<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/NCT03292809</url>
  </required_header>
  <id_info>
    <org_study_id>CYS-003 (ESSENCE)</org_study_id>
    <nct_id>NCT03292809</nct_id>
  </id_info>
  <brief_title>CyclASol for the Treatment of Signs and Symptoms of Dry Eye Disease (DED)</brief_title>
  <official_title>A Phase 2b/3, Multicenter, Randomized, Double-masked, Vehicle-controlled Clinical Study to Assess the Efficacy and Safety of Topical CyclASol® for the Treatment of Signs and Symptoms of Dry Eye Disease (DED) (ESSENCE Trial)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novaliq GmbH</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novaliq GmbH</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this study is to assess the efficacy, safety, and tolerability of CyclASol&#xD;
      Ophthalmic Solution in comparison to vehicle for the treatment of the signs and symptoms of&#xD;
      DED.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This Phase 2b/3 study will assess the efficacy, safety and and tolerability of CyclASol&#xD;
      Ophthalmic Solution as one drop twice daily versus vehicle.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 19, 2017</start_date>
  <completion_date type="Actual">June 20, 2018</completion_date>
  <primary_completion_date type="Actual">May 22, 2018</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Total Corneal Fluorescein Staining at Day 29</measure>
    <time_frame>baseline and 1 month [day 29]</time_frame>
    <description>CFS was assessed in each eye using the National Eye Institute (NEI) scale.&#xD;
A standardized grading system of 0-3 is used for each of the five areas on each cornea. Grade 0 will be specified when no staining is present. The maximum total score for each eye is 15. Higher values describe greater staining and corneal damage.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Ocular Surface Disease Index at Day 29</measure>
    <time_frame>baseline and 1 month [day 29]</time_frame>
    <description>The OSDI score is a composite measure built on 12 questions,with totals ranging from 0 to 100, and higher scores representing a worse disease index.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">328</enrollment>
  <condition>Dry Eye Disease</condition>
  <arm_group>
    <arm_group_label>CyclASol Ophthalmic Solution</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cylclosporine A solution in vehicle</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vehicle Ophthalmic Solution</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Vehicle only</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CyclASol topical ocular, eye drops</intervention_name>
    <description>Cyclosporine A solution in vehicle</description>
    <arm_group_label>CyclASol Ophthalmic Solution</arm_group_label>
    <other_name>Ciclosporine (CsA)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vehicle topical ocular, eye drops</intervention_name>
    <description>Vehicle</description>
    <arm_group_label>Vehicle Ophthalmic Solution</arm_group_label>
    <other_name>Vehicle</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed ICF (Informed Consent Form) and HIPAA (Health Insurance Portability and&#xD;
             Accountability Act)&#xD;
&#xD;
          -  Patient-reported history of DED in both eyes&#xD;
&#xD;
          -  Current use of OTC (over-the-counter) and/or artificial tears for dry eye symptoms&#xD;
&#xD;
          -  Ability and willingness to follow instructions, including participation in all study&#xD;
             assessments and visits&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women who are pregnant, nursing or planning a pregnancy&#xD;
&#xD;
          -  Unwillingness to submit a urine pregnancy test at screening and the last visit (or&#xD;
             early termination visit) if of childbearing potential, or unwillingness to use&#xD;
             acceptable means of birth control&#xD;
&#xD;
          -  Clinically significant slit-lamp findings or abnormal lid anatomy at screening&#xD;
&#xD;
          -  Ocular/periocular malignancy&#xD;
&#xD;
          -  History of herpetic keratitis&#xD;
&#xD;
          -  Active ocular allergies or ocular allergies that may become active during the study&#xD;
             period&#xD;
&#xD;
          -  Ongoing ocular or systemic infection at screening or baseline&#xD;
&#xD;
          -  Wear of contact lenses within 3 months prior to screening or anticipated use of&#xD;
             contact lenses during the study&#xD;
&#xD;
          -  History of no response to previous topical Cyclosporine A and/or use of topical&#xD;
             Cyclosporine A or Liftigrast within 2 months prior to screening&#xD;
&#xD;
          -  Intraocular surgery or ocular laser surgery within the previous 6 months, or have any&#xD;
             planned ocular and/or lid surgeries over the study period&#xD;
&#xD;
          -  Presence of uncontrolled systemic diseases&#xD;
&#xD;
          -  Presence of known allergy and/or sensitivity to the study drug or its components&#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>Sonja Kroesser, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Novaliq GmbH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CYS-003 Investigational Site</name>
      <address>
        <city>Newport Beach</city>
        <state>California</state>
        <zip>92663</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CYS-003 Investigational Site</name>
      <address>
        <city>Torrance</city>
        <state>California</state>
        <zip>90505</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CYS-003 Investigational Site</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46290</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CYS-003 Investigational Site</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CYS-003 Investigational Site</name>
      <address>
        <city>Andover</city>
        <state>Massachusetts</state>
        <zip>01810</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CYS-003 Investigational Site</name>
      <address>
        <city>Raynham</city>
        <state>Massachusetts</state>
        <zip>02767</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CYS-003 Investigational Site</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38119</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CYS-003 Investigational Site</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CYS-003 Investigational Site</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423142/</url>
    <description>Publication of Study Results</description>
  </link>
  <results_reference>
    <citation>Sheppard JD, Wirta DL, McLaurin E, Boehmer BE, Ciolino JB, Meides AS, Schluter T, Ousler GW, Usner D, Krosser S. A Water-free 0.1% Cyclosporine A Solution for Treatment of Dry Eye Disease: Results of the Randomized Phase 2B/3 ESSENCE Study. Cornea. 2021 Oct 1;40(10):1290-1297. doi: 10.1097/ICO.0000000000002633.</citation>
    <PMID>34481407</PMID>
  </results_reference>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>September 21, 2017</study_first_submitted>
  <study_first_submitted_qc>September 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 26, 2017</study_first_posted>
  <results_first_submitted>March 30, 2021</results_first_submitted>
  <results_first_submitted_qc>April 29, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">May 21, 2021</results_first_posted>
  <disposition_first_submitted>June 7, 2019</disposition_first_submitted>
  <disposition_first_submitted_qc>April 29, 2021</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">May 21, 2021</disposition_first_posted>
  <last_update_submitted>December 21, 2022</last_update_submitted>
  <last_update_submitted_qc>December 21, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 22, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dry Eye Syndromes</mesh_term>
    <mesh_term>Keratoconjunctivitis Sicca</mesh_term>
    <mesh_term>Eye Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ophthalmic Solutions</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 29, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/09/NCT03292809/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>After a 2-week run-in period, eligible DED patients were randomized 1:1 to either CyclASol 0.1% or vehicle twice daily.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>CyclASol Ophthalmic Solution</title>
          <description>Cylclosporine A solution in vehicle&#xD;
CyclASol topical ocular, eye drops: Cyclosporine A solution in vehicle</description>
        </group>
        <group group_id="P2">
          <title>Vehicle Ophthalmic Solution</title>
          <description>Vehicle only&#xD;
Vehicle topical ocular, eye drops: Vehicle</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="162"/>
                <participants group_id="P2" count="166"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="155"/>
                <participants group_id="P2" count="163"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>CyclASol Ophthalmic Solution</title>
          <description>Cylclosporine A solution in vehicle&#xD;
CyclASol topical ocular, eye drops: Cyclosporine A solution in vehicle</description>
        </group>
        <group group_id="B2">
          <title>Vehicle Ophthalmic Solution</title>
          <description>Vehicle only&#xD;
Vehicle topical ocular, eye drops: 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="162"/>
            <count group_id="B2" value="166"/>
            <count group_id="B3" value="328"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61.5" spread="13.6"/>
                    <measurement group_id="B2" value="61.3" spread="12.66"/>
                    <measurement group_id="B3" value="61.4" spread="13.11"/>
                  </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="116"/>
                    <measurement group_id="B2" value="119"/>
                    <measurement group_id="B3" value="235"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="46"/>
                    <measurement group_id="B2" value="47"/>
                    <measurement group_id="B3" value="93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="147"/>
                    <measurement group_id="B2" value="155"/>
                    <measurement group_id="B3" value="302"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="130"/>
                    <measurement group_id="B2" value="127"/>
                    <measurement group_id="B3" value="257"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="162"/>
                    <measurement group_id="B2" value="166"/>
                    <measurement group_id="B3" value="328"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Total Corneal Fluorescein Staining at Day 29</title>
        <description>CFS was assessed in each eye using the National Eye Institute (NEI) scale.&#xD;
A standardized grading system of 0-3 is used for each of the five areas on each cornea. Grade 0 will be specified when no staining is present. The maximum total score for each eye is 15. Higher values describe greater staining and corneal damage.</description>
        <time_frame>baseline and 1 month [day 29]</time_frame>
        <group_list>
          <group group_id="O1">
            <title>CyclASol Ophthalmic Solution</title>
            <description>Cylclosporine A solution in vehicle&#xD;
CyclASol topical ocular, eye drops: Cyclosporine A solution in vehicle</description>
          </group>
          <group group_id="O2">
            <title>Vehicle Ophthalmic Solution</title>
            <description>Vehicle only&#xD;
Vehicle topical ocular, eye drops: Vehicle</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Total Corneal Fluorescein Staining at Day 29</title>
          <description>CFS was assessed in each eye using the National Eye Institute (NEI) scale.&#xD;
A standardized grading system of 0-3 is used for each of the five areas on each cornea. Grade 0 will be specified when no staining is present. The maximum total score for each eye is 15. Higher values describe greater staining and corneal damage.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="162"/>
                <count group_id="O2" value="166"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.9" spread="2.59"/>
                    <measurement group_id="O2" value="-2.2" spread="2.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Ocular Surface Disease Index at Day 29</title>
        <description>The OSDI score is a composite measure built on 12 questions,with totals ranging from 0 to 100, and higher scores representing a worse disease index.</description>
        <time_frame>baseline and 1 month [day 29]</time_frame>
        <group_list>
          <group group_id="O1">
            <title>CyclASol Ophthalmic Solution</title>
            <description>Cylclosporine A solution in vehicle&#xD;
CyclASol topical ocular, eye drops: Cyclosporine A solution in vehicle</description>
          </group>
          <group group_id="O2">
            <title>Vehicle Ophthalmic Solution</title>
            <description>Vehicle only&#xD;
Vehicle topical ocular, eye drops: Vehicle</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Ocular Surface Disease Index at Day 29</title>
          <description>The OSDI score is a composite measure built on 12 questions,with totals ranging from 0 to 100, and higher scores representing a worse disease index.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="162"/>
                <count group_id="O2" value="166"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.08" spread="18.650"/>
                    <measurement group_id="O2" value="-5.37" spread="15.291"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>85 Days ± 2 (Randomization until Study Exit)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>CyclASol Ophthalmic Solution</title>
          <description>Cylclosporine A solution in vehicle&#xD;
CyclASol topical ocular, eye drops: Cyclosporine A solution in vehicle</description>
        </group>
        <group group_id="E2">
          <title>Vehicle Ophthalmic Solution</title>
          <description>Vehicle only&#xD;
Vehicle topical ocular, eye drops: Vehicle</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (20.1)</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="162"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="166"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="162"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="166"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Small intestinal obstruction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="162"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="166"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="162"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="166"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Intervertebral disc degeneration</sub_title>
                <description>Degenerated disc disease L1-L4</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="162"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="166"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</frequency_threshold>
        <default_vocab>MedDRA (20.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="26" subjects_at_risk="162"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="166"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Visual acuity reduced</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="162"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="166"/>
              </event>
              <event>
                <sub_title>Instillation site pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="162"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="166"/>
              </event>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="162"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="166"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="162"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="166"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="162"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="166"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Sonja Kroesser</name_or_title>
      <organization>Novaliq GmbH</organization>
      <phone>+49 6221 50259 ext 0</phone>
      <email>info@novaliq.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/NCT03292809
org study id: CYS-003 (ESSENCE)
nct id: NCT03292809
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The objective of this study is to assess the efficacy, safety, and tolerability of CyclASol
      Ophthalmic Solution in comparison to vehicle for the treatment of the signs and symptoms of
      DED.
This Phase 2b/3 study will assess the efficacy, safety and and tolerability of CyclASol
      Ophthalmic Solution as one drop twice daily versus vehicle.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change From Baseline in Total Corneal Fluorescein Staining at Day 29
time frame: baseline and 1 month [day 29]
description: CFS was assessed in each eye using the National Eye Institute (NEI) scale.
A standardized grading system of 0-3 is used for each of the five areas on each cornea. Grade 0 will be specified when no staining is present. The maximum total score for each eye is 15. Higher values describe greater staining and corneal damage.
measure: Change From Baseline in Ocular Surface Disease Index at Day 29
time frame: baseline and 1 month [day 29]
description: The OSDI score is a composite measure built on 12 questions,with totals ranging from 0 to 100, and higher scores representing a worse disease index.
arm group label: CyclASol Ophthalmic Solution
arm group type: Experimental
description: Cylclosporine A solution in vehicle
arm group label: Vehicle Ophthalmic Solution
arm group type: Placebo Comparator
description: Vehicle only
intervention type: Drug
intervention name: CyclASol topical ocular, eye drops
description: Cyclosporine A solution in vehicle
arm group label: CyclASol Ophthalmic Solution
other name: Ciclosporine (CsA)
intervention type: Drug
intervention name: Vehicle topical ocular, eye drops
description: Vehicle
arm group label: Vehicle Ophthalmic Solution
other name: Vehicle
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sonja Kroesser, PhD
role: Study Director
affiliation: Novaliq GmbH
facility: 
facility: 
facility: 
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facility: 
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facility: 
facility: 
facility: 
country: United States
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423142/
description: Publication of Study Results
citation: Sheppard JD, Wirta DL, McLaurin E, Boehmer BE, Ciolino JB, Meides AS, Schluter T, Ousler GW, Usner D, Krosser S. A Water-free 0.1% Cyclosporine A Solution for Treatment of Dry Eye Disease: Results of the Randomized Phase 2B/3 ESSENCE Study. Cornea. 2021 Oct 1;40(10):1290-1297. doi: 10.1097/ICO.0000000000002633.
PMID: 34481407
responsible party type: Sponsor
mesh term: Dry Eye Syndromes
mesh term: Keratoconjunctivitis Sicca
mesh term: Eye Diseases
mesh term: Ophthalmic Solutions
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 