Intravitreal Aflibercept Injection for the Treatment of Submacular Vascularized Pigment Epithelial Detachment (EVEN)
Primary Purpose
Submacular Vascularized Pigment Epithelial Detachments
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Aflibercept
Sponsored by
About this trial
This is an interventional treatment trial for Submacular Vascularized Pigment Epithelial Detachments focused on measuring PED, AMD, CNV
Eligibility Criteria
Inclusion Criteria:
- Subject is ≥ 50 years of age
- Subject is willing to participate in this study and to follow the criteria and protocol of this study.
- The study eye is treatment naïve regarding treatment of neovascular AMD.
- Subject is not involved with another clinical study currently.
- Subject is willing to follow the protocol outlined in the study.
- Ability to understand the informed consent and willingness to sign the informed consent.
Presence of a submacular vascularized or fibrovascular PED. The investigator must search for the characteristic features of a vascularized PED summarized here:
- A notch of irregularity associated with an orange-yellow round, oval, or bean-shaped elevation of the RPE with a smooth, convex surface is seen on examination and fundus photography (FP). Fluorescein angiography (FA) shows uniform staining of the PED with a well-defined margin, and more intense staining (hot-spot) for the focus of the CNV.
- A fibrovascular PED with occult neovascularization typically shows stippled hyperfluorescence in the early phase with increasing hyperfluorescent staining and leakage in later phases of FA and a variable surrounding margin. There may be RPE folds.
- Regarding PED with a component of retinal angiomatous proliferation (RAP), the early features on FP including intraretinal neovascularization (IRN) frequently with adjacent small retinal hemorrhages in its lateral expansion in an irregularly stellate pattern before the development of retinal-choroidal anastomosis and the eventual PED in the later phases. The investigator is required to perform indocyanine-green (ICG) angiography at baseline to establish a RAP lesion and to rule-out polypoidal vasculopathy lesions, since the FA images may not be distinct.
- The investigator must also search for other features associated with a PED indicating the presence of a vascular component, i.e. hemorrhage, exudates, and/or chorioretinal folds.
- The investigator must confirm the presence of a PED on FA/FP and OCT. Spectral Domain OCT will be utilized. Specifically, the Spectralis OCT manufactured by Heidleberg to maintain uniformity for all the sites. The PED height, SA, GLD, and volume will be measured from the OCT images. The characteristic OCT findings of the vascularized PED must be confirmed, including a distinct elevation of the highly hyperreflective RPE layer with mild backscattering of the underlying choroidal layer in the portion of the PED without any CNV. For the portion of the PED with underlying CNV, typical OCT findings consist of moderate hyperreflectivity contiguous to the overlying markedly hyperreflective detached RPE corresponding to the CNV that usually extends to the choroidal layer. Besides the OCT characteristics confirmation must be made on the FP/FA images of the vascularized PED, as outlined above in detail.
- Central foveal involvement by the PED or the CNV due to age-related macular degeneration (AMD). The CNV may be classic, occult, or mixed, as long as it is associated with a PED. The CNV may be within the PED or adjacent to the margin of the PED.
- PED ≤ 12 disc area in size.
- BCVA with ETDRS of ≥ 19 letters and ≤ 73 letters (20/400 to 20/40).
- Evidence of submacular fluid outside or surrounding the PED.
- Surface area of the submacular hemorrhage needs to be < 50% of the entire PED.
- Submacular fibrosis needs to be < 50% of the entire PED.
- Sufficiently clear media (cornea, anterior chamber, lens, vitreous) for OCT, FA and FP.
- Intraocular pressure (IOP) of 25mmHg or less in the study eye, with or without use of ocular hypotensive agents.
- Prior treatment of neovascular AMD or any other forms of neovascularization in the fellow eye, including anti-VEGF or other forms of therapy targeted specifically for the fellow eye does not exclude the fellow eye from enrollment in this study. Prior focal corticosteroid treatment is allowed, as long as there is a lack of involvement of the study eye. However prior (within 90 days of Day 0) or current systemic corticosteroid therapy (oral or intravenous corticosteroid treatment) is not permitted.
Exclusion Criteria:
- Any prior treatment of neovascular AMD in eye for proposed enrollment (non-naïve eye), including previous anti-vascular endothelial factor (anti-VEGF) therapy, photodynamic therapy (PDT), radiation therapy, corticosteroid treatment, surgical treatment for CNV, thermal laser treatment, and any other prior treatment for neovascular AMD.
- Known serious allergies to aflibercept, fluorescein dye, drugs for pupillary dilation, topical anesthetic, sterilizing solution (e.g. Betadine Solution).
- Contraindication to pupillary dilation in study eye.
- Any condition (including inability to read visual acuity charts, or language barrier) that may preclude subjects ability to comply with the study protocol and requirements.
- Presence of any advanced systemic condition or end-stage disease, advanced Alzheimer Syndrome, end-stage cancer, etc., which will likely prevent subject from completing study.
- Previous therapeutic radiation in the region of the study eye.
- Prior retinal pigment epithelial (RPE) tear in study eye.
- Prior ocular surgery (except YAG laser capsulotomy) for study within the past 90 days.
- Anticipated ocular surgery (except YAG laser capsulotomy) for the next 12 months
- Prior therapy for AMD (except minerals and vitamins), including laser.
- Prior vitrectomy
- Presence of any causes of CNV and PED other than due to AMD.
- Presence of any substantial ocular disease (other than the CNV and PED) that may compromise vision in the study eye and/or confound interpretation of the data; e.g. substantial cataracts, concomitant diabetic retinopathy affecting the macula, advanced glaucoma, optic neuritis, optic neuropathy, or atrophy, marked macular atrophy, ocular vascular occlusion, history of retinal detachment, uveitis, viral or other forms of chorioretinitis, etc.
- Presence of ocular disease other than AMD affecting study eye, i.e. presumed ocular histoplasmosis syndrome, android streaks, pathologic myopia (spherical equivalent of ≥ -8 diopters of myopia or axial length of ≥ 25mm), choroidal rupture, multifocal choroiditis, etc.
- Active ocular infection (i.e., bacterial, viral, parasitic, or fungal) in either eye at screening
- Serous PED without neovascularization and polypoidal choroidal vasculopathy (PCV) lesions are excluded.
- Prior or current systemic anti-VEGF
- Prior (within 90 days of Day 0) or current corticosteroid therapy (oral or intravenous corticosteroid treatments).
- Sexually active men* or women of child-bearing potential** who are unwilling to practice adequate contraception during the study (adequate contraception measures include, stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device [IUD]; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly) *Contraception is not required for men with documented vasectomy. ** Post-menopausal women must be amenorrheic for at least 12 months in order not to be considered of child-bearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.
Sites / Locations
- Jules Stein Eye Institute
- Southern California Desert Retina Consultants
- Black Hills Regional Eye Institute
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Aflibercept
Arm Description
All subjects will receive aflibercept
Outcomes
Primary Outcome Measures
Visual Acuity
Mean change in BCVA (Best Corrected Visual Acuity) from baseline measured at 4 meters on an ETDRS (Early Treatment Diabetic Retinopathy Study) chart at 12 months
Anatomic
Detailed anatomic descriptions and grading of lesion components and multi-modal anatomical changes (i.e. FP/FA, ICG, and OCT [Optical Coherence Tomography] findings) in a standardized fashion in a reading center setting at baseline and subsequent follow-up visits.
Secondary Outcome Measures
Proportion of eyes reaching BCVA greater than or equal to 20/200
Proportion of eyes gaining greater than or equal to 0, 5, and 15 letters on ETDRS chart.
Proportion of eyes losing greater than 5 and 15 letters on ETDRS chart
Mean reduction in central macular thickness from baseline (central 1mm subfield) as measured on an OCT.
Mean changes in choroidal neovascular lesion (CNV) size on fluorescein angiography (FA) and fundus photography (FP) from baseline.
Absence or complete resolution of subretinal fluid and cystoid macular edema.
Mean number of injections
Status of fluorescein staining or leakage (increased or decreased) from baseline.
Ocular safety outcome including ocular complications, i.e. RPE tears, uveitis, endophthalmitis
Systemic safety outcome including cardiovascular events, cerebral vascular events
Full Information
NCT ID
NCT01722656
First Posted
November 2, 2012
Last Updated
January 20, 2016
Sponsor
Southern California Desert Retina Consultants, MC
Collaborators
Regeneron Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT01722656
Brief Title
Intravitreal Aflibercept Injection for the Treatment of Submacular Vascularized Pigment Epithelial Detachment
Acronym
EVEN
Official Title
Open Label Study: Intravitreal Aflibercept Injection for the Treatment of Submacular Vascularized Pigment Epithelial Detachment.
Study Type
Interventional
2. Study Status
Record Verification Date
January 2016
Overall Recruitment Status
Completed
Study Start Date
November 2012 (undefined)
Primary Completion Date
September 2015 (Actual)
Study Completion Date
September 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Southern California Desert Retina Consultants, MC
Collaborators
Regeneron Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will evaluate the use of intravitreal aflibercept (anti-VEGF therapy) in patients with a type of macular degeneration known as vascularized pigment epithelial detachment. Previous studies have shown a generally poor outcome in treating this difficult to treat form of wet macular degeneration. More recently, multiple pilot studies have shown positive benefits to using anti-VEGF therapy. This study will evaluate the safety and efficacy of treating vascularize pigment epithelial detachment associated with wet macular degeneration with intravitreal aflibercept injection.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Submacular Vascularized Pigment Epithelial Detachments
Keywords
PED, AMD, CNV
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Aflibercept
Arm Type
Other
Arm Description
All subjects will receive aflibercept
Intervention Type
Drug
Intervention Name(s)
Aflibercept
Primary Outcome Measure Information:
Title
Visual Acuity
Description
Mean change in BCVA (Best Corrected Visual Acuity) from baseline measured at 4 meters on an ETDRS (Early Treatment Diabetic Retinopathy Study) chart at 12 months
Time Frame
12 months
Title
Anatomic
Description
Detailed anatomic descriptions and grading of lesion components and multi-modal anatomical changes (i.e. FP/FA, ICG, and OCT [Optical Coherence Tomography] findings) in a standardized fashion in a reading center setting at baseline and subsequent follow-up visits.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Proportion of eyes reaching BCVA greater than or equal to 20/200
Time Frame
12 months
Title
Proportion of eyes gaining greater than or equal to 0, 5, and 15 letters on ETDRS chart.
Time Frame
12 months
Title
Proportion of eyes losing greater than 5 and 15 letters on ETDRS chart
Time Frame
12 months
Title
Mean reduction in central macular thickness from baseline (central 1mm subfield) as measured on an OCT.
Time Frame
12 Months
Title
Mean changes in choroidal neovascular lesion (CNV) size on fluorescein angiography (FA) and fundus photography (FP) from baseline.
Time Frame
12 months
Title
Absence or complete resolution of subretinal fluid and cystoid macular edema.
Time Frame
12 monts
Title
Mean number of injections
Time Frame
12 months
Title
Status of fluorescein staining or leakage (increased or decreased) from baseline.
Time Frame
12 months
Title
Ocular safety outcome including ocular complications, i.e. RPE tears, uveitis, endophthalmitis
Time Frame
12 months
Title
Systemic safety outcome including cardiovascular events, cerebral vascular events
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subject is ≥ 50 years of age
Subject is willing to participate in this study and to follow the criteria and protocol of this study.
The study eye is treatment naïve regarding treatment of neovascular AMD.
Subject is not involved with another clinical study currently.
Subject is willing to follow the protocol outlined in the study.
Ability to understand the informed consent and willingness to sign the informed consent.
Presence of a submacular vascularized or fibrovascular PED. The investigator must search for the characteristic features of a vascularized PED summarized here:
A notch of irregularity associated with an orange-yellow round, oval, or bean-shaped elevation of the RPE with a smooth, convex surface is seen on examination and fundus photography (FP). Fluorescein angiography (FA) shows uniform staining of the PED with a well-defined margin, and more intense staining (hot-spot) for the focus of the CNV.
A fibrovascular PED with occult neovascularization typically shows stippled hyperfluorescence in the early phase with increasing hyperfluorescent staining and leakage in later phases of FA and a variable surrounding margin. There may be RPE folds.
Regarding PED with a component of retinal angiomatous proliferation (RAP), the early features on FP including intraretinal neovascularization (IRN) frequently with adjacent small retinal hemorrhages in its lateral expansion in an irregularly stellate pattern before the development of retinal-choroidal anastomosis and the eventual PED in the later phases. The investigator is required to perform indocyanine-green (ICG) angiography at baseline to establish a RAP lesion and to rule-out polypoidal vasculopathy lesions, since the FA images may not be distinct.
The investigator must also search for other features associated with a PED indicating the presence of a vascular component, i.e. hemorrhage, exudates, and/or chorioretinal folds.
The investigator must confirm the presence of a PED on FA/FP and OCT. Spectral Domain OCT will be utilized. Specifically, the Spectralis OCT manufactured by Heidleberg to maintain uniformity for all the sites. The PED height, SA, GLD, and volume will be measured from the OCT images. The characteristic OCT findings of the vascularized PED must be confirmed, including a distinct elevation of the highly hyperreflective RPE layer with mild backscattering of the underlying choroidal layer in the portion of the PED without any CNV. For the portion of the PED with underlying CNV, typical OCT findings consist of moderate hyperreflectivity contiguous to the overlying markedly hyperreflective detached RPE corresponding to the CNV that usually extends to the choroidal layer. Besides the OCT characteristics confirmation must be made on the FP/FA images of the vascularized PED, as outlined above in detail.
Central foveal involvement by the PED or the CNV due to age-related macular degeneration (AMD). The CNV may be classic, occult, or mixed, as long as it is associated with a PED. The CNV may be within the PED or adjacent to the margin of the PED.
PED ≤ 12 disc area in size.
BCVA with ETDRS of ≥ 19 letters and ≤ 73 letters (20/400 to 20/40).
Evidence of submacular fluid outside or surrounding the PED.
Surface area of the submacular hemorrhage needs to be < 50% of the entire PED.
Submacular fibrosis needs to be < 50% of the entire PED.
Sufficiently clear media (cornea, anterior chamber, lens, vitreous) for OCT, FA and FP.
Intraocular pressure (IOP) of 25mmHg or less in the study eye, with or without use of ocular hypotensive agents.
Prior treatment of neovascular AMD or any other forms of neovascularization in the fellow eye, including anti-VEGF or other forms of therapy targeted specifically for the fellow eye does not exclude the fellow eye from enrollment in this study. Prior focal corticosteroid treatment is allowed, as long as there is a lack of involvement of the study eye. However prior (within 90 days of Day 0) or current systemic corticosteroid therapy (oral or intravenous corticosteroid treatment) is not permitted.
Exclusion Criteria:
Any prior treatment of neovascular AMD in eye for proposed enrollment (non-naïve eye), including previous anti-vascular endothelial factor (anti-VEGF) therapy, photodynamic therapy (PDT), radiation therapy, corticosteroid treatment, surgical treatment for CNV, thermal laser treatment, and any other prior treatment for neovascular AMD.
Known serious allergies to aflibercept, fluorescein dye, drugs for pupillary dilation, topical anesthetic, sterilizing solution (e.g. Betadine Solution).
Contraindication to pupillary dilation in study eye.
Any condition (including inability to read visual acuity charts, or language barrier) that may preclude subjects ability to comply with the study protocol and requirements.
Presence of any advanced systemic condition or end-stage disease, advanced Alzheimer Syndrome, end-stage cancer, etc., which will likely prevent subject from completing study.
Previous therapeutic radiation in the region of the study eye.
Prior retinal pigment epithelial (RPE) tear in study eye.
Prior ocular surgery (except YAG laser capsulotomy) for study within the past 90 days.
Anticipated ocular surgery (except YAG laser capsulotomy) for the next 12 months
Prior therapy for AMD (except minerals and vitamins), including laser.
Prior vitrectomy
Presence of any causes of CNV and PED other than due to AMD.
Presence of any substantial ocular disease (other than the CNV and PED) that may compromise vision in the study eye and/or confound interpretation of the data; e.g. substantial cataracts, concomitant diabetic retinopathy affecting the macula, advanced glaucoma, optic neuritis, optic neuropathy, or atrophy, marked macular atrophy, ocular vascular occlusion, history of retinal detachment, uveitis, viral or other forms of chorioretinitis, etc.
Presence of ocular disease other than AMD affecting study eye, i.e. presumed ocular histoplasmosis syndrome, android streaks, pathologic myopia (spherical equivalent of ≥ -8 diopters of myopia or axial length of ≥ 25mm), choroidal rupture, multifocal choroiditis, etc.
Active ocular infection (i.e., bacterial, viral, parasitic, or fungal) in either eye at screening
Serous PED without neovascularization and polypoidal choroidal vasculopathy (PCV) lesions are excluded.
Prior or current systemic anti-VEGF
Prior (within 90 days of Day 0) or current corticosteroid therapy (oral or intravenous corticosteroid treatments).
Sexually active men* or women of child-bearing potential** who are unwilling to practice adequate contraception during the study (adequate contraception measures include, stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device [IUD]; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly) *Contraception is not required for men with documented vasectomy. ** Post-menopausal women must be amenorrheic for at least 12 months in order not to be considered of child-bearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clement K Chan, M.D.
Organizational Affiliation
Southern California Desert Retina Consultants
Official's Role
Principal Investigator
Facility Information:
Facility Name
Jules Stein Eye Institute
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Southern California Desert Retina Consultants
City
Palm Desert
State/Province
California
ZIP/Postal Code
92211
Country
United States
Facility Name
Black Hills Regional Eye Institute
City
Rapid City
State/Province
South Dakota
ZIP/Postal Code
57701
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Intravitreal Aflibercept Injection for the Treatment of Submacular Vascularized Pigment Epithelial Detachment
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