<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/NCT03248037</url>
  </required_header>
  <id_info>
    <org_study_id>2017-003</org_study_id>
    <nct_id>NCT03248037</nct_id>
  </id_info>
  <brief_title>Trial of Netarsudil for Prevention of Corticosteroid-induced Intraocular Pressure Elevation</brief_title>
  <official_title>Randomized, Double-masked, Placebo-controlled Evaluation of Netarsudil for Prevention of Corticosteroid-induced Intraocular Pressure Elevation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cornea Research Foundation of America</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cornea Research Foundation of America</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Cornea transplant recipients who are using topical corticosteroids long-term to prevent&#xD;
      transplant rejection will be randomized to use netarsudil or placebo.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 5, 2017</start_date>
  <completion_date type="Actual">July 9, 2019</completion_date>
  <primary_completion_date type="Actual">July 9, 2019</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Intraocular Pressure</measure>
    <time_frame>from date of randomization until the date of first documented intraocular pressure elevation exceeding defined threshold up to 9 months</time_frame>
    <description>Intraocular pressure measurement exceeding 24 mm Hg or more than 10 mm Hg greater than the pre-randomization reading.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">120</enrollment>
  <condition>Fuchs' Endothelial Dystrophy</condition>
  <condition>Bullous Keratopathy</condition>
  <arm_group>
    <arm_group_label>Netarsudil</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Netarsudil ophthalmic solution 0.02%, dosed topically once a day for 9 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo eye drop, dosed topically once a day for 9 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Netarsudil</intervention_name>
    <description>netarsudil opthalmic solution 0.02%</description>
    <arm_group_label>Netarsudil</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo eye drops</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  At least 18 years of age; male or female patient undergoing Descemet membrane&#xD;
             endothelial keratoplasty; patient is able and willing to administer eye drops; patient&#xD;
             is able to comprehend and has signed the Informed Consent form; patient is likely to&#xD;
             complete the nine-month course of the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A patient exhibiting pre-operative intraocular inflammation; a patient with a known&#xD;
             sensitivity to any of the ingredients in the study medications; a patient who has a&#xD;
             condition (i.e., UNCONTROLLED systemic disease) or is in a situation which in the&#xD;
             investigator's opinion may put the patient at significant risk, may confound the study&#xD;
             results, or may interfere significantly with the patient's participation in the study;&#xD;
             a patient with abnormal eyelid function; a patient that is exhibiting active corneal&#xD;
             ulceration, keratitis, or conjunctivitis, or who has a history of herpetic keratitis;&#xD;
             a patient who has been diagnosed with uncontrolled glaucoma, prior aqueous shunt or&#xD;
             trabeculectomy, or with preoperative intraocular pressure &gt; 22 mm Hg in the potential&#xD;
             study eye; presence of any ocular disease that would interfere with the evaluation of&#xD;
             the study treatment (however, patients with a history of cystoid macular edema,&#xD;
             age-related macular degeneration, corneal neovascularization, and other&#xD;
             non-interfering comorbidities may be enrolled); a patient with a history of&#xD;
             non-compliance with using prescribed medication; a patient who is concurrently&#xD;
             involved in or participated in another randomized clinical trial within 30 days prior&#xD;
             to enrollment in this study; patients who are pregnant or planning to become pregnant&#xD;
             within the duration of the study.&#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>Francis W Price, Jr, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Price Vision Group</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Price Vision Group</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46260</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Fini ME, Schwartz SG, Gao X, Jeong S, Patel N, Itakura T, Price MO, Price FW Jr, Varma R, Stamer WD. Steroid-induced ocular hypertension/glaucoma: Focus on pharmacogenomics and implications for precision medicine. Prog Retin Eye Res. 2017 Jan;56:58-83. doi: 10.1016/j.preteyeres.2016.09.003. Epub 2016 Sep 22.</citation>
    <PMID>27666015</PMID>
  </reference>
  <reference>
    <citation>Vajaranant TS, Price MO, Price FW, Gao W, Wilensky JT, Edward DP. Visual acuity and intraocular pressure after Descemet's stripping endothelial keratoplasty in eyes with and without preexisting glaucoma. Ophthalmology. 2009 Sep;116(9):1644-50. doi: 10.1016/j.ophtha.2009.05.034. Epub 2009 Jul 29.</citation>
    <PMID>19643499</PMID>
  </reference>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>August 9, 2017</study_first_submitted>
  <study_first_submitted_qc>August 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 14, 2017</study_first_posted>
  <results_first_submitted>January 25, 2021</results_first_submitted>
  <results_first_submitted_qc>January 25, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">February 12, 2021</results_first_posted>
  <last_update_submitted>January 25, 2021</last_update_submitted>
  <last_update_submitted_qc>January 25, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 12, 2021</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>Fuchs' Endothelial Dystrophy</mesh_term>
  </condition_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>August 23, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/37/NCT03248037/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>As specified in the protocol, a total of 120 unique participants were enrolled in the study; 71 enrolled both eyes in the study and the fellow eyes were automatically assigned to opposite treatment arms, so 71 subjects participated in both treatment arms.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Netarsudil</title>
          <description>Netarsudil ophthalmic solution 0.02%, dosed topically once a day for 9 months&#xD;
Netarsudil: netarsudil opthalmic solution 0.02%</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo eye drop, dosed topically once a day for 9 months&#xD;
Placebo: Placebo eye drops</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="95">Fellow eyes could be enrolled and were automatically assigned to the opposite treatment arm.</participants>
                <participants group_id="P2" count="96">Fellow eyes could be enrolled and were automatically assigned to the opposite treatment arm.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="74"/>
                <participants group_id="P2" count="87"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Netarsudil</title>
          <description>Netarsudil ophthalmic solution 0.02%, dosed topically once a day for 9 months&#xD;
Netarsudil: netarsudil opthalmic solution 0.02%</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo eye drop, dosed topically once a day for 9 months&#xD;
Placebo: Placebo eye drops</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="95"/>
            <count group_id="B2" value="96"/>
            <count group_id="B3" value="191"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="95"/>
                    <count group_id="B2" value="96"/>
                    <count group_id="B3" value="191"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="68" lower_limit="40" upper_limit="88"/>
                    <measurement group_id="B2" value="67" lower_limit="40" upper_limit="90"/>
                    <measurement group_id="B3" value="67" lower_limit="40" upper_limit="90"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="95"/>
                    <count group_id="B2" value="96"/>
                    <count group_id="B3" value="191"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="54"/>
                    <measurement group_id="B2" value="61"/>
                    <measurement group_id="B3" value="115"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="41"/>
                    <measurement group_id="B2" value="35"/>
                    <measurement group_id="B3" value="76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="95"/>
                    <count group_id="B2" value="96"/>
                    <count group_id="B3" value="191"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="95"/>
                    <measurement group_id="B2" value="96"/>
                    <measurement group_id="B3" value="191"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Intraocular Pressure</title>
        <description>Intraocular pressure measurement exceeding 24 mm Hg or more than 10 mm Hg greater than the pre-randomization reading.</description>
        <time_frame>from date of randomization until the date of first documented intraocular pressure elevation exceeding defined threshold up to 9 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Netarsudil</title>
            <description>Netarsudil ophthalmic solution 0.02%, dosed topically once a day for 9 months&#xD;
Netarsudil: netarsudil opthalmic solution 0.02%</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo eye drop, dosed topically once a day for 9 months&#xD;
Placebo: Placebo eye drops</description>
          </group>
        </group_list>
        <measure>
          <title>Intraocular Pressure</title>
          <description>Intraocular pressure measurement exceeding 24 mm Hg or more than 10 mm Hg greater than the pre-randomization reading.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="95"/>
                <count group_id="O2" value="96"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>9 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Netarsudil</title>
          <description>Netarsudil ophthalmic solution 0.02%, dosed topically once a day for 9 months&#xD;
Netarsudil: netarsudil opthalmic solution 0.02%</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo eye drop, dosed topically once a day for 9 months&#xD;
Placebo: Placebo eye drops</description>
        </group>
      </group_list>
      <serious_events>
        <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="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="96"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="96"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>1</frequency_threshold>
        <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="31" subjects_at_risk="95"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="96"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Air re-injection</sub_title>
                <description>Air was re-injected into the eye to promote endothelial keratoplasty attachment</description>
                <counts group_id="E1" events="20" subjects_affected="20" subjects_at_risk="95"/>
                <counts group_id="E2" events="18" subjects_affected="18" subjects_at_risk="96"/>
              </event>
              <event>
                <sub_title>Ocular irritation considered related to study drug use</sub_title>
                <counts group_id="E1" events="22" subjects_affected="22" subjects_at_risk="95"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="96"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Marianne Price</name_or_title>
      <organization>Cornea Research Foundation of America</organization>
      <phone>3178142990</phone>
      <email>mprice@cornea.org</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/NCT03248037
org study id: 2017-003
nct id: NCT03248037
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Cornea transplant recipients who are using topical corticosteroids long-term to prevent
      transplant rejection will be randomized to use netarsudil or placebo.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Intraocular Pressure
time frame: from date of randomization until the date of first documented intraocular pressure elevation exceeding defined threshold up to 9 months
description: Intraocular pressure measurement exceeding 24 mm Hg or more than 10 mm Hg greater than the pre-randomization reading.
arm group label: Netarsudil
arm group type: Experimental
description: Netarsudil ophthalmic solution 0.02%, dosed topically once a day for 9 months
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo eye drop, dosed topically once a day for 9 months
intervention type: Drug
intervention name: Netarsudil
description: netarsudil opthalmic solution 0.02%
arm group label: Netarsudil
intervention type: Drug
intervention name: Placebo
description: Placebo eye drops
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Francis W Price, Jr, MD
role: Principal Investigator
affiliation: Price Vision Group
facility: 
country: United States
citation: Fini ME, Schwartz SG, Gao X, Jeong S, Patel N, Itakura T, Price MO, Price FW Jr, Varma R, Stamer WD. Steroid-induced ocular hypertension/glaucoma: Focus on pharmacogenomics and implications for precision medicine. Prog Retin Eye Res. 2017 Jan;56:58-83. doi: 10.1016/j.preteyeres.2016.09.003. Epub 2016 Sep 22.
PMID: 27666015
citation: Vajaranant TS, Price MO, Price FW, Gao W, Wilensky JT, Edward DP. Visual acuity and intraocular pressure after Descemet's stripping endothelial keratoplasty in eyes with and without preexisting glaucoma. Ophthalmology. 2009 Sep;116(9):1644-50. doi: 10.1016/j.ophtha.2009.05.034. Epub 2009 Jul 29.
PMID: 19643499
responsible party type: Sponsor
mesh term: Fuchs' Endothelial Dystrophy
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 