<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/NCT03784443</url>
  </required_header>
  <id_info>
    <org_study_id>P78912</org_study_id>
    <nct_id>NCT03784443</nct_id>
  </id_info>
  <brief_title>Combined Ranibizumab and Iluvien for Diabetic Macular Oedema</brief_title>
  <acronym>CASSIE</acronym>
  <official_title>Combined Anti-VEGF Intravitreal Injections With Sustained Steroid Implantation for the Treatment of Diabetic Macular Oedema</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Imperial College London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Imperial College London</source>
  <oversight_info>
    <has_dmc>Yes</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>
      This trial investigated whether adding Iluvien sustained release steroid intravitreal eye&#xD;
      implant at the beginning of regular anti-VEGF (anti Vascular Endothelial Growth Factor)&#xD;
      intravitreal eye injection treatment for diabetic macular oedema would improve disease&#xD;
      stability and reduce the need for regular anti-VEGF intravitreal eye injections over first&#xD;
      two years. Diabetic macular oedema, accumulation of microscopic fluid at the back of the eye,&#xD;
      is a major cause of poor vision in patients with diabetes.&#xD;
&#xD;
      This is a double mask randomized control multisite trial, to be conducted at 10 NHS hospital&#xD;
      eye clinics in England.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will recruit 58 participants in a double-masked, multi-centre, sham-controlled&#xD;
      clinical trial. Participants will receive Iluvien implantation or sham implantation (masked)&#xD;
      with a concomitant intravitreal injection of ranibizumab at baseline with an allocation ratio&#xD;
      of 1:1. This is followed by regular monthly clinic review and repeat intravitreal ranibizumab&#xD;
      injections to the study eye according to a PRN (pro re nata) treatment protocol.&#xD;
&#xD;
      This trial aims to evaluate whether Iluvien implantation in addition to standard anti-VEGF&#xD;
      injection treatment for diabetic macular oedema in pseudophakic eyes will show similar visual&#xD;
      acuity outcomes but with an improved reduction in CRT (Central Retinal Thickness) while&#xD;
      reducing the average number of intravitreal injections during the first 2 years of treatment,&#xD;
      due to the continual micro-dosing of Iluvien therapy.&#xD;
&#xD;
      Participants meeting all the eligibility criteria will be randomized to either Iluvien&#xD;
      implant or sham implant procedure with an allocation ratio of 1:1. Participants assigned to&#xD;
      either treatment arms will receive intravitreal injection of ranibizumab after Iluvien&#xD;
      implantation or sham implantation at the same baseline visit.&#xD;
&#xD;
      To maintain double-masking, participants assigned to the control arm will receive sham&#xD;
      implantation. This will be performed with an empty Luer Lock Syringe without a needle&#xD;
      attached to it, that will not penetrate the eye nor deliver any drug. Patients assigned to&#xD;
      either treatment arm will receive ranibizumab intravitreal injection to the study eye at&#xD;
      baseline 30 minutes after the Iluvien or sham implantation. The sham injection should be&#xD;
      performed by the unmasked investigator. The unmasked investigator should not be involved in&#xD;
      any patient assessment in the study.&#xD;
&#xD;
      Participants will be followed up monthly for 2 years. Participants from both arms will&#xD;
      receive compulsory Ranibizumab injection during the first three monthly visit and followed by&#xD;
      monthly Ranibizumab as per PRN protocol. The end of study visit should take place at 104&#xD;
      weeks from the baseline visit.&#xD;
&#xD;
      Visual acuity measurement should be performed by trial certified optometrist according to the&#xD;
      standard ETDRS (Early Treatment of Diabetic Retinopathy Study) protocol. This is to be&#xD;
      conducted in certified examination rooms.&#xD;
&#xD;
      Spectral domain OCT (Optical Coherence Tomography) should be used to assess diabetic macular&#xD;
      oedema and optic disc morphology at each visit. The OCT viewer software should be able to&#xD;
      provide objective retinal thickness measurement of the central 1mm subfield thickness.&#xD;
      Technicians should check for segmentation errors with every OCT scan and make appropriate&#xD;
      manual adjustments.&#xD;
&#xD;
      OCT machines and designated technicians at each site will be certified prior to study&#xD;
      commencement. Patients must always be assessed using the same OCT model.&#xD;
&#xD;
      7-View Fundus Photography and Fluorescein Angiography (FA) will be performed at the screening&#xD;
      visit to confirm the diagnosis of diabetic macular oedema and assess diabetic retinopathy.&#xD;
&#xD;
      Additional FAs may be undertaken during subsequent visits should the investigator believe&#xD;
      that there is a clinical need for it. Investigators at each local site are responsible for FA&#xD;
      and OCT image interpretation. There will be no centralized image reading centre involved in&#xD;
      this study.&#xD;
&#xD;
      IOP (Intraocular Pressure) measurement should be performed with Goldman tonometry either with&#xD;
      undilated or dilated pupils.&#xD;
&#xD;
      The primary outcome analysis will be performed to test the differences in the average number&#xD;
      of intravitreal injections between the two treatment arms up to month 24. This will be&#xD;
      carried out according to an intent to treat principle.&#xD;
&#xD;
      The change of visual acuity from baseline to month 24 will be tested for non-inferiority&#xD;
      against the control arm. We will analyze the stability of visual acuity and CRT using AUC&#xD;
      (Area Under Curve) Analysis and estimate the average cost of resources utilization for both&#xD;
      treatment arms.&#xD;
&#xD;
      Methods of dealing with missing data will follow established techniques, using multiple&#xD;
      imputation to impute missing data. If necessary sensitivity analyses will be undertaken to&#xD;
      examine the dependence of the results on the method of imputation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Funder withdrawn funding.&#xD;
  </why_stopped>
  <start_date type="Anticipated">September 1, 2019</start_date>
  <completion_date type="Anticipated">September 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">September 1, 2022</primary_completion_date>
  <phase>Phase 2/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>
    <intervention_model_description>Double masking randomized control trial with 2 parallel treatment arms: intervention (Iluvien plus Ranibizumab) vs control (Sham plus Ranibizumab)</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    <masking_description>To maintain double-masking, participants assigned to the control arm will receive sham implantation. This will be performed with an empty Luer Lock Syringe without a needle attached to it, that will not penetrate the eye nor deliver any drug.&#xD;
The Iluvien and the sham injection should be performed by the unmasked investigator. The unmasked investigator should not be involved in any patient assessment in the study.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Lucentis Injections received in the study eye</measure>
    <time_frame>24 months</time_frame>
    <description>The total number of Lucentis injections needed over 24 months following the intravitreal injection PRN protocol</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in visual acuity</measure>
    <time_frame>Month 24</time_frame>
    <description>Change in ETDRS (Early Treatment of Diabetic Retinopathy Study) best corrected visual acuity from baseline to month 24</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maintaining at least 20/40 vision</measure>
    <time_frame>Month 24</time_frame>
    <description>Percentage of patients that achieve or maintain 20/40 vision</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants with vision loss</measure>
    <time_frame>Month 24</time_frame>
    <description>Proportion of participants losing 5, 10, 15 ETDRS letters or more</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of participants with visual gain</measure>
    <time_frame>Month 24</time_frame>
    <description>Proportion of participants gaining at least 5, 10, 15 ETDRS letters or more</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stability of vision</measure>
    <time_frame>Over 24 months</time_frame>
    <description>Stability of visual acuity over 24 months using Area Under Curve Analysis (AUC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Central retinal thickness</measure>
    <time_frame>Month 24</time_frame>
    <description>Central retinal thickness (CRT) change as measured by Spectral Domain OCT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CRT stability</measure>
    <time_frame>Over 24 months</time_frame>
    <description>Stability of CRT over 24 months using AUC analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Retinal thickness variability</measure>
    <time_frame>Over 24 months</time_frame>
    <description>The difference between min and max retinal thickness</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Diabetic Retinopathy Severity</measure>
    <time_frame>Between baseline and month 24</time_frame>
    <description>Measured using the ETDRS DRSS (Diabetic Retinopathy Severity Score)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of focal laser treatments</measure>
    <time_frame>Over 24 months</time_frame>
    <description>Number of focal laser treatments</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Diabetic Macular Edema</condition>
  <condition>Diabetes</condition>
  <arm_group>
    <arm_group_label>Iluvien Arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants assigned to the Iluvien treatment arm will receive Iluvien 0.19 MG Drug Implant to the study eye under aseptic condition at baseline visit with monthly Ranibizumab Injection [Lucentis] for first three visits followed by monthly Ranibizumab Injection [Lucentis] PRN.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Arm</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>To maintain double-masking, participants assigned to the control arm will receive Sham Intravitreal Injection at the baseline visit with monthly Ranibizumab Injection [Lucentis] for first three visits followed by monthly Ranibizumab Injection [Lucentis] PRN.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Iluvien 0.19 MG Drug Implant</intervention_name>
    <description>Fluocinolone Acetonide Sustained Release Intravitreal Implant at Baseline Visit</description>
    <arm_group_label>Iluvien Arm</arm_group_label>
    <other_name>Fluocinolone Acetonide Implant</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ranibizumab Injection [Lucentis]</intervention_name>
    <description>Monthly PRN intravitreal injections</description>
    <arm_group_label>Control Arm</arm_group_label>
    <arm_group_label>Iluvien Arm</arm_group_label>
    <other_name>Lucentis</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Sham Intravitreal Injection</intervention_name>
    <description>Sham injection without penetrating needle and without drug delivery at baseline visit.</description>
    <arm_group_label>Control Arm</arm_group_label>
    <other_name>Sham Injection with Luer Lock Syringe</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        General&#xD;
&#xD;
          1. Willingness and the ability to provide informed consent.&#xD;
&#xD;
          2. Ability and willingness to undertake all scheduled visits, assessment and treatment.&#xD;
&#xD;
          3. Age 18 years or above.&#xD;
&#xD;
          4. Documented diagnosis of diabetes mellitus (Type I or Type II) as per WHO (World Health&#xD;
             Organization) criteria.&#xD;
&#xD;
          5. Current regular use of oral anti-hyperglycaemia or insulin therapy.&#xD;
&#xD;
          6. For women of childbearing potential: agreement to remain abstinent (refrain from&#xD;
             heterosexual intercourse) or use contraceptive methods with a failure rate of &lt;1% per&#xD;
             year during the study duration of 24 months.&#xD;
&#xD;
        Ocular&#xD;
&#xD;
          1. Macular thickening due to Diabetic Macular Oedema (DMO) involving the centre of fovea&#xD;
             as measured by Spectral Domain OCT with CRT of at least 400 microns.&#xD;
&#xD;
          2. DMO confirmed by clinical examination and fundus fluorescein angiography.&#xD;
&#xD;
          3. BCVA between 73 to 25 letters inclusive (Snellen equivalent to 6/12 to 6/96) as&#xD;
             measured using ETDRS protocol at 4 meters.&#xD;
&#xD;
          4. Pseudophakia in the study eye.&#xD;
&#xD;
          5. Adequate ocular media clarity and pupillary dilatation allowing for posterior segment&#xD;
             examination and OCT scanning.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        General&#xD;
&#xD;
          1. Cerebral vascular accident, transient ischaemic attack or myocardial infarction within&#xD;
             3 months prior to day 1 (baseline).&#xD;
&#xD;
          2. Pregnancy or breastfeeding, or intention to become pregnant during the study.&#xD;
&#xD;
          3. Participation in an investigational trial involving treatment with any drug or devices&#xD;
             within 3 months prior to day 1 (baseline) and must not be enrolled in another&#xD;
             investigational trial during their participation in this trial.&#xD;
&#xD;
          4. Systemic anti-VEGF-base therapies within 3 months prior to day 1 (baseline).&#xD;
&#xD;
        Ocular&#xD;
&#xD;
          1. History of prior intravitreal anti-VEGF therapy or steroid implant in the study eye.&#xD;
&#xD;
          2. History of proliferative diabetic retinopathy.&#xD;
&#xD;
          3. History of rubeosis or current rubeosis.&#xD;
&#xD;
          4. History of neovascularization, tractional retinal detachment, retinal vein occlusion,&#xD;
             or significant pre-retinal fibrosis distorting the macular architecture.&#xD;
&#xD;
          5. History of retinal detachment or macular hole stage 3 or above.&#xD;
&#xD;
          6. History of vitreoretinal surgery.&#xD;
&#xD;
          7. Aphakia.&#xD;
&#xD;
          8. History of glaucoma or uncontrolled ocular hypertension.&#xD;
&#xD;
          9. Active or suspected ocular or periocular infection or inflammation, including viral&#xD;
             diseases of the cornea, conjunctiva and retina, such as active epithelial herpes&#xD;
             simplex keratitis (dendritic keratitis), varicella, mycobacterial infections, and&#xD;
             fungal diseases.&#xD;
&#xD;
         10. Panretinal Photocoagulation (PRP) laser treatment within 3 months prior to day 1.&#xD;
&#xD;
         11. Macular laser (focal or grid) within 3 months prior to day 1.&#xD;
&#xD;
         12. YAG (yttrium aluminium garnet) laser capsulotomy laser within 3 months prior to day 1.&#xD;
&#xD;
         13. Any periocular steroid treatment within 6 months prior to day 1.&#xD;
&#xD;
         14. Cataract operation within 3 months prior to day 1.&#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>Richard Cheong-Leen</last_name>
    <role>Principal Investigator</role>
    <affiliation>Imperial College London</affiliation>
  </overall_official>
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    <citation>Goni FJ, Stalmans I, Denis P, Nordmann JP, Taylor S, Diestelhorst M, Figueiredo AR, Garway-Heath DF. Elevated Intraocular Pressure After Intravitreal Steroid Injection in Diabetic Macular Edema: Monitoring and Management. Ophthalmol Ther. 2016 Jun;5(1):47-61. doi: 10.1007/s40123-016-0052-8. Epub 2016 May 10.</citation>
    <PMID>27164896</PMID>
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  <reference>
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    <PMID>18670086</PMID>
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    <citation>Minassian DC, Owens DR, Reidy A. Prevalence of diabetic macular oedema and related health and social care resource use in England. Br J Ophthalmol. 2012 Mar;96(3):345-9. doi: 10.1136/bjo.2011.204040. Epub 2011 May 20.</citation>
    <PMID>21602478</PMID>
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  <reference>
    <citation>Wells JA, Glassman AR, Ayala AR, Jampol LM, Bressler NM, Bressler SB, Brucker AJ, Ferris FL, Hampton GR, Jhaveri C, Melia M, Beck RW; Diabetic Retinopathy Clinical Research Network. Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema: Two-Year Results from a Comparative Effectiveness Randomized Clinical Trial. Ophthalmology. 2016 Jun;123(6):1351-9. doi: 10.1016/j.ophtha.2016.02.022. Epub 2016 Feb 27.</citation>
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  <verification_date>June 2019</verification_date>
  <study_first_submitted>December 19, 2018</study_first_submitted>
  <study_first_submitted_qc>December 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 21, 2018</study_first_posted>
  <last_update_submitted>June 25, 2019</last_update_submitted>
  <last_update_submitted_qc>June 25, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 26, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Diabetes</keyword>
  <keyword>Eye</keyword>
  <keyword>Macular Oedema</keyword>
  <keyword>Intravitreal Injection</keyword>
  <keyword>Ranibizumab</keyword>
  <keyword>Fluocinolone Acetonide</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>Ranibizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03784443
org study id: P78912
nct id: NCT03784443
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This trial investigated whether adding Iluvien sustained release steroid intravitreal eye
      implant at the beginning of regular anti-VEGF (anti Vascular Endothelial Growth Factor)
      intravitreal eye injection treatment for diabetic macular oedema would improve disease
      stability and reduce the need for regular anti-VEGF intravitreal eye injections over first
      two years. Diabetic macular oedema, accumulation of microscopic fluid at the back of the eye,
      is a major cause of poor vision in patients with diabetes.

      This is a double mask randomized control multisite trial, to be conducted at 10 NHS hospital
      eye clinics in England.
This study will recruit 58 participants in a double-masked, multi-centre, sham-controlled
      clinical trial. Participants will receive Iluvien implantation or sham implantation (masked)
      with a concomitant intravitreal injection of ranibizumab at baseline with an allocation ratio
      of 1:1. This is followed by regular monthly clinic review and repeat intravitreal ranibizumab
      injections to the study eye according to a PRN (pro re nata) treatment protocol.

      This trial aims to evaluate whether Iluvien implantation in addition to standard anti-VEGF
      injection treatment for diabetic macular oedema in pseudophakic eyes will show similar visual
      acuity outcomes but with an improved reduction in CRT (Central Retinal Thickness) while
      reducing the average number of intravitreal injections during the first 2 years of treatment,
      due to the continual micro-dosing of Iluvien therapy.

      Participants meeting all the eligibility criteria will be randomized to either Iluvien
      implant or sham implant procedure with an allocation ratio of 1:1. Participants assigned to
      either treatment arms will receive intravitreal injection of ranibizumab after Iluvien
      implantation or sham implantation at the same baseline visit.

      To maintain double-masking, participants assigned to the control arm will receive sham
      implantation. This will be performed with an empty Luer Lock Syringe without a needle
      attached to it, that will not penetrate the eye nor deliver any drug. Patients assigned to
      either treatment arm will receive ranibizumab intravitreal injection to the study eye at
      baseline 30 minutes after the Iluvien or sham implantation. The sham injection should be
      performed by the unmasked investigator. The unmasked investigator should not be involved in
      any patient assessment in the study.

      Participants will be followed up monthly for 2 years. Participants from both arms will
      receive compulsory Ranibizumab injection during the first three monthly visit and followed by
      monthly Ranibizumab as per PRN protocol. The end of study visit should take place at 104
      weeks from the baseline visit.

      Visual acuity measurement should be performed by trial certified optometrist according to the
      standard ETDRS (Early Treatment of Diabetic Retinopathy Study) protocol. This is to be
      conducted in certified examination rooms.

      Spectral domain OCT (Optical Coherence Tomography) should be used to assess diabetic macular
      oedema and optic disc morphology at each visit. The OCT viewer software should be able to
      provide objective retinal thickness measurement of the central 1mm subfield thickness.
      Technicians should check for segmentation errors with every OCT scan and make appropriate
      manual adjustments.

      OCT machines and designated technicians at each site will be certified prior to study
      commencement. Patients must always be assessed using the same OCT model.

      7-View Fundus Photography and Fluorescein Angiography (FA) will be performed at the screening
      visit to confirm the diagnosis of diabetic macular oedema and assess diabetic retinopathy.

      Additional FAs may be undertaken during subsequent visits should the investigator believe
      that there is a clinical need for it. Investigators at each local site are responsible for FA
      and OCT image interpretation. There will be no centralized image reading centre involved in
      this study.

      IOP (Intraocular Pressure) measurement should be performed with Goldman tonometry either with
      undilated or dilated pupils.

      The primary outcome analysis will be performed to test the differences in the average number
      of intravitreal injections between the two treatment arms up to month 24. This will be
      carried out according to an intent to treat principle.

      The change of visual acuity from baseline to month 24 will be tested for non-inferiority
      against the control arm. We will analyze the stability of visual acuity and CRT using AUC
      (Area Under Curve) Analysis and estimate the average cost of resources utilization for both
      treatment arms.

      Methods of dealing with missing data will follow established techniques, using multiple
      imputation to impute missing data. If necessary sensitivity analyses will be undertaken to
      examine the dependence of the results on the method of imputation.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Double masking randomized control trial with 2 parallel treatment arms: intervention (Iluvien plus Ranibizumab) vs control (Sham plus Ranibizumab)
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
masking description: To maintain double-masking, participants assigned to the control arm will receive sham implantation. This will be performed with an empty Luer Lock Syringe without a needle attached to it, that will not penetrate the eye nor deliver any drug.
The Iluvien and the sham injection should be performed by the unmasked investigator. The unmasked investigator should not be involved in any patient assessment in the study.
measure: Number of Lucentis Injections received in the study eye
time frame: 24 months
description: The total number of Lucentis injections needed over 24 months following the intravitreal injection PRN protocol
measure: Change in visual acuity
time frame: Month 24
description: Change in ETDRS (Early Treatment of Diabetic Retinopathy Study) best corrected visual acuity from baseline to month 24
measure: Maintaining at least 20/40 vision
time frame: Month 24
description: Percentage of patients that achieve or maintain 20/40 vision
measure: Proportion of participants with vision loss
time frame: Month 24
description: Proportion of participants losing 5, 10, 15 ETDRS letters or more
measure: Proportion of participants with visual gain
time frame: Month 24
description: Proportion of participants gaining at least 5, 10, 15 ETDRS letters or more
measure: Stability of vision
time frame: Over 24 months
description: Stability of visual acuity over 24 months using Area Under Curve Analysis (AUC)
measure: Central retinal thickness
time frame: Month 24
description: Central retinal thickness (CRT) change as measured by Spectral Domain OCT
measure: CRT stability
time frame: Over 24 months
description: Stability of CRT over 24 months using AUC analysis
measure: Retinal thickness variability
time frame: Over 24 months
description: The difference between min and max retinal thickness
measure: Change in Diabetic Retinopathy Severity
time frame: Between baseline and month 24
description: Measured using the ETDRS DRSS (Diabetic Retinopathy Severity Score)
measure: Number of focal laser treatments
time frame: Over 24 months
description: Number of focal laser treatments
arm group label: Iluvien Arm
arm group type: Active Comparator
description: Participants assigned to the Iluvien treatment arm will receive Iluvien 0.19 MG Drug Implant to the study eye under aseptic condition at baseline visit with monthly Ranibizumab Injection [Lucentis] for first three visits followed by monthly Ranibizumab Injection [Lucentis] PRN.
arm group label: Control Arm
arm group type: Sham Comparator
description: To maintain double-masking, participants assigned to the control arm will receive Sham Intravitreal Injection at the baseline visit with monthly Ranibizumab Injection [Lucentis] for first three visits followed by monthly Ranibizumab Injection [Lucentis] PRN.
intervention type: Drug
intervention name: Iluvien 0.19 MG Drug Implant
description: Fluocinolone Acetonide Sustained Release Intravitreal Implant at Baseline Visit
arm group label: Iluvien Arm
other name: Fluocinolone Acetonide Implant
intervention type: Drug
intervention name: Ranibizumab Injection [Lucentis]
description: Monthly PRN intravitreal injections
arm group label: Control Arm
arm group label: Iluvien Arm
other name: Lucentis
intervention type: Procedure
intervention name: Sham Intravitreal Injection
description: Sham injection without penetrating needle and without drug delivery at baseline visit.
arm group label: Control Arm
other name: Sham Injection with Luer Lock Syringe
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Richard Cheong-Leen
role: Principal Investigator
affiliation: Imperial College London
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responsible party type: Sponsor
mesh term: Macular Edema
mesh term: Edema
mesh term: Fluocinolone Acetonide
mesh term: Ranibizumab
sharing ipd: Undecided