<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/NCT03793439</url>
  </required_header>
  <id_info>
    <org_study_id>STUDY00017902</org_study_id>
    <nct_id>NCT03793439</nct_id>
  </id_info>
  <brief_title>Tofacitinib Hypothesis-generating, Pilot Study for Corticosteroid-Dependent Sarcoidosis</brief_title>
  <official_title>Tofacitinib Hypothesis-generating, Pilot Study for Corticosteroid-Dependent Sarcoidosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Oregon Health and Science University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Oregon Health and Science University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a pilot study to determine whether further research is warranted to assess whether&#xD;
      tofacitinib is an effective steroid sparing treatment for pulmonary sarcoidosis. The primary&#xD;
      endpoint for this study is a 50% or greater reduction in corticosteroid requirement.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary Objectives:&#xD;
&#xD;
      Objective 1: Test the hypothesis that the addition of tofacitinib will allow patients with&#xD;
      sarcoidosis to have 50% or greater reduction in their corticosteroid requirement without a&#xD;
      significant decrease in pulmonary function testing, and with a similar quality of life as&#xD;
      measured by a validated questionnaire (1).&#xD;
&#xD;
      Objective 2: Test the hypothesis that the addition of tofacitinib will result in&#xD;
      significantly decreased expression of signal transducer and activator of transcription&#xD;
      (STAT)-1 dependent gene expression.&#xD;
&#xD;
      Outline:&#xD;
&#xD;
      This is a 16-week open-label, interventional, proof of concept, hypothesis-generating study.&#xD;
      All subjects will receive Tofacitinib 5mg twice daily for 16 weeks. After four weeks on&#xD;
      Tofacitinib, the corticosteroid will be tapered per a pre-defined protocol; once a reduction&#xD;
      of 50% has been achieved, any further taper will be per physician discretion. After 16 weeks,&#xD;
      subjects who meet the primary end-point will be permitted an optional one year open-label&#xD;
      extension.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 15, 2019</start_date>
  <completion_date type="Actual">June 24, 2021</completion_date>
  <primary_completion_date type="Actual">June 24, 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>
    <intervention_model_description>Open-label, interventional, proof of concept, hypothesis-generating study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With 50% Reduction in Corticosteroid Requirement</measure>
    <time_frame>16 weeks</time_frame>
    <description>50% reduction in corticosteroid requirement by week 16, without significant decline in their pulmonary function-defined as a &gt;15% decline in forced vital capacity (FVC), forced expiratory volume at 1 second (FEV1), or diffusing capacity of lung for carbon monoxide (DLCO) relative to the baseline value</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Significantly Decreased Expression of STAT1 Mediated Genes as Determined by RNA Sequencing</measure>
    <time_frame>16 weeks</time_frame>
    <description>Peripheral blood RNA sequencing performed before and after 16 weeks of tofacitinib treatment. Significant changes are defined as at least 1.5 fold change in the expression of STAT1-mediated genes, with a false discover rate p value of &lt; 0.05.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Sarcoidosis, Pulmonary</condition>
  <condition>Sarcoidosis Lung</condition>
  <condition>Sarcoidosis</condition>
  <arm_group>
    <arm_group_label>Open-label treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All subjects will receive tofacitinib 5mg twice daily from week 0 to week 16, and a corticosteroid taper starting at week 16. Participants also undergo spirometry, RNA sequence testing, and laboratory evaluations.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tofacitinib 5mg Oral Tablet [Xeljanz] 16 week trial</intervention_name>
    <description>Tofacitinib 5mg oral table twice daily for 16 weeks</description>
    <arm_group_label>Open-label treatment</arm_group_label>
    <other_name>Xeljanz</other_name>
    <other_name>tofacitinib</other_name>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Spirometry</intervention_name>
    <description>Spirometry testing at baseline, week 4, week 8, week 12, and week 16</description>
    <arm_group_label>Open-label treatment</arm_group_label>
    <other_name>Pulmonary function test</other_name>
  </intervention>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>RNA Sequencing</intervention_name>
    <description>RNA sequencing test at baseline and week 16</description>
    <arm_group_label>Open-label treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Laboratory testing</intervention_name>
    <description>Laboratory testing at baseline and weeks 2, 4, 8, 12 and 16</description>
    <arm_group_label>Open-label treatment</arm_group_label>
    <other_name>Blood work</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Corticosteroid</intervention_name>
    <description>Taper corticosteroids starting at week 4</description>
    <arm_group_label>Open-label treatment</arm_group_label>
    <other_name>Corticosteroid taper</other_name>
    <other_name>Prednisone taper</other_name>
    <other_name>Steroid taper</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tofacitinib 5mg [Xeljanz] 1 year open-label extension</intervention_name>
    <description>After 16 weeks, subjects who meet the primary end-point will be permitted an optional one year open-label extension.</description>
    <arm_group_label>Open-label treatment</arm_group_label>
    <other_name>tofacitinib</other_name>
    <other_name>Xeljanz</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Meet World Association of Sarcoidosis and other Granulomatous Disorders (WASOG)&#xD;
             definition of pulmonary sarcoid&#xD;
&#xD;
          -  Histologically proven sarcoid&#xD;
&#xD;
          -  Evidence of pulmonary sarcoid on chest radiograph&#xD;
&#xD;
          -  Forced vital capacity of &gt; 50%&#xD;
&#xD;
          -  Require 15-30mg/day of prednisone or equivalent corticosteroid to control sarcoidosis.&#xD;
&#xD;
          -  Stable dose of prednisone or equivalent corticosteroid for 4 weeks prior to&#xD;
             enrollment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  May be taking methotrexate but not other immunosuppressive or immunomodulatory&#xD;
             treatments in the two months prior to study period. This includes but is not limited&#xD;
             to azathioprine, cyclophosphamide, leflunomide, mycophenolate mofetil, cyclosporine,&#xD;
             tacrolimus, and biologic medications.&#xD;
&#xD;
          -  Patients requiring &gt;30mg/day prednisone or equivalent.&#xD;
&#xD;
          -  Pregnant or lactating women.&#xD;
&#xD;
          -  Hemoglobin &lt; 9g/dL or hematocrit &lt; 30%&#xD;
&#xD;
          -  White blood cell count &lt;3.0 K/cu mm&#xD;
&#xD;
          -  Absolute neutrophil count &lt;1.2 K/cu mm&#xD;
&#xD;
          -  Platelet count &lt;100 K/cu mm&#xD;
&#xD;
          -  Subjects with an estimated glomerular filtration rate (GFR) ≤40 ml/min&#xD;
&#xD;
          -  Subjects with a total bilirubin, aspartate aminotransferase (AST), or alanine&#xD;
             aminotransferase (ALT) more than 1.5 times the upper limit of normal at screening.&#xD;
&#xD;
          -  Severe, progressive, or uncontrolled chronic liver disease including fibrosis,&#xD;
             cirrhosis, or recent or active hepatitis.&#xD;
&#xD;
          -  History of any lymphoproliferative disorder such as Epstein Barr virus (EBV) related&#xD;
             lymphoproliferative disorder, history of lymphoma, leukemia, or signs and symptoms&#xD;
             suggest of current lymphatic disease.&#xD;
&#xD;
          -  Current malignancy or history of malignancy, with the exception of adequately treated&#xD;
             or excised non-metastatic basal cell or squamous cell cancer of the skin, or cervical&#xD;
             carcinoma in situ.&#xD;
&#xD;
          -  Have or have had an opportunistic infection (e.g., herpes zoster [shingles],&#xD;
             cytomegalovirus, Pneumocystis carinii, aspergillosis and aspergilloma, histoplasmosis,&#xD;
             or mycobacteria other than TB) within 6 months prior to screening.&#xD;
&#xD;
          -  Have a known infection with human immunodeficiency virus (HIV)&#xD;
&#xD;
          -  Have current signs and symptoms of systemic lupus erythematosus, or severe,&#xD;
             progressive, or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary,&#xD;
             cardiac (New York Heart Association class III or IV), neurologic, or cerebral diseases&#xD;
             (with the exception of sarcoidosis).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>89 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jim Rosenbaum, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Oregon Health and Science University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Oregon Health &amp; Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Rosenbaum JT, Choi D, Wilson DJ, Grossniklaus HE, Harrington CA, Sibley CH, Dailey RA, Ng JD, Steele EA, Czyz CN, Foster JA, Tse D, Alabiad C, Dubovy S, Parekh P, Harris GJ, Kazim M, Patel P, White V, Dolman P, Korn BS, Kikkawa D, Edward DP, Alkatan H, Al-Hussain H, Yeatts RP, Selva D, Stauffer P, Planck SR. Parallel Gene Expression Changes in Sarcoidosis Involving the Lacrimal Gland, Orbital Tissue, or Blood. JAMA Ophthalmol. 2015 Jul;133(7):770-7. doi: 10.1001/jamaophthalmol.2015.0726.</citation>
    <PMID>25880323</PMID>
  </reference>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>January 2, 2019</study_first_submitted>
  <study_first_submitted_qc>January 2, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 4, 2019</study_first_posted>
  <results_first_submitted>September 8, 2021</results_first_submitted>
  <results_first_submitted_qc>December 3, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">February 18, 2022</results_first_posted>
  <last_update_submitted>December 3, 2021</last_update_submitted>
  <last_update_submitted_qc>December 3, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 18, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Oregon Health and Science University</investigator_affiliation>
    <investigator_full_name>Jim Rosenbaum</investigator_full_name>
    <investigator_title>Professor of Ophthalmology, Medicine, and Cell Biology, OHSU</investigator_title>
  </responsible_party>
  <keyword>Sarcoidosis</keyword>
  <keyword>Corticosteroid dependent sarcoidosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sarcoidosis, Pulmonary</mesh_term>
    <mesh_term>Sarcoidosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prednisone</mesh_term>
    <mesh_term>Tofacitinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>De-identified individual participant data for all primary and secondary outcomes will be made available.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>January 1, 2022 until December 31, 2023</ipd_time_frame>
    <ipd_access_criteria>Email friedmam@ohsu.edu</ipd_access_criteria>
  </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>July 15, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/39/NCT03793439/Prot_SAP_000.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>March 29, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/39/NCT03793439/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Open Label</title>
          <description>Tofacitinib 5 mg twice daily by mouth</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>5 participants were analyzed for baseline characteristics. The overall number of baseline participants did not differ from the number assigned to arms and entire study.</population>
      <group_list>
        <group group_id="B1">
          <title>Open-label Treatment</title>
          <description>All subjects will receive tofacitinib 5mg twice daily from week 0 to week 16, and a corticosteroid taper starting at week 16. Participants also undergo spirometry, RNA sequence testing, and laboratory evaluations.&#xD;
Tofacitinib 5mg Oral Tablet [Xeljanz] 16 week trial: Tofacitinib 5mg oral table twice daily for 16 weeks&#xD;
Spirometry: Spirometry testing at baseline, week 4, week 8, week 12, and week 16&#xD;
RNA Sequencing: RNA sequencing test at baseline and week 16&#xD;
Laboratory testing: Laboratory testing at baseline and weeks 2, 4, 8, 12 and 16&#xD;
Corticosteroid: Taper corticosteroids starting at week 4&#xD;
Tofacitinib 5mg [Xeljanz] 1 year open-label extension: After 16 weeks, subjects who meet the primary end-point will be permitted an optional one year open-label extension.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="5"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <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="40.8" lower_limit="35" upper_limit="50"/>
                  </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="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </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="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </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>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With 50% Reduction in Corticosteroid Requirement</title>
        <description>50% reduction in corticosteroid requirement by week 16, without significant decline in their pulmonary function-defined as a &gt;15% decline in forced vital capacity (FVC), forced expiratory volume at 1 second (FEV1), or diffusing capacity of lung for carbon monoxide (DLCO) relative to the baseline value</description>
        <time_frame>16 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Open Label</title>
            <description>open label tofacitinib</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With 50% Reduction in Corticosteroid Requirement</title>
          <description>50% reduction in corticosteroid requirement by week 16, without significant decline in their pulmonary function-defined as a &gt;15% decline in forced vital capacity (FVC), forced expiratory volume at 1 second (FEV1), or diffusing capacity of lung for carbon monoxide (DLCO) relative to the baseline value</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="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Significantly Decreased Expression of STAT1 Mediated Genes as Determined by RNA Sequencing</title>
        <description>Peripheral blood RNA sequencing performed before and after 16 weeks of tofacitinib treatment. Significant changes are defined as at least 1.5 fold change in the expression of STAT1-mediated genes, with a false discover rate p value of &lt; 0.05.</description>
        <time_frame>16 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Open Label</title>
            <description>open label tofacitinib</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Significantly Decreased Expression of STAT1 Mediated Genes as Determined by RNA Sequencing</title>
          <description>Peripheral blood RNA sequencing performed before and after 16 weeks of tofacitinib treatment. Significant changes are defined as at least 1.5 fold change in the expression of STAT1-mediated genes, with a false discover rate p value of &lt; 0.05.</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="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data were collected from week 0 (start of study drug) until study drug was stopped, plus 4 weeks of post-treatment follow up. This corresponded to 72 weeks for subjects who completed the study and open-label extension: study (16 weeks), open-label extension (52 weeks), and post-treatment follow up (4 weeks). Adverse event data from subjects who terminated the study early were collected until study drug was stopped + 4 weeks.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Open Label</title>
          <description>open label tofacitinib</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>NCI v5.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Peripheral motor neuropathy</sub_title>
                <description>Flare of neurosarcoidosis with peripheral neuropathy requiring escalation of glucocorticoids and subsequent withdrawal from the clinical trial. Treated with high dose glucocorticoids and infliximab, resolved.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin infection</sub_title>
                <description>Upper extremity cellulitis during post-study monitoring period. Occurred while on prednisone 30 mg/day, 9 days after the last study drug dose, 10 days after infliximab 5 mg/kg, resolved.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>NCI v5.0</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="4" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Vomiting</sub_title>
                <description>Emesis after suspected ingestion of spoiled food, resolved without intervention.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <description>3 days of diarrhea, resolved without intervention.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <description>ER visit, arthrocentesis with non-inflammatory fluid, no crystals, resolved with conservative management.&#xD;
Motor vehicle accident w/ ER visit for right knee and left shoulder pain. X-rays without fracture. Resolved with physical therapy</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal colic</sub_title>
                <description>ER visit for renal colic, initially thought to be urinary tract infection and given antibiotic however urinalysis and culture negative. Renal stones on CT, required pain medication and hydration, resolved.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic rhinitis</sub_title>
                <description>Exacerbation of seasonal nasal allergies</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <description>Cough up to 3-4x/week, resolved without intervention.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Bronchial infection</sub_title>
                <description>ER visit for bronchitis, no pneumonia in imaging. Treated with oral antibiotics, resolved.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <description>Mild rash on scalp and face, resolved without intervention.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </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>
    <point_of_contact>
      <name_or_title>Dr. Marcia Friedman</name_or_title>
      <organization>Oregon Health &amp; Science University</organization>
      <phone>5034948637</phone>
      <email>friedmam@ohsu.edu</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/NCT03793439
org study id: STUDY00017902
nct id: NCT03793439
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a pilot study to determine whether further research is warranted to assess whether
      tofacitinib is an effective steroid sparing treatment for pulmonary sarcoidosis. The primary
      endpoint for this study is a 50% or greater reduction in corticosteroid requirement.
Primary Objectives:

      Objective 1: Test the hypothesis that the addition of tofacitinib will allow patients with
      sarcoidosis to have 50% or greater reduction in their corticosteroid requirement without a
      significant decrease in pulmonary function testing, and with a similar quality of life as
      measured by a validated questionnaire (1).

      Objective 2: Test the hypothesis that the addition of tofacitinib will result in
      significantly decreased expression of signal transducer and activator of transcription
      (STAT)-1 dependent gene expression.

      Outline:

      This is a 16-week open-label, interventional, proof of concept, hypothesis-generating study.
      All subjects will receive Tofacitinib 5mg twice daily for 16 weeks. After four weeks on
      Tofacitinib, the corticosteroid will be tapered per a pre-defined protocol; once a reduction
      of 50% has been achieved, any further taper will be per physician discretion. After 16 weeks,
      subjects who meet the primary end-point will be permitted an optional one year open-label
      extension.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Open-label, interventional, proof of concept, hypothesis-generating study
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With 50% Reduction in Corticosteroid Requirement
time frame: 16 weeks
description: 50% reduction in corticosteroid requirement by week 16, without significant decline in their pulmonary function-defined as a >15% decline in forced vital capacity (FVC), forced expiratory volume at 1 second (FEV1), or diffusing capacity of lung for carbon monoxide (DLCO) relative to the baseline value
measure: Number of Participants With Significantly Decreased Expression of STAT1 Mediated Genes as Determined by RNA Sequencing
time frame: 16 weeks
description: Peripheral blood RNA sequencing performed before and after 16 weeks of tofacitinib treatment. Significant changes are defined as at least 1.5 fold change in the expression of STAT1-mediated genes, with a false discover rate p value of < 0.05.
arm group label: Open-label treatment
arm group type: Experimental
description: All subjects will receive tofacitinib 5mg twice daily from week 0 to week 16, and a corticosteroid taper starting at week 16. Participants also undergo spirometry, RNA sequence testing, and laboratory evaluations.
intervention type: Drug
intervention name: Tofacitinib 5mg Oral Tablet [Xeljanz] 16 week trial
description: Tofacitinib 5mg oral table twice daily for 16 weeks
arm group label: Open-label treatment
other name: Xeljanz
other name: tofacitinib
intervention type: Diagnostic Test
intervention name: Spirometry
description: Spirometry testing at baseline, week 4, week 8, week 12, and week 16
arm group label: Open-label treatment
other name: Pulmonary function test
intervention type: Genetic
intervention name: RNA Sequencing
description: RNA sequencing test at baseline and week 16
arm group label: Open-label treatment
intervention type: Diagnostic Test
intervention name: Laboratory testing
description: Laboratory testing at baseline and weeks 2, 4, 8, 12 and 16
arm group label: Open-label treatment
other name: Blood work
intervention type: Drug
intervention name: Corticosteroid
description: Taper corticosteroids starting at week 4
arm group label: Open-label treatment
other name: Corticosteroid taper
other name: Prednisone taper
other name: Steroid taper
intervention type: Drug
intervention name: Tofacitinib 5mg [Xeljanz] 1 year open-label extension
description: After 16 weeks, subjects who meet the primary end-point will be permitted an optional one year open-label extension.
arm group label: Open-label treatment
other name: tofacitinib
other name: Xeljanz
criteria: 
gender: All
minimum age: 18 Years
maximum age: 89 Years
healthy volunteers: No
last name: Jim Rosenbaum, MD
role: Principal Investigator
affiliation: Oregon Health and Science University
facility: 
country: United States
citation: Rosenbaum JT, Choi D, Wilson DJ, Grossniklaus HE, Harrington CA, Sibley CH, Dailey RA, Ng JD, Steele EA, Czyz CN, Foster JA, Tse D, Alabiad C, Dubovy S, Parekh P, Harris GJ, Kazim M, Patel P, White V, Dolman P, Korn BS, Kikkawa D, Edward DP, Alkatan H, Al-Hussain H, Yeatts RP, Selva D, Stauffer P, Planck SR. Parallel Gene Expression Changes in Sarcoidosis Involving the Lacrimal Gland, Orbital Tissue, or Blood. JAMA Ophthalmol. 2015 Jul;133(7):770-7. doi: 10.1001/jamaophthalmol.2015.0726.
PMID: 25880323
responsible party type: Principal Investigator
investigator affiliation: Oregon Health and Science University
investigator full name: Jim Rosenbaum
investigator title: Professor of Ophthalmology, Medicine, and Cell Biology, OHSU
mesh term: Sarcoidosis, Pulmonary
mesh term: Sarcoidosis
mesh term: Prednisone
mesh term: Tofacitinib
sharing ipd: Yes
ipd description: De-identified individual participant data for all primary and secondary outcomes will be made available.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: January 1, 2022 until December 31, 2023
ipd access criteria: Email friedmam@ohsu.edu
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 