A Phase 3 Safety and Efficacy Study of Fovista® (E10030) Intravitreous Administration in Combination With Either Avastin® or Eylea® Compared to Avastin® or Eylea® Monotherapy

• Sponsor: Ophthotech Corporation (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01940887
• Collaborator: (none)
• Enrollment: 645
• Locations: 207
• Arms: 2
• Actual Duration (Months): 40
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The objectives of this study are to evaluate the safety and efficacy of intravitreal administration of Fovista® administered in combination with either Avastin® or Eylea® compared to Avastin® or Eylea® monotherapy in subjects with subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD).

Condition or Disease	Intervention/Treatment	Phase
Age-Related Macular Degeneration	Drug: E10030; Drug: bevacizumab or aflibercept; Drug: E10030 sham injection	Phase 3

Detailed Description

Subjects will be randomized in a 1:1 ratio to the following two arms per study design:

• Fovista® 1.5 mg/eye + Avastin® 1.25 mg/eye or Eylea® 2 mg/eye

• Fovista® sham + Avastin® 1.25 mg/eye or Eylea® 2 mg/eye

Subjects will be treated for up to 24 months with active Fovista® or sham, in combination with either Avastin® or Eylea® with the primary endpoint at 12 months.

Approximately 622 subjects will be randomized into one of the two treatment groups (311 patients per dose group), and the efficacy analysis will be based on the data from these two groups as per the SAP

Study Design

• Study Type: Interventional
• Actual Enrollment: 645 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Randomized, Double-masked, Controlled Trial to Establish the Safety and Efficacy of Intravitreous Administration of Fovista® (Anti PDGF-B Pegylated Aptamer) Administered in Combination With Either Avastin® or Eylea® Compared to Avastin® or Eylea® Monotherapy in Subjects With Subfoveal Neovascular Age-related Macular Degeneration.
• Actual Study Start Date: May 1, 2014
• Actual Primary Completion Date: Jun 1, 2017
• Actual Study Completion Date: Sep 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: E10030 + bevacizumab or aflibercept E10030 1.5 mg intravitreal injection + bevacizumab 1.25 mg intravitreal injection or aflibercept 2 mg intravitreal injection	Drug: E10030; Other Names: Fovista® ; Drug: bevacizumab or aflibercept; Patients are randomized to receive either bevacizumab or aflibercept; Other Names: Avastin® Eylea®
Active Comparator: Sham + bevacizumab or aflibercept E10030 sham injection + bevacizumab 1.25 mg intravitreal injection or aflibercept 2 mg intravitreal injection	Drug: bevacizumab or aflibercept; Patients are randomized to receive either bevacizumab or aflibercept; Other Names: Avastin® Eylea® ; Drug: E10030 sham injection; Pressure on the eye with a syringe with no needle; Other Names: Sham

Outcome Measures

Primary Outcome Measures

1. Mean Change in Visual Acuity (Measured at Baseline and at the Month 12 Visit) [12 months]

   The primary efficacy endpoint is the mean change in visual acuity (ETDRS letters) measured at baseline and at the month 12 visit. Higher ETDRS letters represents higher vision and a higher change in ETDRS letters represents better functioning.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects of either gender aged ≥ 50 years

• Active subfoveal choroidal neovascularization (CNV) secondary to AMD

• Presence of sub-retinal hyper-reflective material (SD-OCT)

Exclusion Criteria:

• Any prior treatment for AMD in the study eye prior to the Day 1 visit, except oral supplements of vitamins and minerals

• Any prior intravitreal treatment in the study eye prior to the Day 1 visit, regardless of indication (including intravitreal corticosteroids)

• Any intraocular surgery or thermal laser within three (3) months of trial entry. Any prior thermal laser in the macular region, regardless of indication

• Subjects with subfoveal scar or subfoveal atrophy are excluded

• Diabetes mellitus

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Gilbert	Arizona	United States	85295
2		Phoenix	Arizona	United States	85014
3		Tucson	Arizona	United States	85704
4		Tucson	Arizona	United States	85710
5		Campbell	California	United States	95008
6		Fresno	California	United States	93720
7		Fullerton	California	United States	92835
8		Irvine	California	United States	92697
9		La Jolla	California	United States	92037
10		Mountain View	California	United States	94040
11		Palm Desert	California	United States	92211
12		Redlands	California	United States	92374
13		Sacramento	California	United States	95819
14		Sacramento	California	United States	95841
15		San Francisco	California	United States	94109
16		Santa Ana	California	United States	92705
17		Ventura	California	United States	93003
18		Aurora	Colorado	United States	80045
19		Colorado Springs	Colorado	United States	80909
20		Denver	Colorado	United States	80210
21		Golden	Colorado	United States	80401
22		Hamden	Connecticut	United States	06518
23		New London	Connecticut	United States	06320
24		Altamonte Springs	Florida	United States	32701
25		Boynton Beach	Florida	United States	33426
26		Fort Lauderdale	Florida	United States	33308
27		Fort Myers	Florida	United States	33912
28		Largo	Florida	United States	33770
29		Melbourne	Florida	United States	32901
30		Palm Beach Gardens	Florida	United States	33410
31		Pensacola	Florida	United States	32503
32		Saint Petersburg	Florida	United States	33711
33		Tallahassee	Florida	United States	32308
34		Tampa	Florida	United States	33609
35		Winter Haven	Florida	United States	33880
36		Atlanta	Georgia	United States	30322
37		Augusta	Georgia	United States	30909
38		Marietta	Georgia	United States	30060
39		Oak Forest	Illinois	United States	60452
40		Peoria	Illinois	United States	61615
41		West Des Moines	Iowa	United States	50266
42		Leawood	Kansas	United States	66211
43		Shawnee Mission	Kansas	United States	66204
44		Topeka	Kansas	United States	66615
45		Wichita	Kansas	United States	67214
46		Paducah	Kentucky	United States	42001
47		Baltimore	Maryland	United States	21209
48		Chevy Chase	Maryland	United States	20815
49		Hagerstown	Maryland	United States	21740
50		Towson	Maryland	United States	21204
51		Boston	Massachusetts	United States	02111
52		Boston	Massachusetts	United States	02114
53		Peabody	Massachusetts	United States	01960
54		Worcester	Massachusetts	United States	01605
55		Jackson	Michigan	United States	49202
56		Lansing	Michigan	United States	48912
57		Southfield	Michigan	United States	48034
58		Minneapolis	Minnesota	United States	55435
59		Chesterfield	Missouri	United States	63017
60		Saint Louis	Missouri	United States	63110
61		Saint Louis	Missouri	United States	63128
62		Omaha	Nebraska	United States	68105
63		Las Vegas	Nevada	United States	89144
64		Reno	Nevada	United States	89502
65		Lawrenceville	New Jersey	United States	08648
66		Albuquerque	New Mexico	United States	87109
67		New York	New York	United States	10021
68		Rochester	New York	United States	14620
69		Syracuse	New York	United States	13224
70		Asheville	North Carolina	United States	28803
71		Winston-Salem	North Carolina	United States	27157
72		Cleveland	Ohio	United States	44122
73		Cleveland	Ohio	United States	44130
74		Columbus	Ohio	United States	43212
75		Oklahoma City	Oklahoma	United States	73104
76		Portland	Oregon	United States	97210
77		Portland	Oregon	United States	97239
78		Camp Hill	Pennsylvania	United States	17011
79		Philadelphia	Pennsylvania	United States	19104
80		Philadelphia	Pennsylvania	United States	19107
81		West Mifflin	Pennsylvania	United States	15122
82		Ladson	South Carolina	United States	29456
83		West Columbia	South Carolina	United States	29169
84		Rapid City	South Dakota	United States	57701
85		Abilene	Texas	United States	79606
86		Amarillo	Texas	United States	79106
87		Dallas	Texas	United States	75231
88		Fort Worth	Texas	United States	43212
89		McAllen	Texas	United States	78503
90		Plano	Texas	United States	75093
91		San Antonio	Texas	United States	78233
92		San Antonio	Texas	United States	78240
93		Willow Park	Texas	United States	76087
94		Salt Lake City	Utah	United States	84107
95		Salt Lake City	Utah	United States	84132
96		Richmond	Virginia	United States	23235
97		Virginia Beach	Virginia	United States	23462
98		Bellevue	Washington	United States	98004
99		Silverdale	Washington	United States	98383
100		Morgantown	West Virginia	United States	25606
101		Buenos Aires		Argentina	B1629ODT
102		Buenos Aires		Argentina	C1015ABO
103		Buenos Aires		Argentina	C1112AAI
104		Buenos Aires		Argentina	C1120AAN
105		Cordoba		Argentina	5000
106		Santa Fe		Argentina	2000
107		Albury	New South Wales	Australia	2640
108		Parramatta	New South Wales	Australia	2150
109		Sydney	New South Wales	Australia	2000
110		Westmead	New South Wales	Australia	2145
111		East Melbourne	Victoria	Australia	3002
112		Graz		Austria	8036
113		Goiânia		Brazil	74210
114		São Paulo		Brazil	01525-001
115		São Paulo		Brazil	04023-062
116		Vancouver	British Columbia	Canada	V5Z 1E9
117		Vancouver	British Columbia	Canada	V5Z 3N9
118		Winnipeg	Manitoba	Canada	R3C 1A2
119		Mississauga	Ontario	Canada	L4W 1W9
120		Montral	Quebec	Canada	H1T 2M4
121		Bogota		Colombia	110231
122		Medellin		Colombia	050016
123		Osijek		Croatia	31000
124		Rijeka		Croatia	51000
125		Zagreb		Croatia	1000
126		Brno		Czechia	625 00
127		Hradec Kralove		Czechia	500 05
128		Olomouc		Czechia	779 00
129		Prague		Czechia	10 100 34
130		Praha		Czechia	169 02
131		Tallinn		Estonia	10138
132		Tallinn		Estonia	11412
133		Helsinki		Finland	00200
134		Kuopio		Finland	70210
135		Creteil		France	94010
136		Lyon		France	69003
137		Lyon		France	69317
138		Marseille		France	13008
139		Paris		France	75006
140		Paris		France	75015
141		Paris		France	75019
142		Paris		France	75745
143		Rouen		France	76100
144		Strasbourg		France	67091
145		Tours		France	37000
146		Aachen	Nordrhein-Westfalen	Germany	52074
147		Munster	Norhdhein-Westfalen	Germany	48145
148		Leipzig	Sachsen	Germany	04103
149		Kiel	Schleswig-Holstein	Germany	24105
150		Göttingen		Germany	37075
151		Hamburg		Germany	20246
152		Karlsruhe		Germany	76133
153		Lübeck		Germany	23538
154		Mainz		Germany	55131
155		Tübingen		Germany	72076
156		Budapest		Hungary	1076
157		Budapest		Hungary	1083
158		Budapest		Hungary	1106
159		Budapest		Hungary	1133
160		Budapest		Hungary	1145
161		Debrecen		Hungary	4012
162		Pecs		Hungary	7621
163		Szeged		Hungary	6720
164		Veszprem		Hungary	8200
165		Haifa		Israel	3109601
166		Jerusalem		Israel	91120
167		Kfar Saba		Israel	4428164
168		Pita Tikva		Israel	4941492
169		Rehovot		Israel	76100
170		Tel Aviv		Israel	64239
171		Ancona		Italy	60126
172		Bologna		Italy	40138
173		Ferrara		Italy	44124
174		Milano		Italy	20122
175		Milano		Italy	20132
176		Milano		Italy	20157
177		Padova		Italy	35128
178		Roma		Italy	00133
179		Roma		Italy	00198
180		Torino		Italy	10122
181		Udine		Italy	33100
182		Riga		Latvia	LV-1002
183		Riga		Latvia	LV-1050
184		Stavanger		Norway	4016
185		Bydgoszcz		Poland	85-631
186		Katowice		Poland	40-594
187		Lodz		Poland	91-134
188		Wroclaw		Poland	50-556
189		Coimbra		Portugal	3000-548
190		Coimbra		Portugal	3030-163
191		Lisboa		Portugal	1050-085
192		Lisboa		Portugal	1169-050
193		Porto		Portugal	4200-319
194		Vila Franca de Xira		Portugal	2600-009
195		Banska Bystrica		Slovakia	975 17
196		Trencin		Slovakia	91171
197		Palmas de Gran Canaria	Islas Canarias	Spain	35016
198		Pamplona	Navarra	Spain	31008
199		Bilbao	Vizcaya	Spain	48006
200		A Coruña		Spain	15706
201		Albacete		Spain	02008
202		Barcelona		Spain	08021
203		Barcelona		Spain	08022
204		Barcelona		Spain	08035
205		Barcelona		Spain	08195
206		Oviedo		Spain	33012
207		Valencia		Spain	46015

Sponsors and Collaborators

• Ophthotech Corporation

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Mar 6, 2014
• Statistical Analysis Plan - Mar 21, 2017

More Information

Publications

None provided.

• Responsible Party: Ophthotech Corporation
• ClinicalTrials.gov Identifier: NCT01940887
• Other Study ID Numbers: OPH1004
• First Posted: Sep 12, 2013
• Last Update Posted: Sep 30, 2020
• Last Verified: Sep 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Ophthotech Corporation: Wet AMD; choroidal neovascularization; Fovista®; E10030; Avastin®; Eylea®
• Additional relevant MeSH terms: Macular Degeneration; Bevacizumab; Aflibercept

Study Results

Participant Flow

Recruitment Details	The study was conducted at 214 centers (107 in North America and 107 in the rest of the world) in 22 countries (20 of which enrolled patients) between 19 May 2014 and 15 September 2017.
Pre-assignment Detail	Three (3) of the 645 patients who were enrolled and randomized did not receive treatments. Remaining 642 subjects were grouped into two treatment groups (E10030 + Eylea/Avastin vs. Sham + Eylea/Avastin) for the purposes of efficacy analyses in accordance with the pre-specified study design, and the SAP.

Arm/Group Title	E10030 + Bevacizumab or Aflibercept	Sham + Bevacizumab or Aflibercept
Arm/Group Description	E10030 1.5 mg intravitreal injection + bevacizumab 1.25 mg intravitreal injection or aflibercept 2 mg intravitreal injection E10030 bevacizumab or aflibercept: Patients are randomized to receive either bevacizumab or aflibercept	E10030 sham injection + bevacizumab 1.25 mg intravitreal injection or aflibercept 2 mg intravitreal injection bevacizumab or aflibercept: Patients are randomized to receive either bevacizumab or aflibercept E10030 sham injection: Pressure on the eye with a syringe with no needle
Period Title: Year 1
STARTED	322	320
COMPLETED	283	297
NOT COMPLETED	39	23
Period Title: Year 1
STARTED	283	297
COMPLETED	66	75
NOT COMPLETED	217	222

Baseline Characteristics

Arm/Group Title	E10030 + Bevacizumab or Aflibercept	Sham + Bevacizumab or Aflibercept	Total
Arm/Group Description	E10030 1.5 mg intravitreal injection + bevacizumab 1.25 mg intravitreal injection or aflibercept 2 mg intravitreal injection E10030 bevacizumab or aflibercept: Patients are randomized to receive either bevacizumab or aflibercept	E10030 sham injection + bevacizumab 1.25 mg intravitreal injection or aflibercept 2 mg intravitreal injection bevacizumab or aflibercept: Patients are randomized to receive either bevacizumab or aflibercept E10030 sham injection: Pressure on the eye with a syringe with no needle	Total of all reporting groups
Overall Participants	322	320	642
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	76.5 (8.36)	76.6 (8.36)	76.6 (8.36)
Age, Customized (Count of Participants)
Adults 18-64 years	31 9.6%	25 7.8%	56 8.7%
Adults 65-84 years	239 74.2%	239 74.7%	478 74.5%
Adults 85 years and over	52 16.1%	56 17.5%	108 16.8%
Sex: Female, Male (Count of Participants)
Female	178 55.3%	192 60%	370 57.6%
Male	144 44.7%	128 40%	272 42.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	28 8.7%	23 7.2%	51 7.9%
Not Hispanic or Latino	294 91.3%	297 92.8%	591 92.1%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
Colombia	7 2.2%	5 1.6%	12 1.9%
Argentina	4 1.2%	4 1.3%	8 1.2%
Hungary	48 14.9%	50 15.6%	98 15.3%
United States	92 28.6%	95 29.7%	187 29.1%
Czechia	15 4.7%	14 4.4%	29 4.5%
Portugal	9 2.8%	12 3.8%	21 3.3%
Spain	10 3.1%	10 3.1%	20 3.1%
Canada	1 0.3%	1 0.3%	2 0.3%
Austria	2 0.6%	3 0.9%	5 0.8%
Latvia	8 2.5%	7 2.2%	15 2.3%
Poland	1 0.3%	3 0.9%	4 0.6%
Brazil	3 0.9%	3 0.9%	6 0.9%
Italy	28 8.7%	29 9.1%	57 8.9%
Israel	32 9.9%	28 8.8%	60 9.3%
Slovakia	1 0.3%	0 0%	1 0.2%
Australia	2 0.6%	3 0.9%	5 0.8%
France	26 8.1%	23 7.2%	49 7.6%
Croatia	22 6.8%	21 6.6%	43 6.7%
Estonia	9 2.8%	7 2.2%	16 2.5%

Outcome Measures

1. Primary Outcome

Title	Mean Change in Visual Acuity (Measured at Baseline and at the Month 12 Visit)
Description	The primary efficacy endpoint is the mean change in visual acuity (ETDRS letters) measured at baseline and at the month 12 visit. Higher ETDRS letters represents higher vision and a higher change in ETDRS letters represents better functioning.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

As pre-specified in the SAP and per the study design, 2 treatment groups (E10030 +Eylea/Avastin vs. Sham + Eylea/Avastin) will be compared. All 642 subjects who received at least one dose of the study drug, irrespective of the dose received, were included in the analysis.

Arm/Group Title	E10030 + Bevacizumab or Aflibercept	Sham + Bevacizumab or Aflibercept
Arm/Group Description	E10030 1.5 mg intravitreal injection + bevacizumab 1.25 mg intravitreal injection or aflibercept 2 mg intravitreal injection E10030 bevacizumab or aflibercept: Patients are randomized to receive either bevacizumab or aflibercept	E10030 sham injection + bevacizumab 1.25 mg intravitreal injection or aflibercept 2 mg intravitreal injection bevacizumab or aflibercept: Patients are randomized to receive either bevacizumab or aflibercept E10030 sham injection: Pressure on the eye with a syringe with no needle
Measure Participants	322	320
Mean (Standard Error) [letters]	9.42 (0.85)	9.04 (0.85)

Adverse Events

Time Frame	All-Cause Mortality data was collected for up to 2 years, and Adverse events (AEs) were collected for up to 12 months of exposure (Year 1) for the 2 pre-specified treatment groups (E10030 + Bevacizumab or Aflibercept vs. Sham + Bevacizumab or Aflibercept), per the study design and the SAP.
Adverse Event Reporting Description	AEs in the safety population (all subjects who received at least one dose of the study treatment) were collected for up to 12 months of exposure (Year 1). All AEs that ultimately resulted in death (regardless of the actual date of death) were included in All Cause Mortality count, and hence the count may differ from the Participant Flow Table which included reported deaths at the time of early discontinuation from the study.
Arm/Group Title	E10030 + Bevacizumab or Aflibercept		Sham + Bevacizumab or Aflibercept
Arm/Group Description	E10030 1.5 mg intravitreal injection + bevacizumab 1.25 mg intravitreal injection or aflibercept 2 mg intravitreal injection E10030 bevacizumab or aflibercept: Patients are randomized to receive either bevacizumab or aflibercept		E10030 sham injection + bevacizumab 1.25 mg intravitreal injection or aflibercept 2 mg intravitreal injection bevacizumab or aflibercept: Patients are randomized to receive either bevacizumab or aflibercept E10030 sham injection: Pressure on the eye with a syringe with no needle
All Cause Mortality
	E10030 + Bevacizumab or Aflibercept		Sham + Bevacizumab or Aflibercept
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/322 (2.2%)		6/320 (1.9%)
Serious Adverse Events
	E10030 + Bevacizumab or Aflibercept		Sham + Bevacizumab or Aflibercept
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	58/322 (18%)		32/320 (10%)
Blood and lymphatic system disorders
Anaemia	3/322 (0.9%)	3	0/320 (0%)	0
Haemorrhagic anaemia	1/322 (0.3%)	1	0/320 (0%)	0
Thrombocytopenia	1/322 (0.3%)	1	0/320 (0%)	0
Cardiac disorders
Atrial fibrillation	2/322 (0.6%)	2	3/320 (0.9%)	3
Cardiac arrest	0/322 (0%)	0	1/320 (0.3%)	1
Cardiac failure	0/322 (0%)	0	1/320 (0.3%)	1
Cardiac failure congestive	2/322 (0.6%)	2	3/320 (0.9%)	3
Myocardial infarction	1/322 (0.3%)	1	0/320 (0%)	0
Ventricular arrhythmia	0/322 (0%)	0	1/320 (0.3%)	1
Ventricular tachycardia	0/322 (0%)	0	1/320 (0.3%)	1
Eye disorders
Autoimmune uveitis	1/322 (0.3%)	1	0/320 (0%)	0
Cataract	1/322 (0.3%)	1	0/320 (0%)	0
Corneal endotheliitis	0/322 (0%)	0	1/320 (0.3%)	1
Iridocyclitis	1/322 (0.3%)	1	0/320 (0%)	0
Macular hole	1/322 (0.3%)	1	0/320 (0%)	0
Retinal detachment	1/322 (0.3%)	2	1/320 (0.3%)	2
Retinal haemorrhage	2/322 (0.6%)	3	0/320 (0%)	0
Vitreous haemorrhage	0/322 (0%)	0	1/320 (0.3%)	1
Gastrointestinal disorders
Duodenal ulcer	1/322 (0.3%)	1	0/320 (0%)	0
Duodenal ulcer haemorrhage	1/322 (0.3%)	1	0/320 (0%)	0
Dysphagia	1/322 (0.3%)	1	0/320 (0%)	0
Gastric dysplasia	1/322 (0.3%)	1	0/320 (0%)	0
Gastrointestinal haemorrhage	1/322 (0.3%)	1	1/320 (0.3%)	1
Gastrooesophageal reflux disease	1/322 (0.3%)	1	0/320 (0%)	0
Hiatus hernia	1/322 (0.3%)	1	0/320 (0%)	0
Ileus	0/322 (0%)	0	1/320 (0.3%)	1
Pancreatitis acute	0/322 (0%)	0	2/320 (0.6%)	2
Salivary gland mass	1/322 (0.3%)	1	0/320 (0%)	0
Small intestinal obstruction	1/322 (0.3%)	1	1/320 (0.3%)	1
Upper gastrointestinal haemorrhage	0/322 (0%)	0	1/320 (0.3%)	1
Melaena	1/322 (0.3%)	1	0/320 (0%)	0
General disorders
Device dislocation	1/322 (0.3%)	1	0/320 (0%)	0
Pyrexia	1/322 (0.3%)	1	0/320 (0%)	0
Death	1/322 (0.3%)	1	0/320 (0%)	0
Hepatobiliary disorders
Cholelithiasis	0/322 (0%)	0	1/320 (0.3%)	1
Infections and infestations
Bronchitis	1/322 (0.3%)	1	2/320 (0.6%)	2
Bronchopulmonary aspergillosis	1/322 (0.3%)	1	0/320 (0%)	0
Cellulitis	1/322 (0.3%)	1	1/320 (0.3%)	1
Clostridium difficile colitis	1/322 (0.3%)	1	0/320 (0%)	0
Endophthalmitis	4/322 (1.2%)	4	1/320 (0.3%)	1
Gastrointestinal infection	0/322 (0%)	0	1/320 (0.3%)	1
Nasopharyngitis	1/322 (0.3%)	1	0/320 (0%)	0
Nosocomial infection	0/322 (0%)	0	1/320 (0.3%)	1
Pneumonia	5/322 (1.6%)	5	2/320 (0.6%)	2
Pyelonephritis	0/322 (0%)	0	1/320 (0.3%)	1
Tracheobronchitis	1/322 (0.3%)	1	0/320 (0%)	0
Viral upper respiratory tract infection	0/322 (0%)	0	1/320 (0.3%)	1
Injury, poisoning and procedural complications
Ankle fracture	2/322 (0.6%)	2	0/320 (0%)	0
Facial bones fracture	1/322 (0.3%)	1	0/320 (0%)	0
Fall	2/322 (0.6%)	3	0/320 (0%)	0
Femur fracture	1/322 (0.3%)	1	1/320 (0.3%)	1
Hip fracture	3/322 (0.9%)	3	0/320 (0%)	0
Ligament sprain	0/322 (0%)	0	1/320 (0.3%)	1
Multiple fractures	1/322 (0.3%)	1	0/320 (0%)	0
Rib fracture	1/322 (0.3%)	1	0/320 (0%)	0
Spinal fracture	0/322 (0%)	0	1/320 (0.3%)	1
Tibia fracture	1/322 (0.3%)	1	0/320 (0%)	0
Musculoskeletal and connective tissue disorders
Osteoarthritis	2/322 (0.6%)	2	0/320 (0%)	0
Pain in extremity	0/322 (0%)	0	1/320 (0.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma	1/322 (0.3%)	1	0/320 (0%)	0
Breast cancer stage I	0/322 (0%)	0	1/320 (0.3%)	1
Colon cancer metastatic	0/322 (0%)	0	1/320 (0.3%)	1
Colon cancer recurrent	0/322 (0%)	0	1/320 (0.3%)	1
Gastric cancer stage IV	0/322 (0%)	0	1/320 (0.3%)	1
Intraductal papilloma of breast	0/322 (0%)	0	1/320 (0.3%)	1
Invasive ductal breast carcinoma	1/322 (0.3%)	1	1/320 (0.3%)	1
Lentigo maligna	1/322 (0.3%)	1	0/320 (0%)	0
Lung neoplasm malignant	1/322 (0.3%)	1	1/320 (0.3%)	1
Metastases to bone	1/322 (0.3%)	1	0/320 (0%)	0
Prostate cancer	3/322 (0.9%)	3	0/320 (0%)	0
Prostate cancer metastatic	1/322 (0.3%)	1	0/320 (0%)	0
Renal cell carcinoma recurrent	0/322 (0%)	0	1/320 (0.3%)	1
Uterine cancer	1/322 (0.3%)	1	0/320 (0%)	0
Nervous system disorders
Cerebral haematoma	1/322 (0.3%)	1	0/320 (0%)	0
Cerebral ischaemia	0/322 (0%)	0	1/320 (0.3%)	1
Cerebrovascular insufficiency	1/322 (0.3%)	1	0/320 (0%)	0
Cognitive disorder	0/322 (0%)	0	1/320 (0.3%)	1
Dizziness	1/322 (0.3%)	1	0/320 (0%)	0
Hypoaesthesia	1/322 (0.3%)	1	0/320 (0%)	0
Polyneuropathy	1/322 (0.3%)	1	0/320 (0%)	0
Seizure	1/322 (0.3%)	1	0/320 (0%)	0
Syncope	0/322 (0%)	0	1/320 (0.3%)	2
Transient ischaemic attack	0/322 (0%)	0	1/320 (0.3%)	1
Psychiatric disorders
Anxiety	1/322 (0.3%)	1	0/320 (0%)	0
Renal and urinary disorders
Calculus bladder	1/322 (0.3%)	1	0/320 (0%)	0
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/322 (0.3%)	1	0/320 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	2/322 (0.6%)	2	0/320 (0%)	0
Acute pulmonary oedema	1/322 (0.3%)	1	0/320 (0%)	0
Chronic obstructive pulmonary disease	1/322 (0.3%)	1	1/320 (0.3%)	1
Pneumonitis	1/322 (0.3%)	1	0/320 (0%)	0
Pulmonary embolism	2/322 (0.6%)	2	0/320 (0%)	0
Respiratory failure	0/322 (0%)	0	1/320 (0.3%)	1
Vascular disorders
Femoral artery occlusion	0/322 (0%)	0	1/320 (0.3%)	2
Peripheral arterial occlusive disease	0/322 (0%)	0	1/320 (0.3%)	1
Other (Not Including Serious) Adverse Events
	E10030 + Bevacizumab or Aflibercept		Sham + Bevacizumab or Aflibercept
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	105/322 (32.6%)		107/320 (33.4%)
Eye disorders
Conjunctival haemorrhage	39/322 (12.1%)	85	31/320 (9.7%)	48
Punctate keratitis	21/322 (6.5%)	34	14/320 (4.4%)	39
Eye pain	18/322 (5.6%)	26	21/320 (6.6%)	35
Vitreous detachment	20/322 (6.2%)	21	19/320 (5.9%)	23
Neovascular age-related macular degeneration	16/322 (5%)	16	19/320 (5.9%)	19
Infections and infestations
Nasopharyngitis	14/322 (4.3%)	15	17/320 (5.3%)	18
Investigations
Intraocular pressure increased	22/322 (6.8%)	46	20/320 (6.3%)	35

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Institution agrees not to individually publish the results of the Study without Ophthotech's prior written consent. Institution may participate in a joint, multi-center publications of the Study results with the other investigators and/or institutions only, upon prior written consent of Ophthotech.