<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/NCT03002649</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00084227</org_study_id>
    <nct_id>NCT03002649</nct_id>
  </id_info>
  <brief_title>Study of Tofacitinib in Refractory Dermatomyositis</brief_title>
  <acronym>STIR</acronym>
  <official_title>Study of Tofacitinib in Refractory Dermatomyositis (STIR): Proof of Concept, Open-Label Study of 10 Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Johns Hopkins University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Johns Hopkins University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to obtain preliminary data regarding the safety and efficacy of&#xD;
      Janus kinase (JAK) inhibitor, tofacitinib, in adults with active, treatment-refractory&#xD;
      dermatomyositis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Dermatomyositis (DM) is a rare, progressively debilitating disorder that affects the muscle&#xD;
      (causing weakness) and skin (causing a rash) in most affected patients. DM can also involve&#xD;
      multiple body systems including the lungs, joints, gut and heart. Therapy for DM involves&#xD;
      administering corticosteroids, typically with an immunosuppressive agent, but treatment&#xD;
      options for refractory DM are very limited. This research is being done to determine the&#xD;
      safety and effectiveness of a Janus kinase (JAK) inhibitor called Tofacitinib in adults with&#xD;
      active, treatment-refractory dermatomyositis. The investigators will also look for specific&#xD;
      biomolecular changes in blood, skin, and muscle when it is exposed to Tofacitinib.&#xD;
      Tofacitinib is approved by the Food and Drug Administration (FDA) for the treatment of&#xD;
      rheumatoid arthritis. The study aim is to conduct a 12-week, open-label, pilot study with up&#xD;
      to 10 patients who have refractory DM to assess whether a JAK inhibitor effectively and&#xD;
      safely reduces the symptoms of DM in both the skin and muscle. This study consists of up to 9&#xD;
      study visits over 6 months. There is an optional treatment extension period of 4 weeks. All&#xD;
      subjects will undergo follow-up assessments 4 weeks after stopping treatment. Results from&#xD;
      this study will contribute to the design of future trials that will further define the role&#xD;
      of JAK inhibitors in the treatment of patients with dermatomyositis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2017</start_date>
  <completion_date type="Actual">September 30, 2020</completion_date>
  <primary_completion_date type="Actual">September 30, 2020</primary_completion_date>
  <phase>Phase 1</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>Number of participants who achieve International Myositis Assessment and Clinical Studies (IMACS) Definition of Improvement (DOI)</measure>
    <time_frame>Up to 12 weeks</time_frame>
    <description>IMACS DOI is 3 of any of the 6 core set measures (CSM) improved by ≥ 20%, with no more than 2 CSM worsening by ≥25% (worsening measure cannot include the manual muscle testing)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in CDASI activity score</measure>
    <time_frame>Up to 16 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability of tofacitinib as assessed by frequency of adverse events reported and observed</measure>
    <time_frame>Up to 16 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability of tofacitinib as assessed by incidence of adverse events reported and observed</measure>
    <time_frame>Up to 16 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Dermatomyositis</condition>
  <arm_group>
    <arm_group_label>Tofacitinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All subjects will be provided Tofacitinib 11mg tablets for oral administration once daily. 12-week treatment period with optional 4-week treatment extension period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tofacitinib</intervention_name>
    <description>Tofacitinib comes as an extended-release (XR) (long-acting) tablet to take by mouth. The extended-release tablet is usually taken with or without food once daily.</description>
    <arm_group_label>Tofacitinib</arm_group_label>
    <other_name>Xeljanz XR</other_name>
    <other_name>Tofacitinib citrate</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Study subjects must meet the following criteria:&#xD;
&#xD;
          -  Definite or probable dermatomyositis by Bohan and Peter Criteria at least 6 months&#xD;
             before screening&#xD;
&#xD;
          -  Active skin disease as defined by a CDASI score of at least 5&#xD;
&#xD;
          -  Skin biopsy proven disease&#xD;
&#xD;
          -  Although not mandatory, patients with muscle weakness are eligible for enrollment.&#xD;
             Those with active muscle disease must have a Manual Muscle Testing (MMT-8) score &lt; 142&#xD;
             out of 150&#xD;
&#xD;
          -  Age &gt; 18&#xD;
&#xD;
          -  Refractory myositis is defined by active disease despite a 12 week trial of steroids&#xD;
             and with failure of response to at least prednisone and 1 other first line&#xD;
             immunosuppressive agents (e.g. methotrexate, mycophenolate mofetil, or azathioprine)&#xD;
             OR have demonstrated significant toxicity or intolerance to such therapies&#xD;
&#xD;
          -  Maximum prednisone dose allowed will be 20mg/daily at time of entry to study provided&#xD;
             that the dose has been stable for at least 2 weeks prior to baseline. Patients should&#xD;
             not have received a daily therapy of more than 80mg of prednisone equivalent within 8&#xD;
             weeks prior to study entry&#xD;
&#xD;
          -  Negative cancer screening conducted in the 6 months prior to screening visit&#xD;
&#xD;
          -  Washout of immunosuppressive agents will be as follows:&#xD;
&#xD;
               1. Azathioprine, mycophenolate, tacrolimus: 12-16 weeks prior to first dose of study&#xD;
                  drug;&#xD;
&#xD;
               2. Rituximab: 12 months;&#xD;
&#xD;
               3. Intravenous Immunoglobulin (IVIg): 3 months;&#xD;
&#xD;
               4. Cyclophosphamide: 1 year;&#xD;
&#xD;
               5. Methotrexate: 12-16 weeks.&#xD;
&#xD;
          -  Women of child-bearing potential must have negative pregnancy test and be willing to&#xD;
             undergo urine pregnancy testing at every on-site visit for the duration of the study&#xD;
&#xD;
          -  Must provide informed consent&#xD;
&#xD;
          -  Must be willing and able to comply with the requirements of the protocol&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        The presence of any of the following excludes subject participation in the study:&#xD;
&#xD;
          -  Use of other investigational drugs at the time of enrollment&#xD;
&#xD;
          -  History of hypersensitivity to any of the study drugs or drugs of similar chemical&#xD;
             classes&#xD;
&#xD;
          -  DM patients having overlap myositis attributable to other causes such as scleroderma,&#xD;
             arthritis, statin myopathy, steroid induced myopathy and/or significant organ damage&#xD;
             e.g. lupus nephritis, central nervous system are present&#xD;
&#xD;
          -  Late stage DM whose muscle weakness, according to the Investigator, could be&#xD;
             attributable to muscle damage rather than myositis disease activity&#xD;
&#xD;
          -  Patients with other types of myositis or myopathies: polymyositis, paraneoplastic&#xD;
             myositis, inclusion body myositis, metabolic or drug induced myopathy, dystrophies&#xD;
&#xD;
          -  Inclusion body myositis, Juvenile dermatomyositis or polymyositis, or myositis in&#xD;
             overlap with other rheumatic diseases such as lupus, scleroderma, Sjogren's, or&#xD;
             vasculitis&#xD;
&#xD;
          -  Patients with advanced clinically symptomatic interstitial lung disease&#xD;
&#xD;
          -  Pregnancy or breast-feeding patients&#xD;
&#xD;
          -  History of bowel rupture or inflammatory bowel diseases&#xD;
&#xD;
          -  History of tuberculosis or mycobacterial infections&#xD;
&#xD;
          -  Recent infection in the past 4 weeks before entry of study&#xD;
&#xD;
          -  History of any malignancy of any organ system (other than localized basal cell&#xD;
             carcinoma of the skin), treated or untreated, within the past 5 years, regardless of&#xD;
             whether there is evidence of local recurrence or metastases&#xD;
&#xD;
          -  Active systemic bacterial, viral or fungal infections, or diagnosis of AIDS, Hepatitis&#xD;
             B, Hepatitis C infection&#xD;
&#xD;
          -  Diverticulitis or ulcers in stomach or intestines&#xD;
&#xD;
          -  Evidence of any other acute or chronic infectious diseases&#xD;
&#xD;
          -  Have received any live or live attenuated vaccines (including varicella or measles)&#xD;
             within 2 months prior to study enrollment&#xD;
&#xD;
          -  Patients with any of the following hepatic conditions prior to study: (a) history of&#xD;
             chronic liver or biliary disease, (b) total conjugated bilirubin greater than 1.5&#xD;
             times upper limits of normal (ULN) range, unless in the context of Gilbert's syndrome,&#xD;
             (c) alkaline phosphatase greater than 1.5 times the ULN range, (d) aspartate&#xD;
             transaminase (AST), alanine transaminase (ALT) greater than 3 times the ULN if the&#xD;
             elevation of AST or ALT, according to the investigator, is attributable to liver&#xD;
             disease. Patients with elevated AST/ALT due to myositis disease activity are eligible,&#xD;
             (e) Gamma-glutamyltransferase (GGT) greater than 3 times the ULN range&#xD;
&#xD;
          -  Current or recent history of uncontrolled renal, hepatic, hematological,&#xD;
             gastrointestinal, metabolic, endocrine, pulmonary, cardiac, or neurological disease&#xD;
&#xD;
          -  Blood dyscrasias within 3 months prior to the first dose of study medication,&#xD;
             including confirmed:&#xD;
&#xD;
               1. Hemoglobin &lt;9 g/dL or Hematocrit &lt;30%;&#xD;
&#xD;
               2. White blood cell count &lt;3.0 x 109/L;&#xD;
&#xD;
               3. Absolute neutrophil count &lt;1.2 x 109/L;&#xD;
&#xD;
               4. Platelet count &lt;100 x 109/L.&#xD;
&#xD;
          -  Estimated glomerular filtration rate (GFR) &lt;40 ml/min based on Cockcroft-Gault&#xD;
             calculation&#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>Julie Paik, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johns Hopkins University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Johns Hopkins University</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>December 20, 2016</study_first_submitted>
  <study_first_submitted_qc>December 21, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 26, 2016</study_first_posted>
  <last_update_submitted>November 5, 2020</last_update_submitted>
  <last_update_submitted_qc>November 5, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 6, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Dermatomyositis</keyword>
  <keyword>Tofacitinib</keyword>
  <keyword>Refractory dermatomyositis</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>Tofacitinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03002649
org study id: IRB00084227
nct id: NCT03002649
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study is to obtain preliminary data regarding the safety and efficacy of
      Janus kinase (JAK) inhibitor, tofacitinib, in adults with active, treatment-refractory
      dermatomyositis.
Dermatomyositis (DM) is a rare, progressively debilitating disorder that affects the muscle
      (causing weakness) and skin (causing a rash) in most affected patients. DM can also involve
      multiple body systems including the lungs, joints, gut and heart. Therapy for DM involves
      administering corticosteroids, typically with an immunosuppressive agent, but treatment
      options for refractory DM are very limited. This research is being done to determine the
      safety and effectiveness of a Janus kinase (JAK) inhibitor called Tofacitinib in adults with
      active, treatment-refractory dermatomyositis. The investigators will also look for specific
      biomolecular changes in blood, skin, and muscle when it is exposed to Tofacitinib.
      Tofacitinib is approved by the Food and Drug Administration (FDA) for the treatment of
      rheumatoid arthritis. The study aim is to conduct a 12-week, open-label, pilot study with up
      to 10 patients who have refractory DM to assess whether a JAK inhibitor effectively and
      safely reduces the symptoms of DM in both the skin and muscle. This study consists of up to 9
      study visits over 6 months. There is an optional treatment extension period of 4 weeks. All
      subjects will undergo follow-up assessments 4 weeks after stopping treatment. Results from
      this study will contribute to the design of future trials that will further define the role
      of JAK inhibitors in the treatment of patients with dermatomyositis.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants who achieve International Myositis Assessment and Clinical Studies (IMACS) Definition of Improvement (DOI)
time frame: Up to 12 weeks
description: IMACS DOI is 3 of any of the 6 core set measures (CSM) improved by ≥ 20%, with no more than 2 CSM worsening by ≥25% (worsening measure cannot include the manual muscle testing)
measure: Change from baseline in CDASI activity score
time frame: Up to 16 weeks
measure: Safety and tolerability of tofacitinib as assessed by frequency of adverse events reported and observed
time frame: Up to 16 weeks
measure: Safety and tolerability of tofacitinib as assessed by incidence of adverse events reported and observed
time frame: Up to 16 weeks
arm group label: Tofacitinib
arm group type: Experimental
description: All subjects will be provided Tofacitinib 11mg tablets for oral administration once daily. 12-week treatment period with optional 4-week treatment extension period.
intervention type: Drug
intervention name: Tofacitinib
description: Tofacitinib comes as an extended-release (XR) (long-acting) tablet to take by mouth. The extended-release tablet is usually taken with or without food once daily.
arm group label: Tofacitinib
other name: Xeljanz XR
other name: Tofacitinib citrate
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Julie Paik, MD
role: Principal Investigator
affiliation: Johns Hopkins University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Dermatomyositis
mesh term: Tofacitinib
sharing ipd: No