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: NCT01944839
• Collaborator: (none)
• Enrollment: 619
• Locations: 115
• Arms: 2
• Duration (Months): 40
• Patients Per Site: 5.4
• 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: 619 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		Phoenix	Arizona	United States	85014
2		Bakersfield	California	United States	93309
3		Beverly Hills	California	United States	90211
4		Los Angeles	California	United States	90095
5		San Francisco	California	United States	94107
6		Santa Barbara	California	United States	93103
7		Colorado Springs	Colorado	United States	80909
8		Bridgeport	Connecticut	United States	06606
9		New London	Connecticut	United States	06320
10		Altamonte Springs	Florida	United States	32701
11		Fort Myers	Florida	United States	33907
12		Sarasota	Florida	United States	34233
13		Tampa	Florida	United States	33609
14		Tampa	Florida	United States	33612
15		Winter Haven	Florida	United States	33880
16		Marietta	Georgia	United States	30060
17		Springfield	Illinois	United States	62704-2173
18		Indianapolis	Indiana	United States	46290
19		Leawood	Kansas	United States	66211
20		Lexington	Kentucky	United States	40509
21		Lexington	Kentucky	United States	40536
22		Louisville	Kentucky	United States	40202
23		New Orleans	Louisiana	United States	70121
24		Chevy Chase	Maryland	United States	20815
25		Boston	Massachusetts	United States	02111
26		Boston	Massachusetts	United States	02114
27		Jackson	Michigan	United States	49202
28		Southfield	Michigan	United States	48034
29		Rochester	Minnesota	United States	55905
30		Saint Louis	Missouri	United States	63110
31		Las Vegas	Nevada	United States	89135
32		Portsmouth	New Hampshire	United States	03801
33		Northfield	New Jersey	United States	08225
34		Albuquerque	New Mexico	United States	87109
35		Great Neck	New York	United States	11021
36		Shirley	New York	United States	11967
37		Cincinnati	Ohio	United States	45242
38		Cleveland	Ohio	United States	44195
39		Ashland	Oregon	United States	97520
40		Camp Hill	Pennsylvania	United States	17011
41		Philadelphia	Pennsylvania	United States	19107
42		Pittsburgh	Pennsylvania	United States	15212
43		Ladson	South Carolina	United States	29456
44		Nashville	Tennessee	United States	37232
45		Abilene	Texas	United States	79606
46		Austin	Texas	United States	78705
47		Tyler	Texas	United States	75701
48		Salt Lake City	Utah	United States	84132
49		Fairfax	Virginia	United States	22031
50		Madison	Wisconsin	United States	53705
51		Graz		Austria	8036
52		Innsbruck		Austria	6020
53		Linz		Austria	4021
54		Wien		Austria	1090
55		Deurne	Antwerpen	Belgium	2100
56		Leuven	Vlaams-Brabant	Belgium	3000
57		Goiânia	Goiás	Brazil	74210
58		Porto Alegre	Rio Grande Do Sul	Brazil	90440
59		Minas Gerais		Brazil	30150-270
60		Sao Paulo		Brazil	01525-001
61		Sao Paulo		Brazil	04021-050
62		Sao Paulo		Brazil	04023-062
63		Calgary	Alberta	Canada	T2H 0C8
64		Vancouver	British Columbia	Canada	V5Z 3N9
65		Winnipeg	Manitoba	Canada	R3P 1A2
66		Halifax	Nova Scotia	Canada	B3H 2Y9
67		London	Ontario	Canada	N6A 4V2
68		Mississauga	Ontario	Canada	L4W 1W9
69		Ottawa	Ontario	Canada	K1H 8L6
70		Toronto	Ontario	Canada	M4N 3M5
71		Toronto	Ontario	Canada	M5T 2S8
72		Montreal	Quebec	Canada	H3A 1A1
73		Saskatoon	Saskatchewan	Canada	S7K 0M7
74		Brno		Czechia	625 00
75		Kralovice		Czechia	500 05
76		Libeň		Czechia	401 13
77		Olomouc		Czechia	775 20
78		Prague		Czechia	10 100 34
79		Praha		Czechia	6 169 02
80		Harju		Estonia	11412
81		Tallinn		Estonia	10138
82		Tartu		Estonia	51003
83		Ancona		Italy	60126
84		Bologna		Italy	40138
85		Ferrara		Italy	44121
86		Firenze		Italy	50134
87		Milano		Italy	20122
88		Milano		Italy	20132
89		Milano		Italy	20157
90		Padova		Italy	35128
91		Roma		Italy	00133
92		Roma		Italy	00198
93		Torino		Italy	10122
94		Udine		Italy	33100
95		Riga		Latvia	LV-1050
96		Riga		Latvia	LV-11002
97		Bydgoszcz		Poland	85-631
98		Katowice		Poland	43-300
99		Lodz		Poland	91 -134
100		Warszawa		Poland	02005
101		Wroclaw		Poland	50-556
102		Banska Bystrica		Slovakia	975 17
103		Bratislava		Slovakia	826 06
104		Trencin		Slovakia	91171
105		Basel		Switzerland	4102
106		Bern		Switzerland	3010
107		Lausanne		Switzerland	1000
108		Zurich		Switzerland	8063
109		Belfast		United Kingdom	BT12 6BA
110		Liverpool		United Kingdom	L7 8XP
111		London		United Kingdom	EC1V 2PD
112		London		United Kingdom	SE5 9RS
113		Plymouth		United Kingdom	PL6 8DH
114		Southampton		United Kingdom	SO16 6YD
115		Surrey Quays		United Kingdom	GU17UJ

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: NCT01944839
• Other Study ID Numbers: OPH1002
• First Posted: Sep 18, 2013
• Last Update Posted: Aug 10, 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

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	309	310
COMPLETED	287	282
NOT COMPLETED	22	28

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	309	310	619
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	76.1 (7.98)	76.9 (8.04)	NA (NA)
Age, Customized (Count of Participants)
Adults 18-64 years	26 8.4%	20 6.5%	46 7.4%
Adults 65 - 84 years	243 78.6%	233 75.2%	476 76.9%
85 years and over	40 12.9%	57 18.4%	97 15.7%
Sex: Female, Male (Count of Participants)
Female	181 58.6%	196 63.2%	377 60.9%
Male	128 41.4%	114 36.8%	242 39.1%
Region of Enrollment (Count of Participants)
United States	106 34.3%	104 33.5%	210 33.9%
Czechia	42 13.6%	42 13.5%	84 13.6%
United Kingdom	13 4.2%	14 4.5%	27 4.4%
Switzerland	3 1%	4 1.3%	7 1.1%
Canada	14 4.5%	9 2.9%	23 3.7%
Austria	5 1.6%	5 1.6%	10 1.6%
Latvia	21 6.8%	25 8.1%	46 7.4%
Belgium	1 0.3%	0 0%	1 0.2%
Poland	23 7.4%	23 7.4%	46 7.4%
Brazil	8 2.6%	8 2.6%	16 2.6%
Italy	56 18.1%	62 20%	118 19.1%
Slovakia	5 1.6%	4 1.3%	9 1.5%
Estonia	12 3.9%	10 3.2%	22 3.6%

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

[Not Specified]

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	309	310
Mean (Standard Error) [letters]	10.74 (0.86)	9.82 (0.86)

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	6/310 (1.9%)		2/309 (0.6%)
Serious Adverse Events
	E10030 + Ranibizumab		Sham + Ranibizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	48/310 (15.5%)		36/309 (11.7%)
Blood and lymphatic system disorders
Anaemia	1/310 (0.3%)	1	0/309 (0%)	0
Cardiac disorders
Atrial fibrillation	3/310 (1%)	3	3/309 (1%)	3
Atrial flutter	2/310 (0.6%)	2	1/309 (0.3%)	1
Acute coronary syndrome	1/310 (0.3%)	1	0/309 (0%)	0
Acute myocardial infarction	1/310 (0.3%)	1	2/309 (0.6%)	2
Angina unstable	1/310 (0.3%)	1	0/309 (0%)	0
Arrhythmia	1/310 (0.3%)	1	0/309 (0%)	0
Cardiac arrest	1/310 (0.3%)	1	0/309 (0%)	0
Cardiac failure	1/310 (0.3%)	1	0/309 (0%)	0
Cardiac failure congestive	1/310 (0.3%)	1	1/309 (0.3%)	1
Cardiac fibrillation	1/310 (0.3%)	1	0/309 (0%)	0
Conduction disorder	1/310 (0.3%)	1	0/309 (0%)	0
Coronary artery disease	1/310 (0.3%)	1	0/309 (0%)	0
Cardiogenic shock	0/310 (0%)	0	1/309 (0.3%)	1
Myocardial infarction	0/310 (0%)	0	1/309 (0.3%)	1
Eye disorders
Cataract	1/310 (0.3%)	1	0/309 (0%)	0
Cataract subcapsular	1/310 (0.3%)	1	0/309 (0%)	0
Retinal tear	1/310 (0.3%)	1	0/309 (0%)	0
Vitreous haemorrhage	1/310 (0.3%)	1	0/309 (0%)	0
Macular hole	0/310 (0%)	0	1/309 (0.3%)	1
Visual acuity reduced	0/310 (0%)	0	1/309 (0.3%)	1
Gastrointestinal disorders
Gastrointestinal haemorrhage	3/310 (1%)	3	0/309 (0%)	0
Abdominal pain	1/310 (0.3%)	1	0/309 (0%)	0
Colitis	1/310 (0.3%)	1	0/309 (0%)	0
Diverticular perforation	1/310 (0.3%)	1	0/309 (0%)	0
Diverticulum	1/310 (0.3%)	1	0/309 (0%)	0
Colitis ischaemic	0/310 (0%)	0	1/309 (0.3%)	1
Diarrhoea haemorrhagic	0/310 (0%)	0	1/309 (0.3%)	1
Large intestine perforation	0/310 (0%)	0	1/309 (0.3%)	1
Oesophageal varices haemorrhage	0/310 (0%)	0	1/309 (0.3%)	1
Oroantral fistula	0/310 (0%)	0	1/309 (0.3%)	1
Small intestinal obstruction	0/310 (0%)	0	1/309 (0.3%)	1
General disorders
Device malfunction	1/310 (0.3%)	1	0/309 (0%)	0
Device failure	0/310 (0%)	0	1/309 (0.3%)	1
Infections and infestations
Pneumonia	4/310 (1.3%)	4	1/309 (0.3%)	1
Endophthalmitis	3/310 (1%)	3	0/309 (0%)	0
Abdominal abscess	1/310 (0.3%)	1	0/309 (0%)	0
Gastroenteritis	1/310 (0.3%)	1	0/309 (0%)	0
Herpes zoster meningoencephalitis	1/310 (0.3%)	1	0/309 (0%)	0
Infective exacerbation of chronic obstructive airways disease	1/310 (0.3%)	1	0/309 (0%)	0
Pneumonia influenzal	1/310 (0.3%)	1	0/309 (0%)	0
Pneumonia respiratory syncytial viral	1/310 (0.3%)	1	0/309 (0%)	0
Urinary tract infection	1/310 (0.3%)	1	0/309 (0%)	0
Urinary tract infection bacterial	1/310 (0.3%)	1	0/309 (0%)	0
Bronchitis	0/310 (0%)	0	1/309 (0.3%)	1
Diverticulitis	0/310 (0%)	0	2/309 (0.6%)	2
Erysipelas	0/310 (0%)	0	1/309 (0.3%)	1
Infected skin ulcer	0/310 (0%)	0	1/309 (0.3%)	1
Sepsis	0/310 (0%)	0	1/309 (0.3%)	1
Sinusitis	0/310 (0%)	0	2/309 (0.6%)	2
Wound infection	0/310 (0%)	0	1/309 (0.3%)	1
Injury, poisoning and procedural complications
Face injury	1/310 (0.3%)	1	0/309 (0%)	0
Fall	1/310 (0.3%)	1	1/309 (0.3%)	1
Ankle fracture	0/310 (0%)	0	1/309 (0.3%)	1
Fractured sacrum	0/310 (0%)	0	1/309 (0.3%)	1
Hip fracture	0/310 (0%)	0	1/309 (0.3%)	1
Humerus fracture	0/310 (0%)	0	1/309 (0.3%)	1
Intestinal anastomosis complication	0/310 (0%)	0	1/309 (0.3%)	3
Musculoskeletal and connective tissue disorders
Osteoarthritis	2/310 (0.6%)	2	0/309 (0%)	0
Spinal column stenosis	1/310 (0.3%)	1	0/309 (0%)	0
Bone infarction	0/310 (0%)	0	1/309 (0.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder neoplasm	1/310 (0.3%)	1	0/309 (0%)	0
Bladder transitional cell carcinoma	1/310 (0.3%)	1	0/309 (0%)	0
Prostate cancer	1/310 (0.3%)	1	0/309 (0%)	0
Rectal cancer	1/310 (0.3%)	1	0/309 (0%)	0
Renal cell carcinoma	1/310 (0.3%)	1	0/309 (0%)	0
Adenocarcinoma gastric	0/310 (0%)	0	1/309 (0.3%)	1
Colon cancer	0/310 (0%)	0	1/309 (0.3%)	1
Gilioma	0/310 (0%)	0	1/309 (0.3%)	1
Meningioma	0/310 (0%)	0	1/309 (0.3%)	1
Myxofibrosarcoma	0/310 (0%)	0	1/309 (0.3%)	1
Non-small cell lung cancer	0/310 (0%)	0	1/309 (0.3%)	1
Nervous system disorders
Syncope	2/310 (0.6%)	2	0/309 (0%)	0
Cerebral infarction	1/310 (0.3%)	1	0/309 (0%)	0
Haemorrhagic stroke	1/310 (0.3%)	1	0/309 (0%)	0
Transient ischaemic attack	1/310 (0.3%)	1	1/309 (0.3%)	1
Cerebral haemorrhage	0/310 (0%)	0	1/309 (0.3%)	1
Epilepsy	0/310 (0%)	0	1/309 (0.3%)	1
Subarachnoidal haemorrhage	0/310 (0%)	0	1/309 (0.3%)	1
VIIth nerve paralysis	0/310 (0%)	0	1/309 (0.3%)	1
Ischaemic stroke	0/310 (0%)	0	1/309 (0.3%)	1
Psychiatric disorders
Depression	1/310 (0.3%)	1	0/309 (0%)	0
Major depression	1/310 (0.3%)	1	0/309 (0%)	0
Renal and urinary disorders
Acute kidney injury	1/310 (0.3%)	1	1/309 (0.3%)	1
Ureteric rupture	1/310 (0.3%)	1	0/309 (0%)	0
Haematuria	0/310 (0%)	0	1/309 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	3/310 (1%)	3	0/309 (0%)	0
Pneumothorax	2/310 (0.6%)	2	0/309 (0%)	0
Acute respiratory failure	0/310 (0%)	0	1/309 (0.3%)	1
Asthma	0/310 (0%)	0	1/309 (0.3%)	1
Pneumonia aspiration	0/310 (0%)	0	1/309 (0.3%)	1
Skin and subcutaneous tissue disorders
Skin ulcer	1/310 (0.3%)	2	0/309 (0%)	0
Vascular disorders
Aortic aneurysm	0/310 (0%)	0	1/309 (0.3%)	1
Aortic stenosis	0/310 (0%)	0	1/309 (0.3%)	1
Deep vein thrombosis	0/310 (0%)	0	1/309 (0.3%)	1
Hypertensive crisis	0/310 (0%)	0	1/309 (0.3%)	1
Peripheral arterial occlusive disease	0/310 (0%)	0	1/309 (0.3%)	1
Thrombophlebitis superficial	0/310 (0%)	0	1/309 (0.3%)	1
Other (Not Including Serious) Adverse Events
	E10030 + Ranibizumab		Sham + Ranibizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	123/310 (39.7%)		114/309 (36.9%)
Eye disorders
Conjunctival haemorrhage	60/310 (19.4%)	197	56/309 (18.1%)	177
Eye pain	23/310 (7.4%)	29	26/309 (8.4%)	47
Punctate keratitis	15/310 (4.8%)	22	18/309 (5.8%)	30
Infections and infestations
Nasopharyngitis	19/310 (6.1%)	20	6/309 (1.9%)	6
Investigations
Intraocular pressure increased	43/310 (13.9%)	157	30/309 (9.7%)	78

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.