Intravitreal Aflibercept Injection for the Treatment of Submacular Vascularized Pigment Epithelial Detachment

NCT01722656 | Completed Phase 4

• 1 other identifier: EVEN Study
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 3

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.

Conditions

Submacular Vascularized Pigment Epithelial Detachments

Keywords

PED; AMD; CNV

Outcome Measures

Primary Outcomes (2)

• 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

  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.

  12 months

Secondary Outcomes (10)

• Proportion of eyes reaching BCVA greater than or equal to 20/200

  12 months

• Proportion of eyes gaining greater than or equal to 0, 5, and 15 letters on ETDRS chart.

  12 months

• Proportion of eyes losing greater than 5 and 15 letters on ETDRS chart

  12 months

• Mean reduction in central macular thickness from baseline (central 1mm subfield) as measured on an OCT.

  12 Months

• Mean changes in choroidal neovascular lesion (CNV) size on fluorescein angiography (FA) and fundus photography (FP) from baseline.

  12 months

Study Arms (1)

Aflibercept

OTHER

All subjects will receive aflibercept

Drug: Aflibercept

Interventions

Aflibercept DRUG

Aflibercept

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Southern California Desert Retina Consultants, MC: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (3)

Jules Stein Eye Institute

Los Angeles, California, 90095, United States

Location

Southern California Desert Retina Consultants

Palm Desert, California, 92211, United States

Location

Black Hills Regional Eye Institute

Rapid City, South Dakota, 57701, United States

Location

MeSH Terms

Interventions

aflibercept

Study Officials

• Clement K Chan, M.D.

  Southern California Desert Retina Consultants

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2012
• First Posted: November 7, 2012
• Study Start: November 1, 2012
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: January 22, 2016

Record last verified: 2016-01

Locations

US (3)