbers). 


 
 
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10.3 
Patient Confidentiality 
A report of the results of this study may be published or sent to the appropriate health 
authorities in any country in which the study drug may ultimately be marketed, but the 
patient’s name will not be disclosed in these documents. The patient’s name may be disclosed 
to the Sponsor of the study, Allergan, or the governing health authorities or the FDA if they 
inspect the study records. Appropriate precautions will be taken to maintain confidentiality of 
medical records and personal information. 
10.3.1 
Patient Privacy 
Written authorization and other documentation in accordance with the relevant country and 
local privacy requirements (where applicable) is to be obtained from each patient prior to 
enrollment into the study, and/or from the patient’s legally authorized representative in 
accordance with the applicable privacy requirements (eg, the Health Insurance Portability 
and Accountability Act Standards for Privacy of Individually Identifiable Health Information 
(“HIPAA”), European Union Data Protection Directive 95/46/EC [“EU Directive”]). 
In accordance with HIPAA requirements, additional purposes of this study may include 
publishing of anonymous patient data from the study. 
10.4 
Documentation 
10.4.1 
Source Documents 
Source documents may include a patient’s medical records, hospital charts, clinic charts, the 
investigator’s patient study files, as well as the results of diagnostic tests such as X-rays, 
laboratory tests, and electrocardiograms. The investigator’s copy of the eCRF serves as part 
of the investigator’s record of a patient’s study-related data. 
The following information should be entered into the patient’s medical record: 
• Patient’s name 
• Patient’s contact information 
• The date that the patient entered the study, patient number, and patient randomization 
[or medication kit] number 
• The study title and/or the protocol number of the study and the name of Allergan 


 
 
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• A statement that informed consent was obtained (including the date). A statement that 
written authorization or other country and local patient privacy required 
documentation for this study has been obtained (including the date). 
• Dates of all patient visits 
• All concurrent medications (List all prescription and non-prescription medications 
being taken at the time of enrollment. At each subsequent visit, changes to the list of 
medications should be recorded.) 
• Occurrence and status of any adverse events 
• Vital signs and general physical examination findings 
• The results of pregnancy tests performed by the site 
• Copies of the laboratory reports generated by the central laboratory for the analysis of 
blood and urine samples 
• Visual acuity worksheets 
• Results of abnormal findings from ophthalmic examination (including slit-lamp 
biomicroscopy, IOP assessment, and indirect ophthalmoscopy examination) 
• SD-OCT imaging files and backup copies of electronic records 
• Dilated fundus photography files and backup copies of electronic records 
• Fluorescein angiography duplicate and backup copies of the electronic records if a 
digital system is used 
• Procedure notes for the study medication administration procedures must include the 
following: 
o Date and time the vial is removed from the refrigerator 
o Date and time of the procedure 
o Evaluation of the injection site 
o Location of the injection to the nearest clock hour 


 
 
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o Complications, if any 
• The date the patient exited the study, and a notation as to whether the patient 
completed the study or reason for discontinuation 
Source documentation practices must follow Section 4.0 of ICH E6, Good Clinical Practice: 
Consolidated Guidance and ALCOA, ie, records must be Attributable, Legible, 
Contemporaneous, Original and Accurate. 
10.4.2 
Case Report Form Completion 
The investigator is responsible for ensuring that data are properly recorded on each patient’s 
eCRFs and related documents. An investigator who has signed the protocol signature page 
should personally sign for the eCRFs (as indicated in the case report forms) to ensure that the 
observations and findings are recorded on the eCRFs correctly and completely. The eCRFs 
are to be submitted to Allergan in a timely manner at the completion of the study, or as 
otherwise specified by Allergan and will be maintained in a central data repository. 
10.4.3 
Study Summary 
An investigator’s summary will be provided to Allergan within a short time after the 
completion of the study, or as designated by Allergan. A summary is also to be provided to 
the responsible IRB/IEC. 
10.4.4 
Retention of Documentation 
All study related correspondence, patient records, consent forms, patient privacy 
documentation, records of the distribution and use of all investigational products, and copies 
of eCRFs should be maintained on file. 
For countries falling within the scope of the ICH guidelines, the sponsor-specific essential 
documents should be retained 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 have elapsed since the formal 
discontinuation of clinical development of the investigational product. These documents 
should be retained for a longer period, however, if required by the applicable regulatory 
requirement(s) or if needed by the sponsor. 


 
 
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Allergan requires that it be notified in writing if the investigator wishes to relinquish 
ownership of the data so that mutually agreed-upon arrangements can be made for transfer of 
ownership to a suitably qualified, responsible person. 
10.5 
Labeling, Packaging, and Return or Disposal of Study 
Medications/Treatments 
10.5.1 
Labeling/Packaging 
Study medication will be packaged, labeled, and supplied by Allergan. All study medications 
will be identified as an investigational compound and will be labeled with the protocol study 
number and medication kit number. The label will also specify the storage conditions and 
state that the study medication is limited to investigational use. 
10.5.2 
Clinical Supply Inventory 
The investigator must keep an accurate accounting of the number of investigational units 
received from Allergan, dispensed or administered to the patients, and the number of units 
returned to Allergan during and at the completion of the study. A detailed inventory must be 
completed for the study medication. The study medication must be dispensed or administered 
only by an appropriately qualified person to patients in the study. The medication is to be 
used in accordance with the protocol for patients who are under the direct supervision of an 
investigator. A unit is defined as a single-dose vial. 
10.5.3 
Return or Disposal of Study Medications/Treatments and/or 
Supplies 
All clinical study medications/treatments and/or supplies will be returned to Allergan or 
Allergan designee for destruction. Used syringes and needles must be destroyed per local site 
procedure. 
10.6 
Monitoring by the Sponsor 
A representative of the sponsor will monitor the study on a periodic basis. The determination 
of the extent and nature of monitoring will be based on considerations such as the objective, 
purpose, design, complexity, blinding, size, and endpoints of the study. 
Authorized representatives of Allergan or regulatory authority representatives will conduct 
on-site visits to review, audit and copy study-related documents. These representatives will 


 
 
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meet with the investigator(s) and appropriate staff at mutually convenient times to discuss 
study-related data and questions. 
10.7 
Handling of Biological Specimens 
Samples of blood and urine for evaluation of hematology, chemistries, and urinalysis will be 
analyzed at a centralized clinical laboratory with certification from a recognized accreditation 
agency (eg, College of American Pathology [CAP] or Clinical Laboratory Improvement 
Amendments [CLIA] certification). 
Serum samples obtained will be analyzed for abicipar concentrations (free and total) and 
anti-drug antibodies (binding and neutralizing) by bioanalytical laboratories using validated 
methods.  
Details about the handling, processing, and shipment of all biological specimens are provided 
in the procedure manual. 
All samples will be returned to Allergan or Allergan designee for destruction. Allergan shall 
have full ownership rights to any biological specimens/samples derived from the study. 
10.8 
Publications 
Allergan as the sponsor, has proprietary interest in this study. Authorship and manuscript 
composition will reflect joint cooperation between multiple investigators and sites and 
Allergan personnel. Authorship will be established prior to the writing of the manuscript. As 
this study involves multiple centers, no individual publications will be allowed prior to 
completion of the final report of the multicenter study except as agreed with Allergan. 
10.9 
Coordinating Investigator 
A signatory Coordinating Investigator will be designated prior to the writing of the Clinical 
Study Report. 


 
 
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11. 
References 
Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical 
trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-
related macular degeneration and vision loss:  AREDS Report No. 8. Arch Ophthalmol. 
2001;119:1417-1436. 
Blinder KJ, Bradley S, Bressler NM, Bressler SB, Donati G, Hao Y, et al. Effect of lesion 
size, visual acuity, and lesion composition on visual acuity change with and without 
verteporfin therapy for choroidal neovascularization secondary to age-related macular 
degeneration: TAP and VIP Report No.1. Am J Ophthalmol. 2003;136:407-418. 
Cheung LK, Eaton A. Age-related macular degeneration. Pharmacotherapy 2013;33(8):838-
855. 
Ciulla TA, Rosenfeld PJ. Antivascular endothelial growth factor therapy for neovascular age-
related macular degeneration. Curr Opin Ophthalmol. 2009;20:158-165. 
Ding X, Patel M, Chan CC. Molecular pathology of age-related macular degeneration. Prog 
Retin Eye Res. 2009;28(1):1-18. 
Ferris FL 3rd. Senile macular degeneration:  review of epidemiologic features. Am J 
Epidemiol. 1983 Aug;118(2):132-151. 
Grisanti S, Tatar O. The role of vascular endothelial growth factor and other endogenous 
interplayers in age-related macular degeneration. Prog Retin Eye Res. 2008;27:372-390. 
Pieramici DJ, Bressler SB, Koester JM, Bressler NM. Occult with no classic subfoveal 
choroidal neovascular lesions in age-related macular degeneration: clinically relevant natural 
history information in larger lesions with good vision from the Verteporfin in Photodynamic 
Therapy (VIP) Trial: VIP Report No. 4. Arch Ophthalmol. 2006;124:660-664. 
Shah AR, Del Priore LV. Natural history of predominantly classic, minimally classic, and 
occult subgroups in exudative age-related macular degeneration. Ophthalmology. 
2009;116:1901-1907. 
Shah AR, Del Priore LV. Progressive visual loss in subfoveal exudation in age-related 
macular degeneration: a meta-analysis using Lineweaver-Burke plots. Am J Ophthalmol. 
2007;143:83-89. 


 
 
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Sommer A, Tielsch JM, Katz J, Quigley HA, Gottsch JD, Javitt JC, et al. Racial differences 
in the cause-specific prevalence of blindness in East Baltimore. N Engl J Med. 
1991;325:1412-1417. 
Wong TY, Chakravarthy U, Klein R, Mitchell P, Zlateva G, Buggage R, et al. The natural 
history and prognosis of neovascular age-related macular degeneration: A systematic review 
of the literature and meta-analysis. Ophthalmology. 2008;115:116-126. 
World Health Organization. Priority eye diseases: age related macular degeneration. 
Prevention of blindness and impairment. Geneva, Switzerland: World Health Organization; 
2013. 
 


 
 
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12. 
Attachments 
12.1 
Glossary of Abbreviations 
Term/Abbreviation 
Definition 
A/G 
albumin/globulin 
ALT 
alanine aminotransferase 
AMD 
age-related macular degeneration 
AREDS 
Age-Related Eye Disease Study 
AST 
aspartate aminotransferase 
BAB 
binding antibodies 
BCVA 
best-corrected visual acuity 
BUN 
blood urea nitrogen 
BLQ 
below the lower limit of quantitation 
CAP 
College of American Pathology 
CFR 
Code of Federal Regulations 
CLIA 
Clinical Laboratory Improvement Amendments 
Cmax 
peak serum concentration after dosing 
CNV 
choroidal neovascularization 
CRT 
central retinal thickness 
DA 
disc area 
DARPin 
designed ankyrin repeat protein 
DME 
diabetic macular edema 
eCRF 
electronic case report form 
ETDRS 
Early Treatment of Diabetic Retinopathy Study  
EU 
European Union 
FA 
fluorescein angiogram 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 


 
 
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GGT 
gamma-glutamyl transferase 
HbA1c 
glycated hemoglobin 
HIPAA 
Health Insurance Portability and Accountability Act 
ICH 
International Council on Harmonisation 
IEC 
independent ethics committee  
IOP 
intraocular pressure 
IRB 
institutional review board 
LDH 
lactate dehydrogenase 
LFT 
liver function test 
MedDRA 
Medical Dictionary for Regulatory Activities 
mPEG20 
maleimide polyethylene glycol of 20 kDa 
NAB 
neutralizing antibodies 
OCT 
optical coherence tomography 
OU 
both eyes 
PDT 
photodynamic therapy 
PEG 
polyethylene glycol 
PK 
pharmacokinetic 
PPV 
pars plana vitrectomy 
RBC 
red blood cell 
RPE 
retinal pigment epithelium 
SAP 
statistical analysis plan 
SD-OCT 
spectral-domain optical coherence tomography 
SE 
study eye 
SGOT 
serum glutamic oxaloacetic transaminase 
SGPT 
serum glutamic pyruvic transaminase 
TEAE 
treatment-emergent adverse event 
US 
United States 


 
 
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VEGF 
vascular endothelial growth factor 
VEGF-A 
vascular endothelial growth factor-A 
WBC 
white blood cell 
YAG 
yttrium aluminum garnet 
 


 
 
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12.2 
Protocol Amendment Summary Amendment 1 
Title: Evaluation of Abicipar Pegol in Patients with Neovascular Age Related Macular 
Degeneration 
Protocol 1771-201-008 Amendment 1 
Date of Amendment: October 2018 
Amendment Summary 
This summary includes changes made to Protocol 1771-201-008 (Approved January 2018). 
Following is a summary of content-oriented changes that were made to each section of the 
protocol, and a brief rationale for these changes. Minor editorial and document formatting 
revisions have not been summarized. 
Section 
Revision 
Rationale 
 
 
 
 
 
 
” 
Administrative change 
Section 4.5.2 
Revised as follows: 
“Systemic (eg, oral, intravenous, 
intramuscular) corticosteroids taken within 
5 days prior to any study visit regularly 
(defined as exposure for 5 or more 
consecutive days)” 
Administrative change 


 
 
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Section 
Revision 
Rationale 
Section 5.6.1 
Section title revised as follows: 
“Treatment Regimen/Dosage 
Adjustments/Dose Discontinuation” 
 
Change made for patient 
safety 
 
Text revised as follows: 
“If the study eye develops a treatment-
related adverse event at any time during the 
study, treatment dose may be temporarily 
held or discontinued and the reason for dose 
holding or discontinuation will be recorded 
on the eCRF.” 
 
 
First bullet point revised as follows: 
“Intraocular inflammation: may hold or 
discontinue the dose and exit the patient 
when the event of intraocular inflammation 
has been resolved at the investigator’s 
discretion, eg, if intraocular inflammation is 
graded as ≥ 2+ as assessed by 
biomicroscopy in the study eye. For more 
information, refer to Section 6.3.2.” 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
. 
 
 
 
 
 
 
 
Note: Stricken text was removed and underlined text was added. 


 
 
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ALLERGAN 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
            
 
           
 
            
 
           
 
            
 
           
 
     
 
           
 
            
 
           
 
            
 
           
 
            
 
           
 
            
 
           
 
            
 
           
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
            
 
        
 
 
Protocol 1771-201-008 Amd 1

SAP_001.pdf: 
NCT03539549 
 
Study ID: 1771‐201‐008 
 
 
 
Title: Evaluation of Abicipar Pegol in Patients with Neovascular Age‐Related Macular Degeneration 
 
Statistical Analysis Plan Amendment 1 Date: 25 July 2018 
 
 


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Analysis Plan 1771-201-008 
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GDD-BSP-T-001 v2014.6 
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16.1.9 Statistical Methods 
 
Analysis Plan  
 
Evaluation of Abicipar Pegol in Patients  
with Neovascular Age-Related Macular Degeneration 
 
Version 1: 2018-07-25 
 
Protocol Number: 
1771-201-008 
Development Phase: 
2 
Product Name: 
Abicipar Pegol (AGN-150998) 
Study Statistician: 
 
Sponsor: 
Allergan plc  
 
This document is the property of Allergan plc and may not, in full or part, be passed on, 
reproduced, published, distributed to any person, or submitted to any regulatory authority 
without the express written permission of Allergan plc. 
 
 
 
 
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Table of Contents 
1. 
Introduction ........................................................................................................................ 4 
1.1 
Primary Study Objectives and Design ..................................................................... 4 
1.2 
Sample Size .............................................................................................................. 5 
1.3 
Database Lock .......................................................................................................... 5 
2. 
Analysis Populations and Data Conventions ..................................................................... 5 
2.1 
Analysis Populations ................................................................................................ 5 
2.2 
Analysis Visit Windows ........................................................................................... 5 
2.3 
Data Conventions ..................................................................................................... 6 
3. 
Disposition, Exit Status, and Significant Protocol Deviations .......................................... 7 
3.1 
Disposition and Exit Status ...................................................................................... 7 
3.2 
Significant Protocol Deviations ............................................................................... 8 
4. 
Demographics and Other Baseline Characteristics ............................................................ 8 
4.1 
Demographics .......................................................................................................... 8 
4.2 
Baseline Characteristics ........................................................................................... 8 
4.3 
Prior Medications/Procedures .................................................................................. 8 
4.4 
Concomitant Medications/Procedures ..................................................................... 9 
4.5 
Medical History ...................................................................................................... 10 
5. 
Efficacy Assessments and Analyses ................................................................................ 10 
5.1 
Efficacy Assessments ............................................................................................. 10 
5.1.1  Best-Corrected Visual Acuity (BCVA) ...................................................... 10 
5.1.2  Central retinal thickness (CRT) .................................................................. 10 
5.2 
Efficacy Analyses ................................................................................................... 11 
6. 
Safety Analyses ................................................................................................................ 12 
6.1 
Study Treatment – Exposure and Administration .................................................. 12 
6.1.1  Exposure to Study Treatments ................................................................... 12 
6.2 
Adverse Events ...................................................................................................... 12 
 
 
 
 
 
 
 
 
 
 
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7. 
Interim Analyses .............................................................................................................. 20 
8. 
Deviations from Protocol  ................................................................................................ 20 
9. 
References ........................................................................................................................ 20 
10.  Amendment(s) ................................................................................................................. 20 
 
List of Tables 
 
 
Table 2 
BCVA Change Categories ............................................................................... 12 
           
 
 
 
 
List of Figures 
 
 
 
 
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1. 
Introduction 
This document describes the planned analysis that will be used for study 1771-201-008 
clinical study report.  This is a multicenter, open-label, 28-week study to evaluate abicipar for 
safety and treatment effect in patients with neovascular AMD.  
1.1 
Primary Study Objectives and Design 
The primary objective is to evaluate abicipar for safety and treatment effect in patients with 
neovascular age-related macular degeneration (AMD). 
This is a multicenter, open-label, 28-week study. Approximately 100 patients will be enrolled 
to receive 2 mg abicipar administered at Baseline (Day 1) and Weeks 4, 8, 16, and 24. The 
summary of the Study Design: 
Structure:  multicenter, open-label, single-arm study  
Duration:  28 weeks 
Study Treatment Groups:  2 mg abicipar  
Controls:  not applicable 
Dosage/Dose Regimen:  intravitreal injections of 2 mg abicipar administered Baseline (Day 
1) and Weeks 4, 8, 16, and 24 
Enrollment/Stratification:  None 
 
 
   
 
 
 
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1.2 
Sample Size  
The study will enroll approximately 100 patients. This sample size is determined empirically 
and is considered as appropriate for the planned assessments. 
1.3 
Database Lock  
The study database will be locked upon study completion. 
2. 
Analysis Populations and Data Conventions 
2.1 
Analysis Populations 
The safety population, consisting of patients who received at least 1 study treatment, will be 
used for all analyses. 
2.2 
Analysis Visit Windows 
Analysis visit windows are defined according to study days, which are defined in Table 1. 
Visit windows defined in Table 1 will be applied to all by-visit analyses of safety and 
treatment effect variables.  Out-of-window visits (including the exit visit) and unscheduled 
visits will be reassigned to the visit that the actual study days fall within. 
In cases where multiple visits occurred within a single visit window, which resulted in 
multiple data points for the same window, the last visit with non-missing data will be used 
for analysis.   
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2.3 
Data Conventions 
Unless stated otherwise in specific subsequent sections, data conventions and definitions 
listed below will be applied to all analyses. 
• Day 1 is defined as the day when the patient receives the 1st study treatment 
Study days = visit date – date of the 1st study treatment + 1 
• Study duration for the final DBL = date of the Week 28 visit (or early exit) – date of 
the 1st study treatment + 1 
• Unless otherwise specified, baseline data refer to assessments performed at Baseline 
(Day 1) visit prior to the 1st study treatment.  Screening or unscheduled visits prior to 
Baseline (Day 1) visit will be used for baseline in the absence of pertinent data at the 
Baseline (Day 1) visit 
• Data collected after the 1st administration of any non-study (concomitant/prohibited) 
ocular anti-VEGF treatment in the study eye will be excluded from all efficacy 
analyses  
• When AE date is partial or missing, the following missing data imputation will be 
used 
o If AE start date is missing, the start date will be assigned to the 1st day of the 
month if the day of the month is missing or to January if the month of the year is 
missing 
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o If AE stop date is missing, the stop date will be assigned to the last day of the 
month if the day of the month is missing or to December if the month of the year 
is missing 
• Descriptive statistics include the sample size (N), mean, standard deviation (SD), 
median, minimum (Min), and maximum (Max) for continuous/ordinal data and the 
frequency distribution includes sample size (N), frequency count, and percentage for 
categorical data 
• Medical Dictionary of Regulatory Activities (MedDRA) nomenclature will be used to 
code adverse events, medical procedures, biomicroscopy, and ophthalmoscopy 
findings 
• The Anatomical-Therapeutic-Chemical classification text from World Health 
Organization (WHO) Drug Dictionary will be used to code all medications for drug 
class and for drug name 
• Whenever applicable, metric systems will be used (eg, kilograms [kg] and 
centimeters [cm]) and all clinical laboratory data will be presented with the Standard 
International (SI) units 
3. 
Disposition, Exit Status, and Significant Protocol Deviations 
3.1 
Disposition and Exit Status 
Patient disposition will be summarized as a frequency distribution using the safety population.    
For Week 12 analysis, patients who are still in the study will be classified into “ongoing” 
category.  Reasons for early exit will be summarized into the following categories as 
captured on the study exit eCRF: 
• Screen Failure 
• Adverse Event 
• Withdrawal by subject 
• Lost to Follow-Up 
• Pregnancy 
• Death 
• Physician decision 
• Progressive disease 
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• Protocol Deviation 
• Study Terminated by the Sponsor 
• Site Terminated by the Sponsor 
• Other 
3.2 
Significant Protocol Deviations 
Significant protocol deviations will be classified based on the type of deviations.  Summary 
of significant protocol deviations will be done for the safety population.  
4. 
Demographics and Other Baseline Characteristics 
4.1 
Demographics 
Demographic data are collected at the screening visit.  Patient’s age (years), sex, and race 
will be summarized.  Patient age will be classified into categories of less than or equal to 65 
years, and greater than 65 years.   
4.2 
Baseline Characteristics 
Baseline characteristics include height (cm), weight (kg), BMI (kg/m2), iris color, subretinal 
or intraretinal fluid, intraretinal cysts, pigment epithelial detachments, and smoking status. 
Ocular characteristics of the study eye at baseline include lens status, study eye as the better-
seeing eye (defined as baseline BCVAstudy-eye > BCVAnon-study eye), BCVA, CRT, and intraocular 
pressure.  Baseline characteristics will be summarized using descriptive statistics.   
4.3 
Prior Medications/Procedures 
Prior medications are defined as those received prior to the first study treatment.  For analysis 
purposes, a medication will be considered as prior medication if it satisfies at least one of the 
following: 
• The start date is prior to Baseline (Day 1), regardless of the stop date; 
• The start date is unknown but marked as > 1 year; or 
• The stop date is prior to or on Baseline (Day 1), regardless of the start date 
For medications with a partial start or stop date where “> 1 year” is not marked for the start 
date or “ongoing” is not marked for the stop date and the day and/or the month is unknown, 
comparison to the 1st study treatment date, Baseline (Day 1), will start with the year followed 
by the month, if applicable, for determination of prior medications.  In cases where a full 
determination cannot be made based on the partial information, the start date will be assigned 
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to the 1st day of the month if the day of the month is missing or to January if the month of the 
year is missing; conversely, the stop date will be assigned to the last day of the month if the 
day of the month is missing or to December if the month is missing.  This missing data 
imputation will only be used to determine whether certain medication is considered as prior 
medication.   
Prior medications will be summarized under each drug class and drug name.  A separate 
analysis for prior ophthalmic medications used in the study eye will be performed based on 
WHODDE base preferred names. 
In addition, ocular anti-VEGF treatment history will be summarized with two categories, 
treatment-naïve and treatment-experienced.  Ocular anti-VEGF treatment includes the 
following anti-VEGF injections ranibizumab, bevacizumab, pegaptanib, and aflibercept or 
treatment with a systemic anti-VEGF agent including bevacizumab, and ziv-aflibercept or 
VEGF-receptor inhibitor such as sunitinib, sorafenib, and pazopanib. 
4.4 
Concomitant Medications/Procedures 
Concomitant medications are defined as those non-study medications received but after the 
first study treatment.  For analysis purposes, a medication will be considered as concomitant 
if it satisfies at least one of the following: 
• The start date is on or after the first treatment date regardless of the stop date;   
• The stop date is after the first treatment date, regardless of the start date; or 
• The stop date is unknown but marked as ongoing  
For medications with a partial start or stop date, the same conventions and algorithms as 
described for prior medications will be used for determination of concomitant medications. 
Concomitant medications will be summarized in the same way as prior medications.   
Concurrent procedures including those ocular and non-ocular procedures performed after 
study treatment will be coded using MedDRA dictionary.  The number and percent of 
patients with any concurrent procedures will be tabulated and presented as a frequency 
distribution for each primary SOC and preferred term.  A separate summary for ocular 
concurrent procedures in the study eye will be performed. 
4.5 
Medical History 
Medical history will be coded using MedDRA dictionary. 
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Data will be summarized by frequency distribution for each unique primary SOC and 
preferred terms based on the following two categories: 
• Previous Medical Conditions, and 
• Medical Conditions at Trial Initiation 
Further, ocular history for the study eye will be summarized similarly. 
5. 
Efficacy Assessments and Analyses 
Efficacy assessments include BCVA and CRT measured in the study eye.  
5.1 
Efficacy Assessments 
5.1.1 Best-Corrected Visual Acuity (BCVA)  
Best-corrected visual acuity (BCVA) will be recorded on the CRF as the number of letters 
correctly read using the Early Treatment of Diabetic Retinopathy Study (ETDRS) letters 
(Age-Related Eye Disease Study [AREDS] Research Group, 2001).  For a given eye, the 4 
meter distance (standard) of BCVA is tested first.  If the patient correctly reads at least 20 
letters at 4 meters, BCVA score will be set as the sum of 30 and the number of letters read 
correctly.  If the patient correctly reads less than 20 letters at 4 meters, the BCVA is measured 
again at 1 meter.  The BCVA score will be set to the number of letters read correctly at 1 
meter plus the number of letters read correctly at 4 meters.   
For each patient, BCVA data will be collected for both eyes at the screening, baseline visit 
(Day 1 but prior to the study treatment), and at 28/early exit visits; and for the study eye only 
at Weeks 4, 8, 12, 16, 20, and 24. 
5.1.2 Central retinal thickness (CRT)  
Central retinal thickness (CRT) will be assessed with spectral-domain optical coherence 
tomography (SD-OCT). The graded results will be captured on the evaluation form and be 
reported by sites and used for statistical analysis.  
The central retinal thickness (CRT) is measured as the thickness of the subfields which is the 
central 1000 µm from the center of the fovea. 
For each patient, CRT data will be collected for both eyes at the screening, baseline visit (day 
1 but prior to the study treatment), Week 12, and at 28/early exit visits; and for the study eye 
only at Weeks 4, 8, 16, 20, and 24. 
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5.2 
Efficacy Analyses 
All summary on efficacy variables will be based on observed data and will be presented for 
the study eye only. Additionally, as part of sensitivity analysis, missing data for BCVA will 
be imputed using the last observation carried forward (LOCF); additionally, data after the 
first use of prohibited medications will be also be replaced by LOCF. Efficacy variables 
include the following: 
• Proportion of patients with stable vision (eg, patients who lose fewer than 15 letters in 
BCVA from baseline) 
• Proportion of patients with a gain of 15 or more ETDRS letters in BCVA from 
baseline 
• Proportion of patients with a gain of 10 or more ETDRS letters in BCVA from 
baseline 
• The proportions of patients with BCVA of 70 letters (20/40 Snellen equivalent) or 
better in the study eye at each post-baseline visit  
• Mean change from baseline in BCVA 
• Mean change from baseline in CRT as assessed with SD-OCT 
For binary response variables (eg, stable vision, 10 or 15 letter gain, and BCVA of 70 letters) 
the proportion of patients with a response at each post-baseline visit will be calculated.  The 
95% Confidence Interval (CI) for the proportion will be calculated using the exact method.    
For continuous variables, change from baseline in BCVA and in CRT will be summarized by 
visit with means, medians, standard deviations, minimum, and maximum.  The 95% of 
confidence interval for the mean change will be calculated based on t-distribution and 
presented. 
BCVA change from baseline for the study eye at each follow-up visit will be classified into 
the following 7 categories:  
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Table 2 
BCVA Change Categories 
Category 
Description 
1 
≥ 15 letters improvement 
2 
≥ 10 and < 15 letters improvement  
3 
≥ 5 and < 10 letters improvement  
4 
no change (ie, change between +5 and -5 letters)  
5 
≥ 5 and < 10 letters worsening 
6 
≥ 10 and < 15 letters worsening 
7 
≥ 15 letters worsening 
 
The distribution of the 7 categories will be summarized by frequency tabulations based on 
safety population and observed data. 
6. 
Safety Analyses 
The Medical Dictionary for Regulatory Activities (MedDRA) nomenclature will be used to 
code all adverse events (AEs).  The incidence of treatment-emergent AEs (TEAEs, as defined 
in Section 6.2) will be summarized and presented as the number and percent of patients 
experiencing the TEAEs during the study period.   
Other safety variables include vision loss as measured by decrease of BCVA, IOP, 
biomicroscopic and ophthalmoscopy findings, post-injection assessment, blood chemistry, 
hematology, urinalysis, physical examinations, vital signs, and urine pregnancy test outcomes. 
6.1 
Study Treatment – Exposure and Administration 
6.1.1 Exposure to Study Treatments 
Exposure to study treatment will be evaluated by the number of study injections and 
exposure days, where exposure days is computed as days between 1st study injection to study 
exit.  Patients who have missed any study treatment(s) will be enumerated.  Duration of 
treatment based on the days from the 1st to the last study injections will be calculated.  
Descriptive statistics will be tabulated using the safety population.   
6.2 
Adverse Events 
A treatment-emergent adverse event (TEAE) is an adverse event that occurs after the 
initiation of the study treatment (ie, the onset date is the same as or after the first study 
treatment date), or an adverse event with onset prior to the study treatment that worsened in 
severity or became serious after the initiation of the study treatment.  The incidence of 
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TEAEs will be calculated and presented as the number and percent of patients experiencing 
the TEAE during the reporting period.   
The following summaries of TEAE data will be performed:  1) overall summary, 2) all 
TEAEs regardless of causality, 3) treatment-related TEAEs, 4) ocular TEAEs in the study eye, 
5) non-ocular TEAEs, 6) treatment-related ocular TEAEs, and 7) TEAEs of special interest. 
An additional summary will be provided for 8) treatment-emergent serious adverse events 
(TE SAEs) and 9) AEs leading to study discontinuation. 
The  overall summary will present the data by the number and percent of patients with 
TEAEs, ocular/non-ocular TEAEs, treatment-related ocular/non-ocular TEAEs, AEs leading 
to study discontinuation, TE SAEs, and death. Treatment-related ocular TEAEs will also be 
summarized for procedure-related and drug-related TEAEs.  Procedure-related TEAEs are 
those TEAEs marked as related to the “Study Procedure” and drug-related TEAEs are those 
marked as related to the “Study Drug”. 
Further, tabulations of TEAEs or TE SAEs based on MedDRA coded terms, primary system 
organ class (SOC) and/or preferred terms (PTs), will be sorted by the frequency of 
occurrence as detailed below. 
Summary for 3) treatment-related TEAEs,  5) non-ocular TEAEs, 8) TE SAEs, and 9) AEs 
leading to study discontinuation will be sorted by primary SOC in alphabetical order.  Within 
each SOC name, TEAEs (TE SAEs or AEs) will be tabulated by PT in descending order.  A 
patient with multiple occurrences of the same PT within the reporting period will be counted 
only once for that PT.   
Summary for 2) TEAEs by severity will be sorted by primary SOC in alphabetical order and 
by the worst severity (maximum severity) experienced for a given patient. Within each SOC, 
TEAEs will be tabulated by PT in descending order and by severity.  The severity of a TEAE 
is defined as the greater of the onset severity and maximum severity recorded on the CRF for 
each unique PT reported by the patient. 
Summary for 4) ocular TEAEs, 6) treatment-related ocular TEAEs, and 7) TEAEs of special 
interest of intraocular inflammation will be sorted by preferred term in descending order.  A 
patient with multiple occurrences of the same preferred term within the reporting period will 
be counted only once for that PT.  
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7. 
Interim Analyses 
An interim analysis (IA) is planned when all patients have completed the Week 12 visit or 
have exited early from the study.  
A data summary will be presented for all available cumulative data by focusing on safety 
especially intraocular inflammation AE rates.    
8. 
Deviations from Protocol  
This is the original analysis plan and there are no deviations from the current study protocol. 
9. 
References 
SAS/STAT User’s Guide Version 9.3, SAS Institute Inc., Cary, NC 
10. 
Amendment(s) 
None. 
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