<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/NCT03249740</url>
  </required_header>
  <id_info>
    <org_study_id>GBV-102-001</org_study_id>
    <nct_id>NCT03249740</nct_id>
  </id_info>
  <brief_title>A Depot Formulation of Sunitinib Malate (GB-102) in Subjects With Neovascular (Wet) Age-related Macular Degeneration</brief_title>
  <official_title>A Phase 1/2 Multicenter Study Evaluating the Safety, Tolerability, and Efficacy of an Intravitreal Depot Formulation of Sunitinib Malate (GB-102) in Subjects With Neovascular Age-related Macular Degeneration</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Graybug Vision</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Graybug Vision</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the safety and efficacy of single and repeated&#xD;
      intravitreal injections of GB-102 in subjects with neovascular (wet) age-related macular&#xD;
      degeneration.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this 2-part study, Part 1 is a multicenter, open-label, safety, tolerability, and systemic&#xD;
      exposure evaluation to Sunitinib in escalating doses of a single IVT injection of GB-102,&#xD;
      while Part 2 is a multicenter, double-masked, randomized (1:1:1), parallel-group, safety, and&#xD;
      efficacy evaluation of repeated IVT injections of 2 dose levels of GB-102 compared with&#xD;
      aflibercept.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 29, 2017</start_date>
  <completion_date type="Actual">January 16, 2019</completion_date>
  <primary_completion_date type="Actual">September 13, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Phase 1: open-label GB-102 dose cohorts are initiated sequentially Phase 2: assignment to and initiation of cohorts occur in parallel - not completed in this study. Separate protocol (GBV-102-002) implemented for Phase 2.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
    <masking_description>Masking is relevant to Phase 2 only</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Phase 1: Occurrence of ocular and nonocular adverse events (AEs)</measure>
    <time_frame>8 months</time_frame>
    <description>Number of adverse events in total and number of subjects with an adverse event</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 2: Change from baseline in best corrected visual acuity by ETDRS</measure>
    <time_frame>Baseline, Month 9</time_frame>
    <description>Mean change from Baseline at Day 270 (Month 9) in best corrected visual acuity (BCVA) measured by early treatment diabetic retinopathy (ETDRS)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Phase 1: Change from baseline in BCVA by ETDRS</measure>
    <time_frame>8 months</time_frame>
    <description>Mean change from baseline in mean BCVA measured by early treatment diabetic retinopathy (ETDRS) method</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1: Change from baseline in sub-retinal thickness</measure>
    <time_frame>8 months</time_frame>
    <description>Mean change from baseline in sub-retinal thickness (microns) by spectral domain - optical coherence tomography (SD-OCT)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1: Change from baseline in retinal fluid by SD-OCT</measure>
    <time_frame>8 months</time_frame>
    <description>Assessment of retinal fluid by SD-OCT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1: Change from baseline in total lesion area by FA/CFP</measure>
    <time_frame>8 months</time_frame>
    <description>Lesion area (total) by fluorescein angiography/color fundus photography (FA/CFP)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1: Change from baseline in CNV lesion area by FA/CFP</measure>
    <time_frame>8 months</time_frame>
    <description>CNV lesion area by FA/CFP</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1: Change from baseline in fluorescein leakage area by FA/CFP</measure>
    <time_frame>8 months</time_frame>
    <description>Area of fluorescein leakage by FA/CFP</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1: Rescue medication</measure>
    <time_frame>8 months</time_frame>
    <description>Proportion of subjects receiving rescue medication and median time to rescue medication</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1: Systemic exposure to sunitinib measured in plasma level</measure>
    <time_frame>8 months</time_frame>
    <description>Plasma levels of sunitinib (ng/mL)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1: Change from baseline in sub retinal hyper reflective material (SHRM) height</measure>
    <time_frame>8 months</time_frame>
    <description>Subretinal hyper reflective material (SHRM) height</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Proportion of subjects with absence of retinal fluid by SD-OCT</measure>
    <time_frame>12 months</time_frame>
    <description>Assessment of retinal fluid by SD-OCT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Proportion of subjects with &lt; 15 BCVA letter loss by ETDRS</measure>
    <time_frame>12 months</time_frame>
    <description>Proportion of subjects with &lt; 15 letters lost in BCVA measured by ETDRS method, baseline comparison to assessments at months 1-12</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Proportion of subjects with ≥ 15 BCVA letters gained by ETDRS</measure>
    <time_frame>12 months</time_frame>
    <description>Proportion of subjects with ≥ 15 letters gained in BCVA measured by ETDRS method, baseline comparison to assessments at months 1-12</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Occurrence of ocular and nonocular adverse events (AEs)</measure>
    <time_frame>12 months</time_frame>
    <description>Number of adverse events in total and number of subjects with an adverse event</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Change from baseline in BCVA by ETDRS</measure>
    <time_frame>12 months</time_frame>
    <description>Mean change from baseline in mean BCVA measured by early treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Systemic exposure to sunitinib measured in plasma level</measure>
    <time_frame>12 months</time_frame>
    <description>Plasma levels of sunitinib (ng/mL)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Change from baseline in sub-retinal thickness</measure>
    <time_frame>12 months</time_frame>
    <description>Mean change from baseline in sub-retinal thickness (microns) by SD-OCT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Rescue medication</measure>
    <time_frame>12 months</time_frame>
    <description>Proportion of subjects receiving rescue medication and median time to rescue medication</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Neovascular Age-Related Macular Degeneration</condition>
  <arm_group>
    <arm_group_label>Experimental: Phase 1 - GB-102</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will be assigned to 1 of 4 cohorts to receive a single intravitreal injection of up to 2.0 mg (50 μL) GB-102.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Experimental: Phase 2 - GB-102</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Low dose or high dose injected every 6 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Active Comparator: Phase 2 - Aflibercept</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Aflibercept 2 mg injected every 2 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GB-102</intervention_name>
    <description>Intravitreal injection of GB-102</description>
    <arm_group_label>Experimental: Phase 1 - GB-102</arm_group_label>
    <arm_group_label>Experimental: Phase 2 - GB-102</arm_group_label>
    <other_name>Sunitinib malate</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aflibercept</intervention_name>
    <description>Intravitreal injection of Aflibercept.</description>
    <arm_group_label>Active Comparator: Phase 2 - Aflibercept</arm_group_label>
    <other_name>Anti-VEGF</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          1. Males or females of any race, ≥ 50 years of age&#xD;
&#xD;
          2. Presence of an active CNV lesion secondary to AMD treated with at least 3 monthly&#xD;
             injections of an anti-VEGF agent (aflibercept, bevacizumab, or ranibizumab)&#xD;
&#xD;
          3. Evidence of increased vascular permeability and/or loss of visual acuity&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          1. History, within 6 months prior to screening, of any of the following: myocardial&#xD;
             infarction, any cardiac event requiring hospitalization, treatment for acute&#xD;
             congestive heart failure, transient ischemic attack, or stroke&#xD;
&#xD;
          2. Uncontrolled hypertension, diabetes mellitus, IOP, hypothyroidism, or hyperthyroidism&#xD;
&#xD;
          3. Chronic renal disease&#xD;
&#xD;
          4. Abnormal liver function&#xD;
&#xD;
          5. Women who are pregnant or lactating&#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>Charles P. Semba, MD</last_name>
    <role>Study Director</role>
    <affiliation>Graybug Vision, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Retinal Consultants of Arizona</name>
      <address>
        <city>Gilbert</city>
        <state>Arizona</state>
        <zip>85296</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina-Vitreous Associates Medical Group</name>
      <address>
        <city>Beverly Hills</city>
        <state>California</state>
        <zip>90211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Midwest Eye Institute</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46290</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ophthalmic Consultants of Long Island</name>
      <address>
        <city>Lynbrook</city>
        <state>New York</state>
        <zip>11563</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Research Institute of Texas</name>
      <address>
        <city>Abilene</city>
        <state>Texas</state>
        <zip>79606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Retina Associates</name>
      <address>
        <city>Arlington</city>
        <state>Texas</state>
        <zip>76012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Research Center, PLLC</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Center Ophthalmology Associates</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78240</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>August 2, 2017</study_first_submitted>
  <study_first_submitted_qc>August 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <last_update_submitted>December 18, 2019</last_update_submitted>
  <last_update_submitted_qc>December 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 20, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Age-related macular degeneration</keyword>
  <keyword>Choroidal neovascularization</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Macular Degeneration</mesh_term>
    <mesh_term>Wet Macular Degeneration</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sunitinib</mesh_term>
    <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/NCT03249740
org study id: GBV-102-001
nct id: NCT03249740
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to evaluate the safety and efficacy of single and repeated
      intravitreal injections of GB-102 in subjects with neovascular (wet) age-related macular
      degeneration.
In this 2-part study, Part 1 is a multicenter, open-label, safety, tolerability, and systemic
      exposure evaluation to Sunitinib in escalating doses of a single IVT injection of GB-102,
      while Part 2 is a multicenter, double-masked, randomized (1:1:1), parallel-group, safety, and
      efficacy evaluation of repeated IVT injections of 2 dose levels of GB-102 compared with
      aflibercept.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Phase 1: open-label GB-102 dose cohorts are initiated sequentially Phase 2: assignment to and initiation of cohorts occur in parallel - not completed in this study. Separate protocol (GBV-102-002) implemented for Phase 2.
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Outcomes Assessor)
masking description: Masking is relevant to Phase 2 only
measure: Phase 1: Occurrence of ocular and nonocular adverse events (AEs)
time frame: 8 months
description: Number of adverse events in total and number of subjects with an adverse event
measure: Phase 2: Change from baseline in best corrected visual acuity by ETDRS
time frame: Baseline, Month 9
description: Mean change from Baseline at Day 270 (Month 9) in best corrected visual acuity (BCVA) measured by early treatment diabetic retinopathy (ETDRS)
measure: Phase 1: Change from baseline in BCVA by ETDRS
time frame: 8 months
description: Mean change from baseline in mean BCVA measured by early treatment diabetic retinopathy (ETDRS) method
measure: Phase 1: Change from baseline in sub-retinal thickness
time frame: 8 months
description: Mean change from baseline in sub-retinal thickness (microns) by spectral domain - optical coherence tomography (SD-OCT)
measure: Phase 1: Change from baseline in retinal fluid by SD-OCT
time frame: 8 months
description: Assessment of retinal fluid by SD-OCT
measure: Phase 1: Change from baseline in total lesion area by FA/CFP
time frame: 8 months
description: Lesion area (total) by fluorescein angiography/color fundus photography (FA/CFP)
measure: Phase 1: Change from baseline in CNV lesion area by FA/CFP
time frame: 8 months
description: CNV lesion area by FA/CFP
measure: Phase 1: Change from baseline in fluorescein leakage area by FA/CFP
time frame: 8 months
description: Area of fluorescein leakage by FA/CFP
measure: Phase 1: Rescue medication
time frame: 8 months
description: Proportion of subjects receiving rescue medication and median time to rescue medication
measure: Phase 1: Systemic exposure to sunitinib measured in plasma level
time frame: 8 months
description: Plasma levels of sunitinib (ng/mL)
measure: Phase 1: Change from baseline in sub retinal hyper reflective material (SHRM) height
time frame: 8 months
description: Subretinal hyper reflective material (SHRM) height
measure: Phase 2: Proportion of subjects with absence of retinal fluid by SD-OCT
time frame: 12 months
description: Assessment of retinal fluid by SD-OCT
measure: Phase 2: Proportion of subjects with < 15 BCVA letter loss by ETDRS
time frame: 12 months
description: Proportion of subjects with < 15 letters lost in BCVA measured by ETDRS method, baseline comparison to assessments at months 1-12
measure: Phase 2: Proportion of subjects with ≥ 15 BCVA letters gained by ETDRS
time frame: 12 months
description: Proportion of subjects with ≥ 15 letters gained in BCVA measured by ETDRS method, baseline comparison to assessments at months 1-12
measure: Phase 2: Occurrence of ocular and nonocular adverse events (AEs)
time frame: 12 months
description: Number of adverse events in total and number of subjects with an adverse event
measure: Phase 2: Change from baseline in BCVA by ETDRS
time frame: 12 months
description: Mean change from baseline in mean BCVA measured by early treatment
measure: Phase 2: Systemic exposure to sunitinib measured in plasma level
time frame: 12 months
description: Plasma levels of sunitinib (ng/mL)
measure: Phase 2: Change from baseline in sub-retinal thickness
time frame: 12 months
description: Mean change from baseline in sub-retinal thickness (microns) by SD-OCT
measure: Phase 2: Rescue medication
time frame: 12 months
description: Proportion of subjects receiving rescue medication and median time to rescue medication
arm group label: Experimental: Phase 1 - GB-102
arm group type: Experimental
description: Subjects will be assigned to 1 of 4 cohorts to receive a single intravitreal injection of up to 2.0 mg (50 μL) GB-102.
arm group label: Experimental: Phase 2 - GB-102
arm group type: Experimental
description: Low dose or high dose injected every 6 months
arm group label: Active Comparator: Phase 2 - Aflibercept
arm group type: Active Comparator
description: Aflibercept 2 mg injected every 2 months
intervention type: Drug
intervention name: GB-102
description: Intravitreal injection of GB-102
arm group label: Experimental: Phase 1 - GB-102
arm group label: Experimental: Phase 2 - GB-102
other name: Sunitinib malate
intervention type: Drug
intervention name: Aflibercept
description: Intravitreal injection of Aflibercept.
arm group label: Active Comparator: Phase 2 - Aflibercept
other name: Anti-VEGF
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Charles P. Semba, MD
role: Study Director
affiliation: Graybug Vision, Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Macular Degeneration
mesh term: Wet Macular Degeneration
mesh term: Sunitinib
mesh term: Aflibercept