A 24 Month Phase 2a Open Label, Randomized Study of Avastin®, Lucentis®, or Eylea® (Anti-VEGF Therapy) Administered in Combination With Fovista® (Anti-PDGF BB Pegylated Aptamer)

• Sponsor: Ophthotech Corporation (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02387957
• Collaborator: (none)
• Enrollment: 63
• Locations: 24
• Arms: 3
• Actual Duration (Months): 8.2
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

To evaluate the safety of intravitreal (IVT) Fovista® administered in combination with anti-VEGF therapy.

Condition or Disease	Intervention/Treatment	Phase
Age-Related Macular Degeneration	Drug: Fovista®; Drug: bevacizumab; Drug: ranibizumab; Drug: aflibercept	Phase 2

Detailed Description

60 subjects randomized 1:1:1 and treated with IVT Fovista® 1.5 mg/eye in combination with anti-VEGF therapy as follows:

• Avastin® 1.25 mg/eye (20 subjects)

• Lucentis® 0.5 mg/eye (20 subjects)

• Eylea® 2.0 mg/eye (20 subjects)

Subjects will be stratified by lesion size (≤2 DA vs. >2 DA).

Subjects will be treated with "combination therapy" of IVT Fovista® and IVT anti-VEGF therapy every month for the first 5 months (Day 1, Months 1,2,3,4), followed by Q12W (every 12 weeks) administration (Months 7,10, 13,16, 19 and 22), for a total of 24 months.

When administered, IVT Fovista® will be given first, followed by IVT anti-VEGF (same day).

Study Design

• Study Type: Interventional
• Actual Enrollment: 63 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Actual Study Start Date: Apr 26, 2016
• Actual Primary Completion Date: Jan 1, 2017
• Actual Study Completion Date: Jan 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fovista® plus bevacizumab Fovista® 1.5 mg intravitreal injection + bevacizumab 1.25 mg intravitreal injection	Drug: Fovista®; Drug: bevacizumab; Other Names: Avastin®
Experimental: Fovista® plus ranibizumab Fovista® 1.5 mg intravitreal injection + 0.5 mg ranibizumab intravitreal injection	Drug: Fovista®; Drug: ranibizumab; Other Names: Lucentis®
Experimental: Fovista® plus aflibercept Fovista® 1.5 mg intravitreal injection + 2.0 mg aflibercept intravitreal injection	Drug: Fovista®; Drug: aflibercept; Other Names: Eylea®

Outcome Measures

Primary Outcome Measures

1. Total Numer of Systemic Adverse Events [2 years]

   Number of Patients with Systemic Adverse Events

2. Total Number of Other Adverse Events (>5%) [2 years]

   Number of Patients with Other Adverse Events

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) due to AMD.

Exclusion Criteria:

• 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

• Any ocular or periocular infection in the past twelve (12) weeks.

• History of any of the following conditions or procedures in the study eye: Rhegmatogenous retinal detachment, pars plana vitrectomy, filtering surgery (e.g. trabeculectomy), glaucoma drainage device, corneal transplant.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Phoenix	Arizona	United States	85014
2		Beverly Hills	California	United States	90211
3		Sacramento	California	United States	95819
4		Santa Ana	California	United States	92705
5		New London	Connecticut	United States	06320
6		Fort Lauderdale	Florida	United States	33308
7		Fort Myers	Florida	United States	33912
8		Augusta	Georgia	United States	30909
9		Oak Forest	Illinois	United States	60452
10		Boston	Massachusetts	United States	02114
11		Worcester	Massachusetts	United States	01605
12		Southfield	Michigan	United States	48034
13		Minneapolis	Minnesota	United States	55435
14		Reno	Nevada	United States	89502
15		Rochester	New York	United States	14620
16		Cleveland	Ohio	United States	44130
17		Huntingdon Valley	Pennsylvania	United States	19006
18		Ladson	South Carolina	United States	29456
19		Abilene	Texas	United States	85014
20		Amarillo	Texas	United States	79106
21		San Antonio	Texas	United States	78240
22		The Woodlands	Texas	United States	77384
23		Silverdale	Washington	United States	98383
24		Morgantown	West Virginia	United States	26506

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: NCT02387957
• Other Study ID Numbers: OPH1006
• First Posted: Mar 13, 2015
• Last Update Posted: Mar 5, 2019
• Last Verified: Feb 1, 2019

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

Study Results

Participant Flow

Arm/Group Title	Fovista® Plus Bevacizumab	Fovista® Plus Ranibizumab	Fovista® Plus Aflibercept
Arm/Group Description	Fovista® 1.5 mg intravitreal injection + bevacizumab 1.25 mg intravitreal injection Fovista® bevacizumab	Fovista® 1.5 mg intravitreal injection + 0.5 mg ranibizumab intravitreal injection Fovista® ranibizumab	Fovista® 1.5 mg intravitreal injection + 2.0 mg aflibercept intravitreal injection Fovista® aflibercept
Period Title: Overall Study
STARTED	21	21	21
COMPLETED	0	0	1
NOT COMPLETED	21	21	20

Baseline Characteristics

Arm/Group Title	Fovista® Plus Bevacizumab	Fovista® Plus Ranibizumab	Fovista® Plus Aflibercept	Total
Arm/Group Description	Fovista® 1.5 mg intravitreal injection + bevacizumab 1.25 mg intravitreal injection Fovista® bevacizumab	Fovista® 1.5 mg intravitreal injection + 0.5 mg ranibizumab intravitreal injection Fovista® ranibizumab	Fovista® 1.5 mg intravitreal injection + 2.0 mg aflibercept intravitreal injection Fovista® aflibercept	Total of all reporting groups
Overall Participants	21	21	21	63
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	3 14.3%	3 14.3%	2 9.5%	8 12.7%
>=65 years	18 85.7%	18 85.7%	19 90.5%	55 87.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	78.5 (9.51)	77.2 (10.43)	77.9 (8.99)	77.9 (9.51)
Sex: Female, Male (Count of Participants)
Female	13 61.9%	16 76.2%	15 71.4%	44 69.8%
Male	8 38.1%	5 23.8%	6 28.6%	19 30.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	1 4.8%	1 1.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	21 100%	21 100%	20 95.2%	62 98.4%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	21 100%	21 100%	21 100%	63 100%

Outcome Measures

1. Primary Outcome

Title	Total Numer of Systemic Adverse Events
Description	Number of Patients with Systemic Adverse Events
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fovista® Plus Bevacizumab	Fovista® Plus Ranibizumab	Fovista® Plus Aflibercept
Arm/Group Description	Fovista® 1.5 mg intravitreal injection + bevacizumab 1.25 mg intravitreal injection Fovista® bevacizumab	Fovista® 1.5 mg intravitreal injection + 0.5 mg ranibizumab intravitreal injection Fovista® ranibizumab	Fovista® 1.5 mg intravitreal injection + 2.0 mg aflibercept intravitreal injection Fovista® aflibercept
Measure Participants	21	21	21
Count of Participants [Participants]	3 14.3%	3 14.3%	5 23.8%

2. Primary Outcome

Title	Total Number of Other Adverse Events (>5%)
Description	Number of Patients with Other Adverse Events
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fovista® Plus Bevacizumab	Fovista® Plus Ranibizumab	Fovista® Plus Aflibercept
Arm/Group Description	Fovista® 1.5 mg intravitreal injection + bevacizumab 1.25 mg intravitreal injection Fovista® bevacizumab	Fovista® 1.5 mg intravitreal injection + 0.5 mg ranibizumab intravitreal injection Fovista® ranibizumab	Fovista® 1.5 mg intravitreal injection + 2.0 mg aflibercept intravitreal injection Fovista® aflibercept
Measure Participants	21	21	21
Count of Participants [Participants]	15 71.4%	16 76.2%	16 76.2%

Adverse Events

Time Frame	Up to a maximum exposure of 24 months
Arm/Group Title	Fovista® Plus Bevacizumab		Fovista® Plus Ranibizumab		Fovista® Plus Aflibercept
Arm/Group Description	Fovista® 1.5 mg intravitreal injection + bevacizumab 1.25 mg intravitreal injection Fovista® bevacizumab		Fovista® 1.5 mg intravitreal injection + 0.5 mg ranibizumab intravitreal injection Fovista® ranibizumab		Fovista® 1.5 mg intravitreal injection + 2.0 mg aflibercept intravitreal injection Fovista® aflibercept
All Cause Mortality
	Fovista® Plus Bevacizumab		Fovista® Plus Ranibizumab		Fovista® Plus Aflibercept
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/21 (0%)		0/21 (0%)
Serious Adverse Events
	Fovista® Plus Bevacizumab		Fovista® Plus Ranibizumab		Fovista® Plus Aflibercept
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/21 (14.3%)		3/21 (14.3%)		5/21 (23.8%)
Cardiac disorders
Myocardial infarction	0/21 (0%)	0	0/21 (0%)	0	1/21 (4.8%)	1
Eye disorders
Retinal detachment	0/21 (0%)	0	1/21 (4.8%)	2	0/21 (0%)	0
Retinal haemorrhage	0/21 (0%)	0	1/21 (4.8%)	1	0/21 (0%)	0
General disorders
Non-cardiac chest pain	0/21 (0%)	0	0/21 (0%)	0	1/21 (4.8%)	1
Infections and infestations
Diverticulitis	1/21 (4.8%)	1	0/21 (0%)	0	0/21 (0%)	0
Pneumonia staphylococcal	1/21 (4.8%)	1	0/21 (0%)	0	0/21 (0%)	0
Injury, poisoning and procedural complications
Joint dislocation	0/21 (0%)	0	1/21 (4.8%)	1	0/21 (0%)	0
Investigations
Intraocular pressure increased	1/21 (4.8%)	1	0/21 (0%)	0	0/21 (0%)	0
Musculoskeletal and connective tissue disorders
Cervical spine stenosis	0/21 (0%)	0	0/21 (0%)	0	1/21 (4.8%)	1
Lumbar spinal stenosis	0/21 (0%)	0	0/21 (0%)	0	1/21 (4.8%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung carcinoma cell type unspecified reccurent	0/21 (0%)	0	0/21 (0%)	0	1/21 (4.8%)	1
Renal and urinary disorders
Renal failure	0/21 (0%)	0	0/21 (0%)	0	1/21 (4.8%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration	0/21 (0%)	0	1/21 (4.8%)	1	0/21 (0%)	0
Other (Not Including Serious) Adverse Events
	Fovista® Plus Bevacizumab		Fovista® Plus Ranibizumab		Fovista® Plus Aflibercept
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/21 (71.4%)		16/21 (76.2%)		16/21 (76.2%)
Eye disorders
Neovascular age-related macular degeneration	4/21 (19%)	4	1/21 (4.8%)	1	6/21 (28.6%)	6
Cataract	1/21 (4.8%)	1	3/21 (14.3%)	6	4/21 (19%)	4
Eye pain	4/21 (19%)	4	0/21 (0%)	0	4/21 (19%)	6
Visual acuity reduced	0/21 (0%)	0	0/21 (0%)	0	4/21 (19%)	5
Vitreous floaters	1/21 (4.8%)	1	2/21 (9.5%)	2	3/21 (14.3%)	3
Vision blurred	0/21 (0%)	0	0/21 (0%)	0	2/21 (9.5%)	2
Conjuctival haemorrhage	7/21 (33.3%)	11	6/21 (28.6%)	16	1/21 (4.8%)	1
Eye irritation	2/21 (9.5%)	2	0/21 (0%)	0	1/21 (4.8%)	1
Retinal haemorrhage	1/21 (4.8%)	1	3/21 (14.3%)	3	1/21 (4.8%)	1
Vitreous detachment	2/21 (9.5%)	2	2/21 (9.5%)	2	0/21 (0%)	0
Ocular Discomfort	2/21 (9.5%)	3	0/21 (0%)	0	0/21 (0%)	0
General disorders
Seasonal allergy	0/21 (0%)	0	2/21 (9.5%)	2	0/21 (0%)	0
Infections and infestations
Sinusitis	0/21 (0%)	0	1/21 (4.8%)	1	3/21 (14.3%)	3
Urinary tract infection	2/21 (9.5%)	2	1/21 (4.8%)	1	2/21 (9.5%)	3
Nasopharyngitis	0/21 (0%)	0	5/21 (23.8%)	5	1/21 (4.8%)	2
Injury, poisoning and procedural complications
Fall	1/21 (4.8%)	1	2/21 (9.5%)	2	0/21 (0%)	0
Investigations
Intraocular pressure increased	3/21 (14.3%)	6	2/21 (9.5%)	4	6/21 (28.6%)	9
Nervous system disorders
Headache	0/21 (0%)	0	1/21 (4.8%)	1	2/21 (9.5%)	2

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.