<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/NCT02204683</url>
  </required_header>
  <id_info>
    <org_study_id>0334-14-FB</org_study_id>
    <nct_id>NCT02204683</nct_id>
  </id_info>
  <brief_title>Pharmacokinetic Study of Intravitreal Aflibercept Injection in Eyes With Wet Age-related Macular Degeneration</brief_title>
  <acronym>DRAW</acronym>
  <official_title>A Pharmacokinetic Study of Intravitreal Aflibercept Injection in Vitrectomized and Non-vitrectomized Eyes With Wet Age-related Macular Degeneration (the DRAW Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Nebraska</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Regeneron Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Nebraska</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main goal is to study way that aflibercept injection behaves in the eye and in the body&#xD;
      of patients with wet macular degeneration, in patients who have had previous vitreous removal&#xD;
      surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A pharmacokinetic study of intravitreal Aflibercept injection vitrectomized and&#xD;
      non-vitrectomized eyes with Wet age-related macular degeneration (the DRAW study).&#xD;
&#xD;
      The primary objective is to investigate and characterize the intraocular pharmacokinetics of&#xD;
      intravitreal aflibercept injection in vitrectomized and non-vitrectomized eyes with&#xD;
      neovascular Age-related Macular Degeneration (AMD). The secondary objective is to assess the&#xD;
      systemic pharmacokinetics of intravitreal aflibercept injection.&#xD;
&#xD;
      Little information is known about the intraocular pharmacokinetics of intravitreal&#xD;
      aflibercept injection in human eyes. In addition, the durability of intravitreal aflibercept&#xD;
      injection in vitrectomized eyes is not known, since individuals with a history of vitrectomy&#xD;
      have been excluded from clinical trials in neovascular AMD. There have also been no studies&#xD;
      on systemic levels following intravitreal aflibercept injection, which would have&#xD;
      implications for normal vascular hemostasis and wound repair in which vascular endothelial&#xD;
      growth factor (VEGF) plays an important role. The proposed research will fill in these gaps&#xD;
      in the knowledge base for intravitreal aflibercept injection.&#xD;
&#xD;
      Two arms (non-vitrectomized, and vitrectomized) are included in the study to evaluate the&#xD;
      intraocular and systemic pharmacokinetics of intravitreal aflibercept injection The study&#xD;
      involves neovascular AMD patients divided into two groups: 5 patients with history of&#xD;
      vitrectomy and 10 patients with no history of vitrectomy. Plasma blood and aqueous fluid will&#xD;
      be collected at baseline, then 2mg of intravitreal aflibercept injection administered at time&#xD;
      0 (day 0). At 4 hours post injection, plasma (blood) and aqueous fluid will be collected&#xD;
      again, as well as on days 1, 3, 7,14, and 28. Intravitreal aflibercept injection levels in&#xD;
      the samples will be assessed and compared among the two groups.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 5, 2014</start_date>
  <completion_date type="Actual">December 14, 2016</completion_date>
  <primary_completion_date type="Actual">December 14, 2016</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetic (PK) aflibercept aqueous</measure>
    <time_frame>28 days</time_frame>
    <description>The primary endpoint in the study consists of intraocular aflibercept (free and bound) concentrations following intravitreal aflibercept injection.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PK Aflibercept plasma</measure>
    <time_frame>28 days</time_frame>
    <description>The secondary endpoints are plasma concentrations of aflibercept (free and bound) following intravitreal aflibercept injection.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Neovascular Macular Degeneration</condition>
  <arm_group>
    <arm_group_label>Aflibercept</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Subjects who have had a vitrectomy previously</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aflibercept in Non-Vitrectomized eyes</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients who have not had vitrectomy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aflibercept</intervention_name>
    <description>Intravitreal aflibercept</description>
    <arm_group_label>Aflibercept</arm_group_label>
    <arm_group_label>Aflibercept in Non-Vitrectomized eyes</arm_group_label>
    <other_name>Eylea</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age &gt; 50 years&#xD;
&#xD;
          2. Active neovascular AMD, with no history of treatment in the study eye 2.1 10 patients&#xD;
             with non-vitrectomized eyes 2.2 5 patients with vitrectomized eyes&#xD;
&#xD;
          3. Phakic and pseudophakic eyes are allowed in the study.&#xD;
&#xD;
          4. Willing and able to provide written informed consent after the nature of the study has&#xD;
             been explained, and prior to any research-related procedures&#xD;
&#xD;
          5. Willing and able to comply with clinic visits and study-related procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Presence of other retinal vascular diseases (diabetic retinopathy, vein occlusion)&#xD;
             that could affect the VEGF levels within the eye&#xD;
&#xD;
          2. Known hypersensitivity to aflibercept&#xD;
&#xD;
          3. Autoimmune disease of the anterior segment or posterior chamber including chronic&#xD;
             keratoconjunctivitis sicca, uveitis, iritis/scleritis, blepharitis of either eye&#xD;
&#xD;
          4. Infectious conjunctivitis, keratitis, or endophthalmitis of either eye&#xD;
&#xD;
          5. Previous participation in any studies of investigational drugs within 1 month&#xD;
             preceding Day 0&#xD;
&#xD;
          6. Any clinically significant acute or chronic medical condition that would preclude&#xD;
             participation in a clinical study&#xD;
&#xD;
          7. Pregnant or breast-feeding women&#xD;
&#xD;
          8. Sexually active men* or women of childbearing potential** who are unwilling to&#xD;
             practice adequate contraception during the study (adequate contraceptive 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. **Postmenopausal women must be amenorrheic&#xD;
             for at least 12 months in order not to be considered of child bearing potential.&#xD;
             Pregnancy testing and contraception are not required for women with documented&#xD;
             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>Diana V Do, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Nebraska</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Nebraska Medical Center, Truhlsen Eye Institute</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>July 28, 2014</study_first_submitted>
  <study_first_submitted_qc>July 28, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 30, 2014</study_first_posted>
  <last_update_submitted>September 1, 2023</last_update_submitted>
  <last_update_submitted_qc>September 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>AMD</keyword>
  <keyword>Neovascularization</keyword>
  <keyword>macular degeneration</keyword>
  <keyword>wet macular degeneration</keyword>
  <keyword>vitrectomy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Macular Degeneration</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aflibercept</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02204683
org study id: 0334-14-FB
nct id: NCT02204683
lead sponsor: 
collaborator: 
has dmc: No
The main goal is to study way that aflibercept injection behaves in the eye and in the body
      of patients with wet macular degeneration, in patients who have had previous vitreous removal
      surgery.
A pharmacokinetic study of intravitreal Aflibercept injection vitrectomized and
      non-vitrectomized eyes with Wet age-related macular degeneration (the DRAW study).

      The primary objective is to investigate and characterize the intraocular pharmacokinetics of
      intravitreal aflibercept injection in vitrectomized and non-vitrectomized eyes with
      neovascular Age-related Macular Degeneration (AMD). The secondary objective is to assess the
      systemic pharmacokinetics of intravitreal aflibercept injection.

      Little information is known about the intraocular pharmacokinetics of intravitreal
      aflibercept injection in human eyes. In addition, the durability of intravitreal aflibercept
      injection in vitrectomized eyes is not known, since individuals with a history of vitrectomy
      have been excluded from clinical trials in neovascular AMD. There have also been no studies
      on systemic levels following intravitreal aflibercept injection, which would have
      implications for normal vascular hemostasis and wound repair in which vascular endothelial
      growth factor (VEGF) plays an important role. The proposed research will fill in these gaps
      in the knowledge base for intravitreal aflibercept injection.

      Two arms (non-vitrectomized, and vitrectomized) are included in the study to evaluate the
      intraocular and systemic pharmacokinetics of intravitreal aflibercept injection The study
      involves neovascular AMD patients divided into two groups: 5 patients with history of
      vitrectomy and 10 patients with no history of vitrectomy. Plasma blood and aqueous fluid will
      be collected at baseline, then 2mg of intravitreal aflibercept injection administered at time
      0 (day 0). At 4 hours post injection, plasma (blood) and aqueous fluid will be collected
      again, as well as on days 1, 3, 7,14, and 28. Intravitreal aflibercept injection levels in
      the samples will be assessed and compared among the two groups.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Pharmacokinetic (PK) aflibercept aqueous
time frame: 28 days
description: The primary endpoint in the study consists of intraocular aflibercept (free and bound) concentrations following intravitreal aflibercept injection.
measure: PK Aflibercept plasma
time frame: 28 days
description: The secondary endpoints are plasma concentrations of aflibercept (free and bound) following intravitreal aflibercept injection.
arm group label: Aflibercept
arm group type: Other
description: Subjects who have had a vitrectomy previously
arm group label: Aflibercept in Non-Vitrectomized eyes
arm group type: Other
description: Patients who have not had vitrectomy.
intervention type: Drug
intervention name: Aflibercept
description: Intravitreal aflibercept
arm group label: Aflibercept
arm group label: Aflibercept in Non-Vitrectomized eyes
other name: Eylea
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Diana V Do, MD
role: Principal Investigator
affiliation: University of Nebraska
facility: 
country: United States
responsible party type: Sponsor
mesh term: Macular Degeneration
mesh term: Aflibercept