<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01722656</url>
  </required_header>
  <id_info>
    <org_study_id>EVEN Study</org_study_id>
    <nct_id>NCT01722656</nct_id>
  </id_info>
  <brief_title>Intravitreal Aflibercept Injection for the Treatment of Submacular Vascularized Pigment Epithelial Detachment</brief_title>
  <acronym>EVEN</acronym>
  <official_title>Open Label Study: Intravitreal Aflibercept Injection for the Treatment of Submacular Vascularized Pigment Epithelial Detachment.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Southern California Desert Retina Consultants, MC</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Regeneron Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Southern California Desert Retina Consultants, MC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will evaluate the use of intravitreal aflibercept (anti-VEGF therapy) in patients&#xD;
      with a type of macular degeneration known as vascularized pigment epithelial detachment.&#xD;
      Previous studies have shown a generally poor outcome in treating this difficult to treat form&#xD;
      of wet macular degeneration. More recently, multiple pilot studies have shown positive&#xD;
      benefits to using anti-VEGF therapy. This study will evaluate the safety and efficacy of&#xD;
      treating vascularize pigment epithelial detachment associated with wet macular degeneration&#xD;
      with intravitreal aflibercept injection.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">September 2015</completion_date>
  <primary_completion_date type="Actual">September 2015</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Visual Acuity</measure>
    <time_frame>12 months</time_frame>
    <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</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Anatomic</measure>
    <time_frame>12 months</time_frame>
    <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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of eyes reaching BCVA greater than or equal to 20/200</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of eyes gaining greater than or equal to 0, 5, and 15 letters on ETDRS chart.</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of eyes losing greater than 5 and 15 letters on ETDRS chart</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean reduction in central macular thickness from baseline (central 1mm subfield) as measured on an OCT.</measure>
    <time_frame>12 Months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean changes in choroidal neovascular lesion (CNV) size on fluorescein angiography (FA) and fundus photography (FP) from baseline.</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absence or complete resolution of subretinal fluid and cystoid macular edema.</measure>
    <time_frame>12 monts</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean number of injections</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Status of fluorescein staining or leakage (increased or decreased) from baseline.</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ocular safety outcome including ocular complications, i.e. RPE tears, uveitis, endophthalmitis</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Systemic safety outcome including cardiovascular events, cerebral vascular events</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Submacular Vascularized Pigment Epithelial Detachments</condition>
  <arm_group>
    <arm_group_label>Aflibercept</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>All subjects will receive aflibercept</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aflibercept</intervention_name>
    <arm_group_label>Aflibercept</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject is ≥ 50 years of age&#xD;
&#xD;
          -  Subject is willing to participate in this study and to follow the criteria and&#xD;
             protocol of this study.&#xD;
&#xD;
          -  The study eye is treatment naïve regarding treatment of neovascular AMD.&#xD;
&#xD;
          -  Subject is not involved with another clinical study currently.&#xD;
&#xD;
          -  Subject is willing to follow the protocol outlined in the study.&#xD;
&#xD;
          -  Ability to understand the informed consent and willingness to sign the informed&#xD;
             consent.&#xD;
&#xD;
          -  Presence of a submacular vascularized or fibrovascular PED. The investigator must&#xD;
             search for the characteristic features of a vascularized PED summarized here:&#xD;
&#xD;
               1. A notch of irregularity associated with an orange-yellow round, oval, or&#xD;
                  bean-shaped elevation of the RPE with a smooth, convex surface is seen on&#xD;
                  examination and fundus photography (FP). Fluorescein angiography (FA) shows&#xD;
                  uniform staining of the PED with a well-defined margin, and more intense staining&#xD;
                  (hot-spot) for the focus of the CNV.&#xD;
&#xD;
               2. A fibrovascular PED with occult neovascularization typically shows stippled&#xD;
                  hyperfluorescence in the early phase with increasing hyperfluorescent staining&#xD;
                  and leakage in later phases of FA and a variable surrounding margin. There may be&#xD;
                  RPE folds.&#xD;
&#xD;
               3. Regarding PED with a component of retinal angiomatous proliferation (RAP), the&#xD;
                  early features on FP including intraretinal neovascularization (IRN) frequently&#xD;
                  with adjacent small retinal hemorrhages in its lateral expansion in an&#xD;
                  irregularly stellate pattern before the development of retinal-choroidal&#xD;
                  anastomosis and the eventual PED in the later phases. The investigator is&#xD;
                  required to perform indocyanine-green (ICG) angiography at baseline to establish&#xD;
                  a RAP lesion and to rule-out polypoidal vasculopathy lesions, since the FA images&#xD;
                  may not be distinct.&#xD;
&#xD;
               4. The investigator must also search for other features associated with a PED&#xD;
                  indicating the presence of a vascular component, i.e. hemorrhage, exudates,&#xD;
                  and/or chorioretinal folds.&#xD;
&#xD;
               5. The investigator must confirm the presence of a PED on FA/FP and OCT. Spectral&#xD;
                  Domain OCT will be utilized. Specifically, the Spectralis OCT manufactured by&#xD;
                  Heidleberg to maintain uniformity for all the sites. The PED height, SA, GLD, and&#xD;
                  volume will be measured from the OCT images. The characteristic OCT findings of&#xD;
                  the vascularized PED must be confirmed, including a distinct elevation of the&#xD;
                  highly hyperreflective RPE layer with mild backscattering of the underlying&#xD;
                  choroidal layer in the portion of the PED without any CNV. For the portion of the&#xD;
                  PED with underlying CNV, typical OCT findings consist of moderate&#xD;
                  hyperreflectivity contiguous to the overlying markedly hyperreflective detached&#xD;
                  RPE corresponding to the CNV that usually extends to the choroidal layer. Besides&#xD;
                  the OCT characteristics confirmation must be made on the FP/FA images of the&#xD;
                  vascularized PED, as outlined above in detail.&#xD;
&#xD;
          -  Central foveal involvement by the PED or the CNV due to age-related macular&#xD;
             degeneration (AMD). The CNV may be classic, occult, or mixed, as long as it is&#xD;
             associated with a PED. The CNV may be within the PED or adjacent to the margin of the&#xD;
             PED.&#xD;
&#xD;
          -  PED ≤ 12 disc area in size.&#xD;
&#xD;
          -  BCVA with ETDRS of ≥ 19 letters and ≤ 73 letters (20/400 to 20/40).&#xD;
&#xD;
          -  Evidence of submacular fluid outside or surrounding the PED.&#xD;
&#xD;
          -  Surface area of the submacular hemorrhage needs to be &lt; 50% of the entire PED.&#xD;
&#xD;
          -  Submacular fibrosis needs to be &lt; 50% of the entire PED.&#xD;
&#xD;
          -  Sufficiently clear media (cornea, anterior chamber, lens, vitreous) for OCT, FA and&#xD;
             FP.&#xD;
&#xD;
          -  Intraocular pressure (IOP) of 25mmHg or less in the study eye, with or without use of&#xD;
             ocular hypotensive agents.&#xD;
&#xD;
          -  Prior treatment of neovascular AMD or any other forms of neovascularization in the&#xD;
             fellow eye, including anti-VEGF or other forms of therapy targeted specifically for&#xD;
             the fellow eye does not exclude the fellow eye from enrollment in this study. Prior&#xD;
             focal corticosteroid treatment is allowed, as long as there is a lack of involvement&#xD;
             of the study eye. However prior (within 90 days of Day 0) or current systemic&#xD;
             corticosteroid therapy (oral or intravenous corticosteroid treatment) is not&#xD;
             permitted.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any prior treatment of neovascular AMD in eye for proposed enrollment (non-naïve eye),&#xD;
             including previous anti-vascular endothelial factor (anti-VEGF) therapy, photodynamic&#xD;
             therapy (PDT), radiation therapy, corticosteroid treatment, surgical treatment for&#xD;
             CNV, thermal laser treatment, and any other prior treatment for neovascular AMD.&#xD;
&#xD;
          -  Known serious allergies to aflibercept, fluorescein dye, drugs for pupillary dilation,&#xD;
             topical anesthetic, sterilizing solution (e.g. Betadine Solution).&#xD;
&#xD;
          -  Contraindication to pupillary dilation in study eye.&#xD;
&#xD;
          -  Any condition (including inability to read visual acuity charts, or language barrier)&#xD;
             that may preclude subjects ability to comply with the study protocol and requirements.&#xD;
&#xD;
          -  Presence of any advanced systemic condition or end-stage disease, advanced Alzheimer&#xD;
             Syndrome, end-stage cancer, etc., which will likely prevent subject from completing&#xD;
             study.&#xD;
&#xD;
          -  Previous therapeutic radiation in the region of the study eye.&#xD;
&#xD;
          -  Prior retinal pigment epithelial (RPE) tear in study eye.&#xD;
&#xD;
          -  Prior ocular surgery (except YAG laser capsulotomy) for study within the past 90 days.&#xD;
&#xD;
          -  Anticipated ocular surgery (except YAG laser capsulotomy) for the next 12 months&#xD;
&#xD;
          -  Prior therapy for AMD (except minerals and vitamins), including laser.&#xD;
&#xD;
          -  Prior vitrectomy&#xD;
&#xD;
          -  Presence of any causes of CNV and PED other than due to AMD.&#xD;
&#xD;
          -  Presence of any substantial ocular disease (other than the CNV and PED) that may&#xD;
             compromise vision in the study eye and/or confound interpretation of the data; e.g.&#xD;
             substantial cataracts, concomitant diabetic retinopathy affecting the macula, advanced&#xD;
             glaucoma, optic neuritis, optic neuropathy, or atrophy, marked macular atrophy, ocular&#xD;
             vascular occlusion, history of retinal detachment, uveitis, viral or other forms of&#xD;
             chorioretinitis, etc.&#xD;
&#xD;
          -  Presence of ocular disease other than AMD affecting study eye, i.e. presumed ocular&#xD;
             histoplasmosis syndrome, android streaks, pathologic myopia (spherical equivalent of ≥&#xD;
             -8 diopters of myopia or axial length of ≥ 25mm), choroidal rupture, multifocal&#xD;
             choroiditis, etc.&#xD;
&#xD;
          -  Active ocular infection (i.e., bacterial, viral, parasitic, or fungal) in either eye&#xD;
             at screening&#xD;
&#xD;
          -  Serous PED without neovascularization and polypoidal choroidal vasculopathy (PCV)&#xD;
             lesions are excluded.&#xD;
&#xD;
          -  Prior or current systemic anti-VEGF&#xD;
&#xD;
          -  Prior (within 90 days of Day 0) or current corticosteroid therapy (oral or intravenous&#xD;
             corticosteroid treatments).&#xD;
&#xD;
          -  Sexually active men* or women of child-bearing potential** who are unwilling to&#xD;
             practice adequate contraception during the study (adequate contraception measures&#xD;
             include, stable use of oral contraceptives or other prescription pharmaceutical&#xD;
             contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device&#xD;
             [IUD]; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or&#xD;
             jelly, or diaphragm plus contraceptive sponge, foam, or jelly) *Contraception is not&#xD;
             required for men with documented vasectomy. ** Post-menopausal women must be&#xD;
             amenorrheic for at least 12 months in order not to be considered of child-bearing&#xD;
             potential. Pregnancy testing and contraception are not required for women with&#xD;
             documented hysterectomy or tubal ligation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clement K Chan, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Southern California Desert Retina Consultants</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Jules Stein Eye Institute</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southern California Desert Retina Consultants</name>
      <address>
        <city>Palm Desert</city>
        <state>California</state>
        <zip>92211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Black Hills Regional Eye Institute</name>
      <address>
        <city>Rapid City</city>
        <state>South Dakota</state>
        <zip>57701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2016</verification_date>
  <study_first_submitted>November 2, 2012</study_first_submitted>
  <study_first_submitted_qc>November 5, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 7, 2012</study_first_posted>
  <last_update_submitted>January 20, 2016</last_update_submitted>
  <last_update_submitted_qc>January 20, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 22, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PED</keyword>
  <keyword>AMD</keyword>
  <keyword>CNV</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Retinal Detachment</mesh_term>
    <mesh_term>Dissociative Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aflibercept</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>August 23, 2022</submitted>
    <returned>September 22, 2022</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01722656
org study id: EVEN Study
nct id: NCT01722656
lead sponsor: 
collaborator: 
has dmc: No
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Visual Acuity
time frame: 12 months
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
measure: Anatomic
time frame: 12 months
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.
measure: Proportion of eyes reaching BCVA greater than or equal to 20/200
time frame: 12 months
measure: Proportion of eyes gaining greater than or equal to 0, 5, and 15 letters on ETDRS chart.
time frame: 12 months
measure: Proportion of eyes losing greater than 5 and 15 letters on ETDRS chart
time frame: 12 months
measure: Mean reduction in central macular thickness from baseline (central 1mm subfield) as measured on an OCT.
time frame: 12 Months
measure: Mean changes in choroidal neovascular lesion (CNV) size on fluorescein angiography (FA) and fundus photography (FP) from baseline.
time frame: 12 months
measure: Absence or complete resolution of subretinal fluid and cystoid macular edema.
time frame: 12 monts
measure: Mean number of injections
time frame: 12 months
measure: Status of fluorescein staining or leakage (increased or decreased) from baseline.
time frame: 12 months
measure: Ocular safety outcome including ocular complications, i.e. RPE tears, uveitis, endophthalmitis
time frame: 12 months
measure: Systemic safety outcome including cardiovascular events, cerebral vascular events
time frame: 12 months
arm group label: Aflibercept
arm group type: Other
description: All subjects will receive aflibercept
intervention type: Drug
intervention name: Aflibercept
arm group label: Aflibercept
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Clement K Chan, M.D.
role: Principal Investigator
affiliation: Southern California Desert Retina Consultants
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Retinal Detachment
mesh term: Dissociative Disorders
mesh term: Aflibercept
submitted: August 23, 2022
returned: September 22, 2022