Clinical trial NCT01414153: Efficacy and Safety Study of iSONEP With & Without Lucentis/Avastin/Eylea to Treat Wet AMD
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Exudative Age-related Macular Degeneration
Keywords: choroidal neovascularization
age-related macular degeneration
iSONEP
sonepcizumab
Lucentis
ranibizumab
Avastin
bevacizumab
Eylea
aflibercept
Lead sponsor: Lpath, Inc.
Sponsor class: INDUSTRY
First posted: 2011-08-11
Enrollment: 158
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Mean Change in Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS)
timeFrame: Baseline to Day 120
Secondary outcomes:
measure: Mean Change in Central Subfield Retinal Thickness
timeFrame: Baseline to Day 120
measure: Mean Change in CNV Lesion Area as Determined by Fluorescein Angiography (FA).
timeFrame: Baseline to Day 120
measure: Proportion of Subjects Gaining Greater Than or Equal to 0, 5, 10 and 15 Letters on the ETDRS Chart.
timeFrame: Baseline to Day 120
measure: Proportion of Subjects Losing 3 Lines or More in ETDRS BCVA.
timeFrame: Baseline to Day 120
measure: Proportion of Subjects With ETDRS BCVA of 20/40 or Better.
timeFrame: Baseline to Day 120
measure: Proportion of Subjects With Adverse Events.
timeFrame: Baseline to Day 120
Other outcomes:
Locations:
city: Peoria
country: United States
facility: Retina Consultants of Arizona
state: Arizona
city: Phoenix
country: United States
facility: Retina Consultants of Arizona
state: Arizona
city: Phoenix
country: United States
facility: Associated Retina Consultants
state: Arizona
city: Tucson
country: United States
facility: Retina Centers, P.C.
state: Arizona
city: Beverly Hills
country: United States
facility: Retina-Vitreous Associates Medical Group
state: California
city: Campbell
country: United States
facility: Retinal Diagnostic Center
state: California
city: Glendale
country: United States
facility: Specialty Eye Care Medical Center
state: California
city: Laguna Hills
country: United States
facility: Retina Associates of Orange County
state: California
city: Mountain View
country: United States
facility: Northern California Retina Vitreous Associates
state: California
city: New Albany
country: United States
facility: Sagar Kenyon American Eye Institute
state: California
city: Sacramento
country: United States
facility: Retinal Consultants Medical Group, Inc.
state: California
city: Santa Ana,
country: United States
facility: Orange County Retina Medical Group
state: California
city: Ventura
country: United States
facility: Miramar Eye Specialists
state: California
city: Boynton Beach
country: United States
facility: Florida Eye Microsurgical Institute
state: Florida
city: Ft. Myers
country: United States
facility: Retina Health Center
state: Florida
city: Pensacola
country: United States
facility: Retina Specialty Institute
state: Florida
city: Plantation
country: United States
facility: Fort Lauderdale Eye Institute
state: Florida
city: Stuart
country: United States
facility: East Florida Eye Institute
state: Florida
city: Winter Haven
country: United States
facility: Center for Retina & Macular Disease
state: Florida
city: Aiea
country: United States
facility: Retina Consultants of Hawaii
state: Hawaii
city: Indianapolis
country: United States
facility: Midwest Eye Institute
state: Indiana
city: Wichita
country: United States
facility: Central Plains Eye MDs
state: Kansas
city: Louisville
country: United States
facility: Bennett & Bloom Eye Centers
state: Kentucky
city: Chevy Chase
country: United States
facility: Retina Group of Washington
state: Maryland
city: Towson
country: United States
facility: Retina Specialists
state: Maryland
city: Boston
country: United States
facility: Ophthalmic Consultants of Boston
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Jackson
country: United States
facility: TLC Eye Care and Laser Center
state: Michigan
city: Southfield
country: United States
facility: Retina Consultants of Michigan
state: Michigan
city: Shirley
country: United States
facility: Island Retina
state: New York
city: Charlotte
country: United States
facility: Charlotte Eye Ear Nose & Throat Associates
state: North Carolina
city: Ashland
country: United States
facility: Retina & Vitreous Center SO
state: Oregon
city: West Mifflin
country: United States
facility: Associates in Ophthalmology
state: Pennsylvania
city: West Columbia
country: United States
facility: Palmetto Retina Center
state: South Carolina
city: Abilene
country: United States
facility: Retina Research Institute of Texas
state: Texas
city: Austin
country: United States
facility: Austin Retina Associates
state: Texas
city: Austin
country: United States
facility: Retina Research Center
state: Texas
city: Dallas
country: United States
facility: Texas Retina Associates
state: Texas
city: Harlingen
country: United States
facility: Valley Retina Institute
state: Texas
city: San Antonio
country: United States
facility: Medical Center Ophthalmology Associates
state: Texas
city: San Antonio
country: United States
facility: Retina Associates of South Texas
state: Texas
city: Salt Lake City
country: United States
facility: Rocky Mountain Retina Consultants
state: Utah
city: Fairfax
country: United States
facility: Retina Group of Washington
state: Virginia
city: Spokane
country: United States
facility: Spokane Eye Clinical Research
state: Washington
Study officials:
affiliation: Lpath, Inc.
name: Dario A Paggiarino, MD
role: STUDY_DIRECTOR
References: