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

Phase 2a, Multicenter, Masked, Randomized, Comparator Controlled Study Evaluating iSONEP™ as Monotherapy or Adjunctive Therapy to Lucentis/Avastin/Eylea Versus Lucentis/Avastin/Eylea Alone for Treatment of Subjects With Choroidal Neovascularization (CNV) Secondary to Age-related Macular Degeneration (AMD)

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.

Study Overview

• Status: Completed
• Conditions: Exudative Age-related Macular Degeneration
• Intervention / Treatment: Drug: 4.0 mg iSONEP; Drug: sham injection; Drug: 0.5 mg iSONEP; Drug: 0.5 mg Lucentis or 1.25 mg Avastin or 2 mg Eylea

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.

• Study Type: Interventional
• Enrollment (Actual): 158
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Peoria, Arizona, United States, 85381
      • Retina Consultants of Arizona
    • Phoenix, Arizona, United States, 85020
      • Associated Retina Consultants
    • Phoenix, Arizona, United States, 85014
      • Retina Consultants of Arizona
    • Tucson, Arizona, United States, 85704
      • Retina Centers, P.C.
  • California
    • Beverly Hills, California, United States, 90211
      • Retina-Vitreous Associates Medical Group
    • Campbell, California, United States, 95008
      • Retinal Diagnostic Center
    • Glendale, California, United States, 91203
      • Specialty Eye Care Medical Center
    • Laguna Hills, California, United States, 92653
      • Retina Associates of Orange County
    • Mountain View, California, United States, 94040
      • Northern California Retina Vitreous Associates
    • New Albany, California, United States, 47150
      • Sagar Kenyon American Eye Institute
    • Sacramento, California, United States, 95819
      • Retinal Consultants Medical Group, Inc.
    • Santa Ana,, California, United States, 92705
      • Orange County Retina Medical Group
    • Ventura, California, United States, 93003
      • Miramar Eye Specialists
  • Florida
    • Boynton Beach, Florida, United States, 33426
      • Florida Eye Microsurgical Institute
    • Ft. Myers, Florida, United States, 33907
      • Retina Health Center
    • Pensacola, Florida, United States, 32503
      • Retina Specialty Institute
    • Plantation, Florida, United States, 33324
      • Fort Lauderdale Eye Institute
    • Stuart, Florida, United States, 34994
      • East Florida Eye Institute
    • Winter Haven, Florida, United States, 33880
      • Center for Retina & Macular Disease
  • Hawaii
    • Aiea, Hawaii, United States, 96701
      • Retina Consultants of Hawaii
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • Midwest Eye Institute
  • Kansas
    • Wichita, Kansas, United States, 67226
      • Central Plains Eye MDs
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Bennett & Bloom Eye Centers
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Retina Group of Washington
    • Towson, Maryland, United States, 21204
      • Retina Specialists
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Ophthalmic Consultants of Boston
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
    • Jackson, Michigan, United States, 49202
      • TLC Eye Care and Laser Center
    • Southfield, Michigan, United States, 48034
      • Retina Consultants of Michigan
  • New York
    • Shirley, New York, United States, 11967
      • Island Retina
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • Charlotte Eye Ear Nose & Throat Associates
  • Oregon
    • Ashland, Oregon, United States, 97520
      • Retina & Vitreous Center SO
  • Pennsylvania
    • West Mifflin, Pennsylvania, United States, 15122
      • Associates in Ophthalmology
  • South Carolina
    • West Columbia, South Carolina, United States, 29169
      • Palmetto Retina Center
  • Texas
    • Abilene, Texas, United States, 79606
      • Retina Research Institute of Texas
    • Austin, Texas, United States, 78705
      • Austin Retina Associates
    • Austin, Texas, United States, 78705
      • Retina Research Center
    • Dallas, Texas, United States, 75231
      • Texas Retina Associates
    • Harlingen, Texas, United States, 78550
      • Valley Retina Institute
    • San Antonio, Texas, United States, 78240
      • Medical Center Ophthalmology Associates
    • San Antonio, Texas, United States, 78240
      • Retina Associates of South Texas
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Rocky Mountain Retina Consultants
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Retina Group of Washington
  • Washington
    • Spokane, Washington, United States, 99204
      • Spokane Eye Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Monotherapy; 4.0 mg iSONEP followed by sham injection; given monthly intravitreously for 4 months	Drug: 4.0 mg iSONEP; 4.0 mg iSONEP given monthly intravitreously for 4 months; Other Names: sonepcizumab; Drug: sham injection; administered monthly for 4 months; Other Names: placebo
Experimental: 0.5 mg iSONEP & Lucentis/Avastin/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	Drug: 0.5 mg iSONEP; 0.5 mg iSONEP given monthly intravitreously for 4 months; Other Names: sonepcizumab; Drug: 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 given monthly intravitreously for 4 months; Other Names: aflibercept; bevacizumab; ranibizumab
Experimental: 4.0 mg iSONEP & Lucentis/Avastin/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	Drug: 4.0 mg iSONEP; 4.0 mg iSONEP given monthly intravitreously for 4 months; Other Names: sonepcizumab; Drug: 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 given monthly intravitreously for 4 months; Other Names: aflibercept; bevacizumab; ranibizumab
Active Comparator: Lucentis or Avastin or 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	Drug: sham injection; administered monthly for 4 months; Other Names: placebo; Drug: 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 given monthly intravitreously for 4 months; Other Names: aflibercept; bevacizumab; ranibizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS)	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.	Baseline to Day 120

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in Central Subfield Retinal Thickness		Baseline to Day 120
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.	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.	Baseline to Day 120
Proportion of Subjects Losing 3 Lines or More in ETDRS BCVA.	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.	Baseline to Day 120
Proportion of Subjects With ETDRS BCVA of 20/40 or Better.	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.	Baseline to Day 120
Proportion of Subjects With Adverse Events.		Baseline to Day 120

Collaborators and Investigators

• Sponsor: Lpath, Inc.
• Investigators: Study Director: Dario A Paggiarino, MD, Lpath, Inc.

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: August 9, 2011
• First Submitted That Met QC Criteria: August 10, 2011
• First Posted (Estimate): August 11, 2011

Study Record Updates

• Last Update Posted (Estimate): October 17, 2016
• Last Update Submitted That Met QC Criteria: August 22, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: bevacizumab; Eylea; Lucentis; Avastin; choroidal neovascularization; age-related macular degeneration; ranibizumab; aflibercept; iSONEP; sonepcizumab
• Additional Relevant MeSH Terms: Pathologic Processes; Eye Diseases; Retinal Degeneration; Retinal Diseases; Uveal Diseases; Choroid Diseases; Metaplasia; Neovascularization, Pathologic; Macular Degeneration; Choroidal Neovascularization; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab; Bevacizumab; Antibodies, Monoclonal; Aflibercept
• Other Study ID Numbers: LT1009-Oph-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO