<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/NCT03287635</url>
  </required_header>
  <id_info>
    <org_study_id>MMT-4223</org_study_id>
    <nct_id>NCT03287635</nct_id>
  </id_info>
  <brief_title>Clinical Efficacy of H.P. Acthar Gel 80 U/ml to Improve the Signs and Symptoms in Subjects With Dry Eye Disease</brief_title>
  <official_title>Study Title: A Phase 4 Study to Assess the Clinical Efficacy of H.P. Acthar Gel 80 U/ml to Improve the Signs and Symptoms in Subjects With Dry Eye Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Toyos Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Mallinckrodt</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Toyos Clinic</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Study Title: A Phase 4 Study to Assess the Clinical Efficacy of H.P. Acthar Gel 80 U/ml to&#xD;
      Improve the Signs and Symptoms in Subjects with Dry Eye Disease&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objectives: The primary objective of this study is to investigate the safety and efficacy of&#xD;
      H.P. Acthar Gel 80 U/ml in subjects with a documented clinical diagnosis of dry eye disease.&#xD;
&#xD;
      Study Population: The study population will consist of subjects diagnosed with dry eye&#xD;
      disease.&#xD;
&#xD;
      Number of Subjects: Approximately 12 subjects&#xD;
&#xD;
      Investigational Product: H.P. Acthar Gel 80 U/ml sufficient for the duration of the study&#xD;
      will be supplied by Mallinkrodt to the enrolled subjects&#xD;
&#xD;
      Route and Duration of Administration: Product will be injected subcutaneously weekly by&#xD;
      subjects for approximately 12 weeks.&#xD;
&#xD;
      Study Design: This is a Phase 4, single center single arm study designed to evaluate the&#xD;
      safety and efficacy of H.P. Achthar Gel in subjects with dry eye disease.&#xD;
&#xD;
      Approximately 25 subjects will be screened and 12 subjects enrolled at one center in the&#xD;
      United States.&#xD;
&#xD;
      Subjects will be given 80 international units of study medication subcutaneously depending on&#xD;
      the severity of the disease as determined by the primary investigator.&#xD;
&#xD;
      The study will include 3 study visits over 12 weeks. At Visit 1 Screening (14 +/- 1 days&#xD;
      prior to Day 1), subjects meeting inclusion/exclusion criteria will begin investigational&#xD;
      drug use. Subjects will return for evaluations at Visit 2 (Day 42+/-3 days) and Visit 3 (Day&#xD;
      84 +/-5 days). Subjects will be released from the study at the end of Visit 3 (Day 84+/- 5&#xD;
      days.)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 1, 2018</start_date>
  <completion_date type="Actual">March 4, 2020</completion_date>
  <primary_completion_date type="Actual">February 1, 2020</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dry Eye Comfort Questionnaire, SANDE</measure>
    <time_frame>12 weeks total. Measure is change on SANDE scale (0 is no dryness and 100mm is maximal dryness) from baseline to final value. Higher values reflect greater amounts of subjective dryness.</time_frame>
    <description>Subjects will be asked to subjectively rate their eye dryness at Visit 1,2 and 3. Subjects will be instructed to rate eye dryness using the scale below. The total length of the line from &quot;no dryness&quot; to &quot;maximal dryness&quot; is 100 mm. The length of the line between the &quot;no dryness&quot; starting point and the first point at which the subject mark crosses the line will be measured in mm. This assessment is a general assessment of the change of both eyes of dryness measure from baseline to final study visit. The measure of discomfort was for the instantaneous measurement at the time of the specific visit.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>1. Conjunctival Staining With Lissamine Green</measure>
    <time_frame>12 weeks total. Measure is change from baseline to final,</time_frame>
    <description>Change in Conjunctival staining with lissamine green.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Intraocular Pressure</measure>
    <time_frame>12 weeks measuring change from baseline to final</time_frame>
    <description>goldmann tonometry used by qualified technician with fluorescein staining</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Dry Eye Disease</condition>
  <arm_group>
    <arm_group_label>Acthar gel 80 U/ml</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients who continue to experience clinically significant symptoms of dry eye disease even after utilizing traditional methods of treatment for dry eye including but not limited to artificial tears, warm compresses, topical anti-inflammatories like cyclosporine and/or lifitegrast. Patients will receive repository corticotropin intramuscular injections 80 u/ml 2-3 times weekly for up to 3 months as judged by the investigator.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Corticotropin 80Unit/Ml Repository Injection</intervention_name>
    <description>H.P. Acthar Gel (repository corticotropin injection) is an adrenocorticotropic hormone (ACTH) analogue used for: Treatment during an exacerbation or as maintenance therapy in selected cases of systemic lupus erythematosus.</description>
    <arm_group_label>Acthar gel 80 U/ml</arm_group_label>
    <other_name>H.P. Acthar gel</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  At Visit 1 (Screening) individuals of either gender or race will be eligible for study&#xD;
             participation if they&#xD;
&#xD;
               1. Provide written informed consent and HIPAA authorization prior to any study&#xD;
                  related procedures&#xD;
&#xD;
               2. Are 18 years of age or older&#xD;
&#xD;
               3. Are willing and able to follow instructions and can be present for required study&#xD;
                  visits.&#xD;
&#xD;
               4. Have documented clinical diagnosis of dry eye disease in one or both eyes.&#xD;
&#xD;
               5. Have a score of at least 40mm on the ocular discomfort scale&#xD;
&#xD;
               6. Have at least 5 spk on one or both corneas&#xD;
&#xD;
               7. Have a grade of 1 or greater in the nasal or temporal areas of one or both eyes.&#xD;
&#xD;
               8. Have normal lid anatomy.&#xD;
&#xD;
               9. Are women of child bearing potential who are not pregnant or lactating and who&#xD;
                  are either abstinent and willing to remain so for the course of the trial or have&#xD;
                  an IUD in place for at least 3 months prior and through Visit 4, barrier method&#xD;
                  with spermicide for at least 3 months prior and through Visit 4, stable hormonal&#xD;
                  contraceptive for at least 3 months prior and through Visit 4 or in a monogamous&#xD;
                  relationship with a surgically sterilized (vasectomized) partner at least 6&#xD;
                  months prior to Visit 1 and through the course of the trial.&#xD;
&#xD;
              10. Are postmenopausal (no menstrual cycle for at least one year prior to Visit 1) or&#xD;
                  have undergone bilateral tubal ligation, hysterectomy, hysterectomy with uni or&#xD;
                  bilateral oophorectomy, or bilateral oophorectomy.&#xD;
&#xD;
                  Exclusion Criteria:&#xD;
&#xD;
                  In order for subjects to be eligible for the study&#xD;
&#xD;
               1. Have a known hypersensitivity or contraindication to the investigational product&#xD;
                  or their components.&#xD;
&#xD;
               2. Have used any of the following medications within 14 days prior to screening&#xD;
&#xD;
                  a. Topical or nasal vasoconstrictors&#xD;
&#xD;
               3. Subjects can be on the following medications if they have been on a stable dose&#xD;
                  for 12 weeks topical cyclosporine, topical lifitegrast and/or topical loteprednol&#xD;
                  etabonate. Tetracycline compounds, omega 3s, anticholinergics, anticonvulsants,&#xD;
                  antidepressants, retinoids, systemic immunosuppressive agents including oral&#xD;
                  corticosteroids, non-steroidals, antihistamines or mast cell stabilizers, punctal&#xD;
                  plugs, contact lens wear and glaucoma medications.&#xD;
&#xD;
               4. Subjects must be unwilling to abstain from eyelash growth medications for the&#xD;
                  duration of the trial.&#xD;
&#xD;
               5. Subjects must not have had penetrating intraocular surgery, refractive surgery or&#xD;
                  corneal transplantation, eyelid surgery within 12 weeks prior to Visit 1.&#xD;
&#xD;
               6. Subjects with a history of herpetic keratitis.&#xD;
&#xD;
               7. Have serious or severe disease or uncontrolled medical condition that in the&#xD;
                  judgement of the investigator could confound study assessments or limit&#xD;
                  compliance.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Melissa Toyos, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Toyos Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Toyos Clinic</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>August 28, 2017</study_first_submitted>
  <study_first_submitted_qc>September 15, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 19, 2017</study_first_posted>
  <results_first_submitted>October 16, 2020</results_first_submitted>
  <results_first_submitted_qc>January 8, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">January 28, 2021</results_first_posted>
  <last_update_submitted>January 8, 2021</last_update_submitted>
  <last_update_submitted_qc>January 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 28, 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>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>Adrenocorticotropic Hormone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>May 10, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/35/NCT03287635/Prot_004.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 10, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/35/NCT03287635/SAP_005.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 16, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/35/NCT03287635/ICF_006.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Additional subjects were added when study participants dropped out due to subject withdrawal, were lost to follow up and physician decision.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Acthar Gel 80 U/ml</title>
          <description>Patients who continue to experience clinically significant symptoms of dry eye disease even after utilizing traditional methods of treatment for dry eye including but not limited to artificial tears, warm compresses, topical anti-inflammatories like cyclosporine and/or lifitegrast. Patients will receive repository corticotropin intramuscular injections 80 u/ml 2-3 times weekly for up to 3 months as judged by the investigator.&#xD;
Corticotropin 80Unit/Ml Repository Injection: H.P. Acthar Gel (repository corticotropin injection) is an adrenocorticotropic hormone (ACTH) analogue used for: Treatment during an exacerbation or as maintenance therapy in selected cases of systemic lupus erythematosus.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Patients experience persistent symptomatic dry eye disease despite treatment with traditional therapies.</population>
      <group_list>
        <group group_id="B1">
          <title>Acthar Gel 80 U/ml</title>
          <description>Patients who continue to experience clinically significant symptoms of dry eye disease even after utilizing traditional methods of treatment for dry eye including but not limited to artificial tears, warm compresses, topical anti-inflammatories like cyclosporine and/or lifitegrast. Patients will receive repository corticotropin intramuscular injections 80 u/ml 2-3 times weekly for up to 3 months as judged by the investigator.&#xD;
Corticotropin 80Unit/Ml Repository Injection: H.P. Acthar Gel (repository corticotropin injection) is an adrenocorticotropic hormone (ACTH) analogue used for: Treatment during an exacerbation or as maintenance therapy in selected cases of systemic lupus erythematosus.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="19"/>
          </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_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="54" lower_limit="27" upper_limit="74"/>
                  </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="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" 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>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Dry Eye Comfort Questionnaire, SANDE</title>
        <description>Subjects will be asked to subjectively rate their eye dryness at Visit 1,2 and 3. Subjects will be instructed to rate eye dryness using the scale below. The total length of the line from &quot;no dryness&quot; to &quot;maximal dryness&quot; is 100 mm. The length of the line between the &quot;no dryness&quot; starting point and the first point at which the subject mark crosses the line will be measured in mm. This assessment is a general assessment of the change of both eyes of dryness measure from baseline to final study visit. The measure of discomfort was for the instantaneous measurement at the time of the specific visit.</description>
        <time_frame>12 weeks total. Measure is change on SANDE scale (0 is no dryness and 100mm is maximal dryness) from baseline to final value. Higher values reflect greater amounts of subjective dryness.</time_frame>
        <population>Patients receiving Acthar gel injections for 90 days were analyzed</population>
        <group_list>
          <group group_id="O1">
            <title>Acthar Gel 80 U/ml</title>
            <description>Patients who continue to experience clinically significant symptoms of dry eye disease even after utilizing traditional methods of treatment for dry eye including but not limited to artificial tears, warm compresses, topical anti-inflammatories like cyclosporine and/or lifitegrast. Patients will receive repository corticotropin intramuscular injections 80 u/ml 2-3 times weekly for up to 3 months as judged by the investigator.&#xD;
Corticotropin 80Unit/Ml Repository Injection: H.P. Acthar Gel (repository corticotropin injection) is an adrenocorticotropic hormone (ACTH) analogue used for: Treatment during an exacerbation or as maintenance therapy in selected cases of systemic lupus erythematosus.</description>
          </group>
        </group_list>
        <measure>
          <title>Dry Eye Comfort Questionnaire, SANDE</title>
          <description>Subjects will be asked to subjectively rate their eye dryness at Visit 1,2 and 3. Subjects will be instructed to rate eye dryness using the scale below. The total length of the line from &quot;no dryness&quot; to &quot;maximal dryness&quot; is 100 mm. The length of the line between the &quot;no dryness&quot; starting point and the first point at which the subject mark crosses the line will be measured in mm. This assessment is a general assessment of the change of both eyes of dryness measure from baseline to final study visit. The measure of discomfort was for the instantaneous measurement at the time of the specific visit.</description>
          <population>Patients receiving Acthar gel injections for 90 days were analyzed</population>
          <units>scores 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="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.77" spread="3.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>1. Conjunctival Staining With Lissamine Green</title>
        <description>Change in Conjunctival staining with lissamine green.</description>
        <time_frame>12 weeks total. Measure is change from baseline to final,</time_frame>
        <population>Patients who received Acthar gel SC for 90 days</population>
        <group_list>
          <group group_id="O1">
            <title>Acthar Gel 80 U/ml</title>
            <description>Patients who continue to experience clinically significant symptoms of dry eye disease even after utilizing traditional methods of treatment for dry eye including but not limited to artificial tears, warm compresses, topical anti-inflammatories like cyclosporine and/or lifitegrast. Patients will receive repository corticotropin intramuscular injections 80 u/ml 2-3 times weekly for up to 3 months as judged by the investigator.&#xD;
Corticotropin 80Unit/Ml Repository Injection: H.P. Acthar Gel (repository corticotropin injection) is an adrenocorticotropic hormone (ACTH) analogue used for: Treatment during an exacerbation or as maintenance therapy in selected cases of systemic lupus erythematosus.</description>
          </group>
        </group_list>
        <measure>
          <title>1. Conjunctival Staining With Lissamine Green</title>
          <description>Change in Conjunctival staining with lissamine green.</description>
          <population>Patients who received Acthar gel SC for 90 days</population>
          <units>staining spots on conjunctiva</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-173.33" spread="464.59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Intraocular Pressure</title>
        <description>goldmann tonometry used by qualified technician with fluorescein staining</description>
        <time_frame>12 weeks measuring change from baseline to final</time_frame>
        <population>Patients who received Acthar gel SC or IM for 90 days.</population>
        <group_list>
          <group group_id="O1">
            <title>Acthar Gel 80 U/ml</title>
            <description>Patients who continue to experience clinically significant symptoms of dry eye disease even after utilizing traditional methods of treatment for dry eye including but not limited to artificial tears, warm compresses, topical anti-inflammatories like cyclosporine and/or lifitegrast. Patients will receive repository corticotropin intramuscular injections 80 u/ml 2-3 times weekly for up to 3 months as judged by the investigator.&#xD;
Corticotropin 80Unit/Ml Repository Injection: H.P. Acthar Gel (repository corticotropin injection) is an adrenocorticotropic hormone (ACTH) analogue used for: Treatment during an exacerbation or as maintenance therapy in selected cases of systemic lupus erythematosus.</description>
          </group>
        </group_list>
        <measure>
          <title>Intraocular Pressure</title>
          <description>goldmann tonometry used by qualified technician with fluorescein staining</description>
          <population>Patients who received Acthar gel SC or IM for 90 days.</population>
          <units>mm Hg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.65" spread="1.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>12 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Acthar Gel 80 U/ml</title>
          <description>Patients who continue to experience clinically significant symptoms of dry eye disease even after utilizing traditional methods of treatment for dry eye including but not limited to artificial tears, warm compresses, topical anti-inflammatories like cyclosporine and/or lifitegrast. Patients will receive repository corticotropin intramuscular injections 80 u/ml 2-3 times weekly for up to 3 months as judged by the investigator.&#xD;
Corticotropin 80Unit/Ml Repository Injection: H.P. Acthar Gel (repository corticotropin injection) is an adrenocorticotropic hormone (ACTH) analogue used for: Treatment during an exacerbation or as maintenance therapy in selected cases of systemic lupus erythematosus.</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="19"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>SNOMED CT</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>hypertension</sub_title>
                <description>patient withdrew due to elevated blood pressure. PI unclear if drug related, PI and study participant agreed to stop trial as a precaution and follow for safety. No further events.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </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>single site, open label study</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr.</name_or_title>
      <organization>Toyos Clinic</organization>
      <phone>9137064408</phone>
      <email>mtoyos@toyosclinic.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/NCT03287635
org study id: MMT-4223
nct id: NCT03287635
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Study Title: A Phase 4 Study to Assess the Clinical Efficacy of H.P. Acthar Gel 80 U/ml to
      Improve the Signs and Symptoms in Subjects with Dry Eye Disease
Objectives: The primary objective of this study is to investigate the safety and efficacy of
      H.P. Acthar Gel 80 U/ml in subjects with a documented clinical diagnosis of dry eye disease.

      Study Population: The study population will consist of subjects diagnosed with dry eye
      disease.

      Number of Subjects: Approximately 12 subjects

      Investigational Product: H.P. Acthar Gel 80 U/ml sufficient for the duration of the study
      will be supplied by Mallinkrodt to the enrolled subjects

      Route and Duration of Administration: Product will be injected subcutaneously weekly by
      subjects for approximately 12 weeks.

      Study Design: This is a Phase 4, single center single arm study designed to evaluate the
      safety and efficacy of H.P. Achthar Gel in subjects with dry eye disease.

      Approximately 25 subjects will be screened and 12 subjects enrolled at one center in the
      United States.

      Subjects will be given 80 international units of study medication subcutaneously depending on
      the severity of the disease as determined by the primary investigator.

      The study will include 3 study visits over 12 weeks. At Visit 1 Screening (14 +/- 1 days
      prior to Day 1), subjects meeting inclusion/exclusion criteria will begin investigational
      drug use. Subjects will return for evaluations at Visit 2 (Day 42+/-3 days) and Visit 3 (Day
      84 +/-5 days). Subjects will be released from the study at the end of Visit 3 (Day 84+/- 5
      days.)
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Dry Eye Comfort Questionnaire, SANDE
time frame: 12 weeks total. Measure is change on SANDE scale (0 is no dryness and 100mm is maximal dryness) from baseline to final value. Higher values reflect greater amounts of subjective dryness.
description: Subjects will be asked to subjectively rate their eye dryness at Visit 1,2 and 3. Subjects will be instructed to rate eye dryness using the scale below. The total length of the line from "no dryness" to "maximal dryness" is 100 mm. The length of the line between the "no dryness" starting point and the first point at which the subject mark crosses the line will be measured in mm. This assessment is a general assessment of the change of both eyes of dryness measure from baseline to final study visit. The measure of discomfort was for the instantaneous measurement at the time of the specific visit.
measure: 1. Conjunctival Staining With Lissamine Green
time frame: 12 weeks total. Measure is change from baseline to final,
description: Change in Conjunctival staining with lissamine green.
measure: Intraocular Pressure
time frame: 12 weeks measuring change from baseline to final
description: goldmann tonometry used by qualified technician with fluorescein staining
arm group label: Acthar gel 80 U/ml
arm group type: Experimental
description: Patients who continue to experience clinically significant symptoms of dry eye disease even after utilizing traditional methods of treatment for dry eye including but not limited to artificial tears, warm compresses, topical anti-inflammatories like cyclosporine and/or lifitegrast. Patients will receive repository corticotropin intramuscular injections 80 u/ml 2-3 times weekly for up to 3 months as judged by the investigator.
intervention type: Drug
intervention name: Corticotropin 80Unit/Ml Repository Injection
description: H.P. Acthar Gel (repository corticotropin injection) is an adrenocorticotropic hormone (ACTH) analogue used for: Treatment during an exacerbation or as maintenance therapy in selected cases of systemic lupus erythematosus.
arm group label: Acthar gel 80 U/ml
other name: H.P. Acthar gel
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Melissa Toyos, MD
role: Principal Investigator
affiliation: Toyos Clinic
facility: 
country: United States
responsible party type: Sponsor
mesh term: Dry Eye Syndromes
mesh term: Keratoconjunctivitis Sicca
mesh term: Eye Diseases
mesh term: Adrenocorticotropic Hormone
sharing ipd: Undecided
provided document: 
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: single site, open label study
point of contact: 