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

• Sponsor: Ophthotech Corporation (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01940900
• Collaborator: (none)
• Enrollment: 627
• Locations: 121
• Arms: 2
• Duration (Months): 40
• Patients Per Site: 5.2
• 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 Lucentis® compared to Lucentis® 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: ranibizumab; Drug: E10030 sham intravitreal injection	Phase 3

Detailed Description

Subjects will be randomized in a 1:1 ratio to the following dose groups:

• Fovista® 1.5 mg/eye + Lucentis® 0.5 mg/eye

• Fovista® sham + Lucentis® 0.5 mg/eye

Subjects will be treated for a total of 24 months with active Fovista® or sham in combination with Lucentis® with the primary endpoint at 12 months.

Primary Efficacy Endpoint:

The primary efficacy endpoint is the mean change in visual acuity (ETDRS letters) from baseline at the month 12 visit.

Safety Endpoints:

Safety endpoints include adverse events, vital signs, ophthalmic variables [ophthalmic examination, intraocular pressure (IOP), fluorescein angiogram (FA), optical coherence tomography (OCT)], ECG, and laboratory variables.

Approximately 622 subjects will be randomized into one of the two treatment cohorts (311 patients per dose group).

Study Design

• Study Type: Interventional
• Actual Enrollment: 627 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 Lucentis® Compared to Lucentis® Monotherapy in Subjects With Subfoveal Neovascular Age-related Macular Degeneration.
• Study Start Date: Aug 1, 2013
• Actual Primary Completion Date: Dec 1, 2016
• Actual Study Completion Date: Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: E10030 + ranibizumab E10030 1.5 mg intravitreal injection + ranibizumab 0.5 mg intravitreal injection	Drug: E10030; Other Names: Fovista® ; Drug: ranibizumab; Other Names: Lucentis®
Active Comparator: Sham + ranibizumab E10030 sham intravitreal injection + ranibizumab 0.5 mg intravitreal injection	Drug: ranibizumab; Other Names: Lucentis® ; Drug: E10030 sham intravitreal 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 From Baseline to 12 Months [12 Months]

   The primary efficacy endpoint is the mean change in visual acuity (ETDRS letters) from baseline to 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		Tucson	Arizona	United States	85704
2		Tucson	Arizona	United States	85710
3		Fresno	California	United States	93720
4		La Jolla	California	United States	92093
5		Loma Linda	California	United States	92354
6		Mountain View	California	United States	94040
7		Sacramento	California	United States	95819
8		Santa Ana	California	United States	92705
9		Aurora	Colorado	United States	80045
10		Golden	Colorado	United States	80401
11		Boynton Beach	Florida	United States	33426
12		Fort Lauderdale	Florida	United States	33308
13		Fort Myers	Florida	United States	33912
14		Largo	Florida	United States	33770
15		Orlando	Florida	United States	32806
16		Atlanta	Georgia	United States	30322
17		Augusta	Georgia	United States	30909
18		Harvey	Illinois	United States	60426
19		West Des Moines	Iowa	United States	50266
20		Shawnee Mission	Kansas	United States	66204
21		Wichita	Kansas	United States	67214
22		Baltimore	Maryland	United States	21209
23		Hagerstown	Maryland	United States	21740
24		Peabody	Massachusetts	United States	01960
25		Worcester	Massachusetts	United States	01605
26		Minneapolis	Minnesota	United States	55435
27		Lawrenceville	New Jersey	United States	08648
28		New York	New York	United States	10022
29		Syracuse	New York	United States	13224
30		Asheville	North Carolina	United States	28803
31		Charlotte	North Carolina	United States	28210
32		Winston-Salem	North Carolina	United States	27157
33		Cleveland	Ohio	United States	44122
34		Cleveland	Ohio	United States	44130
35		Oklahoma City	Oklahoma	United States	73104
36		Greenville	South Carolina	United States	29605
37		West Columbia	South Carolina	United States	29169
38		Rapid City	South Dakota	United States	57701
39		Nashville	Tennessee	United States	37203
40		Austin	Texas	United States	78705
41		Dallas	Texas	United States	75231
42		Houston	Texas	United States	77030
43		McAllen	Texas	United States	78503
44		San Antonio	Texas	United States	78233
45		San Antonio	Texas	United States	78240
46		Salt Lake City	Utah	United States	84107
47		Richmond	Virginia	United States	23226
48		Virginia Beach	Virginia	United States	23454
49		Bellevue	Washington	United States	98004
50		Buenos Aires		Argentina	B1629ODT
51		Buenos Aires		Argentina	C1015ABO
52		Buenos Aires		Argentina	C1120AAN
53		Buenos Aires		Argentina	C1122AAI
54		Cordoba		Argentina	5000
55		Santa Fe		Argentina	2000
56		East Melbourne		Australia	3002
57		Malvern		Australia	3144
58		Nedlands		Australia	6009
59		Parramatta		Australia	2150
60		Sydney		Australia	2000
61		Westmead		Australia	2145
62		Bogota		Colombia	110311
63		Cali		Colombia	76001000
64		Medellin		Colombia
65		Aalborg		Denmark	9000
66		Aarhus C		Denmark	8000
67		Glostrup		Denmark	2600
68		Odense		Denmark	5000
69		Roskilde		Denmark	4000
70		Créteil		France	94010
71		Lyon		France	69003
72		Lyon		France	69317
73		Marseille		France	13008
74		Paris		France	75006
75		Paris		France	75015
76		Paris		France	75019
77		Paris		France	75745
78		Rouen		France	76100
79		Strasbourg		France	67091
80		Tours		France	37000
81		Aachen		Germany	52057
82		Bonn		Germany	53127
83		Freiburg		Germany	79106
84		Göttingen		Germany	37075
85		Hamburg		Germany	20246
86		Heidelberg		Germany	69120
87		Karlsruhe		Germany	76131
88		Kiel		Germany	24105
89		Köln		Germany	50924
90		Leipzig		Germany	D-04103
91		Luebeck		Germany	23538
92		Mainz		Germany	55131
93		Muenchen		Germany	80336
94		Muenster		Germany	48165
95		München		Germany	81675
96		Münster		Germany	48145
97		Tübingen		Germany	72076
98		Budapest		Hungary	1076
99		Budapest		Hungary	1106
100		Budapest		Hungary	1133
101		Budapest		Hungary	H-1083
102		Budapest		Hungary	H-1145
103		Debrecen		Hungary	H-4012
104		Magyarszék		Hungary	8200
105		Pecs		Hungary	7621
106		Szeged		Hungary	6720
107		Haifa		Israel	31096
108		Jerusalem		Israel	91120
109		Kfar-Saba		Israel	4428164
110		Petah Tikva		Israel	49100
111		Rehovot		Israel	76100
112		Tel Aviv		Israel	64239
113		Barcelona		Spain	08022
114		Bilbao		Spain	48006
115		Las Palmas		Spain	35016
116		Navarro		Spain	31008
117		Sant Cugat Del Vallès		Spain	08195
118		Valencia		Spain	46015
119		Ankara		Turkey	6100
120		Izmir		Turkey	35100
121		Izmir		Turkey	35340

Sponsors and Collaborators

• Ophthotech Corporation

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ophthotech Corporation
• ClinicalTrials.gov Identifier: NCT01940900
• Other Study ID Numbers: OPH1003
• First Posted: Sep 12, 2013
• Last Update Posted: Aug 15, 2018
• Last Verified: Aug 1, 2018

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

Study Results

Participant Flow

Recruitment Details	627 patients were randomized but 1 patient was not treated

Arm/Group Title	E10030 + Ranibizumab	Sham + Ranibizumab
Arm/Group Description	E10030 1.5 mg intravitreal injection + ranibizumab 0.5 mg intravitreal injection E10030 ranibizumab	E10030 sham intravitreal injection + ranibizumab 0.5 mg intravitreal injection ranibizumab E10030 sham intravitreal injection: Pressure on the eye with a syringe with no needle
Period Title: Overall Study
STARTED	311	315
COMPLETED	282	284
NOT COMPLETED	29	31

Baseline Characteristics

Arm/Group Title	E10030 + Ranibizumab	Sham + Ranibizumab	Total
Arm/Group Description	E10030 1.5 mg intravitreal injection + ranibizumab 0.5 mg intravitreal injection E10030 ranibizumab	E10030 sham intravitreal injection + ranibizumab 0.5 mg intravitreal injection ranibizumab E10030 sham intravitreal injection: Pressure on the eye with a syringe with no needle	Total of all reporting groups
Overall Participants	311	315	626
Age, Customized (Count of Participants)
Adults 18-64 years	30 9.6%	31 9.8%	61 9.7%
Adults 65-84 years	224 72%	221 70.2%	445 71.1%
Adults 85 years and over	57 18.3%	63 20%	120 19.2%
Sex: Female, Male (Count of Participants)
Female	178 57.2%	189 60%	367 58.6%
Male	133 42.8%	126 40%	259 41.4%
Region of Enrollment (Count of Participants)
Colombia	11 3.5%	9 2.9%	20 3.2%
Argentina	21 6.8%	15 4.8%	36 5.8%
Turkey	3 1%	4 1.3%	7 1.1%
Hungary	58 18.6%	61 19.4%	119 19%
United States	100 32.2%	97 30.8%	197 31.5%
Denmark	11 3.5%	12 3.8%	23 3.7%
Israel	34 10.9%	31 9.8%	65 10.4%
Australia	4 1.3%	9 2.9%	13 2.1%
France	49 15.8%	55 17.5%	104 16.6%
Germany	8 2.6%	9 2.9%	17 2.7%
Spain	12 3.9%	13 4.1%	25 4%

Outcome Measures

1. Primary Outcome

Title	Mean Change in Visual Acuity From Baseline to 12 Months
Description	The primary efficacy endpoint is the mean change in visual acuity (ETDRS letters) from baseline to 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

Mean change in visual acuity (ETDRS letter) from Baseline to Month 12

Arm/Group Title	E10030 + Ranibizumab	Sham + Ranibizumab
Arm/Group Description	E10030 1.5 mg intravitreal injection + ranibizumab 0.5 mg intravitreal injection E10030 ranibizumab	E10030 sham intravitreal injection + ranibizumab 0.5 mg intravitreal injection ranibizumab E10030 sham intravitreal injection: Pressure on the eye with a syringe with no needle
Measure Participants	311	315
Mean (Standard Error) [letters]	9.91 (0.88)	10.36 (0.87)

Adverse Events

Time Frame	Up to 12 months of exposure
Adverse Event Reporting Description	The efficacy (ITT) population, defined as all subjects randomized and received at least one dose of study drug, is different than the safety population, where all subjects who have received at least one dose of E10030 are analyzed as on that group. There was one subject who was randomized to Sham+Ranibizumab but was mis-treated with one dose of E10030 and therefore was analyzed in the E10030+ranibizuma group for safety purposes. This is the same explanation for the SAE and Mortality tables.
Arm/Group Title	E10030 + Ranibizumab		Sham + Ranibizumab
Arm/Group Description	E10030 1.5 mg intravitreal injection + ranibizumab 0.5 mg intravitreal injection E10030 ranibizumab		E10030 sham intravitreal injection + ranibizumab 0.5 mg intravitreal injection ranibizumab E10030 sham intravitreal injection: Pressure on the eye with a syringe with no needle
All Cause Mortality
	E10030 + Ranibizumab		Sham + Ranibizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/312 (1.3%)		4/314 (1.3%)
Serious Adverse Events
	E10030 + Ranibizumab		Sham + Ranibizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	56/312 (17.9%)		49/314 (15.6%)
Blood and lymphatic system disorders
Anaemia	0/312 (0%)	0	2/314 (0.6%)	4
Cardiac disorders
Atrial fibrillation	3/312 (1%)	4	1/314 (0.3%)	1
Acute myocardial infarction	0/312 (0%)	0	3/314 (1%)	4
Angina pectoris	1/312 (0.3%)	1	0/314 (0%)	0
Atrioventricular block complete	0/312 (0%)	0	1/314 (0.3%)	1
Bradycardia	1/312 (0.3%)	1	0/314 (0%)	0
Cardiac failure	0/312 (0%)	0	1/314 (0.3%)	1
Heart valve incompetence	0/312 (0%)	0	1/314 (0.3%)	1
Myocardial ischaemia	0/312 (0%)	0	1/314 (0.3%)	1
Sinus node dysfunction	1/312 (0.3%)	1	1/314 (0.3%)	1
Ventricular tachycardia	1/312 (0.3%)	1	0/314 (0%)	0
Endocrine disorders
Goitre	0/312 (0%)	0	1/314 (0.3%)	1
Eye disorders
Macular hole	3/312 (1%)	3	0/314 (0%)	0
Optic ischaemic neuropathy	1/312 (0.3%)	1	0/314 (0%)	0
Retinal detachment	3/312 (1%)	4	0/314 (0%)	0
Retinal haemorrhage	0/312 (0%)	0	1/314 (0.3%)	1
Retinal pigment epithelial tear	1/312 (0.3%)	1	0/314 (0%)	0
Vitreous haemorrhage	0/312 (0%)	0	1/314 (0.3%)	1
Gastrointestinal disorders
Abdominal wall haematoma	0/312 (0%)	0	1/314 (0.3%)	1
Gastrointestinal haemorrhage	1/312 (0.3%)	1	0/314 (0%)	0
Haemorrhoidal haemorrhage	0/312 (0%)	0	1/314 (0.3%)	1
Inguinal hernia strangulated	0/312 (0%)	0	1/314 (0.3%)	1
Peptic ulcer	1/312 (0.3%)	1	0/314 (0%)	0
Rectal prolapse	1/312 (0.3%)	1	0/314 (0%)	0
General disorders
Asthenia	0/312 (0%)	0	1/314 (0.3%)	1
Chest pain	1/312 (0.3%)	3	0/314 (0%)	0
Device malfunction	1/312 (0.3%)	1	0/314 (0%)	0
Hepatobiliary disorders
Cholecystitis chronic	1/312 (0.3%)	1	0/314 (0%)	0
Infections and infestations
Aspergillus infection	1/312 (0.3%)	1	0/314 (0%)	0
Bronchitis	1/312 (0.3%)	2	0/314 (0%)	0
Cellulitis	1/312 (0.3%)	1	1/314 (0.3%)	1
Chlostridium difficile colitis	0/312 (0%)	0	1/314 (0.3%)	2
Device related sepsis	1/312 (0.3%)	1	0/314 (0%)	0
Diverticulitis	1/312 (0.3%)	1	0/314 (0%)	0
Endophthalmitis	6/312 (1.9%)	6	2/314 (0.6%)	2
Gastroenteritis	1/312 (0.3%)	1	1/314 (0.3%)	1
Gastrointestinal infection	1/312 (0.3%)	1	0/314 (0%)	0
Infectious colitis	1/312 (0.3%)	1	0/314 (0%)	0
Pneumonia	0/312 (0%)	0	2/314 (0.6%)	2
Pneumonia staphylococcal	0/312 (0%)	0	1/314 (0.3%)	1
Pyelonephritis	1/312 (0.3%)	1	0/314 (0%)	0
Skin infection	1/312 (0.3%)	1	0/314 (0%)	0
Urinary tract infection	0/312 (0%)	0	1/314 (0.3%)	1
Vestibular neuronitis	0/312 (0%)	0	1/314 (0.3%)	1
Urinary tract infection enterococcal	1/312 (0.3%)	1	0/314 (0%)	0
Injury, poisoning and procedural complications
Cataract traumatic	1/312 (0.3%)	1	0/314 (0%)	0
Compression fracture	0/312 (0%)	0	1/314 (0.3%)	1
Fall	3/312 (1%)	3	2/314 (0.6%)	2
Femoral neck fracture	0/312 (0%)	0	1/314 (0.3%)	1
Femur fracture	1/312 (0.3%)	1	0/314 (0%)	0
Hip fracture	1/312 (0.3%)	1	3/314 (1%)	3
Limb injury	1/312 (0.3%)	1	0/314 (0%)	0
Lumbar vertebral fracture	0/312 (0%)	0	1/314 (0.3%)	1
Periprosthetic fracture	1/312 (0.3%)	1	1/314 (0.3%)	1
Rib fracture	0/312 (0%)	0	1/314 (0.3%)	1
Splenic rupture	1/312 (0.3%)	1	0/314 (0%)	0
Thoracic vertebral fracture	1/312 (0.3%)	1	0/314 (0%)	0
Upper limb fracture	0/312 (0%)	0	1/314 (0.3%)	1
Wrist fracture	1/312 (0.3%)	1	0/314 (0%)	0
Subdural haematoma	1/312 (0.3%)	1	1/314 (0.3%)	1
Musculoskeletal and connective tissue disorders
Back pain	0/312 (0%)	0	1/314 (0.3%)	1
Lumbar spinal stenosis	1/312 (0.3%)	1	0/314 (0%)	0
Osteoarthritis	1/312 (0.3%)	1	1/314 (0.3%)	1
Spinal osteoarthritis	0/312 (0%)	0	1/314 (0.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer	0/312 (0%)	0	1/314 (0.3%)	1
Diffuse large B-cell lymphoma	1/312 (0.3%)	1	0/314 (0%)	0
Follicle centre, lymphoma, follicular grade I, II, III stage IV	0/312 (0%)	0	1/314 (0.3%)	1
Invasive ductal breast carcinoma	0/312 (0%)	0	1/314 (0.3%)	1
Leukaemia	0/312 (0%)	0	1/314 (0.3%)	1
Lung adenocarcinoma	1/312 (0.3%)	1	0/314 (0%)	0
Lung carcinoma cell type unspecified stage I	0/312 (0%)	0	1/314 (0.3%)	1
Lung neoplasm malignant	2/312 (0.6%)	3	3/314 (1%)	3
Lung squamous cell carcinoma stage III	1/312 (0.3%)	2	0/314 (0%)	0
Metastases to central nervous system	3/312 (1%)	3	0/314 (0%)	0
Metastases to bone	1/312 (0.3%)	2	0/314 (0%)	0
Metastases to liver	1/312 (0.3%)	1	0/314 (0%)	0
Metastatic neoplasm	1/312 (0.3%)	2	0/314 (0%)	0
Non-small cell lung cancer	1/312 (0.3%)	1	0/314 (0%)	0
Oesophageal carcinoma	1/312 (0.3%)	2	0/314 (0%)	0
Prostate cancer	1/312 (0.3%)	1	2/314 (0.6%)	2
Squamous cell carcinoma of lung	1/312 (0.3%)	1	0/314 (0%)	0
Breast cancer recurrent	0/312 (0%)	0	1/314 (0.3%)	1
Malignant melanoma stage III	1/312 (0.3%)	1	0/314 (0%)	0
Nervous system disorders
Cerebral infarction	0/312 (0%)	0	1/314 (0.3%)	1
Ischaemic stroke	0/312 (0%)	0	1/314 (0.3%)	1
Syncope	1/312 (0.3%)	1	0/314 (0%)	0
Transient ischaemic attack	2/312 (0.6%)	2	0/314 (0%)	0
Hepatic encephalopathy	0/312 (0%)	0	1/314 (0.3%)	1
Renal and urinary disorders
Renal cyst	1/312 (0.3%)	1	0/314 (0%)	0
Renal failure	0/312 (0%)	0	1/314 (0.3%)	1
Urethral stenosis	1/312 (0.3%)	1	0/314 (0%)	0
Urinary bladder polyp	1/312 (0.3%)	1	0/314 (0%)	0
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/312 (0.3%)	1	0/314 (0%)	0
Respiratory, thoracic and mediastinal disorders
Bronchiectasis	1/312 (0.3%)	1	0/314 (0%)	0
Chronic obstructive pulmonary disease	3/312 (1%)	3	0/314 (0%)	0
Dyspnoea	1/312 (0.3%)	1	0/314 (0%)	0
Pleural effusion	0/312 (0%)	0	1/314 (0.3%)	1
Pulmonary oedema	1/312 (0.3%)	1	1/314 (0.3%)	2
Vascular disorders
Accelerated hypertension	1/312 (0.3%)	1	0/314 (0%)	0
Hypertension	0/312 (0%)	0	1/314 (0.3%)	1
Hypertensive crisis	2/312 (0.6%)	2	0/314 (0%)	0
Other (Not Including Serious) Adverse Events
	E10030 + Ranibizumab		Sham + Ranibizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	161/312 (51.6%)		136/314 (43.3%)
Eye disorders
Conjunctival haemorrhage	74/312 (23.7%)	166	50/314 (15.9%)	136
Punctate keratitis	35/312 (11.2%)	93	40/314 (12.7%)	97
Conjuctival hyperaemia	24/312 (7.7%)	48	24/314 (7.6%)	53
Eye pain	22/312 (7.1%)	51	21/314 (6.7%)	35
Vitreous floaters	22/312 (7.1%)	28	12/314 (3.8%)	13
Eye irritation	18/312 (5.8%)	34	15/314 (4.8%)	35
Keratitis	18/312 (5.8%)	64	14/314 (4.5%)	47
Infections and infestations
Nasopharyngitis	17/312 (5.4%)	18	18/314 (5.7%)	20
Urinary tract infection	17/312 (5.4%)	23	18/314 (5.7%)	25
Bronchitis	16/312 (5.1%)	18	11/314 (3.5%)	12
Investigations
Intraocular pressure increased	49/312 (15.7%)	101	25/314 (8%)	42

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 publication of the Study results with other investigators and/or institutions only, upon the prior written consent of Ophthotech.