<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/NCT04503551</url>
  </required_header>
  <id_info>
    <org_study_id>GR41675</org_study_id>
    <nct_id>NCT04503551</nct_id>
  </id_info>
  <brief_title>A Multicenter, Randomized Study in Participants With Diabetic Retinopathy Without Center-involved Diabetic Macular Edema To Evaluate the Efficacy, Safety, and Pharmacokinetics of Ranibizumab Delivered Via the Port Delivery System Relative to the Comparator Arm</brief_title>
  <acronym>PAVILION</acronym>
  <official_title>A Phase III, Multicenter, Randomized Study of the Efficacy, Safety, and Pharmacokinetics of the Port Delivery System With Ranibizumab in Patients With Diabetic Retinopathy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hoffmann-La Roche</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>
      Study GR41675 is a Multicenter, Randomized Study in Participants with Diabetic Retinopathy&#xD;
      (DR) Without Center-Involved Diabetic Macular Edema (CI-DME) to Evaluate the Efficacy, Safety&#xD;
      of the Port Delivery System with Ranibizumab (PDS) Relative to the Comparator Arm&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 10, 2020</start_date>
  <completion_date type="Anticipated">May 7, 2024</completion_date>
  <primary_completion_date type="Actual">October 3, 2022</primary_completion_date>
  <phase>Phase 3</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>The visual acuity examiner will only conduct refraction and visual acuity assessments and will be masked, as best as possible, to the following items: study eye assignment; study visit type; and treatment assignment.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of participants with a ≥2-step improvement from baseline on the ETDRS-DRSS at Week 52</measure>
    <time_frame>Week 52</time_frame>
    <description>ETDRS = Early Treatment Diabetic Retinopathy Study&#xD;
DRSS = Diabetic Retinopathy Severity Scale&#xD;
The ETDRS-DRSS includes 13 score levels, ranging from the absence of retinopathy to PDR, including neovascularization and/or vitreous/preretinal hemorrhage.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rate of participants developing a vision-threatening complication (defined as PDR, ASNV, or CI-DME [defined as central foveal thickness [CST] ≥325 μm on spectral-domain optical coherence tomography [SD-OCT]) through Week 52</measure>
    <time_frame>From baseline through 52 weeks</time_frame>
    <description>PDR = proliferative diabetic retinopathy ASNV = Anterior segment neovascularization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of participants developing PDR or ASNV through Week 52</measure>
    <time_frame>From baseline through 52 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of participants developing CI-DME through Week 52</measure>
    <time_frame>From baseline through 52 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of participants developing a ≥ 2-step worsening from baseline on the ETDRS-DRSS through Week 52</measure>
    <time_frame>From baseline through 52 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of participants with a ≥ 3-step improvement from baseline on the ETDRS-DRSS at Week 52</measure>
    <time_frame>Week 52</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of participants developing a ≥ 3-step worsening from baseline on the ETDRS-DRSS through Week 52</measure>
    <time_frame>Baseline up to 52 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of participants with a ≥ 2-step improvement from baseline on the ETDRS-DRSS over time</measure>
    <time_frame>Baseline up to Week 112</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of participants with a ≥ 3-step improvement from baseline on the ETDRS-DRSS over time</measure>
    <time_frame>Baseline up to Week 112</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to first development of either PDR, ASNV, or CI-DME</measure>
    <time_frame>Baseline up to Week 112</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to first development of PDR or ASNV</measure>
    <time_frame>Baseline up to Week 112</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to first development of CI-DME</measure>
    <time_frame>Baseline up to Week 112</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to first development of a ≥ 2-step worsening from baseline on the ETDRS-DRSS</measure>
    <time_frame>Baseline up to Week 112</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to first development of a ≥ 3-step worsening from baseline on the ETDRS-DRSS</measure>
    <time_frame>Baseline up to Week 112</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Best-Corrected Visual Acuity (BCVA) as measured on the ETDRS chart over time</measure>
    <time_frame>Baseline up to Week 112</time_frame>
    <description>A vision score of 20/20 vision is considered normal. A score of 20/200 is considered being legally blind.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of participants who lose &lt;15, &lt; 10 and &lt; 5 letters in BCVA from baseline over time</measure>
    <time_frame>Baseline up to Week 112</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of participants with a BCVA score of 69 letters (20/40 approximate Snellen equivalent) or better over time</measure>
    <time_frame>Baseline up to Week 112</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in CST as measured on SD-OCT over time</measure>
    <time_frame>Baseline up to Week 112</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in total macular volume as measured on SD-OCT over time</measure>
    <time_frame>Baseline up to Week 112</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence and severity of ocular adverse events</measure>
    <time_frame>Baseline up to Week 112</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence and severity of non-ocular adverse events</measure>
    <time_frame>Baseline up to Week 112</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence, severity, and duration of adverse events of special interest</measure>
    <time_frame>Baseline up to Week 112</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence, severity, and duration of ocular adverse events of special interest during the postoperative period (≤ 37 days after initial implant insertion) and follow-up period (&gt; 37 days after implant insertion surgery)</measure>
    <time_frame>Baseline up to Week 112</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum concentration of ranibizumab observed over time</measure>
    <time_frame>Baseline up to Week 112</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic (PK) parameter value area under the concentration- time curve</measure>
    <time_frame>Baseline up to Week 112</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK Parameter minimum serum concentration (Cmin)</measure>
    <time_frame>Baseline up to Week 112</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameter half-life (t1/2) after PDS implant insertion</measure>
    <time_frame>Baseline up to Week 112</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prevalence of anti-drug antibodies (ADAs) prior to study treatment and incidence of ADAs after study treatment</measure>
    <time_frame>Baseline up to Week 112</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prevalence of neutralizing antibodies at baseline and incidence of neutralizing antibodies during the study</measure>
    <time_frame>Baseline up to Week 112</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of participants who do not undergo supplemental treatment with intravitreal ranibizumab within each refill-exchange interval</measure>
    <time_frame>Baseline up to Week 112</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of participants with adverse device effects</measure>
    <time_frame>Baseline up to Week 112</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of participants with serious adverse device effects</measure>
    <time_frame>Baseline up to Week 112</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of participants with absence of intraretinal fluid, subretinal fluid or both (as measured in the central 1 mm subfield) over time</measure>
    <time_frame>Baseline up to Week 112</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of participants who report preferring PDS treatment to intravitreal ranibizumab treatment, as measured by the PPPQ at Week 52</measure>
    <time_frame>Week 52</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reported incidence of device deficiencies</measure>
    <time_frame>Baseline up to Week 52</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">174</enrollment>
  <condition>Diabetic Retinopathy</condition>
  <arm_group>
    <arm_group_label>PDS Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants randomized to the PDS arm will receive two intravitreal ranibizumab injections and will then have the PDS implant (pre-filled with ranibizumab) surgically inserted. PDS implant refill-exchange procedures will be performed on a fixed interval every 36-weeks (Q36W) thereafter</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Comparator Arm</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Participants randomized to the comparator arm will undergo study visits every 4 weeks (Q4W) for comprehensive clinical monitoring until they receive the PDS implant (pre-filled with ranibizumab). PDS implant refill-exchange procedures will be performed on a fixed interval Q36W thereafter. Participants will be eligible to receive intravitreal ranibizumab 0.5 mg injections if treatment eligibility criteria are met.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PDS Implant Pre-Filled with 100 mg/mL Ranibizumab</intervention_name>
    <description>Will be administered as per the schedule described in individual arm.</description>
    <arm_group_label>Comparator Arm</arm_group_label>
    <arm_group_label>PDS Arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intravitreal Ranibizumab 0.5 mg Injection</intervention_name>
    <description>Will be administered as per the schedule described in individual arm.</description>
    <arm_group_label>Comparator Arm</arm_group_label>
    <arm_group_label>PDS Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥18 years at time of signing Informed Consent Form&#xD;
&#xD;
          -  Documented diagnosis of diabetes mellitus (Type 1 or Type 2)&#xD;
&#xD;
          -  HbA1c level of ≤12% within 2 months prior to screening or at screening&#xD;
&#xD;
        Inclusion Criteria for Study Eye&#xD;
&#xD;
          -  Moderately severe or severe NPDR (ETDRS-DRSS level 47 or 53)&#xD;
&#xD;
          -  BCVA score of ≥ 69 letters (20/40 approximate Snellen equivalent or better)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Uncontrolled blood pressure&#xD;
&#xD;
          -  Cerebrovascular accident or myocardial infarction within 6 months prior to&#xD;
             randomization&#xD;
&#xD;
          -  Atrial fibrillation diagnosis or worsening within 6 months prior to randomization&#xD;
&#xD;
          -  Current systemic treatment for a confirmed active systemic infection&#xD;
&#xD;
          -  Renal failure requiring renal transplant, hemodialysis, or peritoneal dialysis, or&#xD;
             anticipated to require hemodialysis or peritoneal dialysis at any time during the&#xD;
             study&#xD;
&#xD;
          -  History of other disease, other non-diabetic metabolic dysfunction, physical&#xD;
             examination finding, or clinical laboratory finding giving reasonable suspicion of a&#xD;
             condition that contraindicates the use of ranibizumab or surgical placement of the PDS&#xD;
             implant; that might affect interpretation of the results of the study; or that renders&#xD;
             the patient at high risk for treatment complications in the opinion of the&#xD;
             investigator or Sponsor&#xD;
&#xD;
        Ocular Exclusion Criteria for Study Eye:&#xD;
&#xD;
          -  Presence of center-involved diabetic macular edema (defined as CST ≥325 µm)&#xD;
&#xD;
          -  Any intravitreal anti-VEGF treatment at any time prior to randomization&#xD;
&#xD;
          -  Any use of medicated intraocular implants, including Ozurdex® or Iluvien® implants at&#xD;
             any time prior to randomization&#xD;
&#xD;
          -  Any intravitreal corticosteroid treatment at any time prior to randomization&#xD;
&#xD;
          -  Any periocular (e.g., subtenon) corticosteroid treatment at any time prior to&#xD;
             randomization&#xD;
&#xD;
          -  Any PRP at any time prior to randomization&#xD;
&#xD;
          -  Any macular laser photocoagulation (such as micropulse and focal or grid laser) at any&#xD;
             time prior to randomization&#xD;
&#xD;
          -  Active intraocular inflammation (grade trace or above)&#xD;
&#xD;
          -  Clinically significant abnormalities of the vitreous-retinal interface involving the&#xD;
             macular area or disrupting the macular architecture, such as vitreous-retinal traction&#xD;
             or epiretinal membrane (assessed by the investigator and confirmed by the central&#xD;
             reading center)&#xD;
&#xD;
          -  Uncontrolled ocular hypertension or glaucoma and any such condition the investigator&#xD;
             determines may require a glaucoma-filtering surgery during a participant's&#xD;
             participation in the study&#xD;
&#xD;
          -  History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery&#xD;
&#xD;
          -  Any concurrent ocular condition (e.g., cataract, epiretinal membrane) that would&#xD;
             require surgical intervention during the study to prevent or treat visual loss that&#xD;
             might result from that condition&#xD;
&#xD;
          -  Any concurrent ocular condition (e.g., amblyopia, strabismus) that may affect&#xD;
             interpretation of study results&#xD;
&#xD;
          -  History of other ocular diseases that gives reasonable suspicion of a disease or&#xD;
             condition that contraindicates the use of ranibizumab, that might affect&#xD;
             interpretation of study results, or that renders the participant at high risk for&#xD;
             treatment complications&#xD;
&#xD;
        Ocular Exclusion Criteria for Either Eye&#xD;
&#xD;
          -  Suspected or active ocular or periocular infection of either eye&#xD;
&#xD;
          -  Any history uveitis including idiopathic, drug-associated or autoimmune-associated&#xD;
             uveitis&#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>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Barnet Dulaney Perkins Eye Center</name>
      <address>
        <city>Mesa</city>
        <state>Arizona</state>
        <zip>85206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Associated Retina Consultants</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85020</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>California Retina Consultants</name>
      <address>
        <city>Bakersfield</city>
        <state>California</state>
        <zip>93309</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Retina Partners</name>
      <address>
        <city>Encino</city>
        <state>California</state>
        <zip>91436</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Consultants of Orange County</name>
      <address>
        <city>Fullerton</city>
        <state>California</state>
        <zip>92835-3424</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>California Eye Specialists Medical group Inc.</name>
      <address>
        <city>Pasadena</city>
        <state>California</state>
        <zip>91107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente Riverside Medical Center</name>
      <address>
        <city>Riverside</city>
        <state>California</state>
        <zip>92505</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retinal Consultants Med Group</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95825</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Orange County Retina Med Group</name>
      <address>
        <city>Santa Ana</city>
        <state>California</state>
        <zip>92705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>California Retina Consultants</name>
      <address>
        <city>Santa Barbara</city>
        <state>California</state>
        <zip>93103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southwest Retina Consultants</name>
      <address>
        <city>Durango</city>
        <state>Colorado</state>
        <zip>81303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Colorado Retina Associates, PC</name>
      <address>
        <city>Lakewood</city>
        <state>Colorado</state>
        <zip>80228</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Group of New England</name>
      <address>
        <city>Waterford</city>
        <state>Connecticut</state>
        <zip>06385</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Specialty Institute</name>
      <address>
        <city>Pensacola</city>
        <state>Florida</state>
        <zip>32503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fort Lauderdale Eye Institute</name>
      <address>
        <city>Plantation</city>
        <state>Florida</state>
        <zip>33324</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Associates of Florida, LLC</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33609</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southeast Retina Center</name>
      <address>
        <city>Augusta</city>
        <state>Georgia</state>
        <zip>30909</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Georgia Retina PC</name>
      <address>
        <city>Marietta</city>
        <state>Georgia</state>
        <zip>30060-1137</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Consultants of Hawaii</name>
      <address>
        <city>'Aiea</city>
        <state>Hawaii</state>
        <zip>96701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern Medical Group/Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois Retina Associates</name>
      <address>
        <city>Joliet</city>
        <state>Illinois</state>
        <zip>60435</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wolfe Eye Clinic</name>
      <address>
        <city>West Des Moines</city>
        <state>Iowa</state>
        <zip>50266</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Associates</name>
      <address>
        <city>Lenexa</city>
        <state>Kansas</state>
        <zip>66215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maine Eye Center</name>
      <address>
        <city>Portland</city>
        <state>Maine</state>
        <zip>04101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Retina Care Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cumberland Valley Retina Associates</name>
      <address>
        <city>Hagerstown</city>
        <state>Maryland</state>
        <zip>21740</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Specialists</name>
      <address>
        <city>Towson</city>
        <state>Maryland</state>
        <zip>21204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Associated Retinal Consultants PC</name>
      <address>
        <city>Royal Oak</city>
        <state>Michigan</state>
        <zip>48073</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vitreo Retinal Surgery</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55435</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Midwest Vision Research Foundation</name>
      <address>
        <city>Chesterfield</city>
        <state>Missouri</state>
        <zip>63017</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sierra Eye Associates</name>
      <address>
        <city>Reno</city>
        <state>Nevada</state>
        <zip>89502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Envision Ocular, LLC</name>
      <address>
        <city>Bloomfield</city>
        <state>New Jersey</state>
        <zip>07003</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Associates of NJ</name>
      <address>
        <city>Teaneck</city>
        <state>New Jersey</state>
        <zip>07666</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Vit Surgeons/Central NY</name>
      <address>
        <city>Liverpool</city>
        <state>New York</state>
        <zip>13088</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York University</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10017</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Western Carolina Retinal Associate PA</name>
      <address>
        <city>Asheville</city>
        <state>North Carolina</state>
        <zip>28803</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Char Eye Ear &amp;Throat Assoc</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke Eye Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cape Fear Retinal Associates</name>
      <address>
        <city>Wilmington</city>
        <state>North Carolina</state>
        <zip>28401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ohio State University</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Vitreous Center</name>
      <address>
        <city>Edmond</city>
        <state>Oklahoma</state>
        <zip>73013</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cumberland Valley Retina Consultants; Chambersburg</name>
      <address>
        <city>Chambersburg</city>
        <state>Pennsylvania</state>
        <zip>17201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mid Atlantic Retina - Wills Eye Hospital</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charleston Neuroscience Inst</name>
      <address>
        <city>Ladson</city>
        <state>South Carolina</state>
        <zip>29456</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Palmetto Retina Center</name>
      <address>
        <city>West Columbia</city>
        <state>South Carolina</state>
        <zip>29169</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charles Retina Institute</name>
      <address>
        <city>Germantown</city>
        <state>Tennessee</state>
        <zip>38138</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southeastern Retina Associates</name>
      <address>
        <city>Knoxville</city>
        <state>Tennessee</state>
        <zip>37923</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Retina PC</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Austin Retina Associates</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78705-1169</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina &amp; Vitreous of Texas</name>
      <address>
        <city>Bellaire</city>
        <state>Texas</state>
        <zip>77401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Retina Associates</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Med Center Ophthalmology Assoc</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78240</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Center of Texas</name>
      <address>
        <city>Southlake</city>
        <state>Texas</state>
        <zip>76092</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Consultants of Texas</name>
      <address>
        <city>The Woodlands</city>
        <state>Texas</state>
        <zip>77384-4167</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Retina</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Piedmont Eye Center</name>
      <address>
        <city>Lynchburg</city>
        <state>Virginia</state>
        <zip>24502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Institute of Virginia</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Center Northwest</name>
      <address>
        <city>Silverdale</city>
        <state>Washington</state>
        <zip>98383</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spokane Eye Clinical Research</name>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emanuelli Research and Development Center LLC</name>
      <address>
        <city>Arecibo</city>
        <zip>00612</zip>
        <country>Puerto Rico</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Puerto Rico</country>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>August 5, 2020</study_first_submitted>
  <study_first_submitted_qc>August 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2020</study_first_posted>
  <disposition_first_submitted>September 7, 2023</disposition_first_submitted>
  <disposition_first_submitted_qc>September 7, 2023</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">September 13, 2023</disposition_first_posted>
  <last_update_submitted>September 7, 2023</last_update_submitted>
  <last_update_submitted_qc>September 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Port Delivery System; ranibizumab; Diabetic Retinopathy; anti-VEGF, nonproliferative diabetic retinopathy, retina, vision loss, retinal disease, eye disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Retinal Diseases</mesh_term>
    <mesh_term>Diabetic Retinopathy</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ranibizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here ( https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT04503551
org study id: GR41675
nct id: NCT04503551
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
Study GR41675 is a Multicenter, Randomized Study in Participants with Diabetic Retinopathy
      (DR) Without Center-Involved Diabetic Macular Edema (CI-DME) to Evaluate the Efficacy, Safety
      of the Port Delivery System with Ranibizumab (PDS) Relative to the Comparator Arm
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: The visual acuity examiner will only conduct refraction and visual acuity assessments and will be masked, as best as possible, to the following items: study eye assignment; study visit type; and treatment assignment.
measure: Percentage of participants with a ≥2-step improvement from baseline on the ETDRS-DRSS at Week 52
time frame: Week 52
description: ETDRS = Early Treatment Diabetic Retinopathy Study
DRSS = Diabetic Retinopathy Severity Scale
The ETDRS-DRSS includes 13 score levels, ranging from the absence of retinopathy to PDR, including neovascularization and/or vitreous/preretinal hemorrhage.
measure: Rate of participants developing a vision-threatening complication (defined as PDR, ASNV, or CI-DME [defined as central foveal thickness [CST] ≥325 μm on spectral-domain optical coherence tomography [SD-OCT]) through Week 52
time frame: From baseline through 52 weeks
description: PDR = proliferative diabetic retinopathy ASNV = Anterior segment neovascularization
measure: Rate of participants developing PDR or ASNV through Week 52
time frame: From baseline through 52 weeks
measure: Rate of participants developing CI-DME through Week 52
time frame: From baseline through 52 weeks
measure: Rate of participants developing a ≥ 2-step worsening from baseline on the ETDRS-DRSS through Week 52
time frame: From baseline through 52 weeks
measure: Percentage of participants with a ≥ 3-step improvement from baseline on the ETDRS-DRSS at Week 52
time frame: Week 52
measure: Rate of participants developing a ≥ 3-step worsening from baseline on the ETDRS-DRSS through Week 52
time frame: Baseline up to 52 weeks
measure: Percentage of participants with a ≥ 2-step improvement from baseline on the ETDRS-DRSS over time
time frame: Baseline up to Week 112
measure: Percentage of participants with a ≥ 3-step improvement from baseline on the ETDRS-DRSS over time
time frame: Baseline up to Week 112
measure: Time to first development of either PDR, ASNV, or CI-DME
time frame: Baseline up to Week 112
measure: Time to first development of PDR or ASNV
time frame: Baseline up to Week 112
measure: Time to first development of CI-DME
time frame: Baseline up to Week 112
measure: Time to first development of a ≥ 2-step worsening from baseline on the ETDRS-DRSS
time frame: Baseline up to Week 112
measure: Time to first development of a ≥ 3-step worsening from baseline on the ETDRS-DRSS
time frame: Baseline up to Week 112
measure: Change from baseline in Best-Corrected Visual Acuity (BCVA) as measured on the ETDRS chart over time
time frame: Baseline up to Week 112
description: A vision score of 20/20 vision is considered normal. A score of 20/200 is considered being legally blind.
measure: Percentage of participants who lose <15, < 10 and < 5 letters in BCVA from baseline over time
time frame: Baseline up to Week 112
measure: Percentage of participants with a BCVA score of 69 letters (20/40 approximate Snellen equivalent) or better over time
time frame: Baseline up to Week 112
measure: Change from baseline in CST as measured on SD-OCT over time
time frame: Baseline up to Week 112
measure: Change from baseline in total macular volume as measured on SD-OCT over time
time frame: Baseline up to Week 112
measure: Incidence and severity of ocular adverse events
time frame: Baseline up to Week 112
measure: Incidence and severity of non-ocular adverse events
time frame: Baseline up to Week 112
measure: Incidence, severity, and duration of adverse events of special interest
time frame: Baseline up to Week 112
measure: Incidence, severity, and duration of ocular adverse events of special interest during the postoperative period (≤ 37 days after initial implant insertion) and follow-up period (> 37 days after implant insertion surgery)
time frame: Baseline up to Week 112
measure: Serum concentration of ranibizumab observed over time
time frame: Baseline up to Week 112
measure: Pharmacokinetic (PK) parameter value area under the concentration- time curve
time frame: Baseline up to Week 112
measure: PK Parameter minimum serum concentration (Cmin)
time frame: Baseline up to Week 112
measure: PK parameter half-life (t1/2) after PDS implant insertion
time frame: Baseline up to Week 112
measure: Prevalence of anti-drug antibodies (ADAs) prior to study treatment and incidence of ADAs after study treatment
time frame: Baseline up to Week 112
measure: Prevalence of neutralizing antibodies at baseline and incidence of neutralizing antibodies during the study
time frame: Baseline up to Week 112
measure: Percentage of participants who do not undergo supplemental treatment with intravitreal ranibizumab within each refill-exchange interval
time frame: Baseline up to Week 112
measure: Percentage of participants with adverse device effects
time frame: Baseline up to Week 112
measure: Percentage of participants with serious adverse device effects
time frame: Baseline up to Week 112
measure: Percentage of participants with absence of intraretinal fluid, subretinal fluid or both (as measured in the central 1 mm subfield) over time
time frame: Baseline up to Week 112
measure: Percentage of participants who report preferring PDS treatment to intravitreal ranibizumab treatment, as measured by the PPPQ at Week 52
time frame: Week 52
measure: Reported incidence of device deficiencies
time frame: Baseline up to Week 52
arm group label: PDS Arm
arm group type: Experimental
description: Participants randomized to the PDS arm will receive two intravitreal ranibizumab injections and will then have the PDS implant (pre-filled with ranibizumab) surgically inserted. PDS implant refill-exchange procedures will be performed on a fixed interval every 36-weeks (Q36W) thereafter
arm group label: Comparator Arm
arm group type: Other
description: Participants randomized to the comparator arm will undergo study visits every 4 weeks (Q4W) for comprehensive clinical monitoring until they receive the PDS implant (pre-filled with ranibizumab). PDS implant refill-exchange procedures will be performed on a fixed interval Q36W thereafter. Participants will be eligible to receive intravitreal ranibizumab 0.5 mg injections if treatment eligibility criteria are met.
intervention type: Drug
intervention name: PDS Implant Pre-Filled with 100 mg/mL Ranibizumab
description: Will be administered as per the schedule described in individual arm.
arm group label: Comparator Arm
arm group label: PDS Arm
intervention type: Drug
intervention name: Intravitreal Ranibizumab 0.5 mg Injection
description: Will be administered as per the schedule described in individual arm.
arm group label: Comparator Arm
arm group label: PDS Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
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country: Puerto Rico
country: United States
responsible party type: Sponsor
mesh term: Retinal Diseases
mesh term: Diabetic Retinopathy
mesh term: Ranibizumab
sharing ipd: Yes
ipd description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here ( https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).