Efficacy and Safety Study of iSONEP With & Without Lucentis/Avastin/Eylea to Treat Wet AMD

Phase 2

Completed

Conditions: Exudative Age-related Macular Degeneration

Interventions: Drug: 0.5 mg Lucentis or 1.25 mg Avastin or 2 mg Eylea
Drug: 4.0 mg iSONEP
Drug: 0.5 mg iSONEP
Drug: sham injection

Registration Number: NCT01414153

Lead Sponsor: Lpath, Inc.

Brief Summary: The purpose of the study is to determine the safety and efficacy of 4 monthly injections of iSONEP given alone or in combination with Lucentis, Avastin or Eylea in subjects with wet Age-related Macular Degeneration (AMD). iSONEP not only has an anti-permeability effect, but also has anti-angiogenic, anti-inflammatory, and anti-fibrotic properties. The drug may therefore have the ability to achieve better visual outcomes than Lucentis, Avastin or Eylea, particularly in those subjects who do not demonstrate a robust response to Lucentis, Avastin or Eylea after several monthly injections. Further, the combination of Lucentis, Avastin or Eylea and iSONEP may be additive or synergistic. By inhibiting the multiple mechanisms that contribute to exudative-AMD-related vision loss, better visual outcomes may be possible than with Lucentis, Avastin or Eylea alone.

Detailed Description: The study will be conducted in subjects who qualify as "sub-responders" to Lucentis, Avastin or Eylea meaning that each subject has (i) residual subretinal or intra-retinal fluid observed on Cirrus or Spectralis Spectral Domain Optical Coherence Tomography (SD-OCT), (ii) leakage on fluorescein angiogram (FA), and (iii) an average central subfield thickness of ≥250 μm. Additionally, each subject will have previously received a minimum of 3 intravitreous (IVT) injections of Lucentis, Avastin or Eylea within the 12-month period prior to screening. Screening must occur between 28 and 65 days from the subject's last Lucentis or Avastin treatment or between 42 and 79 days from the subject's last Eylea treatment. Subjects must be dosed within 14 days of screening, and as of the day of initial study treatment (Day 0), meet the following criteria: (i) Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected visual acuity (BCVA) of ≥25 and ≤73 letters (approximately 20/320 and 20/40 on the Snellen scale), (ii) residual subretinal or intra-retinal fluid observed on Cirrus or Spectralis SDOCT, and (iii) leakage on FA.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 158

Inclusion Criteria

≥50 years of age with a diagnosis of wet AMD
Subjects who have received 3 injections of Lucentis or Avastin or Eylea within 12 months prior to screening
Active subfoveal CNV secondary to AMD (leakage on FA)
Presence of residual subretinal or intraretinal fluid on Cirrus or Spectralis SDOCT
SDOCT in the 1 mm central macular subfield on the retinal map analysis of ≥250 μm at screening
ETDRS BCVA of ≥25 and ≤73 letters (approximately 20/320 and 20/40 on the Snellen scale) at screening and on Day 0
In the fellow eye, ETDRS BCVA of 20/400 or better
Subject with serous pigment epithelial detachment (PED) (any part of which may be subfoveal) with intraretinal and/or subretinal fluid may be included

Exclusion Criteria

Most recent IVT injection of Lucentis or Avastin fewer than 28 days and more than 65 days prior to screening
Most recent IVT injection of Eylea fewer than 42 days and more than 79 days prior to screening
Previous photodynamic therapy (PDT) or Macugen® at any time point
Focal thermal laser or grid laser within 3 months prior to Day 0
Use of IVT, subtenon or subconjunctival steroids within 3 months prior to Day 0
Use of topical ophthalmic corticosteroids 2 weeks prior to Day 0
Intraocular surgery, including cataract surgery, and / or laser of any type within 3 months prior to Day 0 or anticipated need for ocular surgery or ophthalmic laser treatment during the study period
Subjects previously treated with, or are currently receiving treatment with another investigational agent or device for neovascular AMD in the study eye
Retinal total lesion size >12 disc areas (30.5 mm2), including blood, scars and neovascularization as assessed by FA in the study eye
Presence of a fibrovascular PED extending underneath the center of the fovea
Presence of retinal angiomatous proliferation (RAP) lesions
Presence of polypoidal choroidal vasculopathy (PCV) (if suspected, Indocyanine Green Angiography (ICG) should be performed at the discretion of the Investigator)
Subretinal hemorrhage in the study eye if any of the following is true: (i) the subretinal hemorrhage represents 50% or more of the total lesion area; (ii) subfoveal blood is 1 or more disc areas in size (iii) subfoveal blood where the fovea is surrounded by less than 270 degrees of visible CNV on FA
Scar or fibrosis making up >50% of total lesion area in the study eye
Anatomic damage to the center of the fovea including fibrosis, scarring or atrophy
History of a retinal pigment epithelial tear
History of vitreous hemorrhage within 4 weeks prior to screening in the study eye
Clinical evidence of diabetic retinopathy, diabetic macular edema or any other vascular disease affecting the retina, other than AMD, in either eye
Uncontrolled glaucoma defined as: (i) as intraocular pressure ≥25 mmHg despite treatment with anti glaucoma medication in the study eye or (ii) by the Investigator
Prior trabeculectomy or other filtration surgery in the study eye (prior laser trabeculoplasty is allowed)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lucentis or Avastin or Eylea	0.5 mg Lucentis or 1.25 mg Avastin or 2 mg Eylea	0.5 mg Lucentis or 1.25 mg Avastin or 2 mg Eylea followed by a sham injection; given monthly intravitreously for 4 months
4.0 mg iSONEP & Lucentis/Avastin/Eylea	4.0 mg iSONEP	4.0 mg iSONEP followed by 0.5 mg Lucentis or 1.25 mg Avastin or 2 mg Eylea; given monthly intravitreously for 4 months
Monotherapy	sham injection	4.0 mg iSONEP followed by sham injection; given monthly intravitreously for 4 months
0.5 mg iSONEP & Lucentis/Avastin/Eylea	0.5 mg iSONEP	0.5 mg iSONEP and 0.5 mg Lucentis or 1.25 mg Avastin or 2 mg Eylea; given monthly intravitreously for 4 months
4.0 mg iSONEP & Lucentis/Avastin/Eylea	0.5 mg Lucentis or 1.25 mg Avastin or 2 mg Eylea	4.0 mg iSONEP followed by 0.5 mg Lucentis or 1.25 mg Avastin or 2 mg Eylea; given monthly intravitreously for 4 months
Monotherapy	4.0 mg iSONEP	4.0 mg iSONEP followed by sham injection; given monthly intravitreously for 4 months
Lucentis or Avastin or Eylea	sham injection	0.5 mg Lucentis or 1.25 mg Avastin or 2 mg Eylea followed by a sham injection; given monthly intravitreously for 4 months
0.5 mg iSONEP & Lucentis/Avastin/Eylea	0.5 mg Lucentis or 1.25 mg Avastin or 2 mg Eylea	0.5 mg iSONEP and 0.5 mg Lucentis or 1.25 mg Avastin or 2 mg Eylea; given monthly intravitreously for 4 months

Primary Outcome Measures

Name	Time	Method
Mean Change in Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS)	Baseline to Day 120	Visual function was assessed using the ETDRS protocol, for which numerical scores range from 0 to 100 (roughly equivalent to 20/10 vision as measured by Snellen). A higher score represents better functioning. A positive number represents an increase in number of letters read correctly.

Secondary Outcome Measures

Name	Time	Method
Mean Change in Central Subfield Retinal Thickness	Baseline to Day 120
Proportion of Subjects With ETDRS BCVA of 20/40 or Better.	Baseline to Day 120	Visual function was assessed using the ETDRS protocol, for which numerical scores range from 0 to 100 (roughly equivalent to 20/10 vision as measured by Snellen). A higher score represents better functioning. A positive number represents an increase in number of letters read correctly. 20/40 Snellen corresponds to a range of 69-73 letters by ETDRS.
Mean Change in CNV Lesion Area as Determined by Fluorescein Angiography (FA).	Baseline to Day 120
Proportion of Subjects Gaining Greater Than or Equal to 0, 5, 10 and 15 Letters on the ETDRS Chart.	Baseline to Day 120	Visual function was assessed using the ETDRS protocol, for which numerical scores range from 0 to 100 (roughly equivalent to 20/10 vision as measured by Snellen). A higher score represents better functioning. A positive number represents an increase in number of letters read correctly.
Proportion of Subjects Losing 3 Lines or More in ETDRS BCVA.	Baseline to Day 120	Visual function was assessed using the ETDRS protocol, for which numerical scores range from 0 to 100 (roughly equivalent to 20/10 vision as measured by Snellen). A higher score represents better functioning. A positive number represents an increase in number of letters read correctly. One line is equivalent to 5 letters, so a loss of 3 lines is a loss of 15 letters.
Proportion of Subjects With Adverse Events.	Baseline to Day 120

Trial Locations

Locations (42): Retina Centers, P.C.
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Tucson, Arizona, United States
Central Plains Eye MDs
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Wichita, Kansas, United States
Retina Consultants of Hawaii
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Aiea, Hawaii, United States
Valley Retina Institute
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Harlingen, Texas, United States
Retina-Vitreous Associates Medical Group
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Beverly Hills, California, United States
Retinal Diagnostic Center
🇺🇸
Campbell, California, United States
Specialty Eye Care Medical Center
🇺🇸
Glendale, California, United States
Sagar Kenyon American Eye Institute
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New Albany, California, United States
Orange County Retina Medical Group
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Santa Ana,, California, United States
Miramar Eye Specialists
🇺🇸
Ventura, California, United States
Florida Eye Microsurgical Institute
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Boynton Beach, Florida, United States
Retina Health Center
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Ft. Myers, Florida, United States
Retina Specialty Institute
🇺🇸
Pensacola, Florida, United States
East Florida Eye Institute
🇺🇸
Stuart, Florida, United States
Center for Retina & Macular Disease
🇺🇸
Winter Haven, Florida, United States
Retina Specialists
🇺🇸
Towson, Maryland, United States
Island Retina
🇺🇸
Shirley, New York, United States
Retina & Vitreous Center SO
🇺🇸
Ashland, Oregon, United States
Charlotte Eye Ear Nose & Throat Associates
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Charlotte, North Carolina, United States
Retina Research Institute of Texas
🇺🇸
Abilene, Texas, United States
Associates in Ophthalmology
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West Mifflin, Pennsylvania, United States
Austin Retina Associates
🇺🇸
Austin, Texas, United States
Retina Research Center
🇺🇸
Austin, Texas, United States
Spokane Eye Clinical Research
🇺🇸
Spokane, Washington, United States
Retina Consultants of Arizona
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Phoenix, Arizona, United States
Associated Retina Consultants
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Phoenix, Arizona, United States
Retina Associates of Orange County
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Laguna Hills, California, United States
Northern California Retina Vitreous Associates
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Mountain View, California, United States
Retinal Consultants Medical Group, Inc.
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Sacramento, California, United States
Fort Lauderdale Eye Institute
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Plantation, Florida, United States
Midwest Eye Institute
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Indianapolis, Indiana, United States
Bennett & Bloom Eye Centers
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Louisville, Kentucky, United States
Retina Group of Washington
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Fairfax, Virginia, United States
Ophthalmic Consultants of Boston
🇺🇸
Boston, Massachusetts, United States
Henry Ford Health System
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Detroit, Michigan, United States
Retina Consultants of Michigan
🇺🇸
Southfield, Michigan, United States
Retina Associates of South Texas
🇺🇸
San Antonio, Texas, United States
Texas Retina Associates
🇺🇸
Dallas, Texas, United States
Medical Center Ophthalmology Associates
🇺🇸
San Antonio, Texas, United States
Rocky Mountain Retina Consultants
🇺🇸
Salt Lake City, Utah, United States
TLC Eye Care and Laser Center
🇺🇸
Jackson, Michigan, United States
Palmetto Retina Center
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West Columbia, South Carolina, United States