<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/NCT02259088</url>
  </required_header>
  <id_info>
    <org_study_id>CRFB002D2305</org_study_id>
    <nct_id>NCT02259088</nct_id>
  </id_info>
  <brief_title>A 12-month, Randomized, Efficacy and Safety Study of 0.5 mg Ranibizumab vs Laser in Chinese Diabetic Macular Edema (DME) Patients</brief_title>
  <acronym>REFINE</acronym>
  <official_title>A 12-month, Randomized, Double-masked, Multicenter, Laser-controlled Phase III Study Assessing the Efficacy and Safety of 0.5 mg Ranibizumab Dosed PRN in Subjects With Visual Impairment Due to Diabetic Macular Edema in Chinese Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Study of efficacy and safety of 0.5 mg ranibizumab in Chinese patients with diabetic macular&#xD;
      edema (DME)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this study was to provide efficacy and safety data on 0.5 mg ranibizumab&#xD;
      intravitreal injections compared to laser photocoagulation in Chinese patients with visual&#xD;
      impairment due to DME. Treatment was driven by achieving vision stabilization.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 5, 2014</start_date>
  <completion_date type="Actual">January 17, 2017</completion_date>
  <primary_completion_date type="Actual">January 17, 2017</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean Average Change From Baseline in Best-Corrected Visual Acuity (BCVA) (Letters) to Month 1 Through 12</measure>
    <time_frame>Baseline, Monthly from Month 1 through Month 12</time_frame>
    <description>Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. Twelve monthly BCVA values were averaged [(Month1+Month2+...+Month12)/12], and the baseline BCVA value was subtracted from the average. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in BCVA (Letters) at Each Visit</measure>
    <time_frame>Baseline, Monthly from Month 1 through Month 12</time_frame>
    <description>Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit</measure>
    <time_frame>Baseline, Monthly from Month 1 through Month 12</time_frame>
    <description>CSFT (the average retinal thickness of the circular area within 1 millimeter diameter around the foveal center) was assessed using Optical Coherence Tomography (OCT). A negative change value indicates an improvement in macular edema, while a positive change value indicates a worsening. One eye (study eye) contributed to the analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients With BCVA Gain of ≥ 10 and ≥ 15 Letters From Baseline at Month 12</measure>
    <time_frame>Baseline, Month 12</time_frame>
    <description>Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients With BCVA Loss of &lt; 10 and &lt; 15 Letters From Baseline to Month 12</measure>
    <time_frame>Baseline, Month 12</time_frame>
    <description>Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients With BCVA ≥ 73 Letters at Month 12</measure>
    <time_frame>Month 12</time_frame>
    <description>Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. BCVA ≥ 73 letters is approximately equivalent to 20/40 on a Snellen chart. One eye (study eye) contributed to the analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Average Change in BCVA From Month 4 to Month 12 Compared to Month 3</measure>
    <time_frame>Monthly from Month 3 through Month 12</time_frame>
    <description>Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. Nine monthly BCVA values were averaged [(Month4+Month5+...+Month12)/9],and the Month 3 BCVA value was subtracted from the average. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Patient-Reported Visual Functioning at Month 6 and Month 12, Composite Score</measure>
    <time_frame>Baseline, Month 6, Month 12</time_frame>
    <description>Visual functioning was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in visual functioning, while a negative change value indicates a worsening.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Patient-Reported General Health at Month 6 and Month 12</measure>
    <time_frame>Baseline, Month 6, Month 12</time_frame>
    <description>General health was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in general health, while a negative change value indicates a worsening.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Patient-Reported General Vision at Month 6 and Month 12</measure>
    <time_frame>Baseline, Month 6, Month 12</time_frame>
    <description>General vision was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in general vision, while a negative change value indicates a worsening.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Patient-Reported Color Vision at Month 6 and Month 12</measure>
    <time_frame>Baseline, Month 6, Month 12</time_frame>
    <description>Color vision was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in color vision, while a negative change value indicates a worsening.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Patient-Reported Peripheral Vision at Month 6 and Month 12</measure>
    <time_frame>Baseline, Month 6, Month 12</time_frame>
    <description>Peripheral vision was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in peripheral vision, while a negative change value indicates a worsening.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Patient-Reported Ocular Pain at Month 6 and Month 12</measure>
    <time_frame>Baseline, Month 6, Month 12</time_frame>
    <description>Ocular pain was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in ocular pain, while a negative change value indicates a worsening.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Patient-Reported Near Activities at Month 6 and Month 12</measure>
    <time_frame>Baseline, Month 6, Month 12</time_frame>
    <description>Near activities were assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in near activities, while a negative change value indicates a worsening.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Patient-Reported Distance Activities at Month 6 and Month 12</measure>
    <time_frame>Baseline, Month 6, Month 12</time_frame>
    <description>Distance activities were assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in distance activities, while a negative change value indicates a worsening.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Patient-Reported Social Functioning at Month 6 and Month 12</measure>
    <time_frame>Baseline, Month 6, Month 12</time_frame>
    <description>Social functioning was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in social functioning, while a negative change value indicates a worsening.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Patient-Reported Mental Health at Month 6 and Month 12</measure>
    <time_frame>Baseline, Month 6, Month 12</time_frame>
    <description>Mental health was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in mental health, while a negative change value indicates a worsening.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Patient-Reported Roles Difficulties at Month 6 and Month 12</measure>
    <time_frame>Baseline, Month 6, Month 12</time_frame>
    <description>Roles difficulties were assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in roles difficulties, while a negative change value indicates a worsening.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Patient-Reported Dependency at Month 6 and Month 12</measure>
    <time_frame>Baseline, Month 6, Month 12</time_frame>
    <description>Dependency was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in dependency, while a negative change value indicates a worsening.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Patient-Reported Driving at Month 6 and Month 12</measure>
    <time_frame>Baseline, Month 6, Month 12</time_frame>
    <description>Driving was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in driving, while a negative change value indicates a worsening. Note: Many patients did not answer the driving related question as they did not drive at all.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Number of Ranibizumab Re-treatments Received in the Study Eye From Month 3 Onward</measure>
    <time_frame>Monthly from Month 3 through Month 12</time_frame>
    <description>A ranibizumab re-treatment was defined as an administration of ranibizumab injection at a scheduled visit following at least one non-missed visit where ranibizumab was not administered in the study eye due to visual acuity stabilization. This outcome measure was pre-specified for the Ranibizumab 0.5 mg arm only.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">384</enrollment>
  <condition>Diabetic Macular Edema</condition>
  <condition>Visual Impairment</condition>
  <arm_group>
    <arm_group_label>Ranibizumab (RFB002)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Laser</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ranibizumab (RFB002)</intervention_name>
    <description>Ranibizumab 0.5 mg/0.05 mL for intravitreal injection</description>
    <arm_group_label>Ranibizumab (RFB002)</arm_group_label>
    <other_name>Lucentis</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Laser</intervention_name>
    <description>Laser photocoagulation according to Early Treatment Diabetic Retinopathy Study (ETDRS) guidelines</description>
    <arm_group_label>Laser</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sham injection</intervention_name>
    <description>Imitation of an intravitreal injection consisting of an empty vial and an injection syringe without a needle</description>
    <arm_group_label>Laser</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Sham laser</intervention_name>
    <description>Imitation of an active laser</description>
    <arm_group_label>Ranibizumab (RFB002)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Male or female Chinese patients ≥ 18 years of age with diabetes mellitus and with&#xD;
             HbA1c ≤10.0%&#xD;
&#xD;
          -  Stable medication for diabetes within 3 months prior to Visit 1&#xD;
&#xD;
          -  Visual impairment due to DME with BCVA score between 78 and 39 letters as measured by&#xD;
             ETDRS-like charts at 4 meters&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Stroke or myocardial infarction less than 3 months prior to screening visit&#xD;
&#xD;
          -  Uncontrolled hypertension&#xD;
&#xD;
          -  Active ocular infection or intraocular inflammation in any eye&#xD;
&#xD;
          -  Treatment with any anti-angiogenic drugs within 3 months prior to baseline visit in&#xD;
             any eye&#xD;
&#xD;
          -  Active proliferative diabetic retinopathy in study eye&#xD;
&#xD;
          -  Use of other investigational drugs within 30 days and systemic anti-VEGF drugs within&#xD;
             6 months prior to baseline visit&#xD;
&#xD;
          -  Prior laser photocoagulation or intraocular procedure within 3 months prior to&#xD;
             baseline in study eye&#xD;
&#xD;
          -  History of intravitreal corticosteroid treatment in phakic study eye, and in aphakic&#xD;
             or pseudophakic within 3 months prior to screening&#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>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100044</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100191</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100730</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510632</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Shantou</city>
        <state>Guangdong</state>
        <zip>515041</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Harbin</city>
        <state>Heilongjiang</state>
        <zip>150001</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Wuhan</city>
        <state>Hubei</state>
        <zip>430022</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Wuhan</city>
        <state>Hubei</state>
        <zip>430070</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Changsha</city>
        <state>Hunan</state>
        <zip>410011</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Wuxi</city>
        <state>Jiangsu</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Nanchang</city>
        <state>Jiangxi</state>
        <zip>330019</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Qingdao</city>
        <state>Shandong</state>
        <zip>2666000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Xi'an</city>
        <state>Shanxi</state>
        <zip>710032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Chengdu</city>
        <state>Sichuan</state>
        <zip>610041</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Tianjin</city>
        <state>Tianjin</state>
        <zip>300020</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Tianjin</city>
        <state>Tianjin</state>
        <zip>300070</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <zip>310003</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <zip>310014</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Wenzhou</city>
        <state>Zhejiang</state>
        <zip>325027</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Beijing</city>
        <zip>100034</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Beijing</city>
        <zip>100050</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Beijing</city>
        <zip>100053</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Beijing</city>
        <zip>100176</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Beijing</city>
        <zip>100730</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Chongqing</city>
        <zip>400042</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Shanghai</city>
        <zip>200080</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Shanghai</city>
        <zip>200092</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>October 3, 2014</study_first_submitted>
  <study_first_submitted_qc>October 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 8, 2014</study_first_posted>
  <results_first_submitted>November 29, 2017</results_first_submitted>
  <results_first_submitted_qc>January 30, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">February 1, 2019</results_first_posted>
  <last_update_submitted>January 30, 2019</last_update_submitted>
  <last_update_submitted_qc>January 30, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 1, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>DME</keyword>
  <keyword>macular edema</keyword>
  <keyword>vision impairment</keyword>
  <keyword>Chinese</keyword>
  <keyword>diabetes</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vision Disorders</mesh_term>
    <mesh_term>Vision, Low</mesh_term>
    <mesh_term>Macular Edema</mesh_term>
    <mesh_term>Edema</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ranibizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.&#xD;
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com</ipd_description>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>After eligibility confirmation, patients were randomized in a 4:1 ratio to 2 treatment arms.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Ranibizumab (RFB002)</title>
          <description>3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser</description>
        </group>
        <group group_id="P2">
          <title>Laser</title>
          <description>Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="307"/>
                <participants group_id="P2" count="77"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Full Analysis Set</title>
              <participants_list>
                <participants group_id="P1" count="307"/>
                <participants group_id="P2" count="77"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated (Safety Analysis Set)</title>
              <participants_list>
                <participants group_id="P1" count="307"/>
                <participants group_id="P2" count="75"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="279"/>
                <participants group_id="P2" count="63"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="28"/>
                <participants group_id="P2" count="14"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol deviation</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Subject/guardian decision</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Ranibizumab (RFB002)</title>
          <description>3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser</description>
        </group>
        <group group_id="B2">
          <title>Laser</title>
          <description>Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections</description>
        </group>
        <group group_id="B3">
          <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="307"/>
            <count group_id="B2" value="77"/>
            <count group_id="B3" value="384"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="58.6" spread="8.70"/>
                    <measurement group_id="B2" value="59.0" spread="9.19"/>
                    <measurement group_id="B3" value="58.7" spread="8.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="168"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="206"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="139"/>
                    <measurement group_id="B2" value="39"/>
                    <measurement group_id="B3" value="178"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Best Corrected Visual Acuity</title>
          <description>Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. One eye (study eye) contributed to the analysis.</description>
          <units>letters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59.6" spread="10.53"/>
                    <measurement group_id="B2" value="58.2" spread="9.43"/>
                    <measurement group_id="B3" value="59.3" spread="10.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Mean Average Change From Baseline in Best-Corrected Visual Acuity (BCVA) (Letters) to Month 1 Through 12</title>
        <description>Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. Twelve monthly BCVA values were averaged [(Month1+Month2+...+Month12)/12], and the baseline BCVA value was subtracted from the average. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.</description>
        <time_frame>Baseline, Monthly from Month 1 through Month 12</time_frame>
        <population>Full Analysis Set (FAS). Missing values imputed by the mean value last observation carried forward (MV-LOCF).</population>
        <group_list>
          <group group_id="O1">
            <title>Ranibizumab (RFB002)</title>
            <description>3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser</description>
          </group>
          <group group_id="O2">
            <title>Laser</title>
            <description>Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Average Change From Baseline in Best-Corrected Visual Acuity (BCVA) (Letters) to Month 1 Through 12</title>
          <description>Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. Twelve monthly BCVA values were averaged [(Month1+Month2+...+Month12)/12], and the baseline BCVA value was subtracted from the average. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.</description>
          <population>Full Analysis Set (FAS). Missing values imputed by the mean value last observation carried forward (MV-LOCF).</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="303"/>
                <count group_id="O2" value="75"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.8" spread="6.58"/>
                    <measurement group_id="O2" value="1.1" spread="7.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Cochran-Mantel-Haenszel</method>
            <method_desc>One-sided p-value for treatment difference is derived from the two-sided stratified Cochran-Mantel-Haenszel test using the row means score statistics.</method_desc>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>5.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>4.1</ci_lower_limit>
            <ci_upper_limit>7.5</ci_upper_limit>
            <estimate_desc>Estimated from ANOVA (stratified) model. Stratified analysis includes DME type (focal, diffuse, honeycomb and petaloid) and Baseline BCVA(≤ 60 letters and &gt; 60 letters) as factors.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in BCVA (Letters) at Each Visit</title>
        <description>Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.</description>
        <time_frame>Baseline, Monthly from Month 1 through Month 12</time_frame>
        <population>Full Analysis Set (FAS) with missing values imputed by the last observation carried forward (LOCF). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Ranibizumab (RFB002)</title>
            <description>3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser</description>
          </group>
          <group group_id="O2">
            <title>Laser</title>
            <description>Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in BCVA (Letters) at Each Visit</title>
          <description>Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.</description>
          <population>Full Analysis Set (FAS) with missing values imputed by the last observation carried forward (LOCF). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline 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="303"/>
                <count group_id="O2" value="75"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline at Month 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="301"/>
                    <count group_id="O2" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.0" spread="5.59"/>
                    <measurement group_id="O2" value="-0.9" spread="5.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="303"/>
                    <count group_id="O2" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.8" spread="6.44"/>
                    <measurement group_id="O2" value="0.0" spread="8.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="303"/>
                    <count group_id="O2" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.9" spread="6.91"/>
                    <measurement group_id="O2" value="1.1" spread="9.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="303"/>
                    <count group_id="O2" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.6" spread="7.23"/>
                    <measurement group_id="O2" value="0.0" spread="11.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="303"/>
                    <count group_id="O2" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.8" spread="7.41"/>
                    <measurement group_id="O2" value="0.6" spread="10.61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="303"/>
                    <count group_id="O2" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.8" spread="8.00"/>
                    <measurement group_id="O2" value="0.3" spread="11.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="303"/>
                    <count group_id="O2" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.8" spread="7.95"/>
                    <measurement group_id="O2" value="1.3" spread="10.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="303"/>
                    <count group_id="O2" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.4" spread="8.12"/>
                    <measurement group_id="O2" value="1.9" spread="9.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 9</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="303"/>
                    <count group_id="O2" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.3" spread="8.18"/>
                    <measurement group_id="O2" value="1.8" spread="9.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 10</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="303"/>
                    <count group_id="O2" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.2" spread="8.45"/>
                    <measurement group_id="O2" value="1.6" spread="9.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="303"/>
                    <count group_id="O2" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.8" spread="8.55"/>
                    <measurement group_id="O2" value="1.7" spread="9.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="303"/>
                    <count group_id="O2" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.8" spread="8.72"/>
                    <measurement group_id="O2" value="2.5" spread="8.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit</title>
        <description>CSFT (the average retinal thickness of the circular area within 1 millimeter diameter around the foveal center) was assessed using Optical Coherence Tomography (OCT). A negative change value indicates an improvement in macular edema, while a positive change value indicates a worsening. One eye (study eye) contributed to the analysis.</description>
        <time_frame>Baseline, Monthly from Month 1 through Month 12</time_frame>
        <population>Full Analysis Set (FAS) with missing values imputed by the last observation carried forward (LOCF). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Ranibizumab (RFB002)</title>
            <description>3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser</description>
          </group>
          <group group_id="O2">
            <title>Laser</title>
            <description>Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit</title>
          <description>CSFT (the average retinal thickness of the circular area within 1 millimeter diameter around the foveal center) was assessed using Optical Coherence Tomography (OCT). A negative change value indicates an improvement in macular edema, while a positive change value indicates a worsening. One eye (study eye) contributed to the analysis.</description>
          <population>Full Analysis Set (FAS) with missing values imputed by the last observation carried forward (LOCF). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.</population>
          <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="301"/>
                <count group_id="O2" value="75"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline at Month 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="299"/>
                    <count group_id="O2" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-126.7" spread="140.59"/>
                    <measurement group_id="O2" value="-33.1" spread="113.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="301"/>
                    <count group_id="O2" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-141.3" spread="146.15"/>
                    <measurement group_id="O2" value="-48.8" spread="133.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="301"/>
                    <count group_id="O2" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-154.2" spread="147.94"/>
                    <measurement group_id="O2" value="-58.5" spread="157.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="301"/>
                    <count group_id="O2" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-130.4" spread="152.60"/>
                    <measurement group_id="O2" value="-72.6" spread="149.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="301"/>
                    <count group_id="O2" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-141.0" spread="153.28"/>
                    <measurement group_id="O2" value="-72.3" spread="150.45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="301"/>
                    <count group_id="O2" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-146.2" spread="154.87"/>
                    <measurement group_id="O2" value="-72.9" spread="152.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="301"/>
                    <count group_id="O2" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-138.4" spread="161.04"/>
                    <measurement group_id="O2" value="-72.4" spread="150.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="301"/>
                    <count group_id="O2" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-146.9" spread="154.68"/>
                    <measurement group_id="O2" value="-81.8" spread="151.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 9</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="301"/>
                    <count group_id="O2" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-142.4" spread="156.03"/>
                    <measurement group_id="O2" value="-80.9" spread="157.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 10</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="301"/>
                    <count group_id="O2" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-137.6" spread="152.73"/>
                    <measurement group_id="O2" value="-82.9" spread="166.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="301"/>
                    <count group_id="O2" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-144.8" spread="159.87"/>
                    <measurement group_id="O2" value="-88.1" spread="170.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="301"/>
                    <count group_id="O2" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-146.5" spread="157.61"/>
                    <measurement group_id="O2" value="-85.9" spread="166.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Patients With BCVA Gain of ≥ 10 and ≥ 15 Letters From Baseline at Month 12</title>
        <description>Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.</description>
        <time_frame>Baseline, Month 12</time_frame>
        <population>Full Analysis Set (FAS) with missing values imputed by the last observation carried forward (LOCF).</population>
        <group_list>
          <group group_id="O1">
            <title>Ranibizumab (RFB002)</title>
            <description>3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser</description>
          </group>
          <group group_id="O2">
            <title>Laser</title>
            <description>Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients With BCVA Gain of ≥ 10 and ≥ 15 Letters From Baseline at Month 12</title>
          <description>Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.</description>
          <population>Full Analysis Set (FAS) with missing values imputed by the last observation carried forward (LOCF).</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="303"/>
                <count group_id="O2" value="75"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Gain of ≥ 10 letters</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40.6"/>
                    <measurement group_id="O2" value="20.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gain of ≥ 15 letters</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.5"/>
                    <measurement group_id="O2" value="8.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Patients With BCVA Loss of &lt; 10 and &lt; 15 Letters From Baseline to Month 12</title>
        <description>Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.</description>
        <time_frame>Baseline, Month 12</time_frame>
        <population>Full Analysis Set (FAS) with missing values imputed by the last observation carried forward (LOCF).</population>
        <group_list>
          <group group_id="O1">
            <title>Ranibizumab (RFB002)</title>
            <description>3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser</description>
          </group>
          <group group_id="O2">
            <title>Laser</title>
            <description>Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients With BCVA Loss of &lt; 10 and &lt; 15 Letters From Baseline to Month 12</title>
          <description>Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.</description>
          <population>Full Analysis Set (FAS) with missing values imputed by the last observation carried forward (LOCF).</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="303"/>
                <count group_id="O2" value="75"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Loss of &lt; 10 letters</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="97.0"/>
                    <measurement group_id="O2" value="89.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Loss of &lt;15 letters</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="99.0"/>
                    <measurement group_id="O2" value="97.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Patients With BCVA ≥ 73 Letters at Month 12</title>
        <description>Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. BCVA ≥ 73 letters is approximately equivalent to 20/40 on a Snellen chart. One eye (study eye) contributed to the analysis.</description>
        <time_frame>Month 12</time_frame>
        <population>Full Analysis Set (FAS) with missing values imputed by the last observation carried forward (LOCF).</population>
        <group_list>
          <group group_id="O1">
            <title>Ranibizumab (RFB002)</title>
            <description>3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser</description>
          </group>
          <group group_id="O2">
            <title>Laser</title>
            <description>Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients With BCVA ≥ 73 Letters at Month 12</title>
          <description>Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. BCVA ≥ 73 letters is approximately equivalent to 20/40 on a Snellen chart. One eye (study eye) contributed to the analysis.</description>
          <population>Full Analysis Set (FAS) with missing values imputed by the last observation carried forward (LOCF).</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="303"/>
                <count group_id="O2" value="75"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.0"/>
                    <measurement group_id="O2" value="21.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Average Change in BCVA From Month 4 to Month 12 Compared to Month 3</title>
        <description>Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. Nine monthly BCVA values were averaged [(Month4+Month5+...+Month12)/9],and the Month 3 BCVA value was subtracted from the average. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.</description>
        <time_frame>Monthly from Month 3 through Month 12</time_frame>
        <population>Full Analysis Set (FAS) with missing values imputed by the last observation carried forward (LOCF).</population>
        <group_list>
          <group group_id="O1">
            <title>Ranibizumab (RFB002)</title>
            <description>3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser</description>
          </group>
          <group group_id="O2">
            <title>Laser</title>
            <description>Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Average Change in BCVA From Month 4 to Month 12 Compared to Month 3</title>
          <description>Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. Nine monthly BCVA values were averaged [(Month4+Month5+...+Month12)/9],and the Month 3 BCVA value was subtracted from the average. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.</description>
          <population>Full Analysis Set (FAS) with missing values imputed by the last observation carried forward (LOCF).</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="303"/>
                <count group_id="O2" value="75"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Month 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="66.4" spread="10.66"/>
                    <measurement group_id="O2" value="59.2" spread="12.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Average Change from Baseline Month 4 to Month 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.3" spread="4.51"/>
                    <measurement group_id="O2" value="0.2" spread="6.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Patient-Reported Visual Functioning at Month 6 and Month 12, Composite Score</title>
        <description>Visual functioning was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in visual functioning, while a negative change value indicates a worsening.</description>
        <time_frame>Baseline, Month 6, Month 12</time_frame>
        <population>Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Ranibizumab (RFB002)</title>
            <description>3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser</description>
          </group>
          <group group_id="O2">
            <title>Laser</title>
            <description>Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Patient-Reported Visual Functioning at Month 6 and Month 12, Composite Score</title>
          <description>Visual functioning was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in visual functioning, while a negative change value indicates a worsening.</description>
          <population>Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="292"/>
                <count group_id="O2" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline at Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="292"/>
                    <count group_id="O2" value="68"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.5" spread="13.54"/>
                    <measurement group_id="O2" value="0.5" spread="13.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="279"/>
                    <count group_id="O2" value="64"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6" spread="14.99"/>
                    <measurement group_id="O2" value="-0.4" spread="15.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Patient-Reported General Health at Month 6 and Month 12</title>
        <description>General health was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in general health, while a negative change value indicates a worsening.</description>
        <time_frame>Baseline, Month 6, Month 12</time_frame>
        <population>Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Ranibizumab (RFB002)</title>
            <description>3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser</description>
          </group>
          <group group_id="O2">
            <title>Laser</title>
            <description>Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Patient-Reported General Health at Month 6 and Month 12</title>
          <description>General health was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in general health, while a negative change value indicates a worsening.</description>
          <population>Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="292"/>
                <count group_id="O2" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline at Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="292"/>
                    <count group_id="O2" value="68"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.5" spread="22.32"/>
                    <measurement group_id="O2" value="-0.4" spread="21.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="279"/>
                    <count group_id="O2" value="64"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.3" spread="24.34"/>
                    <measurement group_id="O2" value="-4.3" spread="26.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Patient-Reported General Vision at Month 6 and Month 12</title>
        <description>General vision was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in general vision, while a negative change value indicates a worsening.</description>
        <time_frame>Baseline, Month 6, Month 12</time_frame>
        <population>Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Ranibizumab (RFB002)</title>
            <description>3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser</description>
          </group>
          <group group_id="O2">
            <title>Laser</title>
            <description>Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Patient-Reported General Vision at Month 6 and Month 12</title>
          <description>General vision was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in general vision, while a negative change value indicates a worsening.</description>
          <population>Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="292"/>
                <count group_id="O2" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline at Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="292"/>
                    <count group_id="O2" value="68"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.2" spread="18.77"/>
                    <measurement group_id="O2" value="4.7" spread="19.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="279"/>
                    <count group_id="O2" value="64"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.9" spread="18.12"/>
                    <measurement group_id="O2" value="5.9" spread="20.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Patient-Reported Color Vision at Month 6 and Month 12</title>
        <description>Color vision was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in color vision, while a negative change value indicates a worsening.</description>
        <time_frame>Baseline, Month 6, Month 12</time_frame>
        <population>Full Analysis Set, observed data (no missing data imputations).The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Ranibizumab (RFB002)</title>
            <description>3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser</description>
          </group>
          <group group_id="O2">
            <title>Laser</title>
            <description>Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Patient-Reported Color Vision at Month 6 and Month 12</title>
          <description>Color vision was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in color vision, while a negative change value indicates a worsening.</description>
          <population>Full Analysis Set, observed data (no missing data imputations).The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="280"/>
                <count group_id="O2" value="67"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline at Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="280"/>
                    <count group_id="O2" value="67"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0" spread="16.68"/>
                    <measurement group_id="O2" value="2.2" spread="17.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="262"/>
                    <count group_id="O2" value="61"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.2" spread="21.55"/>
                    <measurement group_id="O2" value="1.6" spread="20.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Patient-Reported Peripheral Vision at Month 6 and Month 12</title>
        <description>Peripheral vision was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in peripheral vision, while a negative change value indicates a worsening.</description>
        <time_frame>Baseline, Month 6, Month 12</time_frame>
        <population>Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Ranibizumab (RFB002)</title>
            <description>3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser</description>
          </group>
          <group group_id="O2">
            <title>Laser</title>
            <description>Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Patient-Reported Peripheral Vision at Month 6 and Month 12</title>
          <description>Peripheral vision was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in peripheral vision, while a negative change value indicates a worsening.</description>
          <population>Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="291"/>
                <count group_id="O2" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline at Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="291"/>
                    <count group_id="O2" value="68"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.4" spread="20.51"/>
                    <measurement group_id="O2" value="5.5" spread="22.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="279"/>
                    <count group_id="O2" value="64"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.3" spread="25.07"/>
                    <measurement group_id="O2" value="3.1" spread="27.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Patient-Reported Ocular Pain at Month 6 and Month 12</title>
        <description>Ocular pain was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in ocular pain, while a negative change value indicates a worsening.</description>
        <time_frame>Baseline, Month 6, Month 12</time_frame>
        <population>Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Ranibizumab (RFB002)</title>
            <description>3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser</description>
          </group>
          <group group_id="O2">
            <title>Laser</title>
            <description>Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Patient-Reported Ocular Pain at Month 6 and Month 12</title>
          <description>Ocular pain was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in ocular pain, while a negative change value indicates a worsening.</description>
          <population>Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="292"/>
                <count group_id="O2" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline at Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="292"/>
                    <count group_id="O2" value="68"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.5" spread="20.71"/>
                    <measurement group_id="O2" value="1.5" spread="20.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="279"/>
                    <count group_id="O2" value="64"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3" spread="19.89"/>
                    <measurement group_id="O2" value="4.1" spread="22.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Patient-Reported Near Activities at Month 6 and Month 12</title>
        <description>Near activities were assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in near activities, while a negative change value indicates a worsening.</description>
        <time_frame>Baseline, Month 6, Month 12</time_frame>
        <population>Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Ranibizumab (RFB002)</title>
            <description>3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser</description>
          </group>
          <group group_id="O2">
            <title>Laser</title>
            <description>Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Patient-Reported Near Activities at Month 6 and Month 12</title>
          <description>Near activities were assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in near activities, while a negative change value indicates a worsening.</description>
          <population>Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="291"/>
                <count group_id="O2" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline at Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="291"/>
                    <count group_id="O2" value="68"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.6" spread="23.81"/>
                    <measurement group_id="O2" value="-1.7" spread="24.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="278"/>
                    <count group_id="O2" value="64"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6" spread="24.64"/>
                    <measurement group_id="O2" value="-3.4" spread="21.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Patient-Reported Distance Activities at Month 6 and Month 12</title>
        <description>Distance activities were assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in distance activities, while a negative change value indicates a worsening.</description>
        <time_frame>Baseline, Month 6, Month 12</time_frame>
        <population>Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Ranibizumab (RFB002)</title>
            <description>3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser</description>
          </group>
          <group group_id="O2">
            <title>Laser</title>
            <description>Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Patient-Reported Distance Activities at Month 6 and Month 12</title>
          <description>Distance activities were assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in distance activities, while a negative change value indicates a worsening.</description>
          <population>Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="292"/>
                <count group_id="O2" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline at Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="292"/>
                    <count group_id="O2" value="68"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.4" spread="20.79"/>
                    <measurement group_id="O2" value="-2.8" spread="19.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="279"/>
                    <count group_id="O2" value="64"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6" spread="23.74"/>
                    <measurement group_id="O2" value="-5.5" spread="21.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Patient-Reported Social Functioning at Month 6 and Month 12</title>
        <description>Social functioning was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in social functioning, while a negative change value indicates a worsening.</description>
        <time_frame>Baseline, Month 6, Month 12</time_frame>
        <population>Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Ranibizumab (RFB002)</title>
            <description>3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser</description>
          </group>
          <group group_id="O2">
            <title>Laser</title>
            <description>Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Patient-Reported Social Functioning at Month 6 and Month 12</title>
          <description>Social functioning was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in social functioning, while a negative change value indicates a worsening.</description>
          <population>Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="292"/>
                <count group_id="O2" value="67"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline at Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="292"/>
                    <count group_id="O2" value="67"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.1" spread="19.24"/>
                    <measurement group_id="O2" value="-1.5" spread="15.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="279"/>
                    <count group_id="O2" value="63"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.8" spread="21.58"/>
                    <measurement group_id="O2" value="-3.2" spread="18.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Patient-Reported Mental Health at Month 6 and Month 12</title>
        <description>Mental health was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in mental health, while a negative change value indicates a worsening.</description>
        <time_frame>Baseline, Month 6, Month 12</time_frame>
        <population>Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Ranibizumab (RFB002)</title>
            <description>3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser</description>
          </group>
          <group group_id="O2">
            <title>Laser</title>
            <description>Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Patient-Reported Mental Health at Month 6 and Month 12</title>
          <description>Mental health was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in mental health, while a negative change value indicates a worsening.</description>
          <population>Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="292"/>
                <count group_id="O2" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline at Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="292"/>
                    <count group_id="O2" value="68"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.8" spread="23.07"/>
                    <measurement group_id="O2" value="-0.2" spread="23.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="279"/>
                    <count group_id="O2" value="64"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.3" spread="25.05"/>
                    <measurement group_id="O2" value="0.6" spread="23.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Patient-Reported Roles Difficulties at Month 6 and Month 12</title>
        <description>Roles difficulties were assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in roles difficulties, while a negative change value indicates a worsening.</description>
        <time_frame>Baseline, Month 6, Month 12</time_frame>
        <population>Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Ranibizumab (RFB002)</title>
            <description>3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser</description>
          </group>
          <group group_id="O2">
            <title>Laser</title>
            <description>Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Patient-Reported Roles Difficulties at Month 6 and Month 12</title>
          <description>Roles difficulties were assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in roles difficulties, while a negative change value indicates a worsening.</description>
          <population>Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="292"/>
                <count group_id="O2" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline at Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="292"/>
                    <count group_id="O2" value="68"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.4" spread="27.05"/>
                    <measurement group_id="O2" value="-0.4" spread="24.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="279"/>
                    <count group_id="O2" value="64"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4" spread="27.62"/>
                    <measurement group_id="O2" value="-1.4" spread="28.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Patient-Reported Dependency at Month 6 and Month 12</title>
        <description>Dependency was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in dependency, while a negative change value indicates a worsening.</description>
        <time_frame>Baseline, Month 6, Month 12</time_frame>
        <population>Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Ranibizumab (RFB002)</title>
            <description>3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser</description>
          </group>
          <group group_id="O2">
            <title>Laser</title>
            <description>Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Patient-Reported Dependency at Month 6 and Month 12</title>
          <description>Dependency was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in dependency, while a negative change value indicates a worsening.</description>
          <population>Full Analysis Set, observed data (no missing data imputations). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="292"/>
                <count group_id="O2" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline at Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="292"/>
                    <count group_id="O2" value="68"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.2" spread="27.95"/>
                    <measurement group_id="O2" value="-4.3" spread="27.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="279"/>
                    <count group_id="O2" value="64"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.9" spread="30.47"/>
                    <measurement group_id="O2" value="-5.3" spread="27.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Patient-Reported Driving at Month 6 and Month 12</title>
        <description>Driving was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in driving, while a negative change value indicates a worsening. Note: Many patients did not answer the driving related question as they did not drive at all.</description>
        <time_frame>Baseline, Month 6, Month 12</time_frame>
        <population>Full Analysis Set, observed data (no missing data imputations).The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Ranibizumab (RFB002)</title>
            <description>3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser</description>
          </group>
          <group group_id="O2">
            <title>Laser</title>
            <description>Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Patient-Reported Driving at Month 6 and Month 12</title>
          <description>Driving was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in driving, while a negative change value indicates a worsening. Note: Many patients did not answer the driving related question as they did not drive at all.</description>
          <population>Full Analysis Set, observed data (no missing data imputations).The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from Baseline at Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="44"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.8" spread="15.87"/>
                    <measurement group_id="O2" value="2.8" spread="20.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline at Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="41"/>
                    <count group_id="O2" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.2" spread="12.29"/>
                    <measurement group_id="O2" value="4.5" spread="27.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Number of Ranibizumab Re-treatments Received in the Study Eye From Month 3 Onward</title>
        <description>A ranibizumab re-treatment was defined as an administration of ranibizumab injection at a scheduled visit following at least one non-missed visit where ranibizumab was not administered in the study eye due to visual acuity stabilization. This outcome measure was pre-specified for the Ranibizumab 0.5 mg arm only.</description>
        <time_frame>Monthly from Month 3 through Month 12</time_frame>
        <population>Safety Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>Ranibizumab (RFB002)</title>
            <description>3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Number of Ranibizumab Re-treatments Received in the Study Eye From Month 3 Onward</title>
          <description>A ranibizumab re-treatment was defined as an administration of ranibizumab injection at a scheduled visit following at least one non-missed visit where ranibizumab was not administered in the study eye due to visual acuity stabilization. This outcome measure was pre-specified for the Ranibizumab 0.5 mg arm only.</description>
          <population>Safety Analysis Set</population>
          <units>retreatments</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="301"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6" spread="0.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Day 1 through study completion, an average of 1 year</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Ranibizumab (RFB002)</title>
          <description>3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser</description>
        </group>
        <group group_id="E2">
          <title>Laser</title>
          <description>Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (19.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="57" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Angina unstable</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Arrhythmia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Cardiac failure acute</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Coronary artery disease</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Cataract (Fellow eye)</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Cataract (Study eye)</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Diabetic retinal oedema (Fellow eye)</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Diabetic retinopathy (Fellow eye)</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Eye haemorrhage (Fellow eye)</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Glaucoma (Fellow eye)</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Retinal detachment (Fellow eye)</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Vitreous haemorrhage (Fellow eye)</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Vitreous haemorrhage (Study eye)</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Pancreatitis acute</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Sudden death</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic cirrhosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Chronic sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Conjunctivitis viral (Fellow eye)</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Hepatitis B</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Herpes zoster</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Otitis media chronic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Periodontitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Ankle fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Poisoning</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetes mellitus inadequate control</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Diabetic ketoacidosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Polydipsia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Type 2 diabetes mellitus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Intervertebral disc protrusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Limb mass</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Lumbar spinal stenosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Spinal flattening</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Benign ovarian tumour</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Colon cancer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Gastric cancer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Papillary thyroid cancer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Pituitary tumour benign</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Basilar artery stenosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Cerebral infarction</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Diabetic neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Facial paralysis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Lacunar infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Vertebrobasilar insufficiency</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic kidney disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Diabetic nephropathy</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Renal arteriosclerosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Renal artery stenosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Nasal polyps</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetic dermopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Diabetic foot</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetic vascular disorder</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>3</frequency_threshold>
        <default_vocab>MedDRA (19.1)</default_vocab>
        <default_assessment>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="116" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="30" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Conjunctival haemorrhage (Study eye)</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Dry eye (Fellow eye)</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Dry eye (Study eye)</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Vitreous haemorrhage (Fellow eye)</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Vitreous haemorrhage (Study eye)</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="26" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Intraocular pressure increased (Study eye)</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperlipidaemia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetic nephropathy</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="307"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Novartis Pharmaceuticals</organization>
      <phone>862-778-8300</phone>
      <email>novartis.email@novartis.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/NCT02259088
org study id: CRFB002D2305
nct id: NCT02259088
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Study of efficacy and safety of 0.5 mg ranibizumab in Chinese patients with diabetic macular
      edema (DME)
The purpose of this study was to provide efficacy and safety data on 0.5 mg ranibizumab
      intravitreal injections compared to laser photocoagulation in Chinese patients with visual
      impairment due to DME. Treatment was driven by achieving vision stabilization.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Mean Average Change From Baseline in Best-Corrected Visual Acuity (BCVA) (Letters) to Month 1 Through 12
time frame: Baseline, Monthly from Month 1 through Month 12
description: Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. Twelve monthly BCVA values were averaged [(Month1+Month2+...+Month12)/12], and the baseline BCVA value was subtracted from the average. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.
measure: Mean Change From Baseline in BCVA (Letters) at Each Visit
time frame: Baseline, Monthly from Month 1 through Month 12
description: Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.
measure: Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit
time frame: Baseline, Monthly from Month 1 through Month 12
description: CSFT (the average retinal thickness of the circular area within 1 millimeter diameter around the foveal center) was assessed using Optical Coherence Tomography (OCT). A negative change value indicates an improvement in macular edema, while a positive change value indicates a worsening. One eye (study eye) contributed to the analysis.
measure: Percentage of Patients With BCVA Gain of ≥ 10 and ≥ 15 Letters From Baseline at Month 12
time frame: Baseline, Month 12
description: Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.
measure: Percentage of Patients With BCVA Loss of < 10 and < 15 Letters From Baseline to Month 12
time frame: Baseline, Month 12
description: Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.
measure: Percentage of Patients With BCVA ≥ 73 Letters at Month 12
time frame: Month 12
description: Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. BCVA ≥ 73 letters is approximately equivalent to 20/40 on a Snellen chart. One eye (study eye) contributed to the analysis.
measure: Mean Average Change in BCVA From Month 4 to Month 12 Compared to Month 3
time frame: Monthly from Month 3 through Month 12
description: Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. Nine monthly BCVA values were averaged [(Month4+Month5+...+Month12)/9],and the Month 3 BCVA value was subtracted from the average. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.
measure: Mean Change From Baseline in Patient-Reported Visual Functioning at Month 6 and Month 12, Composite Score
time frame: Baseline, Month 6, Month 12
description: Visual functioning was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in visual functioning, while a negative change value indicates a worsening.
measure: Mean Change From Baseline in Patient-Reported General Health at Month 6 and Month 12
time frame: Baseline, Month 6, Month 12
description: General health was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in general health, while a negative change value indicates a worsening.
measure: Mean Change From Baseline in Patient-Reported General Vision at Month 6 and Month 12
time frame: Baseline, Month 6, Month 12
description: General vision was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in general vision, while a negative change value indicates a worsening.
measure: Mean Change From Baseline in Patient-Reported Color Vision at Month 6 and Month 12
time frame: Baseline, Month 6, Month 12
description: Color vision was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in color vision, while a negative change value indicates a worsening.
measure: Mean Change From Baseline in Patient-Reported Peripheral Vision at Month 6 and Month 12
time frame: Baseline, Month 6, Month 12
description: Peripheral vision was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in peripheral vision, while a negative change value indicates a worsening.
measure: Mean Change From Baseline in Patient-Reported Ocular Pain at Month 6 and Month 12
time frame: Baseline, Month 6, Month 12
description: Ocular pain was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in ocular pain, while a negative change value indicates a worsening.
measure: Mean Change From Baseline in Patient-Reported Near Activities at Month 6 and Month 12
time frame: Baseline, Month 6, Month 12
description: Near activities were assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in near activities, while a negative change value indicates a worsening.
measure: Mean Change From Baseline in Patient-Reported Distance Activities at Month 6 and Month 12
time frame: Baseline, Month 6, Month 12
description: Distance activities were assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in distance activities, while a negative change value indicates a worsening.
measure: Mean Change From Baseline in Patient-Reported Social Functioning at Month 6 and Month 12
time frame: Baseline, Month 6, Month 12
description: Social functioning was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in social functioning, while a negative change value indicates a worsening.
measure: Mean Change From Baseline in Patient-Reported Mental Health at Month 6 and Month 12
time frame: Baseline, Month 6, Month 12
description: Mental health was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in mental health, while a negative change value indicates a worsening.
measure: Mean Change From Baseline in Patient-Reported Roles Difficulties at Month 6 and Month 12
time frame: Baseline, Month 6, Month 12
description: Roles difficulties were assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in roles difficulties, while a negative change value indicates a worsening.
measure: Mean Change From Baseline in Patient-Reported Dependency at Month 6 and Month 12
time frame: Baseline, Month 6, Month 12
description: Dependency was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in dependency, while a negative change value indicates a worsening.
measure: Mean Change From Baseline in Patient-Reported Driving at Month 6 and Month 12
time frame: Baseline, Month 6, Month 12
description: Driving was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in driving, while a negative change value indicates a worsening. Note: Many patients did not answer the driving related question as they did not drive at all.
measure: Mean Number of Ranibizumab Re-treatments Received in the Study Eye From Month 3 Onward
time frame: Monthly from Month 3 through Month 12
description: A ranibizumab re-treatment was defined as an administration of ranibizumab injection at a scheduled visit following at least one non-missed visit where ranibizumab was not administered in the study eye due to visual acuity stabilization. This outcome measure was pre-specified for the Ranibizumab 0.5 mg arm only.
arm group label: Ranibizumab (RFB002)
arm group type: Experimental
description: 3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser
arm group label: Laser
arm group type: Active Comparator
description: Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections
intervention type: Drug
intervention name: Ranibizumab (RFB002)
description: Ranibizumab 0.5 mg/0.05 mL for intravitreal injection
arm group label: Ranibizumab (RFB002)
other name: Lucentis
intervention type: Procedure
intervention name: Laser
description: Laser photocoagulation according to Early Treatment Diabetic Retinopathy Study (ETDRS) guidelines
arm group label: Laser
intervention type: Drug
intervention name: Sham injection
description: Imitation of an intravitreal injection consisting of an empty vial and an injection syringe without a needle
arm group label: Laser
intervention type: Procedure
intervention name: Sham laser
description: Imitation of an active laser
arm group label: Ranibizumab (RFB002)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
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country: China
responsible party type: Sponsor
mesh term: Vision Disorders
mesh term: Vision, Low
mesh term: Macular Edema
mesh term: Edema
mesh term: Ranibizumab
sharing ipd: Undecided
ipd description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
participant flow: 
baseline: 
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reported events: 
certain agreements: 
point of contact: 