<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/NCT03835884</url>
  </required_header>
  <id_info>
    <org_study_id>AR-13503-CS201</org_study_id>
    <nct_id>NCT03835884</nct_id>
  </id_info>
  <brief_title>A Study Assessing AR-13503 Implant in Subjects With nAMD or DME</brief_title>
  <official_title>First-in-Human Study of the Safety of AR-13503 Sustained Release Intravitreal Implant in Subjects With Neovascular Age-Related Macular Degeneration (nAMD) and Subjects With Diabetic Macular Edema (DME)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Aerie Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Aerie Pharmaceuticals</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      First-in-Human Study of the Safety of AR-13503 Sustained Release Intravitreal Implant in&#xD;
      Subjects with Neovascular Age-Related Macular Degeneration (nAMD) and Subjects with Diabetic&#xD;
      Macular Edema (DME)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a first-in-human study conducted in 2 sequential stages; each stage is 24 weeks in&#xD;
      duration. Subjects with nAMD and subjects with DME were evaluated in Stage 1. Subjects with&#xD;
      DME will be evaluated in Stage 2.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 24, 2019</start_date>
  <completion_date type="Actual">May 12, 2022</completion_date>
  <primary_completion_date type="Actual">May 12, 2022</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>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>No masking</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Number of ocular and non-ocular TEAEs</measure>
    <time_frame>24 weeks</time_frame>
    <description>Number of ocular and non-ocular treatment-emergent adverse events (TEAEs), summarized at the subject level by system organ class and preferred term, and also by severity and relatedness to treatment.</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Neovascular Age-related Macular Degeneration</condition>
  <condition>Diabetic Macular Edema</condition>
  <arm_group>
    <arm_group_label>AR-13503 Implant 10.6 Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of AR-13503 Implant 10.6 Dose (10.6 µg) administered as an intravitreal implant into a single eye of up to 6 subjects (3 nAMD and 3 DME) who will be followed for 24 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AR-13503 Implant 21.2 Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of AR-13503 Implant 21.2 Dose (21.2 µg) administered as intravitreal implants into a single eye of up to 6 subjects (3 nAMD and 3 DME) who will be followed for 24 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AR-13503 Implant 42.4 Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single dose of AR-13503 Implant 42.4 Dose (42.4 µg) administered as intravitreal implants into a single eye of up to 6 subjects (3 nAMD and 3 DME) who will be followed for 24 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AR-13503 Implant 63.6 Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose of AR-13503 Implant 63.6 Dose (63.6 µg) administered into a single eye of up to 5 subjects (DME) who will be followed for 24 weeks. Subjects may qualify to receive an additional dose at Week 12.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AR-13503 Implant 10.6 Dose</intervention_name>
    <description>AR-13503 Implant 10.6 Dose (10.6 µg) administered as an intravitreal implant into a single eye</description>
    <arm_group_label>AR-13503 Implant 10.6 Dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AR-13503 Implant 21.2 Dose</intervention_name>
    <description>AR-13503 Implant 21.2 Dose (21.2 µg) administered as intravitreal implants into a single eye</description>
    <arm_group_label>AR-13503 Implant 21.2 Dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AR-13503 42.4 Dose</intervention_name>
    <description>AR-13503 Implant 42.4 Dose (42.4 µg) administered as intravitreal implants into a single eye</description>
    <arm_group_label>AR-13503 Implant 42.4 Dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AR-13503 63.6 Dose</intervention_name>
    <description>AR-13503 Implant 63.6 Dose (63.6 µg) administered as intravitreal implants into a single eye</description>
    <arm_group_label>AR-13503 Implant 63.6 Dose</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria for Subjects with Neovascular Age-Related Macular Degeneration (nAMD)&#xD;
&#xD;
          1. 50 years of age or older&#xD;
&#xD;
          2. Presence of active subfoveal or juxtafoveal Choroidal Neovascularization (CNV) (any&#xD;
             subtype) with leakage affecting the fovea secondary to Age-Related Macular&#xD;
             Degeneration (AMD)&#xD;
&#xD;
          3. Best Corrected Visual Acuity (BCVA) in the study eye at Baseline (Day 0):&#xD;
&#xD;
             Stage 1: between 65 and 10 Early Treatment Diabetic Retinopathy Study (ETDRS) letters&#xD;
             (20/50 and 20/640 Snellen equivalent)&#xD;
&#xD;
          4. Able and willing to give signed informed consent and follow study instructions&#xD;
&#xD;
        Inclusion Criteria for Subjects with Diabetic Macular Edema (DME)&#xD;
&#xD;
        Subjects with Diabetic Macular Edema (DME) must meet all the following criteria to enter&#xD;
        into the study:&#xD;
&#xD;
          1. 18 years of age or older&#xD;
&#xD;
          2. Type 1 or 2 diabetes mellitus with center-involved DME&#xD;
&#xD;
          3. BCVA in the study eye at Baseline (Day 0):&#xD;
&#xD;
             Stage 1: between 65 and 10 ETDRS letters (20/50 and 20/640 Snellen equivalent) Stage&#xD;
             2: between 70 and 20 ETDRS letters (20/40 and 20/400 Snellen equivalent)&#xD;
&#xD;
          4. Able and willing to give signed informed consent and follow study instructions&#xD;
&#xD;
        Exclusion Criteria for Subjects with Neovascular Age-Related Macular Degeneration (nAMD)&#xD;
&#xD;
        Ophthalmic:&#xD;
&#xD;
          1. Use of intravitreal aflibercept within 8 weeks, ranibizumab or bevacizumab within 6&#xD;
             weeks&#xD;
&#xD;
          2. History of vitreoretinal surgery in the study eye&#xD;
&#xD;
          3. Any ocular disease in the study eye that in the Investigator and Reading Center's&#xD;
             opinion may confound assessment of the macula, affect central vision, confound&#xD;
             results, or preclude improvement in visual acuity&#xD;
&#xD;
          4. Any current or history of periocular or intraocular inflammation or evidence of&#xD;
             infection in either eye&#xD;
&#xD;
          5. Media clarity insufficient to obtain quality fundus and OCT images in the study eye&#xD;
&#xD;
        Systemic:&#xD;
&#xD;
          1. History or current systemic condition that in the Investigator opinion preclude the&#xD;
             safe administration of the study treatment or confound results&#xD;
&#xD;
          2. History of allergy or sensitivity to fluorescein or povidone iodine&#xD;
&#xD;
          3. Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or&#xD;
             not using a medically acceptable form of birth control&#xD;
&#xD;
          4. Participation in an investigational study within 30 days of Screening&#xD;
&#xD;
        Exclusion Criteria for Subjects with DME&#xD;
&#xD;
        Ophthalmic:&#xD;
&#xD;
          1. Use of intraocular or periocular corticosteroids within 6 months, aflibercept within 8&#xD;
             weeks, ranibizumab or bevacizumab within 6 weeks&#xD;
&#xD;
          2. History of vitreoretinal surgery in the study eye&#xD;
&#xD;
          3. High risk proliferative diabetic retinopathy in the study eye and related&#xD;
             complications&#xD;
&#xD;
          4. Structural damage to the center or the macula that is likely to preclude improvement&#xD;
             in visual acuity in the study eye after resolution of the DME&#xD;
&#xD;
          5. Media clarity insufficient to obtain quality fundus and OCT images in the study eye&#xD;
&#xD;
        Systemic:&#xD;
&#xD;
          1. History or current medical condition that in the Investigator's opinion preclude the&#xD;
             safe administration of the study treatment or confound results&#xD;
&#xD;
          2. History of allergy or sensitivity to fluorescein or povidone iodine&#xD;
&#xD;
          3. Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or&#xD;
             not using a medically acceptable form of birth control&#xD;
&#xD;
          4. Participation in an investigational study within 30 days of Screening&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kevin Kerr</last_name>
    <role>Study Director</role>
    <affiliation>Aerie Pharmaceuticals, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Retinal Research Institute, LLC</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>Bay Area Retina Associates</name>
      <address>
        <city>Walnut Creek</city>
        <state>California</state>
        <zip>94598</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sterling Vision, PC dba Oregon Retina</name>
      <address>
        <city>Eugene</city>
        <state>Oregon</state>
        <zip>97401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Valley Retina Institute, P.A.</name>
      <address>
        <city>Harlingen</city>
        <state>Texas</state>
        <zip>78550</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Center Ophthamology 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>February 2023</verification_date>
  <study_first_submitted>February 7, 2019</study_first_submitted>
  <study_first_submitted_qc>February 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 11, 2019</study_first_posted>
  <last_update_submitted>February 7, 2023</last_update_submitted>
  <last_update_submitted_qc>February 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Neovascular AMD</keyword>
  <keyword>Diabetic macular edema</keyword>
  <keyword>Diabetic retinopathy</keyword>
  <keyword>Vascular endothelial growth factor</keyword>
  <keyword>Intravitreal injection</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Macular Degeneration</mesh_term>
    <mesh_term>Macular Edema</mesh_term>
    <mesh_term>Wet Macular Degeneration</mesh_term>
    <mesh_term>Edema</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03835884
org study id: AR-13503-CS201
nct id: NCT03835884
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
First-in-Human Study of the Safety of AR-13503 Sustained Release Intravitreal Implant in
      Subjects with Neovascular Age-Related Macular Degeneration (nAMD) and Subjects with Diabetic
      Macular Edema (DME)
This is a first-in-human study conducted in 2 sequential stages; each stage is 24 weeks in
      duration. Subjects with nAMD and subjects with DME were evaluated in Stage 1. Subjects with
      DME will be evaluated in Stage 2.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
masking description: No masking
measure: Number of ocular and non-ocular TEAEs
time frame: 24 weeks
description: Number of ocular and non-ocular treatment-emergent adverse events (TEAEs), summarized at the subject level by system organ class and preferred term, and also by severity and relatedness to treatment.
arm group label: AR-13503 Implant 10.6 Dose
arm group type: Experimental
description: Single dose of AR-13503 Implant 10.6 Dose (10.6 µg) administered as an intravitreal implant into a single eye of up to 6 subjects (3 nAMD and 3 DME) who will be followed for 24 weeks
arm group label: AR-13503 Implant 21.2 Dose
arm group type: Experimental
description: Single dose of AR-13503 Implant 21.2 Dose (21.2 µg) administered as intravitreal implants into a single eye of up to 6 subjects (3 nAMD and 3 DME) who will be followed for 24 weeks
arm group label: AR-13503 Implant 42.4 Dose
arm group type: Experimental
description: Single dose of AR-13503 Implant 42.4 Dose (42.4 µg) administered as intravitreal implants into a single eye of up to 6 subjects (3 nAMD and 3 DME) who will be followed for 24 weeks
arm group label: AR-13503 Implant 63.6 Dose
arm group type: Experimental
description: Dose of AR-13503 Implant 63.6 Dose (63.6 µg) administered into a single eye of up to 5 subjects (DME) who will be followed for 24 weeks. Subjects may qualify to receive an additional dose at Week 12.
intervention type: Drug
intervention name: AR-13503 Implant 10.6 Dose
description: AR-13503 Implant 10.6 Dose (10.6 µg) administered as an intravitreal implant into a single eye
arm group label: AR-13503 Implant 10.6 Dose
intervention type: Drug
intervention name: AR-13503 Implant 21.2 Dose
description: AR-13503 Implant 21.2 Dose (21.2 µg) administered as intravitreal implants into a single eye
arm group label: AR-13503 Implant 21.2 Dose
intervention type: Drug
intervention name: AR-13503 42.4 Dose
description: AR-13503 Implant 42.4 Dose (42.4 µg) administered as intravitreal implants into a single eye
arm group label: AR-13503 Implant 42.4 Dose
intervention type: Drug
intervention name: AR-13503 63.6 Dose
description: AR-13503 Implant 63.6 Dose (63.6 µg) administered as intravitreal implants into a single eye
arm group label: AR-13503 Implant 63.6 Dose
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Kevin Kerr
role: Study Director
affiliation: Aerie Pharmaceuticals, Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Macular Degeneration
mesh term: Macular Edema
mesh term: Wet Macular Degeneration
mesh term: Edema
sharing ipd: No