<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/NCT04469595</url>
  </required_header>
  <id_info>
    <org_study_id>01-20-005</org_study_id>
    <nct_id>NCT04469595</nct_id>
  </id_info>
  <brief_title>A Study of Intravitreal ILUVIEN® Implant as Baseline Therapy in Patients With Early Diabetic Macular Edema (DME)</brief_title>
  <acronym>NEW DAY</acronym>
  <official_title>A Randomized, Masked, Controlled Study of Intravitreal ILUVIEN® Implant as Baseline Therapy in Patients With Early Diabetic Macular Edema (DME)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Alimera Sciences</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Alimera Sciences</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized, masked, active-controlled, parallel-group, multi-center study that will&#xD;
      assess the efficacy of ILUVIEN as a baseline therapy in the treatment of Center Involving DME&#xD;
      (CI-DME). The study will enroll patients who are either treatment naïve or have not received&#xD;
      any DME treatments for the preceding 12 months as documented in medical records. Patients who&#xD;
      received DME treatment &gt;12 months before screening, must not have received &gt;4 intravitreal&#xD;
      injections. The study will compare 2 treatment regimens: ILUVIEN intravitreal implant (0.19&#xD;
      mg) followed by supplemental aflibercept as needed per protocol criteria (2 mg/0.05 mL),&#xD;
      compared to intravitreal aflibercept loading dose (2 mg administered by intravitreal&#xD;
      injection every 4 weeks for 5 consecutive doses) followed by supplemental aflibercept as&#xD;
      needed per protocol criteria (2 mg/0.05 mL).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 31, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2024</primary_completion_date>
  <phase>Phase 4</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>Randomized, masked, active-controlled, multi-center study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The mean total number of supplemental aflibercept injections needed during the study</measure>
    <time_frame>Baseline to 18 months</time_frame>
    <description>The mean total number of supplemental aflibercept injections needed during</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects with 15, 10 and 5 letter (ETDRS) gains from baseline</measure>
    <time_frame>At 18 months</time_frame>
    <description>Proportion of subjects with 15, 10 and 5 letter (ETDRS) gains from baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve (AUC) of Best Corrected Visual Acuity (BCVA)</measure>
    <time_frame>Baseline to 18 months</time_frame>
    <description>Area under the curve (AUC) of Best Corrected Visual Acuity (BCVA)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change from baseline in Center Subfield Thickness (CST)</measure>
    <time_frame>Baseline to 18 months</time_frame>
    <description>Mean change from baseline in Center Subfield Thickness (CST)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve (AUC) of Center Subfield Thickness (CST)</measure>
    <time_frame>Baseline to 18 months</time_frame>
    <description>Area under the curve (AUC) of Center Subfield Thickness (CST)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change from baseline in the National Eye Institute Visual Function Questionnaire (NEI VFQ-25) composite score and subscale scores</measure>
    <time_frame>At 18 months</time_frame>
    <description>The NEI VFQ-25 is a questionnaire that allows the individual to report on their level of visual function. Scores range from 0-100, with a score of 0 being the worst outcome and 100 being the best outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety Outcome Endpoints: The incidence and severity of treatment-related adverse events</measure>
    <time_frame>Baseline to 18 months</time_frame>
    <description>The incidence and severity of treatment-related adverse events</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Diabetic Macular Edema</condition>
  <arm_group>
    <arm_group_label>ILUVIEN Arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intravitreal ILUVIEN</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aflibercept Arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intravitreal aflibercept</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Iluvien 0.19 MG Drug Implant</intervention_name>
    <description>0.19 mg Fluocinolone Acetonide Intravitreal Implant</description>
    <arm_group_label>ILUVIEN Arm</arm_group_label>
    <other_name>ILUVIEN</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aflibercept</intervention_name>
    <description>2 mg/0.05 mL Aflibercept Anti-VEGF intravitreal injection</description>
    <arm_group_label>Aflibercept Arm</arm_group_label>
    <arm_group_label>ILUVIEN Arm</arm_group_label>
    <other_name>Eylea</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Major Inclusion Criteria:&#xD;
&#xD;
          1. Male or female subjects ≥18 years of age at the time of consent.&#xD;
&#xD;
          2. Must have CI-DME confirmed by Spectral Domain Ocular Coherence Tomography (SD-OCT) and&#xD;
             Center Subfield Thickness (CST) of: ≥350 µm in the study eye.&#xD;
&#xD;
          3. Best Corrected Visual Acuity (BCVA) of ≤80 ETDRS Letters and ≥35 ETDRS letters in the&#xD;
             study eye at Screening Visit.&#xD;
&#xD;
        Major Exclusion Criteria:&#xD;
&#xD;
          1. Patients with Proliferative Diabetic Retinopathy (PDR); high risk proliferative&#xD;
             diabetic retinopathy in the study eye and related complications.&#xD;
&#xD;
          2. History or current diagnosis of glaucoma or ocular hypertension (OHT) or a cup to disc&#xD;
             ratio &gt;0.8; History of uncontrolled intraocular pressure (defined as IOP ≥25 mmHg with&#xD;
             maximum topical and systemic medical hypotensive treatment) or previous filtration&#xD;
             surgery in the study eye at Screening Visit.&#xD;
&#xD;
          3. Other conditions that can cause macular edema.&#xD;
&#xD;
          4. Patients who received prior LASER photocoagulation therapy including macular grid or&#xD;
             pan retina photocoagulation (PRP) at any time in the study eye. Prior focal LASER&#xD;
             photocoagulation therapy outside the macula is allowed.&#xD;
&#xD;
          5. Patients who received the following therapies in the study eye:&#xD;
&#xD;
               1. Intravitreal or periocular steroids;&#xD;
&#xD;
               2. Intravitreal injection of aflibercept, brolucizumab, or conbercept ≤12 months&#xD;
                  prior to Screening Visit&#xD;
&#xD;
          6. Patients who received &gt;1 intravitreal injection of ranibizumab or bevacizumab in the&#xD;
             last 12 months; or have received ranibizumab or bevacizumab ≤6 weeks prior to&#xD;
             Screening Visit&#xD;
&#xD;
          7. Patients who have lens opacities due to cataract or other etiologies that would make&#xD;
             it difficult to examine the fundus or that affect the patients Activities of Daily&#xD;
             Living (ADL).&#xD;
&#xD;
          8. Steroid Challenge Exclusion Criterion- At the Baseline Visit, patients who are&#xD;
             determined to have an IOP ≥25 mmHg or an increase ≥8 mmHg from Screening will be&#xD;
             excluded from the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85020</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85704</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Beverly Hills</city>
        <state>California</state>
        <zip>90211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Glendale</city>
        <state>California</state>
        <zip>91203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Laguna Hills</city>
        <state>California</state>
        <zip>92653</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Santa Ana</city>
        <state>California</state>
        <zip>92705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Colorado Springs</city>
        <state>Colorado</state>
        <zip>80909</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Clearwater</city>
        <state>Florida</state>
        <zip>33761</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Palm Beach Gardens</city>
        <state>Florida</state>
        <zip>33418</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33609</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Marietta</city>
        <state>Georgia</state>
        <zip>30060</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Sandy Springs</city>
        <state>Georgia</state>
        <zip>30328</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Elmhurst</city>
        <state>Illinois</state>
        <zip>60126</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Lemont</city>
        <state>Illinois</state>
        <zip>60439</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Oak Park</city>
        <state>Illinois</state>
        <zip>60304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Springfield</city>
        <state>Illinois</state>
        <zip>62704</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Leawood</city>
        <state>Kansas</state>
        <zip>66211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Shawnee Mission</city>
        <state>Kansas</state>
        <zip>66204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>West Monroe</city>
        <state>Louisiana</state>
        <zip>71291</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21237</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Grand Blanc</city>
        <state>Michigan</state>
        <zip>48439</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Independence</city>
        <state>Missouri</state>
        <zip>64055</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Bloomfield</city>
        <state>New Jersey</state>
        <zip>07003</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Beachwood</city>
        <state>Ohio</state>
        <zip>44122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>22106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Youngstown</city>
        <state>Ohio</state>
        <zip>44505</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Tulsa</city>
        <state>Oklahoma</state>
        <zip>74114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Erie</city>
        <state>Pennsylvania</state>
        <zip>16507</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Columbia</city>
        <state>South Carolina</state>
        <zip>29169</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>McAllen</city>
        <state>Texas</state>
        <zip>78503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>72815</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78240</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>The Woodlands</city>
        <state>Texas</state>
        <zip>77384</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Roanoke</city>
        <state>Virginia</state>
        <zip>24018</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigative Site</name>
      <address>
        <city>Warrenton</city>
        <state>Virginia</state>
        <zip>20186</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>July 9, 2020</study_first_submitted>
  <study_first_submitted_qc>July 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 14, 2020</study_first_posted>
  <last_update_submitted>June 23, 2023</last_update_submitted>
  <last_update_submitted_qc>June 23, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 26, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>DME</keyword>
  <keyword>CI-DME</keyword>
  <keyword>Diabetic Macular Edema</keyword>
  <keyword>Diabetic Retinopathy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Macular Edema</mesh_term>
    <mesh_term>Edema</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fluocinolone Acetonide</mesh_term>
    <mesh_term>Aflibercept</mesh_term>
  </intervention_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/NCT04469595
org study id: 01-20-005
nct id: NCT04469595
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This is a randomized, masked, active-controlled, parallel-group, multi-center study that will
      assess the efficacy of ILUVIEN as a baseline therapy in the treatment of Center Involving DME
      (CI-DME). The study will enroll patients who are either treatment naïve or have not received
      any DME treatments for the preceding 12 months as documented in medical records. Patients who
      received DME treatment >12 months before screening, must not have received >4 intravitreal
      injections. The study will compare 2 treatment regimens: ILUVIEN intravitreal implant (0.19
      mg) followed by supplemental aflibercept as needed per protocol criteria (2 mg/0.05 mL),
      compared to intravitreal aflibercept loading dose (2 mg administered by intravitreal
      injection every 4 weeks for 5 consecutive doses) followed by supplemental aflibercept as
      needed per protocol criteria (2 mg/0.05 mL).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized, masked, active-controlled, multi-center study
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: The mean total number of supplemental aflibercept injections needed during the study
time frame: Baseline to 18 months
description: The mean total number of supplemental aflibercept injections needed during
measure: Proportion of subjects with 15, 10 and 5 letter (ETDRS) gains from baseline
time frame: At 18 months
description: Proportion of subjects with 15, 10 and 5 letter (ETDRS) gains from baseline
measure: Area under the curve (AUC) of Best Corrected Visual Acuity (BCVA)
time frame: Baseline to 18 months
description: Area under the curve (AUC) of Best Corrected Visual Acuity (BCVA)
measure: Mean change from baseline in Center Subfield Thickness (CST)
time frame: Baseline to 18 months
description: Mean change from baseline in Center Subfield Thickness (CST)
measure: Area under the curve (AUC) of Center Subfield Thickness (CST)
time frame: Baseline to 18 months
description: Area under the curve (AUC) of Center Subfield Thickness (CST)
measure: Mean change from baseline in the National Eye Institute Visual Function Questionnaire (NEI VFQ-25) composite score and subscale scores
time frame: At 18 months
description: The NEI VFQ-25 is a questionnaire that allows the individual to report on their level of visual function. Scores range from 0-100, with a score of 0 being the worst outcome and 100 being the best outcome.
measure: Safety Outcome Endpoints: The incidence and severity of treatment-related adverse events
time frame: Baseline to 18 months
description: The incidence and severity of treatment-related adverse events
arm group label: ILUVIEN Arm
arm group type: Active Comparator
description: Intravitreal ILUVIEN
arm group label: Aflibercept Arm
arm group type: Active Comparator
description: Intravitreal aflibercept
intervention type: Drug
intervention name: Iluvien 0.19 MG Drug Implant
description: 0.19 mg Fluocinolone Acetonide Intravitreal Implant
arm group label: ILUVIEN Arm
other name: ILUVIEN
intervention type: Drug
intervention name: Aflibercept
description: 2 mg/0.05 mL Aflibercept Anti-VEGF intravitreal injection
arm group label: Aflibercept Arm
arm group label: ILUVIEN Arm
other name: Eylea
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
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country: United States
responsible party type: Sponsor
mesh term: Macular Edema
mesh term: Edema
mesh term: Fluocinolone Acetonide
mesh term: Aflibercept
sharing ipd: No