Submacular Vascularized Pigment Epithelial DetachmentsPhase 4EVENNCT01722656
Intravitreal Aflibercept Injection for the Treatment of Submacular Vascularized Pigment Epithelial Detachment
A Phase 4 study testing Aflibercept in people with Submacular Vascularized Pigment Epithelial Detachments, run by Southern California Desert Retina Consultants, MC at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Submacular Vascularized Pigment Epithelial Detachments
- What is being tested?
- Aflibercept
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 3 sitesUnited States
- Study dates
- Nov 2012to Sep 2015
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Jules Stein Eye Institute
Los Angeles, California, 90095
Southern California Desert Retina Consultants
Palm Desert, California, 92211
Black Hills Regional Eye Institute
Rapid City, South Dakota, 57701
About this study
Official title: Open Label Study: Intravitreal Aflibercept Injection for the Treatment of Submacular Vascularized Pigment Epithelial Detachment.
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.
- Being tested
- Aflibercept
- Keywords
- PED, AMD, CNV
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AfliberceptDrug
| Study group | Role | What they receive |
|---|---|---|
| Aflibercept | Other | All subjects will receive aflibercept Receives: Drug: Aflibercept |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 12 months
Secondary outcomes (10)
Proportion of eyes reaching BCVA greater than or equal to 20/200
Measured: 12 months
Proportion of eyes gaining greater than or equal to 0, 5, and 15 letters on ETDRS chart.
Measured: 12 months
Proportion of eyes losing greater than 5 and 15 letters on ETDRS chart
Measured: 12 months
Mean reduction in central macular thickness from baseline (central 1mm subfield) as measured on an OCT.
Measured: 12 Months
Mean changes in choroidal neovascular lesion (CNV) size on fluorescein angiography (FA) and fundus photography (FP) from baseline.
Measured: 12 months
Absence or complete resolution of subretinal fluid and cystoid macular edema.
Measured: 12 monts
Mean number of injections
Measured: 12 months
Status of fluorescein staining or leakage (increased or decreased) from baseline.
Measured: 12 months
Ocular safety outcome including ocular complications, i.e. RPE tears, uveitis, endophthalmitis
Measured: 12 months
Systemic safety outcome including cardiovascular events, cerebral vascular events
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2012 (estimated)
- Study startNov 2012
- Primary completionSep 2015
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Submacular Vascularized Pigment Epithelial DetachmentsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Southern California Desert Retina Consultants, MC
- Sponsor type
- University, hospital or other
- Collaborators
- Regeneron Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Clement K Chan, M.D., Principal investigator, Southern California Desert Retina Consultants
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01722656
- Sponsor's protocol ID
- EVEN Study
- Acronym
- EVEN
- Status last verified
- Jan 2016
- First submitted
- 2 Nov 2012
- Last updated
- 22 Jan 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Label Study: Intravitreal Aflibercept Injection for the Treatment of Submacular Vascularized Pigment Epithelial Detachment.
- ClinicalTrials.gov ID
- NCT01722656
- Acronym / sponsor ID
- EVEN / EVEN Study
- Keywords
- PED, AMD, CNV
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Southern California Desert Retina Consultants, MCUniversity, hospital or other
- Collaborators
- Regeneron Pharmaceuticals
- Study start
- Nov 2012
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 7 Nov 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Aflibercept | Other | Drug: AfliberceptAll subjects will receive aflibercept |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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.
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aflibercept | Drug | Aflibercept |
Primary outcome
Visual Acuity
Time frame: 12 months
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
Time frame: 12 months
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.
10 secondary outcomes
Proportion of eyes reaching BCVA greater than or equal to 20/200
Time frame: 12 months
Proportion of eyes gaining greater than or equal to 0, 5, and 15 letters on ETDRS chart.
Time frame: 12 months
Proportion of eyes losing greater than 5 and 15 letters on ETDRS chart
Time frame: 12 months
Mean reduction in central macular thickness from baseline (central 1mm subfield) as measured on an OCT.
Time frame: 12 Months
Mean changes in choroidal neovascular lesion (CNV) size on fluorescein angiography (FA) and fundus photography (FP) from baseline.
Time frame: 12 months
Absence or complete resolution of subretinal fluid and cystoid macular edema.
Time frame: 12 monts
Mean number of injections
Time frame: 12 months
Status of fluorescein staining or leakage (increased or decreased) from baseline.
Time frame: 12 months
Ocular safety outcome including ocular complications, i.e. RPE tears, uveitis, endophthalmitis
Time frame: 12 months
Systemic safety outcome including cardiovascular events, cerebral vascular events
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2016.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clement K Chan, M.D. principal investigator
Southern California Desert Retina Consultants
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Aflibercept in people with Submacular Vascularized Pigment Epithelial Detachments, run by Southern California Desert Retina Consultants, MC at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Visual Acuity (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2016.