<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/NCT02227147</url>
  </required_header>
  <id_info>
    <org_study_id>NGF0214</org_study_id>
    <nct_id>NCT02227147</nct_id>
  </id_info>
  <brief_title>Evaluation of Efficacy of 20 µg/ml rhNGF New Formulation (With Anti-oxidant) in Patients With Stage 2 and 3 NK</brief_title>
  <official_title>An 8-week Phase II, Multicenter, Randomized, Double-masked, Vehicle Controlled Parallel Group Study With a 24 or 32 Week Follow-up to Evaluate the Efficacy of rhNGF 20 µg/ml vs Vehicle in Patients With Stage 2 and 3 Neurotrophic Keratitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dompé Farmaceutici S.p.A</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Dompé Farmaceutici S.p.A</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to evaluate the efficacy of 20 µg/ml 6 times a day of&#xD;
      rhNGF eye drops solution (formulation containing anti-oxidant) compared to vehicle&#xD;
      (formulation containing anti-oxidant) given 6 times a day. The evaluation of efficacy is&#xD;
      intended as:&#xD;
&#xD;
        -  complete healing of stage 2 (persistent epithelial defect) and 3 (corneal ulcer)&#xD;
           neurotrophic keratitis (NK) as measured by the central reading center using corneal&#xD;
           fluorescein staining,&#xD;
&#xD;
        -  assessing the duration of complete healing,&#xD;
&#xD;
        -  improvement in visual acuity and improvement in corneal sensitivity.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      An 8-week phase II, multicenter, randomized, double-masked, vehicle-controlled, parallel&#xD;
      group study with a 24 or 32 week follow-up period to evaluate the efficacy of a formulation&#xD;
      containing anti-oxidant of recombinant human nerve growth factor (rhNGF) in 20 μg/ml, eye&#xD;
      drops solution versus vehicle containing anti-oxidant in patients with Stage 2 and 3&#xD;
      Neurotrophic Keratitis. The primary objective was to evaluate the efficacy of 20 μg/ml 6&#xD;
      times a day of recombinant human nerve growth factor (rhNGF) containing anti-oxidant, eye&#xD;
      drops solution compared to vehicle (formulation containing anti-oxidant) given 6 times a day&#xD;
      in inducing a complete healing of stage 2 (PED) and 3 (corneal ulcer) NK as measured by the&#xD;
      central reading center, evaluating the clinical pictures of corneal fluorescein staining.&#xD;
&#xD;
      Secondary objectives were to assess the duration of complete healing, improvement in visual&#xD;
      acuity and improvement in corneal sensitivity, and percentage of patients achieving complete&#xD;
      corneal clearing defined as complete absence of staining on the modified Oxford Scale.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 2015</start_date>
  <completion_date type="Actual">September 2016</completion_date>
  <primary_completion_date type="Actual">June 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Complete Healing of the Persistent Epithelial Defect (PED) or Corneal Ulcer Defined by Central Reviewer</measure>
    <time_frame>Week 8</time_frame>
    <description>Percentage of patients achieving complete healing of the PED or corneal ulcer determined by corneal fluorescein staining at 8 weeks as defined by the central reading center on clinical pictures.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Complete Healing of the Persistent Epithelial Defect (PED) or Corneal Ulcer Defined by the Investigator</measure>
    <time_frame>Week 8</time_frame>
    <description>Percentage of patients experiencing complete healing of the PED or corneal ulcer determined by corneal fluorescein staining at 8 weeks as measured by the investigator.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complete Healing of the Persistent Epithelial Defect (PED) or Corneal Ulcer Defined by Central Reading Center and Investigator.</measure>
    <time_frame>At weeks 4 and 6</time_frame>
    <description>Percentage of patients experiencing complete healing of the PED or corneal ulcer at 4, and 6 weeks as measured by the central reading center evaluating the clinical pictures and investigator.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients With Complete Corneal Clearing</measure>
    <time_frame>at weeks 4, 6, and 8</time_frame>
    <description>Percentage of patients with complete corneal clearing at weeks 4, 6, and 8 defined as grade 0 on the modified Oxford scale. Grade 0 indicates the absence of conjunctival staining; grade V indicates severe conjunctival staining.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA)</measure>
    <time_frame>Baseline, Week 8</time_frame>
    <description>Change in Best Corrected Distance Visual Acuity (BCDVA) from baseline to Week 8.&#xD;
Best Corrected Distance Visual Acuity consists of letters read at 4m only.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients That Achieve a 15 Letter Gain in BCDVA</measure>
    <time_frame>Weeks 4, week 6 and week 8</time_frame>
    <description>Percentage of patients that achieve a 15 letter gain in Best Corrected Distance Visual Acuity (BCDVA) at 4 weeks, 6 weeks, 8 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement in Corneal Sensitivity</measure>
    <time_frame>At 4, 6 and 8 weeks after start of the treatment</time_frame>
    <description>Improvement in corneal sensitivity was measured by the Cochet-Bonnet aesthesiometer at 4, 6 and 8 weeks.&#xD;
Corneal sensitivity is measured continuously in each patient in cm:&#xD;
Area of the Persistent Epithelial Defect (PED) or corneal ulcer&#xD;
All quadrants, but outside the PED or corneal ulcer area: Superior nasal, inferior nasal, superior temporal, inferior temporal.&#xD;
Improvement is defined as an increase of at least 0.5 cm in the location of concern.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients Experiencing Deterioration</measure>
    <time_frame>from baseline to Week 8.</time_frame>
    <description>Number of patients experiencing deterioration (increase in lesion size ≥ 1mm and/or decrease in BCDVA by &gt;5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters and/or progression in lesion depth to corneal melting or perforation and/or onset of infection) in stage 2 or 3 NK from baseline to Week 8.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>Neurotrophic Keratitis</condition>
  <arm_group>
    <arm_group_label>rhNGF 20 µg/ml</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>rhNGF 20 µg/ml eye drops solution, formulation containing anti-oxidant</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Vehicle: formulation containing anti-oxidant</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>rhNGF 20µg/ml</intervention_name>
    <arm_group_label>rhNGF 20 µg/ml</arm_group_label>
    <other_name>cenegermin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Formulation containing antioxidant</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Vehicle</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients 18 years of age or older.&#xD;
&#xD;
          -  Patients with stage 2 (persistent epithelial defect, PED) or stage 3 (corneal ulcer)&#xD;
             neurotrophic keratitis (NK).&#xD;
&#xD;
          -  PED or corneal ulceration of at least 2 weeks duration refractory to one or more&#xD;
             conventional non-surgical treatments for neurotrophic keratitis.&#xD;
&#xD;
          -  Evidence of decreased corneal sensitivity (≤ 4 cm using the Cochet-Bonnet&#xD;
             aesthesiometer) within the area of the PED or corneal ulcer and outside of the area of&#xD;
             the defect in at least one corneal quadrant.&#xD;
&#xD;
          -  Best corrected distance visual acuity (BCDVA) score ≤ 75 ETDRS (Early Treatment&#xD;
             Diabetic Retinopathy Study)letters, (≥ 0.2 LogMAR, ≤ 20/32 Snellen or ≤ 0.625 decimal&#xD;
             fraction) in the affected eye(s).&#xD;
&#xD;
          -  No objective clinical evidence of improvement in the PED or corneal ulceration within&#xD;
             the 2 weeks prior to study enrolment.&#xD;
&#xD;
          -  Only patients who satisfy all Informed Consent requirements may be included in the&#xD;
             study. The patient and/or his/her legal representative must read, sign and date the&#xD;
             Informed Consent document before any study-related procedures are performed. The&#xD;
             Informed Consent form signed by patients and/or legal representative must have been&#xD;
             approved by the IRB (Institutional Review Board) for the current study.&#xD;
&#xD;
          -  Patients must have the ability and willingness to comply with study procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any active ocular infection or active ocular inflammation not related to NK in the&#xD;
             affected eye(s).&#xD;
&#xD;
          -  Any other ocular disease requiring topical ocular treatment during the course of the&#xD;
             study treatment period. No topical treatments other than the study medications&#xD;
             provided by the study sponsor and allowed by the study protocol can be administered in&#xD;
             the affected eye(s) during the course of the study treatment periods.&#xD;
&#xD;
          -  Patients with severe vision loss with no potential for visual improvement in the&#xD;
             opinion of the investigator as a result of the study treatment.&#xD;
&#xD;
          -  Schirmer test without anesthesia ≤3 mm/5 minutes.&#xD;
&#xD;
          -  Patients with severe blepharitis and/or severe meibomian gland disease.&#xD;
&#xD;
          -  History of any ocular surgery (including laser or refractive surgical procedures)&#xD;
             within the three months before study enrolment. (An exception to the preceding&#xD;
             statement will be allowed if the ocular surgery is considered to be the cause of the&#xD;
             stage 2 or 3 NK). Ocular surgery will not be allowed during the study treatment period&#xD;
             and elective ocular surgery procedures should not be planned during the duration of&#xD;
             the follow-up period.&#xD;
&#xD;
          -  Prior surgical procedure(s) for the treatment of NK with the exception of amniotic&#xD;
             membrane transplantation. Patients previously treated with amniotic membrane&#xD;
             transplantation may only be enrolled two weeks after the membrane has disappeared&#xD;
             within the area of the PED or corneal ulcer or at least six weeks after the date of&#xD;
             the amniotic membrane transplantation procedure.&#xD;
&#xD;
          -  Patients previously treated with Botox injections used to induce pharmacologic&#xD;
             blepharoptosis are eligible for enrolment only if the last injection was given at&#xD;
             least 90 days prior to enrolment in the study.&#xD;
&#xD;
          -  Anticipated need to use therapeutic contact lenses or contact lens wear for refractive&#xD;
             correction during the study treatment period in the eye(s) with NK.&#xD;
&#xD;
          -  Anticipated need for punctual occlusion during the study treatment period. Patients&#xD;
             with punctual occlusion or punctual plugs inserted prior to the study are eligible for&#xD;
             enrolment provided that the punctual occlusion is maintained during the study.&#xD;
&#xD;
          -  Evidence of corneal ulceration involving the posterior third of the corneal stroma,&#xD;
             corneal melting or perforation.&#xD;
&#xD;
          -  Presence or history of any ocular or systemic disorder or condition that might hinder&#xD;
             the efficacy of the study treatment or its evaluation, could possibly interfere with&#xD;
             the interpretation of study results, or could be judged by the investigator to be&#xD;
             incompatible with the study visit schedule or conduct.&#xD;
&#xD;
          -  Any need for or anticipated change in the dose of systemic medications known to impair&#xD;
             the function of the trigeminal nerve. These treatments are allowed during the study if&#xD;
             initiated prior study enrolment provided they remain stable throughout the course of&#xD;
             the study treatment periods.&#xD;
&#xD;
          -  Known hypersensitivity to one of the components of the study or procedural medications&#xD;
             (e.g. fluorescein).&#xD;
&#xD;
          -  History of drug, medication or alcohol abuse or addiction.&#xD;
&#xD;
          -  Use of any investigational agent within 4 weeks of screening visit.&#xD;
&#xD;
          -  Participation in another clinical study at the same time as the present study.&#xD;
&#xD;
          -  Females of childbearing potential are excluded from participation in the study if they&#xD;
             meet any one of the following conditions: are currently pregnant or, have a positive&#xD;
             result on the urine pregnancy test at the Randomization Visit or, intend to become&#xD;
             pregnant during the study treatment period or, are breast-feeding or are not willing&#xD;
             to use highly effective birth control measures.&#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>Flavio Mantelli, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Dompé farmaceutici S.p.A., Milan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Loma Linda University Ophthalmology</name>
      <address>
        <city>Loma Linda</city>
        <state>California</state>
        <zip>92354</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jules Stein Eye Institute</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shiley Eye Center University of California</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bascom Palmer Eye Institute University of Miami</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33324</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tufts Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts Eye &amp; Ear Infirmary</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts Eye Research and Surgery Institution</name>
      <address>
        <city>Cambridge</city>
        <state>Massachusetts</state>
        <zip>02451</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York Eye and Ear Infirmary</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10003</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Penn Eye Care Scheie Eye Institute</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC eye center, department of ophthalmology, University of Pittsburgh</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor College of Medicine</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>August 26, 2014</study_first_submitted>
  <study_first_submitted_qc>August 26, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 27, 2014</study_first_posted>
  <results_first_submitted>January 25, 2019</results_first_submitted>
  <results_first_submitted_qc>June 13, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">June 14, 2019</results_first_posted>
  <last_update_submitted>December 5, 2022</last_update_submitted>
  <last_update_submitted_qc>December 5, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Neurotrophic Keratitis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Keratitis</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Recruitment was competitive among the study sites, until the planned number of patients were randomized.&#xD;
Competitive recruitment was chosen to increase the speed of recruitment and to account for any difference in enrolment rate among study sites.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>rhNGF 20 µg/ml</title>
          <description>rhNGF 20 µg/ml eye drops solution, formulation containing anti-oxidant&#xD;
rhNGF 20µg/ml</description>
        </group>
        <group group_id="P2">
          <title>Vehicle</title>
          <description>vehicle, formulation containing anti-oxidant&#xD;
Placebo Vehicle</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Controlled Treatment Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
                <participants group_id="P2" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Follow-up Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>ITT population</population>
      <group_list>
        <group group_id="B1">
          <title>rhNGF 20 µg/ml</title>
          <description>rhNGF 20 µg/ml eye drops solution, formulation containing anti-oxidant&#xD;
rhNGF 20µg/ml</description>
        </group>
        <group group_id="B2">
          <title>Vehicle</title>
          <description>vehicle, formulation containing anti-oxidant&#xD;
Placebo Vehicle</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="24"/>
            <count group_id="B2" value="24"/>
            <count group_id="B3" value="48"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="65.9" spread="13.85"/>
                    <measurement group_id="B2" value="54.5" spread="14.15"/>
                    <measurement group_id="B3" value="65.2" spread="13.87"/>
                  </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="14"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Complete Healing of the Persistent Epithelial Defect (PED) or Corneal Ulcer Defined by Central Reviewer</title>
        <description>Percentage of patients achieving complete healing of the PED or corneal ulcer determined by corneal fluorescein staining at 8 weeks as defined by the central reading center on clinical pictures.</description>
        <time_frame>Week 8</time_frame>
        <population>ITT population, LOCF. One patient (randomized to rhNGF although not eligible) had no post-baseline data, was assumed to be missing, and was excluded from the analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>rhNGF 20 µg/ml</title>
            <description>rhNGF 20 µg/ml eye drops solution, formulation containing anti-oxidant&#xD;
rhNGF 20µg/ml</description>
          </group>
          <group group_id="O2">
            <title>Vehicle</title>
            <description>vehicle, formulation containing anti-oxidant&#xD;
Placebo Vehicle</description>
          </group>
        </group_list>
        <measure>
          <title>Complete Healing of the Persistent Epithelial Defect (PED) or Corneal Ulcer Defined by Central Reviewer</title>
          <description>Percentage of patients achieving complete healing of the PED or corneal ulcer determined by corneal fluorescein staining at 8 weeks as defined by the central reading center on clinical pictures.</description>
          <population>ITT population, LOCF. One patient (randomized to rhNGF although not eligible) had no post-baseline data, was assumed to be missing, and was excluded from the analyses.</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="23"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Completely healed</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70"/>
                    <measurement group_id="O2" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not completely healed</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30"/>
                    <measurement group_id="O2" value="71"/>
                  </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</non_inferiority_type>
            <p_value>=0.006</p_value>
            <method>Chi-squared</method>
            <param_type>Difference in percentage</param_type>
            <param_value>40.4</param_value>
            <ci_percent>90.00</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>14.2</ci_lower_limit>
            <ci_upper_limit>66.6</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Complete Healing of the Persistent Epithelial Defect (PED) or Corneal Ulcer Defined by the Investigator</title>
        <description>Percentage of patients experiencing complete healing of the PED or corneal ulcer determined by corneal fluorescein staining at 8 weeks as measured by the investigator.</description>
        <time_frame>Week 8</time_frame>
        <population>ITT population, LOCF. One patient (randomized to rhNGF although not eligible) had no post-baseline data, was assumed to be missing, and was excluded from the analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>rhNGF 20 µg/ml</title>
            <description>rhNGF 20 µg/ml eye drops solution, formulation containing anti-oxidant&#xD;
rhNGF 20µg/ml</description>
          </group>
          <group group_id="O2">
            <title>Vehicle</title>
            <description>vehicle, formulation containing anti-oxidant&#xD;
Placebo Vehicle</description>
          </group>
        </group_list>
        <measure>
          <title>Complete Healing of the Persistent Epithelial Defect (PED) or Corneal Ulcer Defined by the Investigator</title>
          <description>Percentage of patients experiencing complete healing of the PED or corneal ulcer determined by corneal fluorescein staining at 8 weeks as measured by the investigator.</description>
          <population>ITT population, LOCF. One patient (randomized to rhNGF although not eligible) had no post-baseline data, was assumed to be missing, and was excluded from the analyses.</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="23"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Completely healed</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="65"/>
                    <measurement group_id="O2" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not completely healed</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35"/>
                    <measurement group_id="O2" value="71"/>
                  </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</non_inferiority_type>
            <p_value>=0.013</p_value>
            <method>Chi-squared</method>
            <param_type>Difference in percentage</param_type>
            <param_value>36.1</param_value>
            <ci_percent>95.0</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>9.4</ci_lower_limit>
            <ci_upper_limit>62.7</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Complete Healing of the Persistent Epithelial Defect (PED) or Corneal Ulcer Defined by Central Reading Center and Investigator.</title>
        <description>Percentage of patients experiencing complete healing of the PED or corneal ulcer at 4, and 6 weeks as measured by the central reading center evaluating the clinical pictures and investigator.</description>
        <time_frame>At weeks 4 and 6</time_frame>
        <population>LOCF, ITT population. One patient (randomized to rhNGF although not eligible) had no post-baseline data, was assumed to be missing, and was excluded from the analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>rhNGF 20 µg/ml</title>
            <description>rhNGF 20 µg/ml eye drops solution, formulation containing anti-oxidant&#xD;
rhNGF 20µg/ml</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Vehicle: formulation containing anti-oxidant&#xD;
Placebo: Formulation containing antioxidant</description>
          </group>
        </group_list>
        <measure>
          <title>Complete Healing of the Persistent Epithelial Defect (PED) or Corneal Ulcer Defined by Central Reading Center and Investigator.</title>
          <description>Percentage of patients experiencing complete healing of the PED or corneal ulcer at 4, and 6 weeks as measured by the central reading center evaluating the clinical pictures and investigator.</description>
          <population>LOCF, ITT population. One patient (randomized to rhNGF although not eligible) had no post-baseline data, was assumed to be missing, and was excluded from the analyses.</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="23"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 4 - central reviewer - yes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="56"/>
                    <measurement group_id="O2" value="38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4 - central reviewer - no</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44"/>
                    <measurement group_id="O2" value="62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6 - central reviewer - yes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="56"/>
                    <measurement group_id="O2" value="46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6 - central reviewer - no</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44"/>
                    <measurement group_id="O2" value="54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4 - investigator - yes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="56"/>
                    <measurement group_id="O2" value="42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4 - investigator - no</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44"/>
                    <measurement group_id="O2" value="58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6 - investigator - yes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="65"/>
                    <measurement group_id="O2" value="42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6 - investigator - no</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35"/>
                    <measurement group_id="O2" value="58"/>
                  </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>
            <groups_desc>week 4 - central reviewer</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.191</p_value>
            <method>Chi-squared</method>
            <param_type>difference in percentage</param_type>
            <param_value>19.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-9.0</ci_lower_limit>
            <ci_upper_limit>47.1</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>week 6 - central reviewer</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.464</p_value>
            <method>Chi-squared</method>
            <param_type>difference in percentage</param_type>
            <param_value>10.7</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-17.7</ci_lower_limit>
            <ci_upper_limit>39.1</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>week 4 - investigator</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.308</p_value>
            <method>Chi-squared</method>
            <param_type>difference in percentage</param_type>
            <param_value>14.9</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-13.4</ci_lower_limit>
            <ci_upper_limit>43.1</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>week 6 - investigator</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.106</p_value>
            <method>Chi-squared</method>
            <param_type>difference in percentage</param_type>
            <param_value>23.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.2</ci_lower_limit>
            <ci_upper_limit>51.3</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Patients With Complete Corneal Clearing</title>
        <description>Percentage of patients with complete corneal clearing at weeks 4, 6, and 8 defined as grade 0 on the modified Oxford scale. Grade 0 indicates the absence of conjunctival staining; grade V indicates severe conjunctival staining.</description>
        <time_frame>at weeks 4, 6, and 8</time_frame>
        <population>LOCF, ITT population. Two patients (randomized to rhNGF although not eligible) had no post-baseline data, were assumed to be missing, and were excluded from the analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>rhNGF 20 µg/ml</title>
            <description>rhNGF 20 µg/ml eye drops solution, formulation containing anti-oxidant&#xD;
rhNGF 20µg/ml</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Vehicle: formulation containing anti-oxidant&#xD;
Placebo: Formulation containing antioxidant</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients With Complete Corneal Clearing</title>
          <description>Percentage of patients with complete corneal clearing at weeks 4, 6, and 8 defined as grade 0 on the modified Oxford scale. Grade 0 indicates the absence of conjunctival staining; grade V indicates severe conjunctival staining.</description>
          <population>LOCF, ITT population. Two patients (randomized to rhNGF although not eligible) had no post-baseline data, were assumed to be missing, and were excluded from the analyses.</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="22"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 4 - yes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4 - no</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="86"/>
                    <measurement group_id="O2" value="96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6 - yes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6 - no</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="91"/>
                    <measurement group_id="O2" value="92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8 - yes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8 - no</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="77"/>
                    <measurement group_id="O2" value="96"/>
                  </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>
            <groups_desc>week 4</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.255</p_value>
            <method>Chi-squared</method>
            <param_type>difference in percentage</param_type>
            <param_value>9.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-6.9</ci_lower_limit>
            <ci_upper_limit>25.9</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>week 6</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.927</p_value>
            <method>Chi-squared</method>
            <param_type>difference in percentage</param_type>
            <param_value>0.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-15.6</ci_lower_limit>
            <ci_upper_limit>17.1</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>week 8</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.062</p_value>
            <method>Chi-squared</method>
            <param_type>difference in percentage</param_type>
            <param_value>18.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.7</ci_lower_limit>
            <ci_upper_limit>37.8</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA)</title>
        <description>Change in Best Corrected Distance Visual Acuity (BCDVA) from baseline to Week 8.&#xD;
Best Corrected Distance Visual Acuity consists of letters read at 4m only.</description>
        <time_frame>Baseline, Week 8</time_frame>
        <population>LOCF, ITT Population</population>
        <group_list>
          <group group_id="O1">
            <title>rhNGF 20 µg/ml</title>
            <description>rhNGF 20 µg/ml eye drops solution, formulation containing anti-oxidant&#xD;
rhNGF 20µg/ml</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Vehicle: formulation containing anti-oxidant&#xD;
Placebo: Formulation containing antioxidant</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA)</title>
          <description>Change in Best Corrected Distance Visual Acuity (BCDVA) from baseline to Week 8.&#xD;
Best Corrected Distance Visual Acuity consists of letters read at 4m only.</description>
          <population>LOCF, ITT Population</population>
          <units>letters read correctly</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="23"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.48" spread="9.25"/>
                    <measurement group_id="O2" value="4.33" spread="10.399"/>
                  </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</non_inferiority_type>
            <p_value>=0.745</p_value>
            <method>ANCOVA</method>
            <param_type>difference in least square means</param_type>
            <param_value>1.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-5.6</ci_lower_limit>
            <ci_upper_limit>7.7</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Patients That Achieve a 15 Letter Gain in BCDVA</title>
        <description>Percentage of patients that achieve a 15 letter gain in Best Corrected Distance Visual Acuity (BCDVA) at 4 weeks, 6 weeks, 8 weeks</description>
        <time_frame>Weeks 4, week 6 and week 8</time_frame>
        <population>LOCF, ITT population</population>
        <group_list>
          <group group_id="O1">
            <title>rhNGF 20 µg/ml</title>
            <description>rhNGF 20 µg/ml eye drops solution, formulation containing anti-oxidant&#xD;
rhNGF 20µg/ml</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Vehicle: formulation containing anti-oxidant&#xD;
Placebo: Formulation containing antioxidant</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients That Achieve a 15 Letter Gain in BCDVA</title>
          <description>Percentage of patients that achieve a 15 letter gain in Best Corrected Distance Visual Acuity (BCDVA) at 4 weeks, 6 weeks, 8 weeks</description>
          <population>LOCF, ITT population</population>
          <units>percentage of subjects</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>week 4 - yes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 4 - no</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="91"/>
                    <measurement group_id="O2" value="88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 6 - yes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 6 - no</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="87"/>
                    <measurement group_id="O2" value="88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 8 -yes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 8 - no</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="87"/>
                    <measurement group_id="O2" value="83"/>
                  </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>
            <groups_desc>week 4</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.672</p_value>
            <method>Chi-squared</method>
            <param_type>difference in percentage</param_type>
            <param_value>-3.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-21.3</ci_lower_limit>
            <ci_upper_limit>13.7</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>week 6</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.955</p_value>
            <method>Chi-squared</method>
            <param_type>difference in percentage</param_type>
            <param_value>0.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-18.5</ci_lower_limit>
            <ci_upper_limit>19.6</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>week 8</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.727</p_value>
            <method>Chi-squared</method>
            <param_type>difference in percentage</param_type>
            <param_value>-3.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-23.9</ci_lower_limit>
            <ci_upper_limit>16.7</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Improvement in Corneal Sensitivity</title>
        <description>Improvement in corneal sensitivity was measured by the Cochet-Bonnet aesthesiometer at 4, 6 and 8 weeks.&#xD;
Corneal sensitivity is measured continuously in each patient in cm:&#xD;
Area of the Persistent Epithelial Defect (PED) or corneal ulcer&#xD;
All quadrants, but outside the PED or corneal ulcer area: Superior nasal, inferior nasal, superior temporal, inferior temporal.&#xD;
Improvement is defined as an increase of at least 0.5 cm in the location of concern.</description>
        <time_frame>At 4, 6 and 8 weeks after start of the treatment</time_frame>
        <population>ITT population</population>
        <group_list>
          <group group_id="O1">
            <title>rhNGF 20 µg/ml</title>
            <description>rhNGF 20 µg/ml eye drops solution, formulation containing anti-oxidant&#xD;
rhNGF 20µg/ml</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Vehicle: formulation containing anti-oxidant&#xD;
Placebo: Formulation containing antioxidant</description>
          </group>
        </group_list>
        <measure>
          <title>Improvement in Corneal Sensitivity</title>
          <description>Improvement in corneal sensitivity was measured by the Cochet-Bonnet aesthesiometer at 4, 6 and 8 weeks.&#xD;
Corneal sensitivity is measured continuously in each patient in cm:&#xD;
Area of the Persistent Epithelial Defect (PED) or corneal ulcer&#xD;
All quadrants, but outside the PED or corneal ulcer area: Superior nasal, inferior nasal, superior temporal, inferior temporal.&#xD;
Improvement is defined as an increase of at least 0.5 cm in the location of concern.</description>
          <population>ITT population</population>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.50" spread="1.821"/>
                    <measurement group_id="O2" value="1.56" spread="1.983"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.26" spread="2.009"/>
                    <measurement group_id="O2" value="1.84" spread="2.150"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.91" spread="2.144"/>
                    <measurement group_id="O2" value="1.83" spread="1.952"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline to week 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.88" spread="1.401"/>
                    <measurement group_id="O2" value="1.00" spread="1.254"/>
                  </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</non_inferiority_type>
            <p_value>=0.207</p_value>
            <method>ANCOVA</method>
            <param_type>least square mean difference</param_type>
            <param_value>0.6</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.4</ci_lower_limit>
            <ci_upper_limit>1.5</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Patients Experiencing Deterioration</title>
        <description>Number of patients experiencing deterioration (increase in lesion size ≥ 1mm and/or decrease in BCDVA by &gt;5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters and/or progression in lesion depth to corneal melting or perforation and/or onset of infection) in stage 2 or 3 NK from baseline to Week 8.</description>
        <time_frame>from baseline to Week 8.</time_frame>
        <population>ITT population. As far as this endpoint is concerned, data are available (non-missing) for 18 patients out of 24 in the rhNGF group, and for 15 patients out of 24 for the vehicle group.</population>
        <group_list>
          <group group_id="O1">
            <title>rhNGF 20 µg/ml</title>
            <description>rhNGF 20 µg/ml eye drops solution, formulation containing anti-oxidant&#xD;
rhNGF 20µg/ml</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Vehicle: formulation containing anti-oxidant&#xD;
Placebo: Formulation containing antioxidant</description>
          </group>
        </group_list>
        <measure>
          <title>Patients Experiencing Deterioration</title>
          <description>Number of patients experiencing deterioration (increase in lesion size ≥ 1mm and/or decrease in BCDVA by &gt;5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters and/or progression in lesion depth to corneal melting or perforation and/or onset of infection) in stage 2 or 3 NK from baseline to Week 8.</description>
          <population>ITT population. As far as this endpoint is concerned, data are available (non-missing) for 18 patients out of 24 in the rhNGF group, and for 15 patients out of 24 for the vehicle group.</population>
          <units>Number of subjects</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Deterioration</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>No deterioration</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                    <measurement group_id="O2" value="13"/>
                  </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</non_inferiority_type>
            <p_value>=0.110</p_value>
            <method>Chi-squared</method>
            <param_type>difference in percentage</param_type>
            <param_value>-13.3</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-30.5</ci_lower_limit>
            <ci_upper_limit>3.9</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were analyzed by study period (Controlled Treatment Period, Follow-up Period and Uncontrolled Treatment Period).</time_frame>
      <desc>The number of Participants considered in the Adverse Event Section reflects the safety subset population of the study:&#xD;
23 patients: rhNGF during the Controlled Treatment Period&#xD;
24 patients: vehicle during the Controlled Treatment Period&#xD;
18 patients: rhNGF during the Follow-up Period&#xD;
21 patients: vehicle during the Follow-up Period&#xD;
13 patients: vehicle during the Controlled Treatment Period and rhNGF during the Uncontrolled Treatment Period</desc>
      <group_list>
        <group group_id="E1">
          <title>rhNGF 20 µg/ml - Controlled Treatment Period</title>
          <description>rhNGF 20 µg/ml eye drops solution, formulation containing anti-oxidant&#xD;
rhNGF 20µg/ml</description>
        </group>
        <group group_id="E2">
          <title>Vehicle - Controlled Treatment Period</title>
          <description>vehicle, formulation containing anti-oxidant&#xD;
Placebo Vehicle</description>
        </group>
        <group group_id="E3">
          <title>rhNGF 20 µg/ml - Follow-up Period</title>
          <description>rhNGF 20 µg/ml eye drops solution, formulation containing anti-oxidant&#xD;
rhNGF 20µg/ml</description>
        </group>
        <group group_id="E4">
          <title>Vehicle - Follow-up Period</title>
          <description>vehicle, formulation containing anti-oxidant&#xD;
Placebo Vehicle</description>
        </group>
        <group group_id="E5">
          <title>Uncontrolled Treatment Period</title>
          <description>rhNGF 20 µg/ml eye drops solution, formulation containing anti-oxidant&#xD;
Patients randomized to vehicle at baseline and not completely healed at week 8 who entered a 8-week treatment period before entering follow-up period</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 19.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="18"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="18"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Corneal Thinning</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>decreased visual acuity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E4" events="2" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Corneal perforation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="18"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>ventral hernia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Disease Progression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Disease recurrence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Viral gastroenteritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Aqueous Humour Leakage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E5" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>4</frequency_threshold>
        <default_vocab>MedDRA 19.0</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="21" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="14" subjects_at_risk="14"/>
                <counts group_id="E4" subjects_affected="9" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="7" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Deafness bilateral</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>motion sickness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Visual acuity reduced</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="23"/>
                <counts group_id="E2" events="7" subjects_affected="5" subjects_at_risk="24"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Eye pain</sub_title>
                <counts group_id="E1" events="11" subjects_affected="7" subjects_at_risk="23"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="14"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Corneal Epithelium Defect</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="23"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="14"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Eye Inflammation</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="23"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Lacrimation Increased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="23"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Ocular Hyperaemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="23"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Corneal Thinning</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="23"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Eye Irritation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="24"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Ocular Discomfort</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="23"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Photophobia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="23"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Foreign Body Sensation In Eyes</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Posterior Capsule Opacification</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Anterior Chamber Inflammation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Conjunctivitis Allergic</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Corneal Deposits</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Corneal Neovascularisation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Corneal Perforation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Eye Discharge</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Eye Pruritus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Eye Swelling</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Eyelid Oedema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Eyelid Pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Hyphaema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Iritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Keratitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Macular Fibrosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Meibomian Gland Dysfunction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Punctate Keratitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Trichiasis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Ulcerative Keratitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Vision Blurred</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Vitreous Floaters</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Blepharitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Chalazion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Conjunctivochalasis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Corneal opacity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Floppy eyelid syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Hernia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Lip Swelling</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Noninfective gingivitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Disease Progression</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="23"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Sensation Of Foreign Body</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="23"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Chest Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Disease progression</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Sensation of foreign body</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Eye Infection Intraocular</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Hordeolum</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Ophthalmic Herpes Zoster</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Respiratory Tract Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Vulvovaginal Mycotic Infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Mastoiditis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Ophthalmic herpes simplex</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Animal Bite</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Aqueous Humour Leakage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Foot Fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Intraocular Pressure Increased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="23"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Joint Swelling</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Osteoporosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Pain In Extremity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Bursitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Papilloma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Diabetic Neuropathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Migrane</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal Impairment</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Nasal septum deviation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Blister</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>erythema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>LImitations and caveats non specified</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Flavio Mantelli, MD, PhD</name_or_title>
      <organization>Dompé</organization>
      <phone>02 583831</phone>
      <email>info@dompe.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/NCT02227147
org study id: NGF0214
nct id: NCT02227147
lead sponsor: 
has dmc: No
The primary objective of this study is to evaluate the efficacy of 20 µg/ml 6 times a day of
      rhNGF eye drops solution (formulation containing anti-oxidant) compared to vehicle
      (formulation containing anti-oxidant) given 6 times a day. The evaluation of efficacy is
      intended as:

        -  complete healing of stage 2 (persistent epithelial defect) and 3 (corneal ulcer)
           neurotrophic keratitis (NK) as measured by the central reading center using corneal
           fluorescein staining,

        -  assessing the duration of complete healing,

        -  improvement in visual acuity and improvement in corneal sensitivity.
An 8-week phase II, multicenter, randomized, double-masked, vehicle-controlled, parallel
      group study with a 24 or 32 week follow-up period to evaluate the efficacy of a formulation
      containing anti-oxidant of recombinant human nerve growth factor (rhNGF) in 20 μg/ml, eye
      drops solution versus vehicle containing anti-oxidant in patients with Stage 2 and 3
      Neurotrophic Keratitis. The primary objective was to evaluate the efficacy of 20 μg/ml 6
      times a day of recombinant human nerve growth factor (rhNGF) containing anti-oxidant, eye
      drops solution compared to vehicle (formulation containing anti-oxidant) given 6 times a day
      in inducing a complete healing of stage 2 (PED) and 3 (corneal ulcer) NK as measured by the
      central reading center, evaluating the clinical pictures of corneal fluorescein staining.

      Secondary objectives were to assess the duration of complete healing, improvement in visual
      acuity and improvement in corneal sensitivity, and percentage of patients achieving complete
      corneal clearing defined as complete absence of staining on the modified Oxford Scale.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Complete Healing of the Persistent Epithelial Defect (PED) or Corneal Ulcer Defined by Central Reviewer
time frame: Week 8
description: Percentage of patients achieving complete healing of the PED or corneal ulcer determined by corneal fluorescein staining at 8 weeks as defined by the central reading center on clinical pictures.
measure: Complete Healing of the Persistent Epithelial Defect (PED) or Corneal Ulcer Defined by the Investigator
time frame: Week 8
description: Percentage of patients experiencing complete healing of the PED or corneal ulcer determined by corneal fluorescein staining at 8 weeks as measured by the investigator.
measure: Complete Healing of the Persistent Epithelial Defect (PED) or Corneal Ulcer Defined by Central Reading Center and Investigator.
time frame: At weeks 4 and 6
description: Percentage of patients experiencing complete healing of the PED or corneal ulcer at 4, and 6 weeks as measured by the central reading center evaluating the clinical pictures and investigator.
measure: Percentage of Patients With Complete Corneal Clearing
time frame: at weeks 4, 6, and 8
description: Percentage of patients with complete corneal clearing at weeks 4, 6, and 8 defined as grade 0 on the modified Oxford scale. Grade 0 indicates the absence of conjunctival staining; grade V indicates severe conjunctival staining.
measure: Mean Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA)
time frame: Baseline, Week 8
description: Change in Best Corrected Distance Visual Acuity (BCDVA) from baseline to Week 8.
Best Corrected Distance Visual Acuity consists of letters read at 4m only.
measure: Percentage of Patients That Achieve a 15 Letter Gain in BCDVA
time frame: Weeks 4, week 6 and week 8
description: Percentage of patients that achieve a 15 letter gain in Best Corrected Distance Visual Acuity (BCDVA) at 4 weeks, 6 weeks, 8 weeks
measure: Improvement in Corneal Sensitivity
time frame: At 4, 6 and 8 weeks after start of the treatment
description: Improvement in corneal sensitivity was measured by the Cochet-Bonnet aesthesiometer at 4, 6 and 8 weeks.
Corneal sensitivity is measured continuously in each patient in cm:
Area of the Persistent Epithelial Defect (PED) or corneal ulcer
All quadrants, but outside the PED or corneal ulcer area: Superior nasal, inferior nasal, superior temporal, inferior temporal.
Improvement is defined as an increase of at least 0.5 cm in the location of concern.
measure: Patients Experiencing Deterioration
time frame: from baseline to Week 8.
description: Number of patients experiencing deterioration (increase in lesion size ≥ 1mm and/or decrease in BCDVA by >5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters and/or progression in lesion depth to corneal melting or perforation and/or onset of infection) in stage 2 or 3 NK from baseline to Week 8.
arm group label: rhNGF 20 µg/ml
arm group type: Experimental
description: rhNGF 20 µg/ml eye drops solution, formulation containing anti-oxidant
arm group label: Placebo
arm group type: Placebo Comparator
description: Vehicle: formulation containing anti-oxidant
intervention type: Drug
intervention name: rhNGF 20µg/ml
arm group label: rhNGF 20 µg/ml
other name: cenegermin
intervention type: Other
intervention name: Placebo
description: Formulation containing antioxidant
arm group label: Placebo
other name: Vehicle
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Flavio Mantelli, MD, PhD
role: Study Director
affiliation: Dompé farmaceutici S.p.A., Milan
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country: United States
responsible party type: Sponsor
mesh term: Keratitis
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: LImitations and caveats non specified
point of contact: 