Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Inves... | NCT00943072

Name	Class
Bayer	INDUSTRY

Label	Type	Description	Intervention Names
VEGF Trap-Eye	Experimental	Monthly IVT injection of VEGF Trap-Eye 2.0 mg until Week 24 Primary Endpoint	Biological: VEGF Trap-Eye 2.0mg
Sham	Sham Comparator	Monthly Sham IVT injection until Week 24 Primary Endpoint	Drug: Sham

Name	Type	Description	Arm Group Labels	Other Names
VEGF Trap-Eye 2.0mg	Biological	Monthly intravitreal injection out to the Week 24 Primary endpoint	VEGF Trap-Eye

Measure	Description	Time Frame
Percentage of Participants Who Gained at Least 15 Letters in BCVA at Week 24 as Measured by ETDRS Letter Score	Percentage values indicate the number of subjects in each arm who were able to read an additional 15 letters or more at Week 24 compared to baseline. Defined study baseline range of ETDRS Best Corrected Visual Acuity letter score of 73 to 24 letters (= Acuity of 20/40 to 20/320) in the study eye; a higher score represents better functioning.	Baseline and at Week 24

Measure	Description	Time Frame
Change From Baseline in BCVA as Measured by ETDRS Letter Score at Week 24 - Last Observation Carried Forward (LOCF)	Defined study baseline range of ETDRS Best Corrected Visual Acuity letter score of 73 to 24 (= Acuity of 20/40 to 20/320) in the study eye; a higher score represents better functioning.	Baseline and at Week 24

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subjects at least 18 years of age with center-involved macular edema secondary to CRVO with mean central retinal thickness ≥ 250 μm on OCT
ETDRS best corrected visual acuity of 20/40 to 20/320 (73 to 24 letters) in the study eye

Exclusion Criteria:

Previous treatment with anti-angiogenic drugs in the study eye (Pegaptanib sodium,anecortave acetate, bevacizumab, ranibizumab, etc.)
Prior panretinal laser photocoagulation or macular laser photocoagulation in the study eye
CRVO disease duration > 9 months from date of diagnosis
Previous use of intraocular corticosteroids in the study eye or use of periocular corticosteroids in the study eye within the 3 months prior to Day 1
Iris neovascularization, vitreous hemorrhage, traction retinal detachment, or preretinal fibrosis involving the macula in either the study eye or fellow eye

Name	Affiliation	Role
Clinical Trial Management	Regeneron Pharmaceuticals	Study Director

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye)	Participants received a 2 mg Intravitreal Aflibercept Injection (IAI) every 4 weeks (2Q4) from Baseline (Day 1) to Week 24. Starting at week 24 through week 52, participants were evaluated monthly to receive either the 2 mg IAI PRN or sham injection according to the protocol re-treatment criteria as assessed by the masked physician. If none of the re-treatment criteria were met, participants received a sham injection. From Week 52 to 100, participants were evaluated every three months, but could receive injections of IAI up to monthly if re-treatment criteria were met; sham injections were not given. Participants were observed from Week 24 to Week 100. Participants in the safety population that completed Week 24 were at risk.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00065.5± 13.57 BG00167.5± 14.22 BG00266.3± 13.83

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00045 BG00135 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00018 BG00112 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0002 BG0010 BG002

Baseline Retinal Thickness by Optical Coherence Tomography (OCT)

Mean

Standard Deviation

microns

Title

Denominators

Categories

Title	Measurements
	BG000661.7± 237.37 BG001678.4± 248.66 BG002

Baseline National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Total Score

The NEI VFQ-25 total score ranges from 0-100 with a score of 0 being the worst outcome and 100 being the best outcome. The NEI VFQ questionnaire is organized as a collection of subscales which are all scored from 0-100. To reach the overall composite score, each sub-scale score is averaged in order to give each sub-scale equal weight.

Mean

Standard Deviation

scores on a scale

Title

Denominators

Categories

Title	Measurements
	BG00077.67± 15.96 BG001

Baseline Intraocular Pressure

Mean

Standard Deviation

millimeters of mercury (mmHg)

Title

Denominators

Categories

Title	Measurements
	BG00015.1± 3.26 BG00115.0± 2.83 BG002

Number of Participants with Retinal Perfusion at Baseline

Retinal Perfusion defined as less than 10 disc areas of capillary non-perfusion using fluorescein angiography (FA).

Non-Perfused defined as greater than or equal to 10 disc areas of non-perfusion.

Indeterminate defined as not able to be determined by the reading center; for the purposes of analysis, indeterminate patients were considered non-perfused.

Number

participants

Title

Denominators

Categories

Perfused

Title	Measurements
	BG00077 BG001

Baseline Best Corrected Visual Acuity (BCVA) Letter Score

Only participants with an ETDRS (Early Treatment Diabetic Retinopathy Study) Best Corrected Visual Acuity letter score of 73 to 25 (= Acuity of 20/40 to 20/320) in the study eye at 4 meters were included; a higher score represents better functioning.

Mean

Standard Deviation

letters correctly read

Title

Denominators

Categories

Title	Measurements
	BG00050.7± 13.90 BG001

Time Since Central Retinal Vein Occlusion (CRVO) Diagnosis

Number

participants

Title

Denominators

Categories

</= 2 Months

Title	Measurements
	BG00064 BG00153 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants Who Gained at Least 15 Letters in BCVA at Week 24 as Measured by ETDRS Letter Score

Percentage values indicate the number of subjects in each arm who were able to read an additional 15 letters or more at Week 24 compared to baseline.

Defined study baseline range of ETDRS Best Corrected Visual Acuity letter score of 73 to 24 letters (= Acuity of 20/40 to 20/320) in the study eye; a higher score represents better functioning.

Full Analysis Set

Posted

Number

percentage of participants

Baseline and at Week 24

ID	Title	Description
OG000	Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye)	Participants received a 2 mg Intravitreal Aflibercept Injection (IAI) every 4 weeks (2Q4) from Baseline (Day 1) to Week 24.
OG001	Sham Treatment	Participants received sham treatment every 4 weeks from Baseline (Day 1) to Week 24.

Units	Counts
Participants	OG000114 OG00173

Title

Denominators

Categories

Title	Measurements
	OG00064 OG0019

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Cochran-Mantel-Haenszel	CMH adjusted difference	< 0.0001	P-value for the primary endpoint was calculated using 2-sided Cochran-Mantel-Haenszel test adjusted by regions (North America vs. Rest of World) and baseline BCVA (BCVA > 20/200 and BCVA ≤ 20/200)	Risk Difference (RD)	44.8			2-Sided	95	33.0	56.6			The Risk Difference (RD) indicates the difference between the IAI (EYLEA, VEGF Trap-Eye) Treatment group minus the Sham Treatment group.	No	Superiority or Other

Secondary

Change From Baseline in BCVA as Measured by ETDRS Letter Score at Week 24 - Last Observation Carried Forward (LOCF)

Defined study baseline range of ETDRS Best Corrected Visual Acuity letter score of 73 to 24 (= Acuity of 20/40 to 20/320) in the study eye; a higher score represents better functioning.

Full Analysis Set

Posted

Mean

Standard Deviation

letters correctly read

Baseline and at Week 24

ID	Title	Description
OG000	Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye)	Participants received a 2 mg Intravitreal Aflibercept Injection (IAI) every 4 weeks (2Q4) from Baseline (Day 1) to Week 24.
OG001	Sham Treatment	Participants received sham treatment every 4 weeks from Baseline (Day 1) to Week 24.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Central Retinal Thickness (CRT) at Week 24 - LOCF

Full Analysis Set

Posted

Mean

Standard Deviation

microns

Baseline and at Week 24

ID	Title	Description
OG000	Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye)	Participants received a 2 mg Intravitreal Aflibercept Injection (IAI) every 4 weeks (2Q4) from Baseline (Day 1) to Week 24.
OG001	Sham Treatment	Participants received sham treatment every 4 weeks from Baseline (Day 1) to Week 24.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants Progressing to Any of the Following: Anterior Segment Neovascularization, New Vessels of the Disc (NVD) or New Vessels Elsewhere (NVE) During the First 24 Weeks

Full Analysis Set

Posted

Number

percentage of participants

Baseline to Week 24

ID	Title	Description
OG000	Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye)	Participants received a 2 mg Intravitreal Aflibercept Injection (IAI) every 4 weeks (2Q4) from Baseline (Day 1) to Week 24.
OG001	Sham Treatment	Participants received sham treatment every 4 weeks from Baseline (Day 1) to Week 24.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in the NEI VFQ-25 in Total Score at Week 24 (LOCF)

The NEI VFQ-25 assesses visual function and quality of life. Total score ranges from 0-100 with a score of 0 being the worst outcome and 100 being the best outcome. The NEI VFQ questionnaire is organized as a collection of subscales which are all scored from 0-100. To reach the overall composite score, each sub-scale score is averaged in order to give each sub-scale equal weight.

Posted

Mean

Standard Deviation

scores on a scale

Baseline and at Week 24

ID	Title	Description
OG000	Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye)	Participants received a 2 mg Intravitreal Aflibercept Injection (IAI) every 4 weeks (2Q4) from Baseline (Day 1) to Week 24.
OG001	Sham Treatment	Participants received sham treatment every 4 weeks from Baseline (Day 1) to Week 24.

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Intravitreal Aflibercept Injection (IAI) (Baseline to Week 24)	Participants received a 2 mg Intravitreal Aflibercept Injection (IAI) every 4 weeks (2Q4) from Baseline (Day 1) to Week 20. Participants were observed until Week 24. Participants in the safety population were at risk.	6	114	57	114
EG001	Sham Treatment (Baseline to Week 24)	Participants received sham treatment every 4 weeks from Baseline (Day 1) to Week 20. Participants were observed until Week 24. Participants in the safety population were at risk.	6	74	34	74
EG002	IAI to IAI (Week 24 to Week 100)	Starting at week 24 through week 52, participants were evaluated monthly to receive either the 2 mg Intravitreal Aflibercept Injection (IAI) PRN or sham injection according to the protocol re-treatment criteria as assessed by the masked physician. If none of the re-treatment criteria were met, participants received a sham injection. From Week 52 to 100, participants were evaluated every three months, but could receive injections of IAI up to monthly if re-treatment criteria were met; sham injections were not given. Participants were observed from Week 24 to Week 100. Participants in the safety population that completed Week 24 were at risk.	20	110	76	110
EG003	Sham Treatment to IAI (Week 24 to Week 100)	Starting at week 24 through week 52, participants were eligible for active treatment and were evaluated monthly to receive either 2 mg Intravitreal Aflibercept Injection (IAI) PRN or sham injection according to the protocol re-treatment criteria as assessed by the masked physician. From Week 52 to 100, participants were evaluated every three months, but could receive injections of IAI up to monthly if re-treatment criteria were met; sham injections were not given.	14	60	50	60

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0001 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG0031 affected60 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Pernicious anaemia	Blood and lymphatic system disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Intervertebral disc degeneration	Musculoskeletal and connective tissue disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0001 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0011 affected74 at risk EG0020 affected110 at risk EG003
Mantle cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Metastatic renal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Non-small cell lung cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 13.1	Non-systematic Assessment		EG0001 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Oesophageal adenocarcinoma stage IV	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0011 affected74 at risk EG0020 affected110 at risk EG003
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0011 affected74 at risk EG0020 affected110 at risk EG003
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0011 affected74 at risk EG0020 affected110 at risk EG003
Hypertension	Vascular disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Hypotension	Vascular disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Cataract	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Fellow Eye	EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Conjunctival haemorrhage	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Fellow Eye	EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Cystoid macular oedema	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0000 affected114 at risk EG0010 affected74 at risk EG0022 affected110 at risk EG003
Dry eye	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Eye irritation	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Eye pain	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Glaucoma	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0000 affected114 at risk EG0012 affected74 at risk EG0020 affected110 at risk EG003
Iris neovascularisation	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0000 affected114 at risk EG0012 affected74 at risk EG0020 affected110 at risk EG003
Lacrimation increased	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Macular fibrosis	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Fellow Eye	EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Macular oedema	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Maculopathy	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Optic disc vascular disorder	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Posterior capsule opacification	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Fellow Eye	EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Retinal artery occlusion	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0001 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Retinal exudates	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Retinal haemorrhage	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Fellow Eye	EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Retinal pigment epitheliopathy	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Retinal tear	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0000 affected114 at risk EG0011 affected74 at risk EG0020 affected110 at risk EG003
Retinal vascular disorder	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Retinal vein occlusion	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0000 affected114 at risk EG0011 affected74 at risk EG0021 affected110 at risk EG003
Visual acuity reduced	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0001 affected114 at risk EG0011 affected74 at risk EG0021 affected110 at risk EG003
Vitreous detachment	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Vitreous floaters	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Vitreous haemorrhage	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Fellow Eye	EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Abdominal adhesions	Gastrointestinal disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0001 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0001 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Gastrointestinal motility disorder	Gastrointestinal disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Inguinal hernia	Gastrointestinal disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0022 affected110 at risk EG003
Intestinal ischaemia	Gastrointestinal disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Intestinal obstruction	Gastrointestinal disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Pancreatitis	Gastrointestinal disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0011 affected74 at risk EG0020 affected110 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Adhesion	General disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Chest discomfort	General disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Chest pain	General disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Generalised oedema	General disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Acute myocardial infarction	Cardiac disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0011 affected74 at risk EG0020 affected110 at risk EG003
Aortic valve stenosis	Cardiac disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0001 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Atrial tachycardia	Cardiac disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Atrioventricular block	Cardiac disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Cardiac failure acute	Cardiac disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Coronary artery disease	Cardiac disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Coronary artery stenosis	Cardiac disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0022 affected110 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Supraventricular tachycardia	Cardiac disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Ventricular extrasystoles	Cardiac disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Arthritis bacterial	Infections and infestations	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Bacteriuria	Infections and infestations	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Bronchitis	Infections and infestations	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Bronchitis viral	Infections and infestations	MedDRA Version 13.1	Non-systematic Assessment		EG0001 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Cellulitis	Infections and infestations	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0011 affected74 at risk EG0021 affected110 at risk EG003
Clostridial infection	Infections and infestations	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0011 affected74 at risk EG0020 affected110 at risk EG003
Endophthalmitis	Infections and infestations	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0001 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Herpes oesophagitis	Infections and infestations	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Influenza	Infections and infestations	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Periorbital cellulitis	Infections and infestations	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Fellow Eye	EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Pneumonia	Infections and infestations	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0011 affected74 at risk EG0020 affected110 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0022 affected110 at risk EG003
Accident	Injury, poisoning and procedural complications	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Brain contusion	Injury, poisoning and procedural complications	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Corneal abrasion	Injury, poisoning and procedural complications	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0001 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Craniocerebral injury	Injury, poisoning and procedural complications	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Facial bones fracture	Injury, poisoning and procedural complications	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Fellow Eye	EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Femur fracture	Injury, poisoning and procedural complications	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
In-stent coronary artery restenosis	Injury, poisoning and procedural complications	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Radius fracture	Injury, poisoning and procedural complications	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Renal haematoma	Injury, poisoning and procedural complications	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Skull fracture	Injury, poisoning and procedural complications	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Spinal column injury	Injury, poisoning and procedural complications	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Blood pressure systolic increased	Investigations	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Blood urine present	Investigations	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Intraocular pressure increased	Investigations	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Fellow Eye	EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Protein urine present	Investigations	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Obstructive uropathy	Renal and urinary disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Renal failure acute	Renal and urinary disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Renal failure chronic	Renal and urinary disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0011 affected74 at risk EG0020 affected110 at risk EG003
Bile duct stone	Hepatobiliary disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0011 affected74 at risk EG0020 affected110 at risk EG003
Abnormal loss of weight	Metabolism and nutrition disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0001 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Carotid artery stenosis	Nervous system disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0011 affected74 at risk EG0020 affected110 at risk EG003
Convulsion	Nervous system disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Dementia	Nervous system disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Encephalopathy	Nervous system disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Haemorrhagic cerebral infarction	Nervous system disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Loss of consciousness	Nervous system disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Subarachnoid haemorrhage	Nervous system disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Syncope	Nervous system disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Mental status changes	Psychiatric disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0011 affected74 at risk EG0020 affected110 at risk EG003
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Cystocele	Reproductive system and breast disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Rectocele	Reproductive system and breast disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Apnoea	Respiratory, thoracic and mediastinal disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0011 affected74 at risk EG0020 affected110 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0001 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0021 affected110 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Hypertension	Vascular disorders	MedDRA Version 13.1	Non-systematic Assessment		EG00010 affected114 at risk EG0014 affected74 at risk EG00213 affected110 at risk EG0039 affected60 at risk
Cataract	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Fellow Eye	EG0000 affected114 at risk EG0010 affected74 at risk EG0026 affected110 at risk EG003
Cystoid macular oedema	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0000 affected114 at risk EG0010 affected74 at risk EG00214 affected110 at risk EG003
Dry eye	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Eye irritation	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0006 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Eye pain	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG00016 affected114 at risk EG0014 affected74 at risk EG0029 affected110 at risk EG003
Iris neovascularisation	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0000 affected114 at risk EG0014 affected74 at risk EG0020 affected110 at risk EG003
Lacrimation increased	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Macular oedema	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0000 affected114 at risk EG0010 affected74 at risk EG00220 affected110 at risk EG003
Maculopathy	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG00010 affected114 at risk EG0010 affected74 at risk EG0026 affected110 at risk EG003
Optic disc vascular disorder	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0008 affected114 at risk EG0010 affected74 at risk EG0026 affected110 at risk EG003
Retinal exudates	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0007 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Retinal haemorrhage	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Fellow Eye	EG0000 affected114 at risk EG0010 affected74 at risk EG0026 affected110 at risk EG003
Retinal pigment epitheliopathy	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Retinal vascular disorder	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0006 affected114 at risk EG0014 affected74 at risk EG0028 affected110 at risk EG003
Visual acuity reduced	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0007 affected114 at risk EG00112 affected74 at risk EG00227 affected110 at risk EG003
Vitreous detachment	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0000 affected114 at risk EG0015 affected74 at risk EG0028 affected110 at risk EG003
Vitreous floaters	Eye disorders	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Study Eye	EG0006 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Influenza	Infections and infestations	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0027 affected110 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0014 affected74 at risk EG0026 affected110 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA Version 13.1	Non-systematic Assessment		EG0006 affected114 at risk EG0010 affected74 at risk EG0026 affected110 at risk EG003
Blood pressure systolic increased	Investigations	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Blood urine present	Investigations	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Intraocular pressure increased	Investigations	MedDRA Version 13.1	Non-systematic Assessment	Ocular AE Fellow Eye	EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003
Protein urine present	Investigations	MedDRA Version 13.1	Non-systematic Assessment		EG0000 affected114 at risk EG0010 affected74 at risk EG0020 affected110 at risk EG003

Facility	Status	City	State	ZIP	Country	Contacts
		Phoenix	Arizona	85014	United States

ID	Term
D008268	Macular Degeneration
D012162	Retinal Degeneration
D012164	Retinal Diseases
D005128	Eye Diseases
D020246	Venous Thrombosis
D013927	Thrombosis
D016769	Embolism and Thrombosis
D014652	Vascular Diseases
D002318	Cardiovascular Diseases

ID	Term
C533178	aflibercept
C005703	salicylhydroxamic acid

ID	Title	Description
BG000	Intravitreal Aflibercept Injection (EYLEA, VEGF Trap-Eye)	Participants received a 2 mg Intravitreal Aflibercept Injection (IAI) every 4 weeks (2Q4) from Baseline (Day 1) to Week 24.
BG001	Sham Treatment	Participants received sham treatment every 4 weeks from Baseline (Day 1) to Week 24.
BG002	Total	Total of all reporting groups