<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/NCT02222610</url>
  </required_header>
  <id_info>
    <org_study_id>ML29236</org_study_id>
    <nct_id>NCT02222610</nct_id>
  </id_info>
  <brief_title>Study of the Efficacy and Tolerability of Intravitreal Injections of Ranibizumab Compared to Intravitreal Injections of Ranibizumab Combined With Targeted Retinal Photocoagulation to Treat Radiation Retinopathy.</brief_title>
  <acronym>RRR</acronym>
  <official_title>A Randomized, Active-Controlled, Phase II Study of the Efficacy and Tolerability of Intravitreal Injections of Ranibizumab Compared to Intravitreal Injections of Ranibizumab Combined With Targeted Retinal Photocoagulation in Subjects With Radiation Retinopathy (RRR Study).</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Greater Houston Retina Research</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Genentech, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Greater Houston Retina Research</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess the tolerability and efficacy of ranibizumab treatment&#xD;
      administered in subjects with radiation retinopathy&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      RRR is a phase II, randomized, multicenter, clinical study to assess the tolerability and&#xD;
      efficacy of ranibizumab treatment administered in subjects with radiation retinopathy.&#xD;
      Subjects will be randomized into one of 3 arms; intravitreal (IVT) monthly vs. ranibizumab&#xD;
      treatment administered IVT monthly combined with peripheral targeted photocoagulation vs.&#xD;
      ranibizumab treatment administered IVT for three months followed by as needed treatment of&#xD;
      ranibizumab combined with peripheral targeted photocoagulation over 48 weeks. From week 52 to&#xD;
      week 101, all 3 treatment arms will employ a treat and extend protocol for IVT ranibizumab&#xD;
      treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 23, 2014</start_date>
  <completion_date type="Actual">March 2019</completion_date>
  <primary_completion_date type="Actual">March 2019</primary_completion_date>
  <phase>Phase 2</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity at 104 Weeks From Day 0.</measure>
    <time_frame>104 weeks</time_frame>
    <description>Early Treatment Diabetic Retinopathy Study (ETDRS) Best-Corrected Visual Acuity (BCVA) utilizes the ETDRS visual acuity chart to measure vision in clinical trials. Standard unit of measure is the number of letters subjects are able to read on the chart.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The Mean Number of Intravitreal Injections Required Per Subject Per Cohort.</measure>
    <time_frame>104 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Subjects With Retinal Hemorrhage at 104 Weeks.</measure>
    <time_frame>104 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Subjects With Intraretinal Exudates on Fundus Examination at Week 104.</measure>
    <time_frame>104 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change in Central Mean Thickness According to Spectral-domain Optical Coherence Tomography at Week 104 Compared to Baseline.</measure>
    <time_frame>104 weeks</time_frame>
    <description>Spectral-domain optical coherence tomography (SD-OCT) is a common imaging modality used to visualize the layers of the macula. Central mean thickness (CMT) is the length in microns from the internal limiting membrane to Bruch's membrane.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Radiation Retinopathy</condition>
  <arm_group>
    <arm_group_label>Cohort A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subject's will receive monthly treatment of an intravitreal injection of 0.5 mg ranibizumab for 48 weeks.&#xD;
Starting at week 52, subject's will enter a treat &amp; extend regime, if a subject achieves a &quot;dry&quot; macula. For a macula to be considered &quot;dry&quot; persistent or recurrent fluid must be resolved on spectral domain (SD)-optical coherence tomography (OCT). The interval between injections will not exceed 12 weeks. After a subject is extended beyond 4-weeks &amp; develops recurrent disease activity, the eye is treated &amp; the treatment interval for the next visit is reduced by 1 week, compared to the previous treatment interval. The interval between treatments will be reduced by 1-week intervals until a dry macula is again established. Once a dry macula is again achieved, the interval between visits will be extended by 1-week intervals again.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subject's receive monthly treatment of IVT of 0.5 mg ranibizumab for 48 weeks. 1 week after the initial dose of IVT ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) to areas of peripheral retinal ischemia based on 120° or greater wide field angiography. After the first session of TRP, subjects will have a repeat wide field angiogram at 12 weeks &amp; 24 weeks &amp; will receive additional TRP as needed (PRN) to areas of peripheral retinal ischemia.&#xD;
Starting at week 52, subject's will enter a treat &amp; extend regime as described in cohort A.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subject's will receive 3 consecutive monthly doses of IVT 0.5 mg ranibizumab followed by PRN treatment with 0.5 mg ranibizumab intravitreal injection. 1 week after the initial dose of IVT ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) to areas of peripheral retinal ischemia. After the first session of TRP, subjects will have a repeat wide field angiogram at 12 weeks &amp; 24 weeks &amp; will receive additional TRP as needed (PRN) to areas of peripheral retinal ischemia.&#xD;
Starting at week 52, subject's will enter a treat &amp; extend regime as described in cohort A.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>0.5 mg ranibizumab</intervention_name>
    <arm_group_label>Cohort A</arm_group_label>
    <arm_group_label>Cohort B</arm_group_label>
    <arm_group_label>Cohort C</arm_group_label>
    <other_name>Lucentis</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Targeted Retinal Photocoagulation (TRP)</intervention_name>
    <description>TRP to areas of retinal ischemia</description>
    <arm_group_label>Cohort B</arm_group_label>
    <arm_group_label>Cohort C</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
        Subjects will be eligible to participate if the following criteria are met:&#xD;
&#xD;
          -  Ability to provide written informed consent and comply with study assessments for the&#xD;
             full duration of the study&#xD;
&#xD;
          -  Age &gt; 18 years&#xD;
&#xD;
          -  Active radiation retinopathy resulting from any form of radiation treatment performed&#xD;
             within the last 3 years. Radiation retinopathy is defined as any of the following:&#xD;
             retinal hemorrhages, exudates, edema, and/or neovascularization, not attributable to&#xD;
             other causes.&#xD;
&#xD;
          -  Best Corrected Visual Acuity (BCVA) of 20/25-20/400 in the study eye&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
        Subjects who meet any of the following criteria will be excluded from this study:&#xD;
&#xD;
          -  Pregnancy (verified by positive pregnancy test) or lactation&#xD;
&#xD;
          -  Premenopausal women not using adequate methods of contraception. The following are&#xD;
             considered effective means of contraception: surgical sterilization, use of oral&#xD;
             contraceptives, barrier contraception with either a condom or diaphragm in conjunction&#xD;
             with spermicidal gel, an intrauterine device (IUD), or contraceptive hormone implant&#xD;
             or patch.&#xD;
&#xD;
          -  Any other condition that the investigator believes would pose a significant hazard to&#xD;
             the subject if the investigational therapy were initiated.&#xD;
&#xD;
          -  Participation in any other simultaneous medical investigation or trial&#xD;
&#xD;
          -  Previous participation in any studies involving investigational drugs within 30 days&#xD;
             before Day 0 (excluding vitamins and minerals).&#xD;
&#xD;
          -  History of allergy fluorescein, not amenable to treatment&#xD;
&#xD;
          -  Previous intravitreal treatment with any anti-vascular endothelial growth factor&#xD;
             (VEGF) drug within 60 days of Day 0&#xD;
&#xD;
          -  Previous intravitreal or subconjunctival treatment with cortical steroids within 90&#xD;
             days of Day 0&#xD;
&#xD;
          -  History of vitrectomy&#xD;
&#xD;
          -  History of treatment with more than one form of radiation to the eye (e.g. proton beam&#xD;
             therapy and plaque therapy).&#xD;
&#xD;
          -  Subjects who have more than 7 disc diameters of ischemia in the central macula that&#xD;
             would hinder visual acuity improvement&#xD;
&#xD;
          -  History of panretinal photocoagulation treatment in the study eye.&#xD;
&#xD;
          -  Inability to obtain fundus photographs or fluorescein angiograms of sufficient quality&#xD;
             to be analyzed&#xD;
&#xD;
          -  Any concurrent intraocular condition in the study eye that, in the opinion of the&#xD;
             investigator, could:&#xD;
&#xD;
               -  Require medical or surgical intervention during the 12 month study period to&#xD;
                  prevent or treat visual loss that might result from that condition.&#xD;
&#xD;
               -  Contribute to loss of at least 2 Snellen equivalent lines of BCVA over the&#xD;
                  12-month study period, if allowed to progress untreated.&#xD;
&#xD;
          -  Active intraocular inflammation (grade 2+ or above) in the study eye&#xD;
&#xD;
          -  Current vitreous hemorrhage in the study eye&#xD;
&#xD;
          -  History of rhegmatogenous retinal detachment or macular hole (stage 3 or 4) in the&#xD;
             study eye.&#xD;
&#xD;
          -  Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either&#xD;
             eye.&#xD;
&#xD;
          -  Aphakia or absence of the posterior capsule in the study eye.&#xD;
&#xD;
          -  Intraocular surgery (including cataract surgery) in the study eye within 2 months&#xD;
             preceding Day 0.&#xD;
&#xD;
          -  Uncontrolled glaucoma in the study eye (defined as intraocular pressure (IOP) &gt; 30&#xD;
             mmHg despite treatment with anti-glaucoma medication).&#xD;
&#xD;
          -  History of glaucoma-filtering surgery in the study eye&#xD;
&#xD;
          -  History of corneal transplant in the study eye&#xD;
&#xD;
          -  Uncontrolled blood pressure (defined as systolic and/or diastolic &gt; 180/110 mmHg while&#xD;
             subject is seated). If the subject's initial reading exceeds these values, a second&#xD;
             reading may be taken at least 30 minutes later. If the subject requires&#xD;
             antihypertensive medication, the subject can become eligible if medication is taken&#xD;
             continuously for at least 14 days prior to Day 0 and blood pressure is less that&#xD;
             180/110 mmHg.&#xD;
&#xD;
          -  New diagnosis of atrial fibrillation not managed by subject's primary care physician&#xD;
             or cardiologist within 3 months of Day 0.&#xD;
&#xD;
          -  History of stroke within the last 3 months of Day 0.&#xD;
&#xD;
          -  History of myocardial infarction within 3 months of Day 0.&#xD;
&#xD;
          -  History of other disease, metabolic dysfunction, or physical examination finding&#xD;
             giving reasonable suspicion of a disease or condition that contraindicates the use of&#xD;
             an investigational drug or that might affect interpretation of the results of the&#xD;
             study or renders the subject at high risk for treatment complications.&#xD;
&#xD;
          -  Current treatment for active systemic infection&#xD;
&#xD;
          -  Active malignancy other than uveal melanoma&#xD;
&#xD;
          -  Presence of metastases&#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>Amy C Schefler, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Retina Consultants Houston</affiliation>
  </overall_official>
  <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>Retina Consultants of Houston/The Medical Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Consultants of Houston</name>
      <address>
        <city>Katy</city>
        <state>Texas</state>
        <zip>77494</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Retina Consultants of Houston</name>
      <address>
        <city>The Woodlands</city>
        <state>Texas</state>
        <zip>77384</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Jampol LM, Moy CS, Murray TG, Reynolds SM, Albert DM, Schachat AP, Diddie KR, Engstrom RE Jr, Finger PT, Hovland KR, Joffe L, Olsen KR, Wells CG; Collaborative Ocular Melanoma Study Group (COMS Group). The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma: IV. Local treatment failure and enucleation in the first 5 years after brachytherapy. COMS report no. 19. Ophthalmology. 2002 Dec;109(12):2197-206. doi: 10.1016/s0161-6420(02)01277-0. Erratum In: Ophthalmology. 2004 Aug;111(8):1514.</citation>
    <PMID>12466159</PMID>
  </reference>
  <reference>
    <citation>Melia BM, Abramson DH, Albert DM, Boldt HC, Earle JD, Hanson WF, Montague P, Moy CS, Schachat AP, Simpson ER, Straatsma BR, Vine AK, Weingeist TA; Collaborative Ocular Melanoma Study Group. Collaborative ocular melanoma study (COMS) randomized trial of I-125 brachytherapy for medium choroidal melanoma. I. Visual acuity after 3 years COMS report no. 16. Ophthalmology. 2001 Feb;108(2):348-66. doi: 10.1016/s0161-6420(00)00526-1.</citation>
    <PMID>11158813</PMID>
  </reference>
  <reference>
    <citation>Gunduz K, Shields CL, Shields JA, Cater J, Freire JE, Brady LW. Radiation retinopathy following plaque radiotherapy for posterior uveal melanoma. Arch Ophthalmol. 1999 May;117(5):609-14. doi: 10.1001/archopht.117.5.609.</citation>
    <PMID>10326957</PMID>
  </reference>
  <reference>
    <citation>Finger PT, Chin KJ. High-dose (2.0 mg) intravitreal ranibizumab for recalcitrant radiation retinopathy. Eur J Ophthalmol. 2013 Nov-Dec;23(6):850-6. doi: 10.5301/ejo.5000333. Epub 2013 Jun 28.</citation>
    <PMID>23813109</PMID>
  </reference>
  <reference>
    <citation>Finger PT, Chin KJ. Intravitreous ranibizumab (lucentis) for radiation maculopathy. Arch Ophthalmol. 2010 Feb;128(2):249-52. doi: 10.1001/archophthalmol.2009.376. No abstract available.</citation>
    <PMID>20142553</PMID>
  </reference>
  <reference>
    <citation>Finger PT, Chin KJ. Antivascular endothelial growth factor bevacizumab for radiation optic neuropathy: secondary to plaque radiotherapy. Int J Radiat Oncol Biol Phys. 2012 Feb 1;82(2):789-98. doi: 10.1016/j.ijrobp.2010.11.075. Epub 2011 Jan 27.</citation>
    <PMID>21277107</PMID>
  </reference>
  <reference>
    <citation>Finger PT, Mukkamala SK. Intravitreal anti-VEGF bevacizumab (Avastin) for external beam related radiation retinopathy. Eur J Ophthalmol. 2011 Jul-Aug;21(4):446-51. doi: 10.5301/EJO.2011.6213.</citation>
    <PMID>21218391</PMID>
  </reference>
  <reference>
    <citation>Mason JO 3rd, Albert MA Jr, Persaud TO, Vail RS. Intravitreal bevacizumab treatment for radiation macular edema after plaque radiotherapy for choroidal melanoma. Retina. 2007 Sep;27(7):903-7. doi: 10.1097/IAE.0b013e31806e6042.</citation>
    <PMID>17891015</PMID>
  </reference>
  <reference>
    <citation>Finger PT. Radiation retinopathy is treatable with anti-vascular endothelial growth factor bevacizumab (Avastin). Int J Radiat Oncol Biol Phys. 2008 Mar 15;70(4):974-7. doi: 10.1016/j.ijrobp.2007.11.045.</citation>
    <PMID>18313522</PMID>
  </reference>
  <reference>
    <citation>Finger PT, Chin K. Anti-vascular endothelial growth factor bevacizumab (avastin) for radiation retinopathy. Arch Ophthalmol. 2007 Jun;125(6):751-6. doi: 10.1001/archopht.125.6.751.</citation>
    <PMID>17562985</PMID>
  </reference>
  <reference>
    <citation>Gupta A, Muecke JS. Treatment of radiation maculopathy with intravitreal injection of bevacizumab (Avastin). Retina. 2008 Jul-Aug;28(7):964-8. doi: 10.1097/IAE.0b013e3181706302.</citation>
    <PMID>18698298</PMID>
  </reference>
  <reference>
    <citation>Shields CL, Demirci H, Dai V, Marr BP, Mashayekhi A, Materin MA, Manquez ME, Shields JA. Intravitreal triamcinolone acetonide for radiation maculopathy after plaque radiotherapy for choroidal melanoma. Retina. 2005 Oct-Nov;25(7):868-74. doi: 10.1097/00006982-200510000-00009.</citation>
    <PMID>16205566</PMID>
  </reference>
  <reference>
    <citation>Finger PT, Kurli M. Laser photocoagulation for radiation retinopathy after ophthalmic plaque radiation therapy. Br J Ophthalmol. 2005 Jun;89(6):730-8. doi: 10.1136/bjo.2004.052159.</citation>
    <PMID>15923510</PMID>
  </reference>
  <reference>
    <citation>Kinyoun JL. Long-term visual acuity results of treated and untreated radiation retinopathy (an AOS thesis). Trans Am Ophthalmol Soc. 2008;106:325-35.</citation>
    <PMID>19277244</PMID>
  </reference>
  <reference>
    <citation>Hykin PG, Shields CL, Shields JA, Arevalo JF. The efficacy of focal laser therapy in radiation-induced macular edema. Ophthalmology. 1998 Aug;105(8):1425-9. doi: 10.1016/S0161-6420(98)98023-X.</citation>
    <PMID>9709753</PMID>
  </reference>
  <reference>
    <citation>Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, Sy JP, Schneider S; ANCHOR Study Group. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006 Oct 5;355(14):1432-44. doi: 10.1056/NEJMoa062655.</citation>
    <PMID>17021319</PMID>
  </reference>
  <reference>
    <citation>Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, Kim RY; MARINA Study Group. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006 Oct 5;355(14):1419-31. doi: 10.1056/NEJMoa054481.</citation>
    <PMID>17021318</PMID>
  </reference>
  <reference>
    <citation>Regillo CD, Brown DM, Abraham P, Yue H, Ianchulev T, Schneider S, Shams N. Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER Study year 1. Am J Ophthalmol. 2008 Feb;145(2):239-248. doi: 10.1016/j.ajo.2007.10.004.</citation>
    <PMID>18222192</PMID>
  </reference>
  <reference>
    <citation>Brown DM, Michels M, Kaiser PK, Heier JS, Sy JP, Ianchulev T; ANCHOR Study Group. Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: Two-year results of the ANCHOR study. Ophthalmology. 2009 Jan;116(1):57-65.e5. doi: 10.1016/j.ophtha.2008.10.018.</citation>
    <PMID>19118696</PMID>
  </reference>
  <reference>
    <citation>Boyer DS, Heier JS, Brown DM, Francom SF, Ianchulev T, Rubio RG. A Phase IIIb study to evaluate the safety of ranibizumab in subjects with neovascular age-related macular degeneration. Ophthalmology. 2009 Sep;116(9):1731-9. doi: 10.1016/j.ophtha.2009.05.024. Epub 2009 Jul 29.</citation>
    <PMID>19643495</PMID>
  </reference>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>August 20, 2014</study_first_submitted>
  <study_first_submitted_qc>August 20, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 21, 2014</study_first_posted>
  <results_first_submitted>February 22, 2021</results_first_submitted>
  <results_first_submitted_qc>March 24, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">March 25, 2021</results_first_posted>
  <last_update_submitted>March 24, 2021</last_update_submitted>
  <last_update_submitted_qc>March 24, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 25, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Radiation Retinopathy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Retinal Diseases</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>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 17, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/10/NCT02222610/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 14, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/10/NCT02222610/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Cohort A</title>
          <description>Subject's will receive monthly treatment of an intravitreal injection of 0.5 mg ranibizumab for 48 weeks.&#xD;
Starting at week 52, subject's will enter a treat &amp; extend regime, if a subject achieves a &quot;dry&quot; macula. For a macula to be considered &quot;dry&quot; persistent or recurrent fluid must be resolved on SD-OCT. The interval between injections will not exceed 12 weeks. After a subject is extended beyond 4-weeks &amp; develops recurrent disease activity, the eye is treated &amp; the treatment interval for the next visit is reduced by 1 week, compared to the previous treatment interval. The interval between treatments will be reduced by 1-week intervals until a dry macula is again established. Once a dry macula is again achieved, the interval between visits will be extended by 1-week intervals again.&#xD;
0.5 mg ranibizumab</description>
        </group>
        <group group_id="P2">
          <title>Cohort B</title>
          <description>Subject's receive monthly treatment of intravitreal (IVT) 0.5 mg ranibizumab for 48 weeks. 1 week after the initial dose of IVT ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) to areas of peripheral retinal ischemia based on 120° or greater wide field angiography. After the first session of TRP, subjects will have a repeat wide field angiogram at 12 weeks &amp; 24 weeks &amp; will receive additional TRP as needed (PRN) to areas of peripheral retinal ischemia.&#xD;
Starting at week 52, subject's will enter a treat &amp; extend regime as described in cohort A.&#xD;
0.5 mg ranibizumab&#xD;
Targeted Retinal Photocoagulation (TRP): TRP to areas of retinal ischemia</description>
        </group>
        <group group_id="P3">
          <title>Cohort C</title>
          <description>Subject's will receive 3 consecutive monthly doses of IVT 0.5 mg ranibizumab followed by PRN treatment with 0.5 mg ranibizumab intravitreal injection. 1 week after the initial dose of IVT ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) to areas of peripheral retinal ischemia. After the first session of TRP, subjects will have a repeat wide field angiogram at 12 weeks &amp; 24 weeks &amp; will receive additional TRP as needed (PRN) to areas of peripheral retinal ischemia.&#xD;
Starting at week 52, subject's will enter a treat &amp; extend regime as described in cohort A.&#xD;
0.5 mg ranibizumab&#xD;
Targeted Retinal Photocoagulation (TRP): TRP to areas of retinal ischemia</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Baseline to W48</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="16"/>
                <participants group_id="P3" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Baseline to W104</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="16"/>
                <participants group_id="P3" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="11"/>
                <participants group_id="P3" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="6"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Cohort A</title>
          <description>Subject's will receive monthly treatment of an intravitreal injection of 0.5 mg ranibizumab for 48 weeks.&#xD;
Starting at week 52, subject's will enter a treat &amp; extend regime, if a subject achieves a &quot;dry&quot; macula. For a macula to be considered &quot;dry&quot; persistent or recurrent fluid must be resolved on SD-OCT. The interval between injections will not exceed 12 weeks. After a subject is extended beyond 4-weeks &amp; develops recurrent disease activity, the eye is treated &amp; the treatment interval for the next visit is reduced by 1 week, compared to the previous treatment interval. The interval between treatments will be reduced by 1-week intervals until a dry macula is again established. Once a dry macula is again achieved, the interval between visits will be extended by 1-week intervals again.&#xD;
0.5 mg ranibizumab</description>
        </group>
        <group group_id="B2">
          <title>Cohort B</title>
          <description>Subject's receive monthly treatment of IVT of 0.5 mg ranibizumab for 48 weeks. 1 week after the initial dose of IVT ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) to areas of peripheral retinal ischemia based on 120° or greater wide field angiography. After the first session of TRP, subjects will have a repeat wide field angiogram at 12 weeks &amp; 24 weeks &amp; will receive additional TRP as needed (PRN) to areas of peripheral retinal ischemia.&#xD;
Starting at week 52, subject's will enter a treat &amp; extend regime as described in cohort A.&#xD;
0.5 mg ranibizumab&#xD;
Targeted Retinal Photocoagulation (TRP): TRP to areas of retinal ischemia</description>
        </group>
        <group group_id="B3">
          <title>Cohort C</title>
          <description>Subject's will receive 3 consecutive monthly doses of IVT 0.5 mg ranibizumab followed by PRN treatment with 0.5 mg ranibizumab intravitreal injection. 1 week after the initial dose of IVT ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) to areas of peripheral retinal ischemia. After the first session of TRP, subjects will have a repeat wide field angiogram at 12 weeks &amp; 24 weeks &amp; will receive additional TRP as needed (PRN) to areas of peripheral retinal ischemia.&#xD;
Starting at week 52, subject's will enter a treat &amp; extend regime as described in cohort A.&#xD;
0.5 mg ranibizumab&#xD;
Targeted Retinal Photocoagulation (TRP): TRP to areas of retinal ischemia</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="8"/>
            <count group_id="B2" value="16"/>
            <count group_id="B3" value="16"/>
            <count group_id="B4" value="40"/>
          </count_list>
        </analyzed>
        <analyzed>
          <units>Eyes</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="8"/>
            <count group_id="B2" value="16"/>
            <count group_id="B3" value="16"/>
            <count group_id="B4" value="40"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <units_analyzed>Eyes</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="66.125" lower_limit="52" upper_limit="76"/>
                    <measurement group_id="B2" value="54.813" lower_limit="29" upper_limit="72"/>
                    <measurement group_id="B3" value="60.438" lower_limit="21" upper_limit="81"/>
                    <measurement group_id="B4" value="57" lower_limit="22" upper_limit="80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <units_analyzed>Participants</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <units_analyzed>Participants</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="39"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <units_analyzed>Participants</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="16"/>
                    <measurement group_id="B4" value="39"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <units_analyzed>Participants</units_analyzed>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="16"/>
                    <measurement group_id="B4" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Best-Corrected Visual Acuity</title>
          <description>Early Treatment Diabetic Retinopathy Study (ETDRS) Best-Corrected Visual Acuity (BCVA) utilizes the ETDRS visual acuity chart to measure vision in clinical trials. Standard unit of measure is the number of letters subjects are able to read on the chart.</description>
          <units>letters</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <units_analyzed>Participants</units_analyzed>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="60.875" lower_limit="36" upper_limit="81"/>
                    <measurement group_id="B2" value="55.813" lower_limit="27" upper_limit="76"/>
                    <measurement group_id="B3" value="55.375" lower_limit="23" upper_limit="74"/>
                    <measurement group_id="B4" value="56.7" lower_limit="23" upper_limit="81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity at 104 Weeks From Day 0.</title>
        <description>Early Treatment Diabetic Retinopathy Study (ETDRS) Best-Corrected Visual Acuity (BCVA) utilizes the ETDRS visual acuity chart to measure vision in clinical trials. Standard unit of measure is the number of letters subjects are able to read on the chart.</description>
        <time_frame>104 weeks</time_frame>
        <population>Subjects analyzed only include those that completed the W104 visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort A</title>
            <description>Subject's will receive monthly treatment of an intravitreal injection of 0.5 mg ranibizumab for 48 weeks.&#xD;
Starting at week 52, subject's will enter a treat &amp; extend regime, if a subject achieves a &quot;dry&quot; macula. For a macula to be considered &quot;dry&quot; persistent or recurrent fluid must be resolved on SD-OCT. The interval between injections will not exceed 12 weeks. After a subject is extended beyond 4-weeks &amp; develops recurrent disease activity, the eye is treated &amp; the treatment interval for the next visit is reduced by 1 week, compared to the previous treatment interval. The interval between treatments will be reduced by 1-week intervals until a dry macula is again established. Once a dry macula is again achieved, the interval between visits will be extended by 1-week intervals again.&#xD;
0.5 mg ranibizumab</description>
          </group>
          <group group_id="O2">
            <title>Cohort B</title>
            <description>Subject's receive monthly treatment of IVT of 0.5 mg ranibizumab for 48 weeks. 1 week after the initial dose of IVT ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) to areas of peripheral retinal ischemia based on 120° or greater wide field angiography. After the first session of TRP, subjects will have a repeat wide field angiogram at 12 weeks &amp; 24 weeks &amp; will receive additional TRP as needed (PRN) to areas of peripheral retinal ischemia.&#xD;
Starting at week 52, subject's will enter a treat &amp; extend regime as described in cohort A.&#xD;
0.5 mg ranibizumab&#xD;
Targeted Retinal Photocoagulation (TRP): TRP to areas of retinal ischemia</description>
          </group>
          <group group_id="O3">
            <title>Cohort C</title>
            <description>Subject's will receive 3 consecutive monthly doses of IVT 0.5 mg ranibizumab followed by PRN treatment with 0.5 mg ranibizumab intravitreal injection. 1 week after the initial dose of IVT ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) to areas of peripheral retinal ischemia. After the first session of TRP, subjects will have a repeat wide field angiogram at 12 weeks &amp; 24 weeks &amp; will receive additional TRP as needed (PRN) to areas of peripheral retinal ischemia.&#xD;
Starting at week 52, subject's will enter a treat &amp; extend regime as described in cohort A.&#xD;
0.5 mg ranibizumab&#xD;
Targeted Retinal Photocoagulation (TRP): TRP to areas of retinal ischemia</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity at 104 Weeks From Day 0.</title>
          <description>Early Treatment Diabetic Retinopathy Study (ETDRS) Best-Corrected Visual Acuity (BCVA) utilizes the ETDRS visual acuity chart to measure vision in clinical trials. Standard unit of measure is the number of letters subjects are able to read on the chart.</description>
          <population>Subjects analyzed only include those that completed the W104 visit.</population>
          <units>letters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="11"/>
                <count group_id="O3" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.9" spread="7.4"/>
                    <measurement group_id="O2" value="-3.9" spread="16.5"/>
                    <measurement group_id="O3" value="1.3" spread="11.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Mean Number of Intravitreal Injections Required Per Subject Per Cohort.</title>
        <time_frame>104 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cohort A</title>
            <description>Subject's will receive monthly treatment of an intravitreal injection of 0.5 mg ranibizumab for 48 weeks.&#xD;
Starting at week 52, subject's will enter a treat &amp; extend regime, if a subject achieves a &quot;dry&quot; macula. For a macula to be considered &quot;dry&quot; persistent or recurrent fluid must be resolved on SD-OCT. The interval between injections will not exceed 12 weeks. After a subject is extended beyond 4-weeks &amp; develops recurrent disease activity, the eye is treated &amp; the treatment interval for the next visit is reduced by 1 week, compared to the previous treatment interval. The interval between treatments will be reduced by 1-week intervals until a dry macula is again established. Once a dry macula is again achieved, the interval between visits will be extended by 1-week intervals again.&#xD;
0.5 mg ranibizumab</description>
          </group>
          <group group_id="O2">
            <title>Cohort B</title>
            <description>Subject's receive monthly treatment of IVT of 0.5 mg ranibizumab for 48 weeks. 1 week after the initial dose of IVT ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) to areas of peripheral retinal ischemia based on 120° or greater wide field angiography. After the first session of TRP, subjects will have a repeat wide field angiogram at 12 weeks &amp; 24 weeks &amp; will receive additional TRP as needed (PRN) to areas of peripheral retinal ischemia.&#xD;
Starting at week 52, subject's will enter a treat &amp; extend regime as described in cohort A.&#xD;
0.5 mg ranibizumab&#xD;
Targeted Retinal Photocoagulation (TRP): TRP to areas of retinal ischemia</description>
          </group>
          <group group_id="O3">
            <title>Cohort C</title>
            <description>Subject's will receive 3 consecutive monthly doses of IVT 0.5 mg ranibizumab followed by PRN treatment with 0.5 mg ranibizumab intravitreal injection. 1 week after the initial dose of IVT ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) to areas of peripheral retinal ischemia. After the first session of TRP, subjects will have a repeat wide field angiogram at 12 weeks &amp; 24 weeks &amp; will receive additional TRP as needed (PRN) to areas of peripheral retinal ischemia.&#xD;
Starting at week 52, subject's will enter a treat &amp; extend regime as described in cohort A.&#xD;
0.5 mg ranibizumab&#xD;
Targeted Retinal Photocoagulation (TRP): TRP to areas of retinal ischemia</description>
          </group>
        </group_list>
        <measure>
          <title>The Mean Number of Intravitreal Injections Required Per Subject Per Cohort.</title>
          <units>injections</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.2" lower_limit="19" upper_limit="25"/>
                    <measurement group_id="O2" value="18.5" lower_limit="11" upper_limit="25"/>
                    <measurement group_id="O3" value="16.1" lower_limit="6" upper_limit="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Subjects With Retinal Hemorrhage at 104 Weeks.</title>
        <time_frame>104 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cohort A</title>
            <description>Subject's will receive monthly treatment of an intravitreal injection of 0.5 mg ranibizumab for 48 weeks.&#xD;
Starting at week 52, subject's will enter a treat &amp; extend regime, if a subject achieves a &quot;dry&quot; macula. For a macula to be considered &quot;dry&quot; persistent or recurrent fluid must be resolved on SD-OCT. The interval between injections will not exceed 12 weeks. After a subject is extended beyond 4-weeks &amp; develops recurrent disease activity, the eye is treated &amp; the treatment interval for the next visit is reduced by 1 week, compared to the previous treatment interval. The interval between treatments will be reduced by 1-week intervals until a dry macula is again established. Once a dry macula is again achieved, the interval between visits will be extended by 1-week intervals again.&#xD;
0.5 mg ranibizumab</description>
          </group>
          <group group_id="O2">
            <title>Cohort B</title>
            <description>Subject's receive monthly treatment of IVT of 0.5 mg ranibizumab for 48 weeks. 1 week after the initial dose of IVT ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) to areas of peripheral retinal ischemia based on 120° or greater wide field angiography. After the first session of TRP, subjects will have a repeat wide field angiogram at 12 weeks &amp; 24 weeks &amp; will receive additional TRP as needed (PRN) to areas of peripheral retinal ischemia.&#xD;
Starting at week 52, subject's will enter a treat &amp; extend regime as described in cohort A.&#xD;
0.5 mg ranibizumab&#xD;
Targeted Retinal Photocoagulation (TRP): TRP to areas of retinal ischemia</description>
          </group>
          <group group_id="O3">
            <title>Cohort C</title>
            <description>Subject's will receive 3 consecutive monthly doses of IVT 0.5 mg ranibizumab followed by PRN treatment with 0.5 mg ranibizumab intravitreal injection. 1 week after the initial dose of IVT ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) to areas of peripheral retinal ischemia. After the first session of TRP, subjects will have a repeat wide field angiogram at 12 weeks &amp; 24 weeks &amp; will receive additional TRP as needed (PRN) to areas of peripheral retinal ischemia.&#xD;
Starting at week 52, subject's will enter a treat &amp; extend regime as described in cohort A.&#xD;
0.5 mg ranibizumab&#xD;
Targeted Retinal Photocoagulation (TRP): TRP to areas of retinal ischemia</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects With Retinal Hemorrhage at 104 Weeks.</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Subjects With Intraretinal Exudates on Fundus Examination at Week 104.</title>
        <time_frame>104 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cohort A</title>
            <description>Subject's will receive monthly treatment of an intravitreal injection of 0.5 mg ranibizumab for 48 weeks.&#xD;
Starting at week 52, subject's will enter a treat &amp; extend regime, if a subject achieves a &quot;dry&quot; macula. For a macula to be considered &quot;dry&quot; persistent or recurrent fluid must be resolved on SD-OCT. The interval between injections will not exceed 12 weeks. After a subject is extended beyond 4-weeks &amp; develops recurrent disease activity, the eye is treated &amp; the treatment interval for the next visit is reduced by 1 week, compared to the previous treatment interval. The interval between treatments will be reduced by 1-week intervals until a dry macula is again established. Once a dry macula is again achieved, the interval between visits will be extended by 1-week intervals again.&#xD;
0.5 mg ranibizumab</description>
          </group>
          <group group_id="O2">
            <title>Cohort B</title>
            <description>Subject's receive monthly treatment of IVT of 0.5 mg ranibizumab for 48 weeks. 1 week after the initial dose of IVT ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) to areas of peripheral retinal ischemia based on 120° or greater wide field angiography. After the first session of TRP, subjects will have a repeat wide field angiogram at 12 weeks &amp; 24 weeks &amp; will receive additional TRP as needed (PRN) to areas of peripheral retinal ischemia.&#xD;
Starting at week 52, subject's will enter a treat &amp; extend regime as described in cohort A.&#xD;
0.5 mg ranibizumab&#xD;
Targeted Retinal Photocoagulation (TRP): TRP to areas of retinal ischemia</description>
          </group>
          <group group_id="O3">
            <title>Cohort C</title>
            <description>Subject's will receive 3 consecutive monthly doses of IVT 0.5 mg ranibizumab followed by PRN treatment with 0.5 mg ranibizumab intravitreal injection. 1 week after the initial dose of IVT ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) to areas of peripheral retinal ischemia. After the first session of TRP, subjects will have a repeat wide field angiogram at 12 weeks &amp; 24 weeks &amp; will receive additional TRP as needed (PRN) to areas of peripheral retinal ischemia.&#xD;
Starting at week 52, subject's will enter a treat &amp; extend regime as described in cohort A.&#xD;
0.5 mg ranibizumab&#xD;
Targeted Retinal Photocoagulation (TRP): TRP to areas of retinal ischemia</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects With Intraretinal Exudates on Fundus Examination at Week 104.</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change in Central Mean Thickness According to Spectral-domain Optical Coherence Tomography at Week 104 Compared to Baseline.</title>
        <description>Spectral-domain optical coherence tomography (SD-OCT) is a common imaging modality used to visualize the layers of the macula. Central mean thickness (CMT) is the length in microns from the internal limiting membrane to Bruch's membrane.</description>
        <time_frame>104 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cohort A</title>
            <description>Subject's will receive monthly treatment of an intravitreal injection of 0.5 mg ranibizumab for 48 weeks.&#xD;
Starting at week 52, subject's will enter a treat &amp; extend regime, if a subject achieves a &quot;dry&quot; macula. For a macula to be considered &quot;dry&quot; persistent or recurrent fluid must be resolved on SD-OCT. The interval between injections will not exceed 12 weeks. After a subject is extended beyond 4-weeks &amp; develops recurrent disease activity, the eye is treated &amp; the treatment interval for the next visit is reduced by 1 week, compared to the previous treatment interval. The interval between treatments will be reduced by 1-week intervals until a dry macula is again established. Once a dry macula is again achieved, the interval between visits will be extended by 1-week intervals again.&#xD;
0.5 mg ranibizumab</description>
          </group>
          <group group_id="O2">
            <title>Cohort B</title>
            <description>Subject's receive monthly treatment of IVT of 0.5 mg ranibizumab for 48 weeks. 1 week after the initial dose of IVT ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) to areas of peripheral retinal ischemia based on 120° or greater wide field angiography. After the first session of TRP, subjects will have a repeat wide field angiogram at 12 weeks &amp; 24 weeks &amp; will receive additional TRP as needed (PRN) to areas of peripheral retinal ischemia.&#xD;
Starting at week 52, subject's will enter a treat &amp; extend regime as described in cohort A.&#xD;
0.5 mg ranibizumab&#xD;
Targeted Retinal Photocoagulation (TRP): TRP to areas of retinal ischemia</description>
          </group>
          <group group_id="O3">
            <title>Cohort C</title>
            <description>Subject's will receive 3 consecutive monthly doses of IVT 0.5 mg ranibizumab followed by PRN treatment with 0.5 mg ranibizumab intravitreal injection. 1 week after the initial dose of IVT ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) to areas of peripheral retinal ischemia. After the first session of TRP, subjects will have a repeat wide field angiogram at 12 weeks &amp; 24 weeks &amp; will receive additional TRP as needed (PRN) to areas of peripheral retinal ischemia.&#xD;
Starting at week 52, subject's will enter a treat &amp; extend regime as described in cohort A.&#xD;
0.5 mg ranibizumab&#xD;
Targeted Retinal Photocoagulation (TRP): TRP to areas of retinal ischemia</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change in Central Mean Thickness According to Spectral-domain Optical Coherence Tomography at Week 104 Compared to Baseline.</title>
          <description>Spectral-domain optical coherence tomography (SD-OCT) is a common imaging modality used to visualize the layers of the macula. Central mean thickness (CMT) is the length in microns from the internal limiting membrane to Bruch's membrane.</description>
          <units>micrometers</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.5" spread="216.7"/>
                    <measurement group_id="O2" value="-87" spread="174.8"/>
                    <measurement group_id="O3" value="-74.6" spread="176.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline through 104 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Cohort A</title>
          <description>Subject's will receive monthly treatment of an intravitreal injection of 0.5 mg ranibizumab for 48 weeks.&#xD;
Starting at week 52, subject's will enter a treat &amp; extend regime, if a subject achieves a &quot;dry&quot; macula. For a macula to be considered &quot;dry&quot; persistent or recurrent fluid must be resolved on SD-OCT. The interval between injections will not exceed 12 weeks. After a subject is extended beyond 4-weeks &amp; develops recurrent disease activity, the eye is treated &amp; the treatment interval for the next visit is reduced by 1 week, compared to the previous treatment interval. The interval between treatments will be reduced by 1-week intervals until a dry macula is again established. Once a dry macula is again achieved, the interval between visits will be extended by 1-week intervals again.&#xD;
0.5 mg ranibizumab</description>
        </group>
        <group group_id="E2">
          <title>Cohort B</title>
          <description>Subject's receive monthly treatment of IVT of 0.5 mg ranibizumab for 48 weeks. 1 week after the initial dose of IVT ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) to areas of peripheral retinal ischemia based on 120° or greater wide field angiography. After the first session of TRP, subjects will have a repeat wide field angiogram at 12 weeks &amp; 24 weeks &amp; will receive additional TRP as needed (PRN) to areas of peripheral retinal ischemia.&#xD;
Starting at week 52, subject's will enter a treat &amp; extend regime as described in cohort A.&#xD;
0.5 mg ranibizumab&#xD;
Targeted Retinal Photocoagulation (TRP): TRP to areas of retinal ischemia</description>
        </group>
        <group group_id="E3">
          <title>Cohort C</title>
          <description>Subject's will receive 3 consecutive monthly doses of IVT 0.5 mg ranibizumab followed by PRN treatment with 0.5 mg ranibizumab intravitreal injection. 1 week after the initial dose of IVT ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) to areas of peripheral retinal ischemia. After the first session of TRP, subjects will have a repeat wide field angiogram at 12 weeks &amp; 24 weeks &amp; will receive additional TRP as needed (PRN) to areas of peripheral retinal ischemia.&#xD;
Starting at week 52, subject's will enter a treat &amp; extend regime as described in cohort A.&#xD;
0.5 mg ranibizumab&#xD;
Targeted Retinal Photocoagulation (TRP): TRP to areas of retinal ischemia</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Chronic Diastolic Heart Failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Chronic Atrial Fibrillation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Worsening of Hypertension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Central Retinal Artery Occlusion</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Recurrence of Choroidal Melanoma</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Metastatic Uveal Melanom</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Broken Wrist</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Chronic Renal Failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Corneal Abrasion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Dry Eyes</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Increased Cup-to-Disc Rratio</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Ocular Irritation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Ocular Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Posterior Capsular Opacification</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" events="3" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Posterior Vitreous Detachment</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="16"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Subconjunctival Hemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Worsening of Cataracts</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="16"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Amy C. Schefler</name_or_title>
      <organization>Retina Consultants of Texas</organization>
      <phone>(713) 524-3434</phone>
      <email>acsmd@retinaconsultantstexas.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02222610
org study id: ML29236
nct id: NCT02222610
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study is to assess the tolerability and efficacy of ranibizumab treatment
      administered in subjects with radiation retinopathy
RRR is a phase II, randomized, multicenter, clinical study to assess the tolerability and
      efficacy of ranibizumab treatment administered in subjects with radiation retinopathy.
      Subjects will be randomized into one of 3 arms; intravitreal (IVT) monthly vs. ranibizumab
      treatment administered IVT monthly combined with peripheral targeted photocoagulation vs.
      ranibizumab treatment administered IVT for three months followed by as needed treatment of
      ranibizumab combined with peripheral targeted photocoagulation over 48 weeks. From week 52 to
      week 101, all 3 treatment arms will employ a treat and extend protocol for IVT ranibizumab
      treatment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity at 104 Weeks From Day 0.
time frame: 104 weeks
description: Early Treatment Diabetic Retinopathy Study (ETDRS) Best-Corrected Visual Acuity (BCVA) utilizes the ETDRS visual acuity chart to measure vision in clinical trials. Standard unit of measure is the number of letters subjects are able to read on the chart.
measure: The Mean Number of Intravitreal Injections Required Per Subject Per Cohort.
time frame: 104 weeks
measure: Percentage of Subjects With Retinal Hemorrhage at 104 Weeks.
time frame: 104 weeks
measure: Percentage of Subjects With Intraretinal Exudates on Fundus Examination at Week 104.
time frame: 104 weeks
measure: Mean Change in Central Mean Thickness According to Spectral-domain Optical Coherence Tomography at Week 104 Compared to Baseline.
time frame: 104 weeks
description: Spectral-domain optical coherence tomography (SD-OCT) is a common imaging modality used to visualize the layers of the macula. Central mean thickness (CMT) is the length in microns from the internal limiting membrane to Bruch's membrane.
arm group label: Cohort A
arm group type: Experimental
description: Subject's will receive monthly treatment of an intravitreal injection of 0.5 mg ranibizumab for 48 weeks.
Starting at week 52, subject's will enter a treat & extend regime, if a subject achieves a "dry" macula. For a macula to be considered "dry" persistent or recurrent fluid must be resolved on spectral domain (SD)-optical coherence tomography (OCT). The interval between injections will not exceed 12 weeks. After a subject is extended beyond 4-weeks & develops recurrent disease activity, the eye is treated & the treatment interval for the next visit is reduced by 1 week, compared to the previous treatment interval. The interval between treatments will be reduced by 1-week intervals until a dry macula is again established. Once a dry macula is again achieved, the interval between visits will be extended by 1-week intervals again.
arm group label: Cohort B
arm group type: Experimental
description: Subject's receive monthly treatment of IVT of 0.5 mg ranibizumab for 48 weeks. 1 week after the initial dose of IVT ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) to areas of peripheral retinal ischemia based on 120° or greater wide field angiography. After the first session of TRP, subjects will have a repeat wide field angiogram at 12 weeks & 24 weeks & will receive additional TRP as needed (PRN) to areas of peripheral retinal ischemia.
Starting at week 52, subject's will enter a treat & extend regime as described in cohort A.
arm group label: Cohort C
arm group type: Experimental
description: Subject's will receive 3 consecutive monthly doses of IVT 0.5 mg ranibizumab followed by PRN treatment with 0.5 mg ranibizumab intravitreal injection. 1 week after the initial dose of IVT ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) to areas of peripheral retinal ischemia. After the first session of TRP, subjects will have a repeat wide field angiogram at 12 weeks & 24 weeks & will receive additional TRP as needed (PRN) to areas of peripheral retinal ischemia.
Starting at week 52, subject's will enter a treat & extend regime as described in cohort A.
intervention type: Drug
intervention name: 0.5 mg ranibizumab
arm group label: Cohort A
arm group label: Cohort B
arm group label: Cohort C
other name: Lucentis
intervention type: Procedure
intervention name: Targeted Retinal Photocoagulation (TRP)
description: TRP to areas of retinal ischemia
arm group label: Cohort B
arm group label: Cohort C
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Amy C Schefler, MD
role: Principal Investigator
affiliation: Retina Consultants Houston
facility: 
facility: 
facility: 
facility: 
country: United States
citation: Jampol LM, Moy CS, Murray TG, Reynolds SM, Albert DM, Schachat AP, Diddie KR, Engstrom RE Jr, Finger PT, Hovland KR, Joffe L, Olsen KR, Wells CG; Collaborative Ocular Melanoma Study Group (COMS Group). The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma: IV. Local treatment failure and enucleation in the first 5 years after brachytherapy. COMS report no. 19. Ophthalmology. 2002 Dec;109(12):2197-206. doi: 10.1016/s0161-6420(02)01277-0. Erratum In: Ophthalmology. 2004 Aug;111(8):1514.
PMID: 12466159
citation: Melia BM, Abramson DH, Albert DM, Boldt HC, Earle JD, Hanson WF, Montague P, Moy CS, Schachat AP, Simpson ER, Straatsma BR, Vine AK, Weingeist TA; Collaborative Ocular Melanoma Study Group. Collaborative ocular melanoma study (COMS) randomized trial of I-125 brachytherapy for medium choroidal melanoma. I. Visual acuity after 3 years COMS report no. 16. Ophthalmology. 2001 Feb;108(2):348-66. doi: 10.1016/s0161-6420(00)00526-1.
PMID: 11158813
citation: Gunduz K, Shields CL, Shields JA, Cater J, Freire JE, Brady LW. Radiation retinopathy following plaque radiotherapy for posterior uveal melanoma. Arch Ophthalmol. 1999 May;117(5):609-14. doi: 10.1001/archopht.117.5.609.
PMID: 10326957
citation: Finger PT, Chin KJ. High-dose (2.0 mg) intravitreal ranibizumab for recalcitrant radiation retinopathy. Eur J Ophthalmol. 2013 Nov-Dec;23(6):850-6. doi: 10.5301/ejo.5000333. Epub 2013 Jun 28.
PMID: 23813109
citation: Finger PT, Chin KJ. Intravitreous ranibizumab (lucentis) for radiation maculopathy. Arch Ophthalmol. 2010 Feb;128(2):249-52. doi: 10.1001/archophthalmol.2009.376. No abstract available.
PMID: 20142553
citation: Finger PT, Chin KJ. Antivascular endothelial growth factor bevacizumab for radiation optic neuropathy: secondary to plaque radiotherapy. Int J Radiat Oncol Biol Phys. 2012 Feb 1;82(2):789-98. doi: 10.1016/j.ijrobp.2010.11.075. Epub 2011 Jan 27.
PMID: 21277107
citation: Finger PT, Mukkamala SK. Intravitreal anti-VEGF bevacizumab (Avastin) for external beam related radiation retinopathy. Eur J Ophthalmol. 2011 Jul-Aug;21(4):446-51. doi: 10.5301/EJO.2011.6213.
PMID: 21218391
citation: Mason JO 3rd, Albert MA Jr, Persaud TO, Vail RS. Intravitreal bevacizumab treatment for radiation macular edema after plaque radiotherapy for choroidal melanoma. Retina. 2007 Sep;27(7):903-7. doi: 10.1097/IAE.0b013e31806e6042.
PMID: 17891015
citation: Finger PT. Radiation retinopathy is treatable with anti-vascular endothelial growth factor bevacizumab (Avastin). Int J Radiat Oncol Biol Phys. 2008 Mar 15;70(4):974-7. doi: 10.1016/j.ijrobp.2007.11.045.
PMID: 18313522
citation: Finger PT, Chin K. Anti-vascular endothelial growth factor bevacizumab (avastin) for radiation retinopathy. Arch Ophthalmol. 2007 Jun;125(6):751-6. doi: 10.1001/archopht.125.6.751.
PMID: 17562985
citation: Gupta A, Muecke JS. Treatment of radiation maculopathy with intravitreal injection of bevacizumab (Avastin). Retina. 2008 Jul-Aug;28(7):964-8. doi: 10.1097/IAE.0b013e3181706302.
PMID: 18698298
citation: Shields CL, Demirci H, Dai V, Marr BP, Mashayekhi A, Materin MA, Manquez ME, Shields JA. Intravitreal triamcinolone acetonide for radiation maculopathy after plaque radiotherapy for choroidal melanoma. Retina. 2005 Oct-Nov;25(7):868-74. doi: 10.1097/00006982-200510000-00009.
PMID: 16205566
citation: Finger PT, Kurli M. Laser photocoagulation for radiation retinopathy after ophthalmic plaque radiation therapy. Br J Ophthalmol. 2005 Jun;89(6):730-8. doi: 10.1136/bjo.2004.052159.
PMID: 15923510
citation: Kinyoun JL. Long-term visual acuity results of treated and untreated radiation retinopathy (an AOS thesis). Trans Am Ophthalmol Soc. 2008;106:325-35.
PMID: 19277244
citation: Hykin PG, Shields CL, Shields JA, Arevalo JF. The efficacy of focal laser therapy in radiation-induced macular edema. Ophthalmology. 1998 Aug;105(8):1425-9. doi: 10.1016/S0161-6420(98)98023-X.
PMID: 9709753
citation: Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, Sy JP, Schneider S; ANCHOR Study Group. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006 Oct 5;355(14):1432-44. doi: 10.1056/NEJMoa062655.
PMID: 17021319
citation: Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, Kim RY; MARINA Study Group. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006 Oct 5;355(14):1419-31. doi: 10.1056/NEJMoa054481.
PMID: 17021318
citation: Regillo CD, Brown DM, Abraham P, Yue H, Ianchulev T, Schneider S, Shams N. Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER Study year 1. Am J Ophthalmol. 2008 Feb;145(2):239-248. doi: 10.1016/j.ajo.2007.10.004.
PMID: 18222192
citation: Brown DM, Michels M, Kaiser PK, Heier JS, Sy JP, Ianchulev T; ANCHOR Study Group. Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: Two-year results of the ANCHOR study. Ophthalmology. 2009 Jan;116(1):57-65.e5. doi: 10.1016/j.ophtha.2008.10.018.
PMID: 19118696
citation: Boyer DS, Heier JS, Brown DM, Francom SF, Ianchulev T, Rubio RG. A Phase IIIb study to evaluate the safety of ranibizumab in subjects with neovascular age-related macular degeneration. Ophthalmology. 2009 Sep;116(9):1731-9. doi: 10.1016/j.ophtha.2009.05.024. Epub 2009 Jul 29.
PMID: 19643495
responsible party type: Sponsor
mesh term: Retinal Diseases
mesh term: Ranibizumab
sharing ipd: No
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