<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/NCT03759860</url>
  </required_header>
  <id_info>
    <org_study_id>CSDME_P01</org_study_id>
    <nct_id>NCT03759860</nct_id>
  </id_info>
  <brief_title>Laser (Selective Retina Therapy) and Drug Combined Intervention in Clinically Significant Diabetic Macular Edema</brief_title>
  <official_title>A Prospective, Single-Center, Randomized, Double Blind, Double Arm, Comparative Clinical Trial to Compare the Safety and Preliminary Efficacy Between Ranibizumab Monotherapy and Ranibizumab Combined With R:GEN (Selective Retina Therapy) in Clinically Significant Diabetic Macular Edema (a Pilot Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>LUTRONIC Corporation</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>LUTRONIC Corporation</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</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>
      The objective of this clinical trial is to compare and evaluate the safety and efficacy of&#xD;
      Ranibizumab (Lucentis®; Novartis AG, Basel, Switzerland) monotherapy and Ranibizumab combined&#xD;
      with R:GEN (Selective Retina Therapy) in patients with clinically significant diabetic&#xD;
      macular edema.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective, single-center, randomized, double blind, double arm, comparative&#xD;
      clinical trial to compare the safety and efficacy between ranibizumab monotherapy and&#xD;
      ranibizumab combined with Selective Retina Therapy (SRT) in clinically significant diabetic&#xD;
      macular edema (a pilot study).&#xD;
&#xD;
      Screening visit should be conducted within 30 days before the baseline visit. After assigning&#xD;
      a screening number (SN) to the participants who voluntarily agreed in writing to participate&#xD;
      in the clinical trial, conduct a screening test to determine whether the subject meet the&#xD;
      inclusion/ exclusion criteria.&#xD;
&#xD;
      Proceed with the clinical trial with the appropriate subjects determined based on the&#xD;
      inclusion/exclusion criteria. Random allocation numbers (AN) are assigned.&#xD;
&#xD;
      Participants are randomly assigned to study group or control group. Combination therapy of&#xD;
      SRT and ranibizumab is performed in the study group and sham SRT and ranibizumab monotherapy&#xD;
      is performed in the control group. (Sham) SRT and ranibizumab (re-performance) is performed&#xD;
      by the institution's investigator other than the independent evaluator.&#xD;
&#xD;
      In the study group and control group, after the completion of 5 ranibizumab injections during&#xD;
      the loading period, if the independent evaluator judges the following criteria apply based on&#xD;
      Best Corrected Visual Acuity (BCVA) and Optical Coherence Tomography (OCT) findings at each&#xD;
      visit from the 5th month, ranibizumab is re-administered by an investigator other than the&#xD;
      independent evaluator, within 14 days of the visit or on the day of visit; If the independent&#xD;
      evaluator judges that CMT on the OCT is equal to or greater than the baseline; or if the&#xD;
      independent evaluator judges that BCVA is equal to or worse than the baseline.&#xD;
&#xD;
      The study group and the control group visit the hospital at the time of (Sham) SRT and&#xD;
      ranibizumab performance from the baseline until 5 months and make a visit every month from 6&#xD;
      months to 12 months.&#xD;
&#xD;
      From 13 months ± 14 days after the baseline, the schedule of visits can be determined at&#xD;
      intervals of 1 month ± 14 days to 3 months ± 14 days at the discretion of the investigator&#xD;
      other than the independent evaluator. However, at the time of 24 months, both the study group&#xD;
      and the control group should visit the hospital for efficacy and safety evaluation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">January 8, 2018</start_date>
  <completion_date type="Anticipated">July 30, 2020</completion_date>
  <primary_completion_date type="Anticipated">July 30, 2019</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
    <masking_description>The participant must be masked from the information on the treatment group assignment.&#xD;
The BCVA and image (OCT, Color Fundus Photography (CFP), Fundus Autofluorescence (FAF), Fluorescence Angiography (FAG)) investigator of the institution must be blinded on the participants' treatment group assignment to eliminate bias in evaluation.&#xD;
Based on the images (OCT, CFP, FAF) and quantified measurement results (BCVA, OCT), the blinded principal investigator (independent evaluator) evaluates efficacy and adverse events and determines whether ranibizumab should be administered again.&#xD;
An investigator not blinded performs SRT and ranibizumab administration.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Best Corrected Visual Acuity (BCVA) change in the study group</measure>
    <time_frame>12 months</time_frame>
    <description>Compare BCVA change evaluated between the group where Ranibizumab was combined with R:GEN (Selective Retina Therapy) and the group where Ranibizumab monotherapy was applied</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Best Corrected Visual Acuity (BCVA) change in the study group</measure>
    <time_frame>12, 24 months</time_frame>
    <description>Compare BCVA change evaluated between the group where Ranibizumab was combined with R:GEN (Selective Retina Therapy) and the group where Ranibizumab monotherapy was applied</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Central Macular Thickness (CMT) change in the study group</measure>
    <time_frame>12, 24 months</time_frame>
    <description>Compare CMT change evaluated between the group where Ranibizumab was combined with R:GEN (SRT) and the group where Ranibizumab monotherapy was applied.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Macular Thickness (MMT) change in the study group</measure>
    <time_frame>12, 24 months</time_frame>
    <description>Compare MMT change evaluated between the group where Ranibizumab was combined with R:GEN (SRT) and the group where Ranibizumab monotherapy was applied.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate and number of Ranibizumab re-performance in the study group</measure>
    <time_frame>24 months</time_frame>
    <description>Compare the rate of participants who received Ranibizumab re-performance and the number of Ranibizumab re-performance between the group where Ranibizumab was combined with R:GEN (SRT) and the group where Ranibizumab monotherapy was applied.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Event analysis</measure>
    <time_frame>24 months</time_frame>
    <description>Evaluate safety by comparing the rate of participants who experienced Adverse Event.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Diabetic Macular Edema</condition>
  <arm_group>
    <arm_group_label>Selective Retina Therapy and ranibizumab combination therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Perform R:GEN laser (SRT) on the 6,000 microns diameter region including macular edema, while excluding the 500 microns diameter region from the fovea, with the appropriate treatment energy determined.&#xD;
Ranibizumab (Lucentis®; Novartis AG, Basel, Switzerland) injection into the vitreous cavity at 3.5-4.0 mm posterior to the corneal limbus, towards the center of the eye, avoiding horizontal meridians. Then, 0.05 mL of the injection solution is slowly injected.&#xD;
In study group and the control group, ranibizumab is administered 5 times in total from the baseline to month 4.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham Selective Retina Therapy and ranibizumab monotherapy</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>For the participants assigned to the control group, sham procedures are performed in Sham Mode. All procedures except for the absence of laser light emission at the laser irradiation stage are the same with the study group.&#xD;
Sham SRT is performed three times in total, one time for each visit for month 1, 3, and 5. At the time of month 1 and 3, Sham SRT should be performed before administration of ranibizumab.</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>R:GEN laser treatment (Selective Retina Therapy) and Lucentis (ranibizumab) combination therapy</intervention_name>
    <description>Lucentis (ranibizumab) injection into the vitreous cavity after R:GEN laser treatment (Selective Retina Therapy)</description>
    <arm_group_label>Selective Retina Therapy and ranibizumab combination therapy</arm_group_label>
    <arm_group_label>Sham Selective Retina Therapy and ranibizumab monotherapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adults older than 19 years of age&#xD;
&#xD;
          2. Patients with Type-I or Type-II diabetes&#xD;
&#xD;
          3. Patients diagnosed with Clinically Significant Diabetic macular edema (CSME) based on&#xD;
             the criteria of Early Treatment Diabetic Retinopathy Study (ETDRS).&#xD;
&#xD;
               -  If thickened retina is within or lies on the circle with a radius of 500µm from&#xD;
                  the center of the fovea, or&#xD;
&#xD;
               -  If the hard exudate is within or lies on the circle with a radius of 500 ㎛ and if&#xD;
                  the retina adjacent to it is thickened, or&#xD;
&#xD;
               -  If there is a thickened retina larger than 1 disc area and if a part of it is&#xD;
                  over the circle with a radius of 1 disc diameter from the center of the macula.&#xD;
&#xD;
          4. Central Macular Thickness (CMT) of study eye is more than 300㎛ on OCT&#xD;
&#xD;
          5. Patients with BCVA of the study eye between 20/320 and 20/25.&#xD;
&#xD;
          6. Patients who have agreed to participate in this study and signed the consent form, and&#xD;
             patients whose legally acceptable representative signed the consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with Ischemic DME that showed rupture in the Foveal Avascular Zone due to the&#xD;
             obstruction of more than 30% of the capillary vessels in the central circle, as&#xD;
             observed using fluorescein angiography&#xD;
&#xD;
          2. Patients with a history of focal steroid treatment in the study eye within 4 months&#xD;
&#xD;
          3. Patients with a history of anti-VEGF agent injection in the study eye within 3 months&#xD;
&#xD;
          4. Patients with rubeosis iridis, vitreous hemorrhage or tractional retinal detachment in&#xD;
             the study eye&#xD;
&#xD;
          5. Patients with uncontrolled glaucoma in the study eye&#xD;
&#xD;
          6. Patients with active inflammation or infection in the study eye (in or around the eye)&#xD;
&#xD;
          7. Patients with disorders in the study eye that may confuse interpretation of the&#xD;
             clinical trial results, cause severe visual loss, and require medical or surgical&#xD;
             intervention during the study, based on the investigator's judgment (media opacity&#xD;
             such as corneal opacity, cataract, and vitreous opacity, vitreous macular traction,&#xD;
             uveitis, macular atrophy, macular degeneration, choroidal neovascularization, retinal&#xD;
             vascular occlusion)&#xD;
&#xD;
          8. Persons with a history of treatment with anti-VEGF drugs within the past 6 months, or&#xD;
             if they anticipate future use (e.g.: sorafenib (Nexavar®), sunitinib (Sutent®),&#xD;
             bevacizumab (Avastin®))&#xD;
&#xD;
          9. Persons with confirmed allergy to fluorescein, indocyanine green or iodine&#xD;
&#xD;
         10. Patients with a clinically significant disorder such as uncontrolled renal failure&#xD;
             that would make it difficult for them to participate in this study, based on the&#xD;
             investigator's judgment&#xD;
&#xD;
         11. Pregnant or lactating woman&#xD;
&#xD;
         12. Patient not using contraception or with a possibility of pregnancy during the clinical&#xD;
             trial period&#xD;
&#xD;
         13. Other persons deemed to be difficult to participate in this study, based on the&#xD;
             investigator's judgment&#xD;
&#xD;
         14. Persons participating in a study other than observational or non-interventional study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hakyung Kim, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hallym University Kangnam Sacred Heart Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hallym University Kangnam Sacred Heart Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>November 27, 2018</study_first_submitted>
  <study_first_submitted_qc>November 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 30, 2018</study_first_posted>
  <last_update_submitted>November 28, 2018</last_update_submitted>
  <last_update_submitted_qc>November 28, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 30, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>Ranibizumab</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/NCT03759860
org study id: CSDME_P01
nct id: NCT03759860
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
The objective of this clinical trial is to compare and evaluate the safety and efficacy of
      Ranibizumab (Lucentis®; Novartis AG, Basel, Switzerland) monotherapy and Ranibizumab combined
      with R:GEN (Selective Retina Therapy) in patients with clinically significant diabetic
      macular edema.
This is a prospective, single-center, randomized, double blind, double arm, comparative
      clinical trial to compare the safety and efficacy between ranibizumab monotherapy and
      ranibizumab combined with Selective Retina Therapy (SRT) in clinically significant diabetic
      macular edema (a pilot study).

      Screening visit should be conducted within 30 days before the baseline visit. After assigning
      a screening number (SN) to the participants who voluntarily agreed in writing to participate
      in the clinical trial, conduct a screening test to determine whether the subject meet the
      inclusion/ exclusion criteria.

      Proceed with the clinical trial with the appropriate subjects determined based on the
      inclusion/exclusion criteria. Random allocation numbers (AN) are assigned.

      Participants are randomly assigned to study group or control group. Combination therapy of
      SRT and ranibizumab is performed in the study group and sham SRT and ranibizumab monotherapy
      is performed in the control group. (Sham) SRT and ranibizumab (re-performance) is performed
      by the institution's investigator other than the independent evaluator.

      In the study group and control group, after the completion of 5 ranibizumab injections during
      the loading period, if the independent evaluator judges the following criteria apply based on
      Best Corrected Visual Acuity (BCVA) and Optical Coherence Tomography (OCT) findings at each
      visit from the 5th month, ranibizumab is re-administered by an investigator other than the
      independent evaluator, within 14 days of the visit or on the day of visit; If the independent
      evaluator judges that CMT on the OCT is equal to or greater than the baseline; or if the
      independent evaluator judges that BCVA is equal to or worse than the baseline.

      The study group and the control group visit the hospital at the time of (Sham) SRT and
      ranibizumab performance from the baseline until 5 months and make a visit every month from 6
      months to 12 months.

      From 13 months ± 14 days after the baseline, the schedule of visits can be determined at
      intervals of 1 month ± 14 days to 3 months ± 14 days at the discretion of the investigator
      other than the independent evaluator. However, at the time of 24 months, both the study group
      and the control group should visit the hospital for efficacy and safety evaluation.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
masking description: The participant must be masked from the information on the treatment group assignment.
The BCVA and image (OCT, Color Fundus Photography (CFP), Fundus Autofluorescence (FAF), Fluorescence Angiography (FAG)) investigator of the institution must be blinded on the participants' treatment group assignment to eliminate bias in evaluation.
Based on the images (OCT, CFP, FAF) and quantified measurement results (BCVA, OCT), the blinded principal investigator (independent evaluator) evaluates efficacy and adverse events and determines whether ranibizumab should be administered again.
An investigator not blinded performs SRT and ranibizumab administration.
measure: Best Corrected Visual Acuity (BCVA) change in the study group
time frame: 12 months
description: Compare BCVA change evaluated between the group where Ranibizumab was combined with R:GEN (Selective Retina Therapy) and the group where Ranibizumab monotherapy was applied
measure: Best Corrected Visual Acuity (BCVA) change in the study group
time frame: 12, 24 months
description: Compare BCVA change evaluated between the group where Ranibizumab was combined with R:GEN (Selective Retina Therapy) and the group where Ranibizumab monotherapy was applied
measure: Central Macular Thickness (CMT) change in the study group
time frame: 12, 24 months
description: Compare CMT change evaluated between the group where Ranibizumab was combined with R:GEN (SRT) and the group where Ranibizumab monotherapy was applied.
measure: Maximum Macular Thickness (MMT) change in the study group
time frame: 12, 24 months
description: Compare MMT change evaluated between the group where Ranibizumab was combined with R:GEN (SRT) and the group where Ranibizumab monotherapy was applied.
measure: Rate and number of Ranibizumab re-performance in the study group
time frame: 24 months
description: Compare the rate of participants who received Ranibizumab re-performance and the number of Ranibizumab re-performance between the group where Ranibizumab was combined with R:GEN (SRT) and the group where Ranibizumab monotherapy was applied.
measure: Adverse Event analysis
time frame: 24 months
description: Evaluate safety by comparing the rate of participants who experienced Adverse Event.
arm group label: Selective Retina Therapy and ranibizumab combination therapy
arm group type: Experimental
description: Perform R:GEN laser (SRT) on the 6,000 microns diameter region including macular edema, while excluding the 500 microns diameter region from the fovea, with the appropriate treatment energy determined.
Ranibizumab (Lucentis®; Novartis AG, Basel, Switzerland) injection into the vitreous cavity at 3.5-4.0 mm posterior to the corneal limbus, towards the center of the eye, avoiding horizontal meridians. Then, 0.05 mL of the injection solution is slowly injected.
In study group and the control group, ranibizumab is administered 5 times in total from the baseline to month 4.
arm group label: Sham Selective Retina Therapy and ranibizumab monotherapy
arm group type: Sham Comparator
description: For the participants assigned to the control group, sham procedures are performed in Sham Mode. All procedures except for the absence of laser light emission at the laser irradiation stage are the same with the study group.
Sham SRT is performed three times in total, one time for each visit for month 1, 3, and 5. At the time of month 1 and 3, Sham SRT should be performed before administration of ranibizumab.
intervention type: Combination Product
intervention name: R:GEN laser treatment (Selective Retina Therapy) and Lucentis (ranibizumab) combination therapy
description: Lucentis (ranibizumab) injection into the vitreous cavity after R:GEN laser treatment (Selective Retina Therapy)
arm group label: Selective Retina Therapy and ranibizumab combination therapy
arm group label: Sham Selective Retina Therapy and ranibizumab monotherapy
criteria: 
gender: All
minimum age: 19 Years
maximum age: N/A
healthy volunteers: No
last name: Hakyung Kim, Professor
role: Principal Investigator
affiliation: Hallym University Kangnam Sacred Heart Hospital
facility: 
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Macular Edema
mesh term: Edema
mesh term: Ranibizumab