<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/NCT02245841</url>
  </required_header>
  <id_info>
    <org_study_id>14-1015</org_study_id>
    <nct_id>NCT02245841</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of H.P. Acthar Gel for the Treatment of Refractory Cutaneous Manifestations of Dermatomyositis</brief_title>
  <acronym>Acthar Gel</acronym>
  <official_title>Efficacy and Safety of H.P. Acthar Gel for the Treatment of Refractory Cutaneous Manifestations of Dermatomyositis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Cleveland Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Mallinckrodt</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>The Cleveland Clinic</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will assess the safety and efficacy of H.P. Acthar gel for treating the cutaneous&#xD;
      manifestations in patients with refractory classic dermatomyositis, juvenile dermatomyositis,&#xD;
      and amyopathic dermatomyositis. Our hypothesis is that H.P. Acthar gel will be both safe and&#xD;
      effective for such patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Adult and juvenile dermatomyositis (DM) are systemic immune-mediated inflammatory diseases&#xD;
      most commonly affecting the skin and musculoskeletal system. Amyopathic dermatomyositis is a&#xD;
      subtype of dermatomyositis that affects only the skin and lacks the characteristic muscle&#xD;
      involvement. Treatment of these conditions, in particular the cutaneous manifestations, is&#xD;
      challenging and currently no universally effective single treatment exists. Many patients&#xD;
      have cutaneous manifestations that are refractory to numerous medications.&#xD;
&#xD;
      H.P. Acthar gel (adrenocorticotropic hormone gel) received FDA approval for treatment of a&#xD;
      variety of diseases, including dermatomyositis, in 1952. Despite this there is a paucity of&#xD;
      clinical data concerning the efficacy of H.P. Acthar gel for treating dermatomyositis.&#xD;
      Recently a small, retrospective case series describing significant improvement in both&#xD;
      cutaneous and musculoskeletal symptoms in 5 patients with refractory dermatomyositis treated&#xD;
      with H.P. Acthar gel was reported and has resulted in renewed interest in use of this&#xD;
      medication in dermatomyositis patient (reference below). The proposed efficacy of H.P. Acthar&#xD;
      gel has been attributed to its unique ability to induce production of endogenous cortisol,&#xD;
      corticosterone, aldosterone, and to bind melanocortin receptors on lymphocytes and other&#xD;
      cells to modulate immunologic responses.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 15, 2015</start_date>
  <completion_date type="Actual">July 14, 2021</completion_date>
  <primary_completion_date type="Actual">July 14, 2021</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>Change from baseline in cutaneous manifestations of dermatomyositis at 1, 3, and 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Statistically significant change between baseline and 1, 3, and 6 months in cutaneous manifestations of dermatomyositis based on modified CDASI (modified Cutaneous Dermatomyositis Disease Area and Severity Index) scores at these timepoints.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline in cutaneous manifestations of dermatomyositis at 1, 3, and 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Change between baseline and 1, 3, and 6 months in cutaneous manifestations of dermatomyositis based on Physician's Global Assessment scores at these timepoints.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in patient assessment of dermatomyositis at 1, 3, and 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Statistically significant change between baseline and 1, 3, and 6 months in patient assessed &quot;Global Patient Score&quot; at these timepoints.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in patient assessment of dermatomyositis at 1, 3, and 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Statistically significant change between baseline and 1, 3, and 6 months in patient assessed &quot;Global Itch Score&quot; at these timepoints.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in patient assessment of dermatomyositis at 1, 3, and 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Statistically significant change between baseline and 1, 3, and 6 months in patient assessed Dermatology Life Quality Index (DLQI) scores at these timepoints.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Number of patients with adverse effects.</measure>
    <time_frame>6 months</time_frame>
    <description>Safety and tolerability of H.P. Acthar gel based on frequency and types of adverse effects.</description>
  </other_outcome>
  <other_outcome>
    <measure>Number of patients with change in dose of systemic corticosteroids and/or steroid-sparing immunosuppressive agents</measure>
    <time_frame>6 months</time_frame>
    <description>Median/mean change in dose of systemic corticosteroids and/or steroid-sparing immunosuppressive agents from initiation to completion of study</description>
  </other_outcome>
  <other_outcome>
    <measure>Number of patients with change in HbA1c</measure>
    <time_frame>6 months</time_frame>
    <description>Median/mean change in HbA1c</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Dermatomyositis</condition>
  <condition>Juvenile Dermatomyositis</condition>
  <arm_group>
    <arm_group_label>H.P Acthar Gel</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>80 U (1 mL) of H.P. Acthar gel via subcutaneous injection twice weekly for 24 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>H.P. Acthar Gel</intervention_name>
    <description>80 U (1 mL) of H.P. Acthar gel via subcutaneous injection twice weekly for 24 weeks</description>
    <arm_group_label>H.P Acthar Gel</arm_group_label>
    <other_name>Acthar Gel</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Must be 18 years of age or older with refractory cutaneous symptoms related to either&#xD;
             classic dermatomyositis (CD), juvenile dermatomyositis (JD), or amyopathic&#xD;
             dermatomyositis(AD). Diagnosis will be based on either Bohan and Peter criteria (CD&#xD;
             and JD) or Sontheimer's criteria (AD)&#xD;
&#xD;
          -  Must have had a skin biopsy with histologic features consistent with dermatomyositis&#xD;
             and current cutaneous manifestations consistent with dermatomyositis.&#xD;
&#xD;
          -  Although not mandatory, patients with evidence of current or previous active myositis&#xD;
             will be eligible for enrollment. Patients will be considered to have refractory&#xD;
             disease if cutaneous manifestations exist despite treatment with steroids and at least&#xD;
             one steroid-sparing systemic treatment commonly found to be useful in patients with&#xD;
             dermatomyositis. These may include azathioprine, cyclosporine, mycophenolate mofetil,&#xD;
             IVIG, methotrexate, cyclophosphamide, chlorambucil, sirolimus, adalimumab, infliximab&#xD;
             and rituximab.&#xD;
&#xD;
          -  Use of topical medications and sunscreen currently and in past will be noted but not&#xD;
             weighed for assessment of refractory cutaneous disease.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with dermatomyositis who have minimal-to-no active cutaneous features (focal&#xD;
             involvement with less than 1% total body surface area involved or minimal modified&#xD;
             CDASI activity score).&#xD;
&#xD;
          -  Patients whose cutaneous findings are not consistent with dermatomyositis and/or have&#xD;
             previous biopsy results suggestive of an alternative diagnosis&#xD;
&#xD;
          -  Patients with inflammatory myositis other than dermatomyositis, such as polymyositis&#xD;
             or inclusion body myositis.&#xD;
&#xD;
          -  Patients with malignancy-associated dermatomyositis&#xD;
&#xD;
          -  Patients with clear features of an overlap myositis&#xD;
&#xD;
          -  Patients younger than 18 years old&#xD;
&#xD;
          -  Patients with acutely active or chronic infections.&#xD;
&#xD;
          -  Patients with uncontrolled diabetes, hypertension, cardiovascular, hepatic, or renal&#xD;
             disease&#xD;
&#xD;
          -  Pregnant or lactating females.&#xD;
&#xD;
          -  Patients with any medical condition that is felt by the primary investigator to place&#xD;
             the patient at unreasonable risk for adverse effects during treatment with H.P.&#xD;
             Acthar.&#xD;
&#xD;
          -  Hypersensitivity to H.P. Acthar, any of its components (allergy to pig-derived&#xD;
             proteins)&#xD;
&#xD;
          -  Patients with osteoporosis&#xD;
&#xD;
          -  Patients who have had surgery within 8 weeks of screening&#xD;
&#xD;
          -  Patients with a history of or current gastric ulcers&#xD;
&#xD;
          -  Patients taking daily doses of systemic corticosteroids greater than the equivalent of&#xD;
             40mg prednisone.&#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>Anthony P Fernandez, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Cleveland Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Levine T. Treating refractory dermatomyositis or polymyositis with adrenocorticotropic hormone gel: a retrospective case series. Drug Des Devel Ther. 2012;6:133-9. doi: 10.2147/DDDT.S33110. Epub 2012 Jun 11. Erratum In: Drug Des Devel Ther. 2012;6:163.</citation>
    <PMID>22787386</PMID>
  </reference>
  <reference>
    <citation>Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med. 1975 Feb 13;292(7):344-7. doi: 10.1056/NEJM197502132920706. No abstract available.</citation>
    <PMID>1090839</PMID>
  </reference>
  <reference>
    <citation>Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). N Engl J Med. 1975 Feb 20;292(8):403-7. doi: 10.1056/NEJM197502202920807. No abstract available.</citation>
    <PMID>1089199</PMID>
  </reference>
  <reference>
    <citation>Gerami P, Schope JM, McDonald L, Walling HW, Sontheimer RD. A systematic review of adult-onset clinically amyopathic dermatomyositis (dermatomyositis sine myositis): a missing link within the spectrum of the idiopathic inflammatory myopathies. J Am Acad Dermatol. 2006 Apr;54(4):597-613. doi: 10.1016/j.jaad.2005.10.041. Epub 2006 Jan 23.</citation>
    <PMID>16546580</PMID>
  </reference>
  <reference>
    <citation>Euwer RL, Sontheimer RD. Amyopathic dermatomyositis: a review. J Invest Dermatol. 1993 Jan;100(1):124S-127S. doi: 10.1111/1523-1747.ep12356896.</citation>
    <PMID>8423381</PMID>
  </reference>
  <reference>
    <citation>Klein RQ, Bangert CA, Costner M, Connolly MK, Tanikawa A, Okawa J, Rose M, Fakharzadeh SS, Fiorentino D, Lee LA, Sontheimer RD, Taylor L, Troxel AB, Werth VP. Comparison of the reliability and validity of outcome instruments for cutaneous dermatomyositis. Br J Dermatol. 2008 Sep;159(4):887-94. doi: 10.1111/j.1365-2133.2008.08711.x. Epub 2008 Jul 4.</citation>
    <PMID>18616782</PMID>
  </reference>
  <reference>
    <citation>Yassaee M, Fiorentino D, Okawa J, Taylor L, Coley C, Troxel AB, Werth VP. Modification of the cutaneous dermatomyositis disease area and severity index, an outcome instrument. Br J Dermatol. 2010 Mar;162(3):669-73. doi: 10.1111/j.1365-2133.2009.09521.x. Epub 2009 Oct 26.</citation>
    <PMID>19863510</PMID>
  </reference>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>September 11, 2014</study_first_submitted>
  <study_first_submitted_qc>September 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 22, 2014</study_first_posted>
  <last_update_submitted>September 10, 2021</last_update_submitted>
  <last_update_submitted_qc>September 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 16, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Cleveland Clinic</investigator_affiliation>
    <investigator_full_name>Anthony Fernandez, MD, PhD</investigator_full_name>
    <investigator_title>Md, PhD</investigator_title>
  </responsible_party>
  <keyword>dermatomyositis</keyword>
  <keyword>Acthar gel</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dermatomyositis</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>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT02245841
org study id: 14-1015
nct id: NCT02245841
lead sponsor: 
collaborator: 
has dmc: No
This study will assess the safety and efficacy of H.P. Acthar gel for treating the cutaneous
      manifestations in patients with refractory classic dermatomyositis, juvenile dermatomyositis,
      and amyopathic dermatomyositis. Our hypothesis is that H.P. Acthar gel will be both safe and
      effective for such patients.
Adult and juvenile dermatomyositis (DM) are systemic immune-mediated inflammatory diseases
      most commonly affecting the skin and musculoskeletal system. Amyopathic dermatomyositis is a
      subtype of dermatomyositis that affects only the skin and lacks the characteristic muscle
      involvement. Treatment of these conditions, in particular the cutaneous manifestations, is
      challenging and currently no universally effective single treatment exists. Many patients
      have cutaneous manifestations that are refractory to numerous medications.

      H.P. Acthar gel (adrenocorticotropic hormone gel) received FDA approval for treatment of a
      variety of diseases, including dermatomyositis, in 1952. Despite this there is a paucity of
      clinical data concerning the efficacy of H.P. Acthar gel for treating dermatomyositis.
      Recently a small, retrospective case series describing significant improvement in both
      cutaneous and musculoskeletal symptoms in 5 patients with refractory dermatomyositis treated
      with H.P. Acthar gel was reported and has resulted in renewed interest in use of this
      medication in dermatomyositis patient (reference below). The proposed efficacy of H.P. Acthar
      gel has been attributed to its unique ability to induce production of endogenous cortisol,
      corticosterone, aldosterone, and to bind melanocortin receptors on lymphocytes and other
      cells to modulate immunologic responses.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change from baseline in cutaneous manifestations of dermatomyositis at 1, 3, and 6 months
time frame: 6 months
description: Statistically significant change between baseline and 1, 3, and 6 months in cutaneous manifestations of dermatomyositis based on modified CDASI (modified Cutaneous Dermatomyositis Disease Area and Severity Index) scores at these timepoints.
measure: Change from baseline in cutaneous manifestations of dermatomyositis at 1, 3, and 6 months
time frame: 6 months
description: Change between baseline and 1, 3, and 6 months in cutaneous manifestations of dermatomyositis based on Physician's Global Assessment scores at these timepoints.
measure: Change from baseline in patient assessment of dermatomyositis at 1, 3, and 6 months
time frame: 6 months
description: Statistically significant change between baseline and 1, 3, and 6 months in patient assessed "Global Patient Score" at these timepoints.
measure: Change from baseline in patient assessment of dermatomyositis at 1, 3, and 6 months
time frame: 6 months
description: Statistically significant change between baseline and 1, 3, and 6 months in patient assessed "Global Itch Score" at these timepoints.
measure: Change from baseline in patient assessment of dermatomyositis at 1, 3, and 6 months
time frame: 6 months
description: Statistically significant change between baseline and 1, 3, and 6 months in patient assessed Dermatology Life Quality Index (DLQI) scores at these timepoints.
measure: Number of patients with adverse effects.
time frame: 6 months
description: Safety and tolerability of H.P. Acthar gel based on frequency and types of adverse effects.
measure: Number of patients with change in dose of systemic corticosteroids and/or steroid-sparing immunosuppressive agents
time frame: 6 months
description: Median/mean change in dose of systemic corticosteroids and/or steroid-sparing immunosuppressive agents from initiation to completion of study
measure: Number of patients with change in HbA1c
time frame: 6 months
description: Median/mean change in HbA1c
arm group label: H.P Acthar Gel
arm group type: Experimental
description: 80 U (1 mL) of H.P. Acthar gel via subcutaneous injection twice weekly for 24 weeks
intervention type: Drug
intervention name: H.P. Acthar Gel
description: 80 U (1 mL) of H.P. Acthar gel via subcutaneous injection twice weekly for 24 weeks
arm group label: H.P Acthar Gel
other name: Acthar Gel
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Anthony P Fernandez, MD, PhD
role: Principal Investigator
affiliation: The Cleveland Clinic
facility: 
country: United States
citation: Levine T. Treating refractory dermatomyositis or polymyositis with adrenocorticotropic hormone gel: a retrospective case series. Drug Des Devel Ther. 2012;6:133-9. doi: 10.2147/DDDT.S33110. Epub 2012 Jun 11. Erratum In: Drug Des Devel Ther. 2012;6:163.
PMID: 22787386
citation: Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med. 1975 Feb 13;292(7):344-7. doi: 10.1056/NEJM197502132920706. No abstract available.
PMID: 1090839
citation: Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). N Engl J Med. 1975 Feb 20;292(8):403-7. doi: 10.1056/NEJM197502202920807. No abstract available.
PMID: 1089199
citation: Gerami P, Schope JM, McDonald L, Walling HW, Sontheimer RD. A systematic review of adult-onset clinically amyopathic dermatomyositis (dermatomyositis sine myositis): a missing link within the spectrum of the idiopathic inflammatory myopathies. J Am Acad Dermatol. 2006 Apr;54(4):597-613. doi: 10.1016/j.jaad.2005.10.041. Epub 2006 Jan 23.
PMID: 16546580
citation: Euwer RL, Sontheimer RD. Amyopathic dermatomyositis: a review. J Invest Dermatol. 1993 Jan;100(1):124S-127S. doi: 10.1111/1523-1747.ep12356896.
PMID: 8423381
citation: Klein RQ, Bangert CA, Costner M, Connolly MK, Tanikawa A, Okawa J, Rose M, Fakharzadeh SS, Fiorentino D, Lee LA, Sontheimer RD, Taylor L, Troxel AB, Werth VP. Comparison of the reliability and validity of outcome instruments for cutaneous dermatomyositis. Br J Dermatol. 2008 Sep;159(4):887-94. doi: 10.1111/j.1365-2133.2008.08711.x. Epub 2008 Jul 4.
PMID: 18616782
citation: Yassaee M, Fiorentino D, Okawa J, Taylor L, Coley C, Troxel AB, Werth VP. Modification of the cutaneous dermatomyositis disease area and severity index, an outcome instrument. Br J Dermatol. 2010 Mar;162(3):669-73. doi: 10.1111/j.1365-2133.2009.09521.x. Epub 2009 Oct 26.
PMID: 19863510
responsible party type: Principal Investigator
investigator affiliation: The Cleveland Clinic
investigator full name: Anthony Fernandez, MD, PhD
investigator title: Md, PhD
mesh term: Dermatomyositis
mesh term: Adrenocorticotropic Hormone
sharing ipd: Undecided